Rhodoferax

Rhodoferax is a genus of Betaproteobacteria belonging to the purple nonsulfur bacteriarophic. Originally, "Rhodoferax" species were included in the genus "Rhodocyclus" as the "Rhodocyclus gelatinous"-like group. The genus "Rhodoferax" was first proposed in 1991 to accommodate the taxonomic and phylogenetic discrepancies arising from its inclusion in the genus "Rhodocyclus". "Rhodoferax" currently comprises four described species: "R. fermentans", "R. antarcticus", "R. ferrireducens," and "R. saidenbachensis". "R. ferrireducens", lacks the typical phototrophic character common to two other "Rhodoferax" species. This difference has led researchers to propose the creation of a new genus, "Albidoferax", to accommodate this divergent species. The genus name was later corrected to "Albidiferax". Based on geno- and phenotypical characteristics, "A. ferrireducens" was reclassified in the genus Rhodoferax in 2014." R. saidenbachensis," a second non-phototrophic species of the genus "Rhodoferax" was described by Kaden "et al." in 2014.""
Taxonomy.
"Rhodoferax" species are Gram-negative rods, ranging in diameter from 0.5 to 0.9 µm with a single polar flagellum. The first two species described for the genus, "R. fermentans" and "R. antarcticus", are facultative photoheterotrophs that can grow anaerobically when exposed to light and aerobically under dark conditions at atmospheric levels of oxygen. "R. ferrireducens" is a nonphototrophic facultative anaerobe capable of reducing Fe(III) at temperatures as low as 4 °C. "R. saidenbachensis" grows strictly aerobic and has a very low rate of cell division. "" All "Rhodoferax" species possess ubiquinone and rhodoquinone derivatives with eight unit isoprenoid side chains. Dominant fatty acids in "Rhodoferax" cells are palmitoleic acid (16:1) and palmitic acid (16:0), as well as 3-OH octanoic acid (8:0). Major carotenoids found in the phototrophic species are spheroidene, OH-spheroidene, and spirilloxanthin.
Genomes.
As of 2014, three genomes have been sequenced from the genus "Rhodoferax". Sequencing of the "R. ferrireducens" T118 genome was carried out by the Joint Genome Institute, and assembly was completed in 2005. The "R. ferrireducens" genome contains a 4.71 Mbp chromosome with 59.9% GC content and a 257-kbp plasmid with 54.4% GC content. It has 4,169 protein-coding genes, six rRNA genes, and 44 tRNA genes on the chromosome, as well as 75 pseudogenes. The plasmid contains 248 protein coding genes, one tRNA gene, and 2 pseudogenes. Examination of the "R. ferrireducens" genome indicates that though it cannot grow autotrophically, several genes associated with CO2 fixation are present. The genome contains the gene for the ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) large subunit, while the small subunit is missing. Other Calvin-cycle enzymes are present, but the phosphoketolase and sedoheptulose-bisphosphatase genes are missing. The genome also contains several genes suggesting "R. ferrireducens" may have some ability to resist exposure to metalloids and heavy metals. These genes include a putative arsenite efflux pump and an arsenate reductase, as well as genes similar to those found in organisms capable of tolerating copper, chromium, cadmium, zinc, and cobalt. Despite its psychrotolerance, the genome appears to lack any known major cold-shock proteins.
Another sequenced genome in the genus "Rhodoferax" comes from "R. antarcticus". This genome consists of a 3.8-Mbp chromosome with 59.1% GC content and a 198-kbp plasmid with 48.4% GC content. The chromosome contains 4,036 putative open reading frames (ORFs), and the plasmid contains 226 ORFs. Within the genome are 64 tRNA, and three rRNA genes. Analysis of the genome reveals the presence of two forms of rubisco. The presence of two forms may allow "R. antarcticus" to take advantage of changing CO2 concentrations.
The third "Rhodoferax" genome, "Rhodoferax saidenbachensis " , was sequenced by the Swedish Veterinary Institute SVA. The GC content of the 4.26 Mb genome is 60.9%. There are 3949 protein-coding genes, 46 tRNA, and six rRNA genes in the genome of the "R. sidenbachensis" type strain ED16 = DSM22694.
Habitats.
"Rhodoferax" species are frequently found in stagnant aquatic systems exposed to light. Isolates of "R. fermentans" used for the type description of the genus were first isolated from ditch water and activated sludge. Other environments from which this species has been isolated include pond water and sewage. In the case of "R. antarcticus", strains were first isolated from microbial mats collected from saline ponds in Cape Royds, Ross Island, Antarctica. In contrast to other "Rhodoferax" species, where isolation sources were exposed to light, the isolation of the nonphototrophic "R. ferrireducens" was carried out using anaerobic subsurface aquifer sediments.
Physiology/biochemistry.
Growth of some "Rhodoferax" species can be supported by anoxygenic photoorganotrophy, anaerobic-dark fermentation, or aerobic respiration. The species "R. fermentans" and "R. antarcticus" are capable of phototrophic growth using carbon sources such as acetate, pyruvate, lactate, succinate, malate, fumarate, glucose, fructose, citrate, and aspartate. Anaerobic growth via sugar fermentation can be carried out in the dark by "R. fermentans", and is stimulated by the addition of bicarbonate. "R. antarcticus" has not yet demonstrated the ability to ferment under dark anaerobic conditions, but is capable of aerobic chemoorganotrophy. In contrast, "R. ferrireducens" is not capable of photoorganotrophy or fermentation, but is capable of anaerobic growth using organic electron donors (i.e. acetate, lactate, propionate, pyruvate, malate, succinate, and benzoate) to reduce Fe(III) to Fe(II).
Growth temperatures for "Rhodoferax" species range from 2 to 30 °C. "R. fermentans" is a mesophilic species with an optimal growth temperature between 25 and 30 °C. The other three species, "R. antarcticus" , "R. ferrireducens", and "R. saidenbachensis" are psychrotolerant species with optimal growth temperatures above 15 °C, but capable of growth at temperatures near 0 °C.
Biotechnology.
Currently, research in the area of sustainable energy is investigating the application and design of microbial fuel cells (MFC) using "R. ferrireducens". In an MFC, a bacterial suspension is provided a reduced compound, which the bacteria use as a source of electrons. The bacteria metabolize this compound and shuttle the released electrons through their respiratory networks and ultimately donate them to a synthetic electron acceptor, also known as an anode. When connected to a cathode, the bacterial metabolism of the reduced compound generates electricity and CO2. The advantage of MFCs over conventional electricity generation is the direct conversion of chemical energy into electricity, improving energy conversion efficiency. A unique feature of using "R. ferrireducens" over other bacteria is that many other bacteria require the addition of a mediator to shuttle the electrons from the bacterial cells to the anode. For" R. ferrireducens", through an unknown membrane protein, electrons are directly shuttled from the membrane to the anode.


Large-eared tenrec

The large-eared tenrec ("Geogale aurita") is a species of mammal in the family Tenrecidae. It is the only species in the monotypic genus Geogale, and the only member of the subfamily Geogalinae. It is endemic to Madagascar where its natural habitats are subtropical or tropical dry forests and subtropical or tropical dry shrubland. It is threatened by habitat loss, but to a lesser extent than was previously thought and is listed by the IUCN as being of "Least Concern".
"Geogale" is thought to have split from the ancestors of its sister clade, the subfamily Oryzorictinae, about 30 million years ago.
Description.
The large-eared tenrec is a small shrew-like animal with short, soft fur, a long hairy tail and large projecting ears. Adults weigh between and measure in length, with a tail half as long again. The dorsal (upper) surface is greyish brown or reddish brown and the ventral (under) surface is buffish white. The large-eared tenrec differs from other tenrecs in the family by having 34 teeth instead of 36. It is also unique within the family in that females come into oestrus while they are lactating and so are able to be carrying one litter while still feeding another.
Behaviour.
The large-eared tenrec feeds on insects, particularly termites which it locates by sound. It is itself preyed on by several predators including the barn owl ("Tyto alba"), the Madagascar owl ("Asio madagascariensis"), the Malagasy cat-eye snake ("Madagascarophis colubrinus") and the narrow-striped mongoose ("Mungotictis decemlineata").
The large-eared tenrec has a low metabolic rate and is heterothermic. This means that its body temperature fluctuates with the surrounding environment, although pregnant and lactating females may maintain a more steady, higher temperature. The animals are often torpid in the heat of the day, hiding in concealed locations such as hollow logs or holes. Reproduction has been little studied in this species, but the breeding season is between September and March. It is known that development can be arrested temporarily and the gestation period may vary between about 54 and 69 days. A litter consists of up to five blind, deaf and helpless young and these are weaned when between 21 and 33 days old, soon after their eyes have opened.
Status.
The large-eared tenrec is listed by the IUCN in its Red List of Threatened Species as being of "Least Concern". The population trend is unknown and although this tenrec has been recorded in various scattered areas of Madagascar, it is a small, inconspicuous animal and is likely to also be present in intervening locations. It had been thought to be restricted to dry deciduous forest but it has now also been found in grassland and is probably more resilient to disturbed habitat than had previously been realised. Some of the areas in which it occurs are in national parks and nature reserves.


