title: Limited recognition of Mycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice

text: Immune responses following Mycobacterium tuberculosis (Mtb) infection or vaccination are frequently assessed by measuring T-cell recognition of crude Mtb antigens, recombinant proteins, or peptide epitopes. We previously showed that not all Mtb-specific T cells recognize Mtb-infected macrophages. Thus, an important question is what proportion of T cells elicited by Mtb infection recognize Mtb-infected macrophages. We address this question by developing a modified elispot assay using viable Mtb-infected macrophages, a low multiplicity of infection and purified T cells. In C57BL/6 mice, CD4 and CD8 T cells were classically MHC restricted. Comparable frequencies of T cells that recognize Mtb-infected macrophages were determined using interferon-γ elispot and intracellular cytokine staining, and lung CD4 T cells more sensitively recognized Mtb-infected macrophages than lung CD8 T cells. Compared to the relatively high frequencies of T cells specific for antigens such as ESAT-6 and TB10.4, low frequencies of total pulmonary T cells elicited by aerosolized Mtb infection recognize Mtb-infected macrophages. Finally, we demonstrate that BCG vaccination elicits T cells that recognize Mtb-infected macrophages. We propose that the frequency of T cells that recognize infected macrophages could correlate with protective immunity and may be an alternative approach to measuring T-cell responses to Mtb antigens.


The Role of Chemical Biology in the Discovery and Understanding of Ferroptosis


Role of the Urologist During a Pandemic: Early Experience in Practicing on the Front Lines in Brooklyn, New York


title: Immune-Related Adverse Events: Pneumonitis

text: Checkpoint inhibitors are part of the family of immunotherapies and are increasingly being used in a wide variety of cancers. Immune-related adverse events pose a major challenge in the treatment of cancer patients. Pneumonitis is a rare immune-related adverse event that presents in distinct patterns. The goal of this chapter is to instruct readers on the incidence and clinical manifestations of pneumonitis and to offer guidance in the evaluation and treatment of patients with pneumonitis.


title: SPINE bioinformatics and data‐management aspects of high‐throughput structural biology

text: SPINE (Structural Proteomics In Europe) was established in 2002 as an integrated research project to develop new methods and technologies for high‐throughput structural biology. Development areas were broken down into workpackages and this article gives an overview of ongoing activity in the bioinformatics workpackage. Developments cover target selection, target registration, wet and dry laboratory data management and structure annotation as they pertain to high‐throughput studies. Some individual projects and developments are discussed in detail, while those that are covered elsewhere in this issue are treated more briefly. In particular, this overview focuses on the infrastructure of the software that allows the experimentalist to move projects through different areas that are crucial to high‐throughput studies, leading to the collation of large data sets which are managed and eventually archived and/or deposited.


Respiratory virus infection triggers acute psoriasis flares across different clinical subtypes and genetic backgrounds


title: Retrovirus vectors and their uses in molecular biology

text: Retroviral vectors utilize the biochemical processes unique to retroviruses, to transfer genes with high efficiency into a wide variety of cell types in tissue culture and in living animals. With such vectors, the effect of newly introduced genes and the mechanism of gene expression can be studied in cell types so far refractory to other methods of transfer.


title: Search for an aetiological virus candidate in chronic lymphocytic leukaemia by extensive transcriptome analysis