Anita Mahadevan-Jansen

Anita Mahadevan-Jansen is a Professor of Biomedical Engineering and holds the Orrin H. Ingram Chair in Biomedical Engineering at Vanderbilt University. Her research considers the development of optical techniques for clinical diagnosis and surgical guidance, particularly using Raman and fluorescence spectroscopy. She serves on the Board of Directors of SPIE, and is a Fellow of SPIE, The Optical Society, Society for Applied Spectroscopy, and the American Society for Lasers in Medicine and Surgery. She has been elected to serve as the 2020 Vice President of SPIE. With her election, Mahadevan-Jansen joins the SPIE presidential chain and will serve as President-Elect in 2021 and Society's President in 2022.
Early life and education.
As a child Mahadevan-Jansen wanted to be a medical doctor. She studied physics at the University of Mumbai, and earned her Bachelor's and master's degree there in 1990. As an undergraduate student she was disinterested in optics. Her professor, S.B. Patel, proposed that she applied to work in biomedical engineering. She moved to the University of Texas at Austin for her doctoral studies, where she completed a Master's and PhD in 1996. There, she began working with fluorescence spectroscopy under the supervision of Rebecca Richards-Kortum.
Research and career.
Mahadevan-Jansen joined the faculty at Vanderbilt University in 1996 and is currently Orrin H. Ingram Professor of Biomedical Engineering, Professor of Neurological Surgery. She founded the "Vanderbilt Biophotonics Center", where she works on optical diagnostics, surgical guidance, and neurophotonics. She is interested in translating optical technologies into in vivo diagnostic tools. Mahadevan-Jansen pioneered the use of "in vivo" Raman spectroscopy for non-invasive diagnostics cervical dysplasia. Her methodology is being developed for use in clinical medicine, for example, it may be used by surgeons in the treatment of breast and brain cancer. She created optical blood testing methodologies for neonatal babies, which was selected by the Vanderbilt University Center for Technology Transfer as one of the "coolest inventions" of the year. She developed sensors that can detect inflammation caused by bowel disease into a typical colonoscopy procedure.
In 2005, Dr. Mahadevan-Jansen and collaborators (including her husband, Dr. E Duco Jansen) discovered the ability to control peripheral and central nervous system electrical activity label-free with short pulses of infrared light. Termed infrared neural stimulation (INS), the field of label-free neuromodulation has evolved over the last decade built on these initial findings. This technology has demonstrated as safe and clinically translatable in humans.
In 2014, Mahadevan-Jansen was elected as conference co-chair to the 2018 Gordon Research Conference on Lasers in Medicine Biology with Paul French. She is exploring the use of Raman spectroscopy for investigating pre-term cervical remodeling. In 2018, 10 years after Mahadevan-Jensen demonstrated that parathyroid gland tissues glow under near-infrared light, the Food and Drug Administration approved that the technology could be used for surgeries. Her technology, the PTeye, was tested in a 81 patient clinical trial, and enables "in situ" monitoring of the parathyroid tissue during thyroid surgery. Before Mahadevan-Jansen's technology, surgeons relied on a visual assessment to identify the location of the parathyroid gland. She is also working on a development of Raman spectroscopy for the early diagnosis of throat cancer related to HPV. She leads a $3 million Vanderbilt University program that develops microscopy tools. Both projects are part of the Trans-Institutional Programs (TIPs) program at Vanderbilt University.
Since 1995, Mahadevan-Jansen is listed as co-inventor on more than 20 USPTO patents, several of which being licensed towards commercial development.
Academic service.
Dr. Mahadevan-Jansen has served as an reviewer for nearly two dozen journals over her career, including her role on the editorial board for the Journal of Biomedical Optics from 2007 to 2014. She started the Biomedical Vibrational Spectroscopy conference at SPIE's Photonics West BiOS conference in 2002, which has been running ever since. In 2007 she featured in the SPIE "Women in Optics" planner. Her advocacy for improving diversity and inclusion in optics and photonics has led to her chairing the SPIE Equity, Diversity, and Inclusion Committee. She is a Fellow of SPIE and served on the Board of Directors from 2014 to 2019. In 2014 Mahadaevan-Jansen was the second woman to be elected Chair of the Gordon Research Conference on Lasers in Medicine & Biology. She also serves as a Fellow of The Optical Society and the American Institute for Medical and Biological Engineering. She and her students have received numerous awards for research excellence and mentoring, for which she remains a strong advocate.
Selected publications.
Her publications include;
Personal life.
Mahadevan-Jansen is married to Duco Jansen, a Professor of Biomedical Engineering at Vanderbilt University. Together they have two children.


Small molecule drug conjugate

Small molecule drug conjugates or SMDCs are built with three modules: a targeting ligand, a linker and a drug payload. The targeting ligands consist of low molecular weight, high-affinity ligands that are precisely linked to potent drugs. The linkers are designed to be stable in the bloodstream and then release the active drug from the targeting ligand when the SMDC is taken up by the diseased cell. The drug payloads are highly active molecules that are too toxic to be administered in their untargeted forms at therapeutic dose levels. This modular approach allows varying targeting ligands, linker systems and drug payloads and generate SMDCs for different diseases.
The most advanced SMDC is vintafolide, a derivative of the anti-mitotic chemotherapy drug vinblastine which is chemically linked to folic acid. Potent, bioactive natural products like triptolide that inhibit mammalian transcription has been recently reported as a glucose conjugate for targeting hypoxic cancer cells with increased glucose transporter expression.
SMDCs are currently being developed by Endocyte for treating cancer, inflammatory diseases and kidney disease, as well as a companion imaging agent that is created by replacing the potent drug with an imaging agent.


TM0436

TM0436 is a putative zinc-binding alcohol dehydrogenase enzyme isolated from "Thermotoga maritima". It contains both structural zinc sites and catalytic zinc sites, as well as a Rossmann fold to bind NADH-type ligands. It's a member of the MDR superfamily, which also contains class I mammalian ADH1.


Intralytix

Intralytix, Inc. () is a privately held “C” corporation that was incorporated in the State of Maryland on July 28, 1998. Intralytix specializes in bacteriophage-based products used to control bacterial pathogens in environmental, agricultural, food processing, and medical (including skin care and oral care) settings.
Company Background.
Intralytix was founded in 1998 in Baltimore, Maryland, by Drs. John Glenn Morris, Jr. and Alexander Sulakvelidze together with a group of other scientists and business professionals. The platform technology of Intralytix is based on using naturally occurring, non-genetically modified (non-GMO) lytic bacteriophages for developing “green” commercial products for a variety of applications. These products are all-natural, antibiotic-free ways to control disease causing bacterial pathogens.
Major Milestones.
In 2006, Intralytix was the first company in the world to receive FDA/USDA approval for a bacteriophage-based food safety product, ListShield™.
That same year, Intralytix was also the first company in the world to successfully assemble a Master Drug File (MDF) application with the FDA, and to manufacture and supply its phage product for the first-ever in the US human clinical trial when phages were used to treat infected venous ulcers.
In 2018, Intralytix was granted the first FDA approved IND for a double-blind, randomized, placebo-controlled clinical trial in the US for an orally administered phage preparation.
As of 2020, Intralytix has the largest number of commercial FDA-approved phage food safety products with four FDA- and USDA-approved bacteriophage-based food safety products, and the fifth food safety product approval expected in 2021.
As of 2020, Intralytix is the largest commercial manufacturer of phage products for food safety applications in the US with successful scale up to a 1,500 L fermenter.
Intralytix Facilities.
Intralytix is located at 8681 Robert Fulton Drive, Columbia MD 21046, US. The 33,000 square foot building has a dedicated C-suite and state-of-the-art R&D and GMP (21 CFR Part 111 and 117 compliant) production facilities with capabilities for:
Pioneer in Food Safety.
The first commercial bacteriophage food safety product developed was ListShield™, which targets "Listeria monocytogenes" contamination of foods. It received FDA/USDA approval in 2006. Two years later, ListShield™ was approved for use as an environmental decontaminant (e.g., for decontaminating inanimate surfaces in food processing facilities) by the Environmental Protection Agency (EPA) (EPA registration #74234-1). In 2010, Intralytix began large scale commercial sales of ListShield™ to the food industry.
Other phage-based food safety phage products followed. In 2011, Intralytix received regulatory clearance from the FDA for its EcoShield™ food safety product effective against "E. coli" (FCN No. 1018) specific for the use of EcoShield™ on red meat parts and trim intended to be ground. In the same year, EcoShield™ received regulatory clearance from the USDA’s Food Safety & Inspection Service (FSIS) for use on red meat to be ground and was determined to constitute an incidental aid that will not require labeling (i.e., “clean label”).
Subsequent phage preparations received regulatory clearance from the FDA through Generally Recognized As Safe (GRAS) acknowledgements. SalmoFresh™, which is used to target "Salmonella" contamination, was declared GRAS in 2013 and ShigaShield™, used to treat "Shigella", received clearance by the FDA in 2017. As of May 2020, Intralytix has four FDA- and USDA-approved bacteriophage-based food safety products on the market. This is the largest number of FDA-approved phage food safety products for any company in the world.
Expansion into Human Therapeutics.
In addition to its line of food safety products, Intralytix is a world leader in human health applications for phage products. It has several all-natural, antibiotic-free phage-based products capable of treating human diseases of bacterial origin in various stages of development (preclinical through Phase2a). In 2006, under Intralytix’s MDF and an investigator-initiated IND at the Southwest Regional Wound Care Center in Lubbock, Texas, Intralytix was the first company in the US to perform a first-in-human clinical trial where phages were used to treat infected venous ulcers.
As of 2019, the company is sponsoring a Phase1/2a clinical trial (under an IND approval from the FDA) of the EcoActive™ phage preparation for targeting adherent-invasive "E. coli" associated with Crohn’s disease. This trial is currently enrolling patients at the Icahn School of Medicine at the Mount Sinai Hospital in New York, NY, and is expected to be completed in 2022.
In May 2020, Intralytix received a multimillion-dollar grant (AI 148054) from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), for the clinical development of its bacteriophage therapy preparation, ShigActive™, for managing infections caused by the bacterial pathogen "Shigella". These Phase1/2a studies are anticipated to begin in 2021.
Also in 2021, the company plans to begin clinical trials of another human therapeutic product, VRELysin™, to treat Vancomycin Resistant "Enterococci".
Intellectual Property (IP) Portfolio.
Intralytix is the world leader in bacteriophage technology, with experience in all technical, regulatory, and manufacturing aspects of the phage business. Intralytix is headed by Dr. Alexander Sulakvelidze, President and Chief Executive Officer, who is recognized as one of the world’s leading experts in bacteriophage technology.
Intralytix’s patent strategy is based on a multi-pronged approach, which provides broad and strong protection ranging from protecting specific bacteriophages that serve as the cornerstone of various company products to methods and applications of those bacteriophages in various settings.
As of May 2020, Intralytix has:
Intralytix Products.
Food Safety Products.
These phage-based products are designed to be applied to food before, during, or after processing or packaging, as appropriate. They work by targeting and killing specific human (including animal) pathogenic bacteria that may be present in food. These products do not alter the color, taste, or smell of food in any way.
All of these products are 100% natural and non-GMO. Most of them are also certified Kosher and Halal, and are OMRI-listed as suitable ingredients in the production of organic foods.
Pre-Harvest Intervention Products.
These food safety related products are designed to be applied to live animals prior to entering the processing facility, through spray application to the animals’ hide, skin, or feathers. After application, the phages act to reduce the contamination of specific target bacteria, if present on the animal, and prevent it from entering the facility.


Molecular and Cellular Probes

Molecular and Cellular Probes is a peer-reviewed scientific journal covering research on the location, diagnosis, and monitoring of inherited and infectious disease utilizing genomic, proteomic, and immunological techniques.
Abstracting and indexing.
The journal is abstracted and indexed in BIOSIS, Biotechnology Citation Index, Chemical Abstracts, Current Contents/Life Sciences, EMBASE, EMBiology, MEDLINE, and Scopus. According to the "Journal Citation Reports", the journal has a 2013 impact factor of 1.859.


Anthony Guiseppi-Elie

Anthony "Tony" Guiseppi-Elie, Sc.D., FRSC, FAIMBE, FIEEE is a professor in the Department of Biomedical Engineering of Texas A&M University where he holds a TEES Research Professorship and is a member of the EnMed Working Group. He is also founder, President and Scientific director of ABTECH Scientific, Inc. He is noted for his research and commercial development of biologically inspired and chemically responsive polymers, as related to bioanalytics, bioinformatics, and bionics.
Career.
Guiseppi-Elie initially focused on chemical engineering and materials science with his Sc.D research on the "Synthesis and Characterization of Polyacetylene". However, medicine was the interest of his youth and eventually drew him to the expanding field of bioengineering, specifically research and commercial development of biologically inspired and chemically responsive polymers that combine hydrogels possessing biologically inspired moieties with one-dimensional organic conductors (conductive polymers and carbon nanotubes). The resulting stimuli-responsive polymers are being developed as smart materials for controlled drug release, biosensors and for use in bionics. He is noted for his work on the development of controversial implantable biochips, DNA microarrays, and for his Guiseppi Prediction (...continued progress in the density of molecular recognition features on biochips will approach single molecule detection - by analogy to Moore's Law). He currently pursues the development of electronic noses, implantable bioanalytical biochips and implantable bio-smart materials for human health applications. His work has resulted in the commercialization of a wide variety of biochip substrates used in BioMEMS devices (Lateral Flow Bioassays and Microfluidic Devices) and his implantable biochip is under commercial development at ABTECH Scientific, Inc.
Awards and honors.
Guiseppi-Elie has been named chair-elect (2016) of the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows where he was inducted as a fellow in 2006. He is also a Fellow of the Royal Society of Chemistry (FRSC) and a fellow of the Institute of Electrical and Electronics Engineers (FIEEE). He is a lifetime member of the American Institute of Chemical Engineers and holds memberships in the American Association for the Advancement of Science, the American Chemical Society, the Materials Research Society and the Biomedical Engineering Society.
He has been the inaugural visiting distinguished lecturer in the Interdisciplinary Scientific Seminar Series at Wrocław University of Science and Technology (), Wrocław, Poland (2017). He has served as a member of the international review panel for the Science for Technological Innovation (SfTI) of the New Zealand National Science Challenge (NSC) (2017). During Spring of 2013, Dr. Guiseppi-Elie came up with the III pillars of Chemical Engineering (I if you do not know, measure, tissue engineering, and do not forget unit conversions.) He has tested on this multiple times and plans to integrate this into standard curriculum. He has been an IEEE EMBS distinguished lecturer (2012-2013) and in 2014 was selected for Fulbright Specialists Roster (2014-2019). He was selected for service on a Fulbright Specialist project at Universidad Nacional de Tucumán (UNT), Facultad de Ciencias Exactas y Tecnología (FACET) in Argentina. In 1999, Dr. Guiseppi-Elie was the recipient of the SEAM Award from the Polymer Research Institute at Polytechnic University for his work on “…bio-technical properties and applications of electroactive polymers”. He is a recipient of the 2003 “Pioneers in Biomedical Engineering” Lecture Award from Purdue University, a 2004 lecturer in the MIT Program in Polymer Science and Technology, a recipient of the 2013 Distinguished AVIS Professorship in Pharmaceutical Sciences at the University of Tennessee Health Science Center (UTHSC) and the 2014 and 2015 recipient of the Visiting Distinguished Professorship in industrial bioelectronics at L’Ecole de Mines d'Alès, France. He also serves as editor-in-chief of "Bioengineering", and associate editor of "Biomedical Microdevices" and is a member of the editorial boards of "The Journal of Bioactive and Compatible Polymers", "NanoBiotechnology", and "Applied Biochemistry and Biotechnology".


Sampa Das

Sampa Das is an Indian biotechnologist, scientist, and an expert on public sector agricultural biotechnology. She is a fellow of the Indian National Science Academy (FNA) and the National Academy of Sciences, India (FNASc). Currently, she is Senior Professor and Head of the Division of Plant Biology at Bose Institute in Kolkata, which is a multi-disciplinary research institution focused on science and technology.
Education.
Working under the supervision of Prof S K Sen of Bose Institute, Sampa Das received her doctorate degree in 1981. Das has worked with national and international individuals studying the mechanisms of plant defence responses against pests and pathogens, with an aim to combat their stress. She did her post-doctoral training at the Friedrich Miescher Institute in Switzerland, where she became interested in plant transformation, including rice, mustard, and tomatoes.
Career.
Dr. Das became a faculty member of Bose Institute.
She expanded her research of plant transformation to include chickpeas and mung bean, two important sources of protein for India's predominantly vegetarian population. Dr. Das began seeking ways to tweak the genetic constitution of these plants to improve their quality and quantity of the produce. After successfully completing her research on primary levels, she expanded her research to T3 and T4 level plants.
Her research at Bose has included isolation, characterization and monitoring the functionality of insecticidal proteins from plant sources. She has studied expression of agronomically important genes in crop plants.
She has worked on development of insect resistant transgenic rice, chickpea and mustard plants free of antibiotic resistant selection marker through the expression of mannose binding monocot plant lectins and different Bt toxin genes. She has studied the molecular interaction between receptor proteins identified from target insects and insecticidal lectins as well as different Bt proteins.
Dr. Das has worked on developing understanding of the mechanism of defense response in plants when challenged by various fungal and bacterial pathogens. Isolation and characterization of differentially expressed defense response related genes, proteins from rice and chickpea plants detected at early stage of infection by Fusarium oxysporum f.sp.ciceris and Xanthomonas oryzae pv oryzae, respectively.
She has worked on identification, characterisation and purification of few insecticidal lectins and other proteins from plant sources and isolation and cloning of effective insecticidal lectin and other protein coding gene(s) from respective plant genome(s).
Dr. Das has worked on establishment of efficient plant regeneration and transformation protocol for mustard, chickpea and pigeonpea. Other areas of interest are construction of a number of vectors with different T-DNA border elements for a better understanding of mechanism of T-DNA integration into host plant and construction of chimeric Bt, protease inhibitor gene (s) and other agronomically important gene(s) constructs for their expression in important crops namely, rice and mustard for increased productivity.
Awards and honors.
In 2007, she became a fellow of the Indian National Science Academy and two years later she became a fellow of the National Academy of Sciences India.


2-Me-DET

2-Me-DET, or 2-methyl-diethyltryptamine, is a lesser-known psychedelic drug. It is the 2-methyl analog of DET. 2-Me-DET was first synthesized by Alexander Shulgin. In his book "TiHKAL" ("Tryptamines I Have Known and Loved"), the minimum dosage is listed as 80-120 mg, and the duration listed as 6–8 hours. 2-Me-DET produces pitch distortion, like that of DiPT. Very little data exists about the pharmacological properties, metabolism, and toxicity of 2-Me-DET.


Levomoprolol

Levomoprolol is a beta adrenergic antagonist. It is the ("S")-enantiomer of moprolol.


IXICO

IXICO plc is a UK clinical research firm that provides neuroimaging and digital biomarker analytics to biopharmaceutical firms conducting clinical trials into neurological diseases such as Alzheimer’s disease (AD) and Huntington’s disease (HD).
Company history.
IXICO was incorporated in 2004 as a spin-out from three London academic institutions: Imperial College London, University College London and King's College London. The initial 3-year research project was called ‘Information eXtraction from Images’ (hence the IXI name), and funded by the UK e-science core and other industry partners.
In October 2013, IXICO entered the Alternative Investment Market (AIM) of the London Stock Exchange through a reverse takeover of defunct pharmaceutical drug company Phytopharm.
Phytopharm.
Phytopharm was a British pharmaceutical company, incorporated on 28 November 1995. Briefly known as Lawnhale, it changed its name to Phytopharm in March 1996 and listed on the London Stock Exchange on 25 April of the same year (LSE:PYM). It announced plans for a secondary listing on NASDAQ in 2004 (NASDAQ:PHYOF). By 2012, the Phytopharm group consisted of a parent company, Phytopharm plc, a wholly owned trading subsidiary, Phytotech Limited, and a dormant subsidiary, Phytodevelopments Limited.
Amongst other activity, Phytopharm raised funds for research into treatment of Parkinson’s disease (PD) from sources including the Michael J Fox Foundation, but the company collapsed in 2013 following the failure of its main PD drug (Cogane) during clinical trials. Its shares were suspended from trading on 20 May 2013.


2-Bromomescaline

2-Bromomescaline (2-Br-M) is a derivative of the phenethylamine hallucinogen mescaline which has an unusual 2-bromo substitution. It is an agonist for serotonin receptors, with a binding affinity of 215 nM at 5-HT1A, 513 nM at 5-HT2A and 379 nM at 5-HT2C, so while it is around ten times more tightly binding than mescaline at 5-HT1A and 5-HT2A receptors, it is over twenty times more potent at 5-HT2C.


Axial Biotech

Axial Biotech, Inc. was a privately held molecular diagnostics company based in Salt Lake City, Utah. It was founded in 2002 by a group of spine surgeons and geneticists, and was closed in March 2013.
The company's mission was to deliver diagnostics that improve and personalize the treatment of spine disorders. Axial Biotech conducted genetic research on scoliosis and degenerative disc disease.
In September 2009, Axial Biotech announced the commercial launch of the ScoliScore AIS Prognostic Test with the claim of it being a DNA-based diagnostic test for scoliosis. In 2012 Transgenomic acquired the rights to the ScoliScore test.
AIS genetic testing.
AIS genetic testing is the process of analyzing the DNA of a patient who has been diagnosed with adolescent idiopathic scoliosis to determine his or her likelihood of progression to a severe spinal curve.
Approximately 4% of AIS patients will progress to the point where surgery is done. The majority of adolescents with idiopathic scoliosis are observed at regular intervals (usually between 4–6 months) with a physical exam and x-ray to evaluate the magnitude of the curve.
Adolescent Idiopathic Scoliosis is a polygenic trait, meaning it is affected by the characteristics of more than a single gene. The heritability of scoliosis has long been suspected, and many research projects have been conducted in search of the genes responsible for the disease.
Axial Biotech performed a genome-wide association study, testing millions of genetic markers to find any associated with scoliosis. The study of DNA heritability was enhanced through the use of rich genealogical data available in Utah. Utah contains the headquarters of The Church of Jesus Christ of Latter-day Saints, which emphasizes the knowledge of ancestry and genealogy. Over the course of the research, DNA samples from over 9500 patients from 100 clinical sites worldwide were analyzed.
Researchers at Axial Biotech identified 53 genetic markers (28 which, when positive, contribute to the progression of the scoliosis curve and 25 which, when positive, protect against the progression of the curve.) The ScoliScore test was developed around these 53 markers.
ScoliScore.
ScoliScore AIS Prognostic Test is a genetic test, which analyzes the DNA of patients who are diagnosed with Adolescent Idiopathic Scoliosis, the most common type of scoliosis. The test shows the likelihood of spinal curve progression. In other words, it helps doctors and patients to see how likely it is that a patient's spine will become more curved and whether it is likely that the patient will eventually need surgery or other interventions.
Approximately 85-90% of patients initially diagnosed with AIS will never have their mild scoliotic curve progress to a magnitude that requires surgical treatment. The test results may be used to predict, with over 99% probability, when a mild scoliotic curve is unlikely to progress to the point of requiring surgical treatment. This knowledge can make it unnecessary for these patients to undergo numerous office visits and be exposed to radiographic imaging over many years to monitor potential curve progression. The ScoliScore test is a powerful tool, which helps physicians predict spinal curvature through one test, accomplishing what was previously only possible through years of observation.
The test is distributed by DePuy Spine, a Johnson & Johnson company. It was made available in a few physicians offices in September, 2009, and will be commercially launched in 2010.
In 2012 Transgenomic acquired the rights to the ScoliScore test.


Athenahealth

Athenahealth (stylized as athenahealth) is a private American company that provides network-enabled services for healthcare and point-of-care mobile apps in the United States.
The company was founded in 1997 in San Diego and is now headquartered in Watertown, Massachusetts. They have also grown to include operational sites in Belfast, Maine, Atlanta, Georgia, Austin, Texas, Burlington, Vermont, Seattle, Washington, Princeton, New Jersey, with international operations in Chennai, Bangalore, and Pune, India.
Company history.
Inception.
Athenahealth began in 1997 as Athena Women's Health, a women's health and birthing center in San Diego, California. Cofounders Jonathan Bush and Todd Park set out to create a comfortable and comprehensive center, where mothers could receive "a warm and supportive environment, personal attention, better care, and superior results" while the back-end business was "a ruthlessly efficient operation, with a laser focus on costs."
At the birthing center, only 10% of babies were delivered by C-section, one third of the national average, and 90% of mothers were able to breastfeed their newborns, beating the national average of 67% at the time. Yet while quality increased, costs followed in suit, and Bush and Park eventually closed their birthing center and started a medical data company called Athenahealth on the heels of the Internet boom of 1999.
Athenahealth.
In 1998, venture funder Mark Wilson offered to buy Athenahealth's software for $11 million. Bush and Park turned down the offer and transitioned the business model from birthing centers to internet-based healthcare. They transformed Athena Women's Health to Athenahealth, Inc., pulling in Ed Park, Todd Park's younger brother and engineer, to develop a practice management system. Their new business endeavor aimed to “let doctors be doctors” and remove incessant and burdensome paperwork off doctors’ desks.
In 2000, Athenahealth's first client, Anchor Medical Associates, went live on athenaCollector, and in February, its first electronic claim was submitted. While its first office opened its doors in Waltham, Massachusetts in 2002, Athenahealth moved to Watertown, Massachusetts in 2005 and is still headquartered there today.
Growth.
Athenahealth announced an initial public offering of its common stock on June 22, 2007. The offering was completed on September 20, 2007, at a price of $18 per share. It traded on the NASDAQ exchange under the symbol ATHN until it was taken private in 2019.
Since moving its headquarters to Watertown in 2005, Athenahealth has created campuses in: Chennai, India, in 2005; Belfast, Maine, in 2008; Princeton, New Jersey, in 2013; Atlanta, Georgia, and San Francisco, California, in 2014; Austin, Texas, in 2015; and Bangalore and Pune, India, in 2017.
On February 7, 2018, former CEO of General Electric, Jeffrey Immelt became the chairman of the board. On June 6, 2018, Immelt was named executive chairman.
Involvement of Elliott Management.
In 2017–2018, under pressure from investor Elliott Management, Athenahealth undertook substantial cost-cutting measures, and Bush resigned.
In November 2018, Athenahealth was bought by Elliott and Veritas Capital for $5.7 billion, and then merged with an organisation that Veritas Capital had acquired from GE Healthcare in April 2018.
Illegal kickback allegations
On Thursday, January 28. 2021, the justice department reported that Athenahealth has agreed to pay $18.25 million to resolve allegations that it violated the False Claims Act (FCA) by paying illegal kickbacks to generate sales of its EHR product, athenaClinicals.
Products and services.
athenaOne.
athenaOne is Athenahealth's fully integrated suite of cloud-based services, combining practice management (athenaCollector), an electronic health record (EHR) system (athenaClinicals), and care coordination (athenaCommunicator) into a single packaged offering.
athenaCollector.
Athenahealth's first product, athenaCollector, a cloud-based revenue cycle and practice management service, was launched in 2000. Built by Ed Park, the revenue cycle management system formed the foundation of athenaNet, Athenahealth's web-based system at large. (Ed Park would go on to become Athenahealth's Chief Operating Officer and member of its board.)
athenaClinicals.
In 2006, the company launched athenaClinicals, reported as the "first economically sustainable, service-based" electronic medical records (EMR) system. athenaClinicals has been ranked as leading the market in EHR usability, due to its productivity and ability to reduce providers’ work, effectiveness of delivering patient care, and intuitive user interface.
athenaCommunicator.
In 2008, Athenahealth introduced athenaCommunicator to manage phone calls. Since then, the product has evolved into a suite of "patient engagement services," including a patient portal, patient self-scheduling solution, and live operator service to better help patients to schedule appointments, reschedule appointments, and make payments.
Epocrates.
In 2013, the company purchased the Epocrates mobile brand, and continued to occupy Epocrates's offices in Princeton, New Jersey and San Francisco, California. As an Athenahealth service, Epocrates aggregates treatment information, including dosing and contraindications, to provide clinical decision support in the prescribing moments of care.
Epocrates drug monographs have also been embedded into the athenaClinicals EHR system to enhance productivity and reduce time not spent on patients.
Partnerships and acquisitions.
More Disruption Please.
Athenahealth's More Disruption Please (MDP) program was launched in 2011. The initiative is both a partner program and an incubator environment for independent companies to develop products and services connected to Athenahealth's ecosystem.
In 2014, Athenahealth created the More Disruption Please accelerator, an opportunity for young startups still finding their legs to begin developing in Athenahealth's MDP space. “The goal of [the MDP accelerator] is to lower the barrier of entry for the best solutions to help us build the healthcare Internet,” said Mandira Singh, director of the More Disruption Please program. In its first full year, the accelerator added five companies to its portfolio.
In April 2016, Athenahealth acquired Arsenal Health, which developed a Smart Scheduling service for healthcare providers. Arsenal Health was Athenahealth's first MDP investment, in 2014.
Athenahealth launched MDP Labs in 2017. The program invites all entrepreneurs, from startups to mature companies, to innovate in healthcare and fix what's broken. Athenahealth's MDP Labs offered workspace in its downtown San Francisco office, tailored programming, dedicated mentorship, opportunities for partnerships and funding, and exposure to potential clients., though ended around 2019 with the closure of the San Francisco and other offices..
Other acquisitions and collaborations.
In January 2015, Athenahealth announced the acquisition of RazorInsights, a "leader in cloud-based EHR and financial solutions" for rural, critical access, and community hospitals. The purchase extended Athenahealth's established position in the outpatient market into the 50-bed and under inpatient care environment, which makes up nearly one third of the hospital market.
In February 2015, Athenahealth announced that it had purchased webOMR, a web-based clinical applications and EHR platform developed by Boston's Beth Israel Deaconess Medical Center. Athenahealth collaborated with BIDMC on the development of Athenahealth's acute care service offering, using Beth Israel Deaconess Hospital-Needham, a 58-bed community hospital, as the alpha development site.
Athenahealth announced its acquisition of Praxify Technologies in June 2017.
In late 2018, Athenahealth's private equity firm announce it was combining Virence Health into Athenahealth.. This merged the former IDX business, which had been owned by GE, into Athenahealth.


Coproporphyrinogen III

Coproporphyrinogen III is a metabolic intermediate in the biosynthesis of many compounds that are critical for living organisms, such as hemoglobin and chlorophyll. It is a colorless solid.
The compound is a porphyrinogen, a class of compounds characterized by a hexahydroporphine core with various side chains. The coproporphyrinogens have the outermost hydrogen atoms of the core replaced by four methyl groups (M) and four propionic acid groups (P). In coproporphyrogen III, the order around the outer ring is MP-MP-MP-PM. For comparison, coproporphyrinogen I has them in the sequence MP-MP-MP-MP. heme.
Biosynthesis and metabolism.
In the main porphyrin biosynthesis pathway, coproporphyrinogen III is derived from uroporphyrinogen III by the action of the enzyme uroporphyrinogen III decarboxylase:
The conversion entails four decarboxylations, which turn the four acetic acid groups into methyl groups , with release of four carbon dioxide molecules.
Coproporphyrinogen III is further used as a substrate for the enzyme coproporphyrinogen III oxidase which oxidizes and further decarboxylates it to protoporphyrinogen IX.


Ptolemaiidae


Macroscelides

Macroscelides is a genus of small shrew-like animals, the round-eared sengis (also called elephant shrews), found in western Namibia and in South Africa; they are members of the clade Afrotheria.
There are three known species:


Glycine dehydrogenase (cyanide-forming)

In enzymology, a glycine dehydrogenase (cyanide-forming) () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are glycine and A, whereas its 3 products are hydrogen cyanide, CO2, and AH2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with other acceptors. The systematic name of this enzyme class is glycine:acceptor oxidoreductase (hydrogen-cyanide-forming). Other names in common use include hydrogen cyanide synthase, and HCN synthase.


Staggered extension process

The staggered extension process (also referred to as StEP) is a common technique used in biotechnology and molecular biology to create new, mutated genes with qualities of one or more initial genes.
The technique itself is a modified polymerase chain reaction with very short (approximately 10 seconds) cycles.
In these cycles the elongation of DNA is very quick (only a few hundred base pairs) and synthesized fragments anneal with complementary fragments of other strands. In this way, mutations of the initial genes are shuffled and in the end genes with new combinations of mutations are amplified.
The StEP protocol has been found to be useful as a method of directed evolution for the discovery of enzymes useful to industry.


Alteromonas

Alteromonas is a genus of Proteobacteria found in sea water, either in the open ocean or in the coast. It is Gram-negative. Its cells are curved rods with a single polar flagellum.
Etymology.
The etymology of the genus is Latin "alter" -"tera" -"terum", another, different; "monas" (μονάς), a noun with a special meaning in microbiology used to mean unicellular organism; to give "Alteromonas", another monad
Members of the genus "Alteromonas" can be referred to as alteromonads ("viz." Trivialisation of names).
Authority.
The genus was described by Baumann "et al." in 1972, but was emended by Novick and Tyler 1985 to accommodate "Alteromonas luteoviolacea" (now "Pseudoalteromonas luteoviolacea"), Gauthier et al. 1995, who split the genus in two ("Pseudoalteromonas") and Van Trappen et al. in 2004 to accommodate "Alteromonas stellipolaris".
Species.
The genus contains eight species (but 21 basonyms), namely
Former alteromonads.
Many alteromonads were reclassified as members of "Pseudoalteromonas" in 1995
Other former alteromonads:


Complete Genomics

Complete Genomics is a life sciences company that has developed and commercialized a DNA sequencing platform for human genome sequencing and analysis. This solution combines the company’s proprietary human genome sequencing technology with its informatics and data management software to provide finished variant reports and assemblies at Complete Genomics’ own commercial genome center in Mountain View, California. In March 2013 Complete Genomics was acquired by BGI-Shenzhen, a genomics services company in Shenzhen, Guangdong, China. After the acquisition Complete Genomics moved to San Jose, and in June 2018 become part of MGI, the instruments manufacturing business of BGI.
History.
Complete Genomics was founded in March 2006 by Clifford Reid, Radoje (Rade) Drmanac, and John Curson. Clifford Reid was the chairman, president and chief executive officer of Complete Genomics before leaving in 2015 to setup Genos, a spinoff of Complete Genomics' consumer division.
In February 2009, Complete Genomics announced that it had sequenced its first human genome and submitted the resulting variant data to the National Center for Biotechnology Information database. Then, in November 2009, Complete Genomics published sequence data for three human genomes in the journal Science. By the end of 2009, Complete Genomics had sequenced 50 human genomes. To date, the company has sequenced more than 20,000 genomes.
The resulting data has supported research in diverse areas such as screening of embryos, detection of genetic relationships, neurology, aging, a novel Mendelian disease with neuromuscular and cardiac involvement, eating disorders, Prader-Willi syndrome and autism, ophthalmology, and oncology. In 2014, a collaboration among Radboud University (The Netherlands), Maastricht University Medical Centre (The Netherlands), Central South University (China) and Complete Genomics identified major causes of intellectual disability using whole genome sequencing.
In 2016, Complete Genomics contributed over 184 phased human genomes to George Church's Personal Genome Project. In 2019, they published on their new single-tube long fragment read (stLFR) technology, enabling construction of long DNA molecules from short reads using a combinatorial process of DNA barcoding. This enables phasing, SV detection, scaffolding, and cost-effective diploid "de novo" genome assembly, from second generation sequencing technology.
Technology platform.
Complete Genomics’ proprietary human genome sequencing technology is optimized for the exclusive study of human DNA, providing assembled sequences and variation files. The technology relies on DNA nanoball sequencing, which assembles short sequences of DNA into a full genome. It is designed to use lower volumes and concentrations of reagents than existing systems, and have large numbers of base reads per image.


GRIN2D

Glutamate [NMDA] receptor subunit epsilon-4 is a protein that in humans is encoded by the "GRIN2D" gene.
Function.
N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heteromers composed of the key receptor subunit NMDAR1 (GRIN1) and 1 or more of the 4 NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D).
Interactions.
GRIN2D has been shown to interact with Interleukin 16.


Tertatolol

Tertatolol (Artex, Artexal, Prenalex) is a medication in the class of beta blockers, used in the treatment of high blood pressure. It was discovered by the French pharmaceutical company Servier and is marketed in Europe.
Tertatolol has also been shown to act as a serotonin 5-HT1A and 5-HT1B receptor antagonist, similarly to propranolol and pindolol.


6-MAPB

6-MAPB (1-(benzofuran-6-yl)-N-methylpropan-2-amine) is a psychedelic and entactogenic drug which is structurally related to 6-APB and MDMA. It is not known to have been widely sold as a "designer drug" but has been detected in analytical samples taken from individuals hospitalised after using drug combinations that included other benzofuran derivatives. 6-MAPB was banned in the UK in June 2013, along with 9 other related compounds which were thought to produce similar effects.


Promyelocyte

A promyelocyte (or progranulocyte) is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte. Promyelocytes measure 12-20 microns in diameter. The nucleus of a promyelocyte is approximately the same size as a myeloblast but their cytoplasm is much more abundant. They also have less prominent nucleoli than myeloblasts and their chromatin is more coarse and clumped. The cytoplasm is basophilic and contains primary red/purple granules.


Clostridiales-2 RNA motif

The Clostridiales-2 RNA motif is a conserved RNA structure that was discovered by bioinformatics.
Clostridiales-2 motifs are found in Clostridiales.
Clostridiales-2 RNAs likely function in "trans" as sRNAs, and are often (but not always) preceded and also followed by Rho-independent transcription terminators.


Guanabenz

Guanabenz (pronounced GWAHN-a-benz, sold under the trade name Wytensin) is an alpha agonist of the alpha-2 adrenergic receptor that is used as an antihypertensive drug. It is used to treat high blood pressure (hypertension).
The most common side effects during guanabenz therapy are dizziness, drowsiness, dry mouth, headache and weakness.
Guanabenz can make one drowsy or less alert, therefore driving or operating dangerous machinery is not recommended.


Intellia Therapeutics

Intellia Therapeutics is a biotechnology company developing biopharmaceuticals using a CRISPR gene-editing system invented by Jennifer Doudna (with colleagues at University of California, Berkeley) and Virginijus Šikšnys (with colleagues at Vilnius University). The company has partnerships with Novartis and Regeneron.
History.
Intellia Therapeutics was founded in May 2014 to develop biopharmaceuticals using CRISPR.
It was backed by Atlas Venture and Novartis; the founding CEO was Nessan Bermingham from Atlas and the founding CSO was John Leonard, formerly CSO of AbbVie. The academic scientists involved in the founding included Rodolphe Barrangou, Rachel Haurwitz, Luciano Marraffini, Erik Sontheimer, and Derrick Rossi. The intellectual property around CRISPR was contested from the beginning; Intellia in-licensed patents from Caribou Biosciences, which had licensed patents from University of California invented by Jennifer Doudna.
Novartis had funded the Series A round because of its interest in applying CRISPR in CAR-T, and in January 2015 Novartis and Intellia reached a deal through which Novartis obtained rights to use CRISPR for its CAR-T program, and the companies agreed to collaborate on ways to use CRISPR to treat diseases involving hematopoietic stem cells including beta thalassemia and sickle cell disease. Intellia formed a division called eXtellia Therapeutics to manage the CAR-T collaboration with Novartis.
As of February 2015, Intellia's competitors included CRISPR Therapeutics (with IP invented by Emmanuelle Charpentier), Editas Medicine (with IP invented by Feng Zhang from the Broad Institute) and Horizon Discovery. Among large pharmaceutical companies, AstraZeneca had the broadest set of collaborations in CRISPR.
In April 2017 Intellia entered into a partnership with Regeneron Pharmaceuticals under which Regeneron gained the exclusive right to use Intellia's CRISPR platform on up to 10 drug targets, of which up to five could be outside of the liver, and the companies agreed to co-develop other targets. Regeneron paid $75 million upfront, as well as milestones and royalties. The company said it planned to put $10 million of the funds into its bioinformatics program, to help it evaluate targets.
In December 2016, the company moved to its new 80,000 sq. ft. laboratory and office space in Cambridge, Massachusetts. By that time, it had in-licensed a lipid nanoparticle drug delivery system to help with its efforts to deliver its CRISPR drugs to the liver, without being degraded in the bloodstream; at that time it had not disclosed the licensor.
In March 2017 Intellia and Regeneron, its partner in co-developing a CRISPR-based treatment for transthyretin amyloidosis, presented data from a gene editing experiment in mice. By that time, University of California had lost a challenge to Broad's CRISPR patents, putting Intellia at a disadvantage relative to Editas.
In December 2017 Leonard, who had experience in drug development, took over as CEO.
In October 2019, Intellia named Glenn Goddard as its executive vice president and CFO. Prior to Intellia, Goddard was the CFO at Generation Bio Company and senior vice president of finance at Agios Pharmaceuticals.
Funding.
In November 2014, Intellia Therapeutics raised $15 million in Series A round. In September 2015, a Series B round secured $70 million. In May 2016, Intellia announced the closing of its initial public offering which raised approximately $112.1 million. In the course of going public, the company disclosed that it had licensed the lipid drug delivery system from Novartis, and that it involved creating lipid droplets to encapsulate the CRISPR agents.


Guilty Gear (video game)

Guilty Gear, subtitled "The Missing Link" in Japan, is a 2D fighting video game developed by Team Neo Blood, an Arc System Works production group led by Daisuke Ishiwatari, and published by Arc System Works. First released on May 14, 1998, for the PlayStation, it is the first installment in the series of the same name. Set in a world destroyed by a war between humans and bio-organic weapons called Gears, it follows ten fighters as they enter a tournament held to prevent resurrection of the Gears' leader. Its gameplay consists of one-on-one fights, with a main four-button configuration, featuring special moves and instant kill techniques, as well as three different playable modes.
Devised by Ishiwatari, it took a year and a half in production, primarily drawing influence from "Street Fighter", manga, and creator Daisuke Ishiwatari's love of 1970s and 1980s heavy metal. After its original release, it was brought to North America, Europe and PAL region, and reached a cult status among fans. It has received favorable critical reception, with praise towards its characters' roster, 2D graphics and fast gameplay that differentiates it from other games of the same genre. It has been labeled as one of few games of its era to cause any sort of impact on the genre, except from Capcom and SNK hegemonic games. However, it received criticism due to its difficulty and unbalanced set of characters.
Gameplay.
After selecting one of the ten characters available from outset, the player must to defeat the enemy in battle by winning two out of three rounds. It uses a six-button layout: four of which are responsible for the attacks—one punch, one kick, and the other two for weapon attacks—, and the other two for special actions. "Guilty Gear" also features instant kill techniques that, if successfully lands on an opponent, ends the match.
It uses a tension gauge, which fills up when the character lands a hit or takes damage. When the gauge is full, characters become stronger, and can input certain commands to activate special moves called Chaos Attacks. The game has a feature called Chaos Mode that is activated when a character's health is at the half-way point (yellow bar). A red aura will surround the character and he/she is able to perform unlimited Chaos Attacks.
It features three modes: "Arcade Mode", a single-player mode, culminating in battles with the bosses, and the only one that reveals character's reasoning for fighting; "Versus Mode", which gives the opportunity to play against another player; and "Training Mode", which allows players to freely practice. The game settings allow the player to set the duration of the round, but not allow to change the number of rounds in a fight, or the difficulty in the single mode.
Synopsis.
Plot.
In 2010, mankind discovered an unlimited energy source of incredible power, which was labeled “magic”. Despite providing a solution for the world energy crisis, war conflicts continued to exist. The power of magic was combined with humans and other creatures via experiments, creating living weapons known as "Gears". Eventually, the Gears turned on the human race, beginning a global war known as the Crusades. After a century of battles, a military group known as the Sacred Order of Holy Knights fought and defeated Justice, the leader of the Gears. With Justice having been locked away in a dimensional prison, all other Gears seemingly ceased to function, bringing an end to an age of conflict.
The story of "Guilty Gear" takes place in the 22nd century, in the year 2180, five years after the end of the Crusades. A Gear named Testament began a plan to resurrect Justice, and wipe out the human race. Fearing this, the Union of Nations organized a fighting tournament in order to find fighters who would be able to defeat Testament and prevent her revival, awarding the winner with anything they may desire.
Ten combatants sign up to enter "The Second Sacred Order Tournament". As the combatants fight through the stages of the tournament they begin to discover the true goal behind it. A bounty hunter named Sol Badguy defeats Testament in the second to last stage of the tournament. However, he is too late to prevent Justice's resurrection. After an arduous battle, Justice is defeated by Sol restoring peace for the time being.
Characters.
"Guilty Gear" features ten playable characters available from outset. The characters have different styles of fight, special abilities, as well as weapons, which some do not have, fighting only with their bodies. Aside from the initial ten, the player can unlock three hidden characters to use them only in the "Versus Mode". The outset characters are Axl Low, Chipp Zanuff, Dr. Baldhead, Kliff Undersn, Ky Kiske, May, Millia Rage, Potemkin, Sol Badguy—the main character—, and Zato-1, while Baiken, Justice, and Testament are boss characters that are unlockable.
Development and release.
Daisuke Ishiwatari had conceived the game before joining Arc System Works, during the period he was in a vocational school. Eventually, Ishiwatari entered the company, where he was working on other things until the day he revealed to the president he wanted to make a game in "Street Fighter"-likeness. With the president's acceptance, Ishiwatari started to work on it along with a cast of about 12 people, the so-called "Team Neo Blood", lasting a year and a half in its development. With influences of the manga "Bastard‼", Ishiwatari created the series hoping it would appeal not only to game fans but to anime fans too. Originally, the game was designed with rendered 3-D visuals, but this was later replaced by hand-drawn artwork.
Ishiwatari was convinced that the game "should be something difficult" because he saw fighting games trying to appeal to casual players and failing on it. He explained his main focus was to create a product that would satisfy its players, and that could "expand the possibilities of the game itself." A different layout of buttons, "one of the things that defined" the game, was necessary because "we wanted to come up with something different to the other games – it needed to be different." For this reason, the instant-kill techniques were added; its function was also to add tension to the fight—as someone who was winning could be defeated suddenly—, "something we really wanted to be a strong theme for the game."
"Guilty Gear" was first released in Japan on May 14, 1998 for the PlayStation by Arc System Works. In August of the same year, Arc System Works licensed a North American release to Atlus. The company let players choose the game's box art by voting for their favorites from three available box arts. When the contest ended, Atlus released the game on October 31, 1998. In Europe, it was licensed and published by Studio 3 in May 2000.
Reception.
Reviews for it were generally positive, with an aggregate score of 78.44% from GameRankings. "PlayStation Power" reported that both Japanese and American reviewers commended the combination of humor and "futuristic manga-style" action, and the variety of moves and combos. IGN staff said it would be well received by fans of traditional 2D fighting video games and considered it one of the bests of the genre on PlayStation. Writing for "Electronic Gaming Monthly" ("EGM"), a reviewer dubbed "Sushi" said it is the second best 2D fighter on PlayStation behind "Street Fighter Alpha 2". Harry Slater of "Pocket Gamer" and Eurogamer's Wesley Yin-Poole affirmed it has been regarded "by many to be the greatest 2D, one on one fighter of the era" and "the greatest fighting game off all time", respectively.
Its graphics have been well received by James Mielke of GameSpot, who qualified it as "fast and fluid animation". Allgame's Michael L. House also used the latter adjective. Writing for Eurogamer, Tom Bramwell noted "The classic 'cartoon' look suits "Guilty Gear" perfectly", and Randy Nelson from IGN qualified it as "unrivaled animation quality". Slater stated "it's one of the coolest 2D fighters from a time when 2D fighters just weren't cool". In opposition, Ed Lomas of "Computer and Video Games" declared, "The graphics aren't great, but a lot of effort has been put into certain characters, especially in terms of animation. An "EGM" reviewer deemed the graphics and animation as "the big draw" of "Guilty Gear", while a Jeuxvideo.com contributor said it could be "more polished".
Its gameplay has been praised, with Mielke, House, and Nelson describing it as "fast, [and] furious". Conversely, "Play" criticized its speed as ""Guilty Gear" takes it away too far." Lomas praised its combo system, and compared to "Street Fighter Alpha" games, while IGN staff also commended its "over-the-top" combos. Bobba Fatt of "GamePro", however, complained about the difficult to perform some special moves. Mielke declared it is "one of the few non-Capcom or SNK 2D fighters to make any sort of impact on the genre." Though stated Capcom was still the best developer, Nelson said "Guilty Gear" is "better than 90% of those [2D fighting games] on the market". Similarly, Jeuxvideo.com writer thought it was the game that "finally provide a valid alternative to Capcom's hegemony" in the niche.
While Lomas called the characters "unoriginal", "OK" and "cool-looking" were used by John R and Shawn from "EGM" to describe the characters. Nelson, on other hand, called them "the best ... outside Capcom/SNK", and Mielke found they "truly awesome", noting their diversity "keeps "Guilty Gear" fresh". House declared "superb is the only way to describe them", asserting they are all "pretty original". Jeuxvideo.com commentator wrote that they are "varied enough not to bore", while Fatt praised the characters' uniqueness as each have "distinct looks and strategies."
Jeuxvideo.com reviewer praised its music and sound, while Mielke said its combination create "a truly awesome sound experience". Conversely, House and Nelson felt it "is very unoriginal", and "[s]trictly average", respectively. Most of criticism, however, is directed to how the AI makes the game difficult and how there are some attacks that cause too much damage. "EGM"s four critics consensus was that the worst feature of the game was the balance of characters. Both Nelson and Bramwell felt the aforementioned problemes are the two major issues of the game. On this matter, House commented "the computer will destroy you a lot", and that "[a] few characters can execute attacks that really take off way too much damage and this is real the problem with the game". In spite of it, "Game Informer" considered the instant-kill move to be the "biggest" concept introduced by "Guilty Gear".
Lomas did a more negative review, saying it "is initially totally unappealing, with ... nothing that hasn't been done loads of times before", and "Game Informer" has named the game one of the top ten weirdest of all time. In contrast, most of critics were positive in the statements that summarize their opinions. Mielke said it "is as good as it gets", and it was described by House as "just a solid, well-executed 2D fighting game that has class, personality and a great engine". Nelson declared "[n]o true fan of the genre should be without a copy", and Bramwell urged "If 2D beat-em-ups are moving toward extinction, they really are ending on a high note with stuff like this." In retrospect, Evan Shamoon wrote for the "Official Dreamcast Magazine" that "Guilty Gear" is one of the most "beloved-yet-under-appreciated" games, commenting it defined itself for its balance, "wonderful art design", and "extremely tight control."
Legacy.
The "Guilty Gear" game was the first installment of the series that is considered a cult classic among video game fans. It was followed by four direct sequels, "Guilty Gear X" (2000), "Guilty Gear X2" (2002), "" (2007), "Guilty Gear Xrd" (2014), and several spin-offs. Arc System Works rereleased "Guilty Gear" in a on September 22, 1999 for a cheaper price. It later became available by download on PlayStation Store as a PSone Classic in Japan on May 31, 2007, in Europe on January 7, 2010, and in PAL region on January 8, 2010. It was also released as a mobile game for PlayStation certified devices in 2012. By the game's 20th anniversary, Arc System Works announced the production of a port for the Nintendo Switch, PlayStation 4 and PC.
Other media.
In the same year of the game release, a strategy guide titled was released by Takarajimasha on May 28 in Japan.
Following the game's original release, a soundtrack album was released by Nippon Columbia on May 21, 1998. "Guilty Gear Original Sound Collection" was composed by Ishiwatari, Takahiro Uematsu, Hatsuaki Takami, Takuya Moritou, arranged by Yasuharu Takanashi, and consisting mostly of rock and heavy metal music.
The album was well received by critics; Don Kotowski of Square Enix Music called the tracks "very enjoyable", but he felt it is "less refined" than subsequent soundtracks. Another reviewer from the same site, GoldfishX, said the only drawback the disc has is the mastering of the CD which can difficult to hear the guitars on rhythm in some tracks. As it is not a problem related to composition, he gave a perfect score to the soundtrack.
Several themes featured in the game, such as "Keep Yourself Alive" and "Holy Orders (Be Just or Be Dead)", were used in subsequent games, and its soundtrack as a whole became one of the aspects the series is most known for.


(Methionine synthase) reductase

[Methionine synthase] reductase, or Methionine synthase reductase, encoded by the gene MTRR, is an enzyme that is responsible for the reduction of methionine synthase inside human body. This enzyme is crucial for maintaining the one carbon metabolism, specifically the folate cycle. The enzyme employs one coenzyme, flavoprotein.
Mechanism.
MTRR works by catalyzing the following chemical reaction:
The 3 products of this enzyme are methionine synthase-methylcob(I)alamin, S-adenosylhomocysteine, and NADP, whereas its 4 substrates are methionine synthase-cob(II)alamin, NADPH, H, and S-adenosyl-L-methionine.
Physiologically speaking, one crucial enzyme participated in the folate cycle is methionine synthase, which incorporated a coenzyme, cobalamin, also known as Vitamin B12. The coenzyme utilizes its cofactor, cobalt to catalyze the transferring function, in which the cobalt will switch between having 1 or 3 valence electrons, dubbed cob(I)alamin, and cob(III)alamin.
Over time, the cob(I)alamin cofactor of methionine synthase becomes oxidized to cob(II)alamin, rendering the enzyme inactive. Therefore, regeneration of the enzyme is necessary. Regeneration requires reductive methylation via a reaction catalyzed by (methionine synthase) reductase in which S-adenosylmethionine is utilized as a methyl donor, reducing cob(II)alamin to cob(I)alamin.
Systematic naming.
This enzyme belongs to the family of oxidoreductases, to be specific those oxidizing metal ion with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is [methionine synthase]-methylcob(I)alamin,S-adenosylhomocysteine:NADP+ oxidoreductase. Other names in common use include methionine synthase cob(II)alamin reductase (methylating), methionine synthase reductase, [methionine synthase]-cobalamin methyltransferase (cob(II)alamin, and reducing).


Indoramin

Indoramin (trade names Baratol and Doralese) is a piperidine antiadrenergic agent.
It is an alpha-1 selective adrenoceptor antagonist with direct myocardial depression action; therefore, it results in no reflex tachycardia. It is also used in benign prostatic hyperplasia (BPH).
It is commonly synthesized from tryptophol.
Dosage.
Indoramin is commonly prescribed as 20 mg tablets when used in BPH.
Side Effects.
Drowsiness, dizziness, dry mouth, nasal congestion, headache, fatigue, weight gain, hypotension, postural hypotension, depression, problems with ejaculation, diarrhoea, nausea, increased need to pass urine, and palpitations.
Synthesis.
Tryptamine and serotonin are naturally occurring indole ethylamino compounds with pronounced pharmacological activities. They have served as the inspiration for synthesis of numerous analogues.
One such study involved alkylation of 4-benzamidopyridine (2) with 3-(2-Bromoethyl)-1H-indole (1) to give quaternary salt (3); this intermediate was in turn hydrogenated with a Raney nickel catalyst to give indoramine (4).


Glutathione oxidase

In enzymology, a glutathione oxidase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are glutathione and O2, whereas its two products are glutathione disulfide and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on a sulfur group of donors with oxygen as acceptor. The systematic name of this enzyme class is glutathione:oxygen oxidoreductase. This enzyme participates in glutathione metabolism. It employs one cofactor, FAD.


Indole 2,3-dioxygenase

In enzymology, an indole 2,3-dioxygenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are indole and O2, whereas its product is 2-formylaminobenzaldehyde.
This enzyme belongs to the family of oxidoreductases, specifically those acting on single donors with O2 as oxidant and incorporation of two atoms of oxygen into the substrate (oxygenases). The oxygen incorporated need not be derived from O2. The systematic name of this enzyme class is indole:oxygen 2,3-oxidoreductase (decyclizing). Other names in common use include indole oxidase, indoleamine 2,3-dioxygenase (ambiguous), indole:O2 oxidoreductase, indole-oxygen 2,3-oxidoreductase (decyclizing), and IDO (ambiguous). This enzyme participates in tryptophan metabolism. It has 3 cofactors: copper, Flavin, and Flavoprotein.
Indole dioxygenase is not specific to indole but rather operates on a broad range of indole derivatives, including the amino acids tryptophan and 5-hydroxytryptophan (5-HTP), and many indole-analog plant phytochemicals. IDO is a peripheral enzyme, in contrast to tryptophan oxidase, an enzyme of similar amino acid sequence, which is active only in the liver. IDO is induced (produced on demand) by activation of inflammatory processes involving cytokine expression by white blood cells.


SpoT

SpoT is a bacterial protein that hydrolizes alarmones, (p)ppGpp, in the bacterial stringent response. Its hydrolase activity is Mn2+-dependent with a conserved His-Asp (HD) motif. In "E. coli", SpoT protein consists of 693 amino acids. SpoT belongs to the RSH protein family.
It is bifunctional, has both hydrolase and synthase activities. When relA is deleted, "E. coli" still can produce (p)ppGpp by SpoT.
SpoT can sense many sources of nutrient stress other than amino acid starvation and to respond by limiting hydrolase. The acyl carrier protein (ACP) binds to the TGS domain of SpoT; this binding is probably influenced by the ratio of unacylated ACP to acylated ACP in the cell. Fatty acid starvation leads to a shift in the balance of the two SpoT activities in favor of synthesis. Phosphate starvation is sensed by SpoT hydrolase to elevate (p)ppGpp, which induces IraP, a RssB antiadaptor that antagonizes RssB activation of RpoS turnover, thereby inducing RpoS.


Rough-haired golden mole

The rough-haired golden mole ("Chrysospalax villosus") is a species of mammal that live mostly below ground. They have shiny coats of dense fur and a streamlined, formless appearance. They have no visible eyes or ears; in fact, they are blind - the small eyes are covered with hairy skin. The ears are small and are hidden in the animal's fur.[10]
Physical description.
The rough-haired golden mole is generally larger than most of the other species of golden mole, with a total length of 120–175 mm and a mass of 90-160 g.[5] In the Transvaal region which is associated with land north of modern-day Vaal river in South Africa, males had an average mass of 105 grams while females had a range of mass from 65 to 142 grams.[2] It characteristically has a coarse and long pelage with hairs 18–20 mm long on the back. The glossy individual hairs of the guard coat on the mid-back are slate-grey at the base with reddish brown to brown at the tip. The under fur is woolly and grey. The claws of the third digit on the front feet are powerful and about 1.6 cm in length.[5][9]
Historic distribution.
Its natural habitats are temperate grasslands, arable lands, pasturelands, plantations, rural gardens, and urban areas. Historically throughout Africa it was found scattered throughout the Eastern Cape, KwaZulu-Natal, Gauteng and Mpumalanga.[5] One particular historical site for the mole has been completely transformed by urbanization, the greater Pretoria West region of Gauteng which consists of grasslands where extensive searches for this species over the last 10 years have not yielded any sign of their presence. The Gauteng, KwaZulu Natal and Mpumulanga provincial conservation departments are currently attempting to document and record potential habitat sites that may support rough-haired golden mole populations. There is major concern by these bodies that this mammal may be more threatened than its red list status suggests. The rareness of the species is exemplified by the fact that the capture of one individual in the Glengary region of KwaZulu-Natal in 2003 was the first specimen recorded since 1974, nearly 30 years ago.[5]
Natural distribution.
The rough-haired golden mole (Chrysospalax villosus), endemic to South Africa, has a distribution that is characteristically disjunct with records from a number of provinces including the Eastern Cape, KwaZulu Natal, Gauteng and Mpumalanga.[5]
Recorded from the extreme eastern parts of the Cape Province through southern and central Kwazulu-Natal to the south-eastern Gauteng.[3][9]
Habitat requirements.
It frequents grasslands and meadows in the savanna and grassland biomes of South Africa, and is extremely secretive. Detecting the presence of rough-haired golden moles is made all the more difficult by their preference for areas with sandy soils and dense vegetation, normally close to water sources.[5] They have a preference for the use of dry ground on the fringes of marshes or damp veils.[9] Possibly for the ease of excavating invertebrates such as worms. They apparently do not make subsurface runs like other golden moles, but excavate burrows, the entrances to which are characterized by loose piles of soil thrown up at the sides and back and which are left open when they leave the burrows to forage. Roberts (1951) thought solitary moles lived in chambers within their burrow systems from which they emerge only after rain. From the entrances, through repeated use, tracks are formed to feeding areas, which are marked by the disturbance of the soil in rooting with the horny pad on their noses. If suddenly alarmed when out of the burrows they quickly return to their shelter. In captivity, Roberts (1951) noted that, irrespective of the direction in which they faced, when they were disturbed their reactions were so rapid and the location of the burrow entrance apparently so well known that it was difficult to follow them as they sought refuge within it.[3][8]
Behavior & social organization.
The rough-haired and giant golden moles live in chambers and passages in mounds reached by a system of tunnels made in part by the golden moles and in part by mole-rats. [7] They are generally solitary and territorial, and have been known to fight with competing moles.[11]
Their burrow systems open to the surface via a number of ovoid holes that resemble the holes of freshwater crab chambers. These openings often are filled with shallow soil tailings (soil that has been displaced to the side and back), also similar to those of crabs; sometimes a shallow depression is also found at the burrow entrance, and possibly serves as a latrine. The telltale indicators of rough-haired golden moles are rootings made by the leathery nose pad during nocturnal surface foraging bouts. These signs resemble a scuff made by the edge of the heel of a shoe that has been dug superficially into the soil, and are usually located very close to the open holes. In wet soils the imprint of their feet can sometimes also be seen. Surface foraging and activity usually follows a period of rainfall. It is not known if these moles also forage in tunnels like other golden moles, but this seems likely given the long periods without rainfall during the dry winter months throughout most of its range.[5]
Feeding and foraging.
The rough-haired golden mole sometimes feeds above ground, and, when it does, it roots about like a pig in search of worms and insects. It walks at night to foraging sites that are recognizable by the disturbed soil where these golden moles have rooted for insects with their horny nose pads.[6] They have a pair of bones, called tabulars, in the occipital area of the skull, which are not found in other mammals. The zygomatic arches are formed by elongations of the maxillae. The malleus is tremendously enlarged, and it has been suggested that this actually aids hearing underground (that is, the detection of ground-born vibrations).[11]
The diet comprises insects and earthworms, but has not been well documented. It is possible that they are generalists that will take any invertebrate or even small vertebrate prey they come across, as is the case with the giant golden mole, Chrysospalax tervelyani.[3][9]
Adaptations to adverse environment.
If disturbed when on the surface, rough-haired golden moles quickly retreat back to the safety of the nearest burrow, and they apparently have a remarkable ability to retrace their steps even under the cover of darkness.[5]
Threats and conservation.
The distribution of this golden mole has probably contracted during historical times as a result of habitat alteration associated with mining, power generating plants, as well as urbanization and ecologically unsound agricultural practices in parts of its range. The greatest degradation of its preferred habitat has taken place in the Highveld grasslands of Mpumalanga and Gauteng, as a result of mining shallow coal deposits to fuel the numerous coal fired power stations in this region. Rehabilitation of these sites has largely been ineffective in Afrotherian Conservation Number 3(April 2005) restoring natural plant and animal communities. These power stations form the backbone of South Africa’s electricity network, so the magnitude of disturbance is likely to increase as human populations grow and the demand for power increases.[5]
Continual habitat destruction, alteration and human disturbances will result in the disappearance of the majority of sensitive or secretive species. Limited suitable grasslands and seasonal wetland areas remain in the Gauteng Province, especially in the Benoni area. It must be stressed however that the above-mentioned species are extremely difficult to observe and more intensive surveys are required in order to ascertain their current conservation status in the Gauteng Province. No evidence of any of the above-mentioned threatened mammals, although suitable habitat occurs for hedgehogs as well as Rough-haired Golden Moles (seasonally inundated grass and sedge zone).[3]
Reproduction.
Very little information is known about this aspect of their life history. Roberts (1951) recorded a female with two fetuses, but gave no date of recover of specimen.[8]


Richard D. Smith

Richard Dale Smith is a chemist and a Battelle Fellow and Chief Scientist within the Biological Sciences Division, as well as the Director of Proteomics Research at the Pacific Northwest National Laboratory (PNNL). Dr. Smith is also Director of the NIH Proteomics Research Resource for Integrative Biology, an adjunct faculty member in the chemistry departments at Washington State University and the University of Utah, and an affiliate faculty member at the University of Idaho and the Department of Molecular Microbiology & Immunology, Oregon Health & Science University. He is the author or co-author of approximately 1100 peer-reviewed publications and has been awarded 70 US patents.
Education.
Smith obtained his B.S. in Chemistry in 1971 from Lowell Technological Institute (currently the University of Massachusetts Lowell). He then received his PhD in the field of Physical Chemistry from the University of Utah in 1975.
Early career.
Starting in the 1970s Smith published peer-reviewed papers on several subjects, including mass spectrometry, ion cyclotron resonance mass spectrometry, ion-molecule reactions, molecular assemblies, and supercritical fluid solutions. This early work has led him to be considered an internationally recognized expert in mass spectrometry and separation techniques, and his research has led to advancements in instrumentation for the medical and environmental analysis fields, as well as biological research.
In the medical field, Smith's work has produced benefits in the areas of drug testing, analysis of pharmaceuticals and medical diagnostics in the clinical arena. His most successful invention has been the combination of capillary electro-phoresis with mass spectrometry. By the end of the 1990s, Smith's achievements included the electrodynamic ion funnel and a micro-dialysis device for the rapid purification of samples analyzed using mass spectrometry. Other notable contributions have been in the fields of supercritical fluids and related reverse micelle phenomena.
On August 22, 2000, Smith demonstrated and patented the electrodynamic ion funnel for highly efficient capture and focusing of ions in gases. He applied it for increasing the sensitivity of ESI-MS. His group has continued to refine and extend ion funnel technology, which is now widely applied in mass spectrometry and ion mobility instrumentation.
In the late 1990s, Smith's group was also extensively involved in the development and application of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry, which provided the basis for much greater MS resolution and mass measurement accuracy, and particularly in the development of these technologies for applications in proteomics. More recent work has centered on extending application of these proteomics technologies to mammalian systems, which pose additional challenges due to their much greater complexity. One early focus has been the human blood plasma proteome due to its broad biomedical applications. Plasma proteome measurements potentially can provide the basis for discovery of protein biomarkers or signatures for virtually every disease state.
In September 1999, "R&D Magazine" picked the top 40 technologies of all time based on their impact on society, industry and commercial applications. The Top 40 were selected from a list of 3,600 past R&D 100 Awards. Smith was the recipient of one of these awards, for the development of capillary electrophoresis-mass spectrometry.
Current research.
Since the Human Genome Project developed a blueprint of all human genes in our chromosomes, proteomics researchers have pushed to understand how that blueprint creates life. Diseases and infections are often the result of proteins going wrong, and finding the aberrant one requires sifting through thousands of other proteins. In addition, many problem proteins have not been given names yet or are too rare to find easily.
In the last few years, Smith and his team have led work that has reduced analytical steps from hours to minutes. This increased speed has enabled many samples to be processed faster in high-throughput experiments. Smith has led other advances in sensitivity and accuracy that have improved the ability to find rare proteins, bringing proteomics technology to the doorstep of clinical researchers.
Smith and collaborators have applied the technology to liver disease and cancer in the hopes of finding rare markers of disease in blood, making diagnosis or treatment safer and faster. In 2007, Scientific American magazine listed Smith and his collaborator Desmond Smith as one of the top 50 researchers for work to understand the origins of Parkinson's disease by mapping where proteins amass in diseased mouse brains.
Among other work, Smith and colleagues at PNNL have looked at how bacteria and viruses might cause illness. They've learned breast cancer leaves traces behind in the blood that doctors might exploit someday. Smith led early studies for DOE into possible roles for microbes in making biofuels. In other DOE studies, he's examined how large environmental communities of microbes function in our ecosystem and affect our environment. An intimate understanding of how microbes work will let researchers employ them to trap radioactive contaminants or greenhouse gases.
In other recent work he has been leading the development of structures for lossless ion manipulations (SLIM) and their application for very high speed sample processing, reactions, separations, and other manipulations of ions in the gas phase, and particularly their use for ion mobility spectrometry (IMS) separations in conjunction with mass spectrometry. Smith and colleagues at PNNL, including Drs. Yehia Ibrahim and Sandilya Gerimella,have extended the range of SLIM technologies to include the use of travel wave electric fields for SLIM IMS. This has enabled extremely high resolution separations based on 'multi-pass" separations, and has enabled the separation of ions previously impractical, such as isotopomers and isotopologues.
Awards and affiliations.
Smith a principal investigator at NIH Biomedical Technology Resource Center for Integrative Biology and the U.S. Department of Energy High Throughput Proteomics Facility at PNNL. He is an adjunct faculty member in the chemistry departments at Washington State University and the University of Utah and an affiliate faculty member Department of Chemistry at the University of Idaho and the Department of Molecular Microbiology & Immunology, Oregon Health & Science University. Smith serves on the Board of Scientific Counselors, Office of Public Health Preparedness and Response of the Centers for Disease Control and Prevention. He is also a Fellow of the American Association for the Advancement of Science, and has been elected to the Washington State Academy of Sciences.
In 2011, "Discover Magazine" selected a peer-reviewed paper on Lyme disease that he coauthored with immunologist Steven Schutzer of the University of Medicine and Dentistry of New Jersey as one of the top 100 articles of the year, placing it at number 90.
He was the recipient of the 2003 ACS award in Analytical Chemistry, the 2009 Human Proteome Organization (HUPO) Discovery Award in Proteomics Sciences, and was selected by "R&D Magazine" as the 2010 R&D Scientist of the Year. He has also received ten R&D 100 Awards: Combined Orthogonal Mobility & Mass Evaluation Technology (2013); Ion Mobility Spectrometer on a Microchip (2010); Ultrasensitive Electrospray Ionization Mass Spectrometry Source and Interface (2009); FT-MS Proteome Express (2003); Electrodynamic Ion Funnel (1999); Rapid Microdialyzer (1998); MICLEAN/MICARE Process (1998); Rapid Expansion of Supercritical Fluid Solutions Process (1988); Capillary Electrophoresis-Electrospray Ionization-MS (1988); and Supercritical Fluid Chromatography-MS (1983). He was the recipient of the 2013 Award for a Distinguished Contribution in Mass Spectrometry.


Rufous elephant shrew

The rufous elephant shrew, rufous sengi or East African long-eared elephant-shrew ("Elephantulus rufescens") is a species of elephant shrew in the family Macroscelididae. Found in Ethiopia, Kenya, Somalia, South Sudan, Tanzania and Uganda, its natural habitats are dry savanna and subtropical or tropical dry shrubland.
Distribution.
"Elephantulus rufescens" occupies the drywood land and grassland zone of East Africa.
Characteristics.
"Elephantulus rufescens" exhibits no sexual dimorphism. The proboscis is long and flexible. The species' tails are dark-brown and can be long up to its head-to-tail length. Both adults and juveniles are similar in color. The dorsal fur is of fine texture and the coloring is brown, reddish-brown in color, or buff while the ventral fur coloring is white. The coloration of the dorsal fur is influenced by the color of the soil in which the E. rufescens lives. However, adults have white feet while juveniles' feet are brown. The large eye is surrounded by a white ring which is interrupted by a dark patch which extended towards the rear of the animal. The ears are large and without fur. A sternal gland is present on both males and females. The sternal gland is indicated by short, fringed white hairs. Females have three pair of teats and the males have internal testes.
Ecology, diet, and behavior.
Rufous elephant shrews are active throughout the day, with peaks in activity at dusk and dawn while having a midday rest. A mating male and female will build trails beneath leaf litter. The trails act as shelter and protection because the rufous elephant shrew does not build or use shelters or burrows. Throughout the trails are several rest spots for scent-marking and sunbathing. Moving the forefoot laterally to push aside leaf litter and other loose debris, "E. rufescens" constructs and maintains trails. The males usually spend most of their time cleaning the foraging trails. Except for foraging, all activities are performed in these trails. Trails act as an important means for escaping from predators. Insects form the major food resource of their diet in the dry season, while seeds are consumed during periods of rain.
"E. rufescens" has not been observed sleeping with closed eyes, but has been observed resting with eyes partially closed for a period of 1 – 2 minutes. During these rest periods, which occur in rest spot along the trails, "E. rufescens" keeps their feet under their body to allow for a quick escape. This species takes flight when even the smallest noise is heard.
This species is fairly monogamous; however, members of a monogamous pair spend little time together and are limited in social interaction. They live in a matriarchal society in which the female of the pair usually dominates the male.
The rufous elephant shrew gives birth to one or two precocial young per litter. The female gives birth at the base of bushes or by fallen tree limbs beside the trails. She does not stay will the neonates and only nurses them in infrequently and for only a short amount of time. The neonates remain in the parental trails, expanding their familiarity of the parental territory up to 14 days after birth. If the young wander into any neighboring rufous elephant shrew trails, the residing residents chase them out of their trails. Before the next litter is born, parents chase the previous litter for the trails resulting in dispersal or death of the previous litter.
Olfactory communication between young "E. rufescens" and their parents is achieved through apocrine glands (pedal glands) located on the underside of the young's feet. Neonates less than five days old have been observed back-rubbing one of its parents. Parents crouch down, allowing the neonates to climb on their backs and vigorously rub their four feet in the fur in a rapid vibrating motion. Cooperation between the neonates and adults is necessary or the neonates will fall off. The act of back-rubbing allows neonates to deposit pedal gland products on the fur of the parents and in turn transfer parental odors to their own fur. The mixture of the scents creates a family odor that can be used for recognizing family members.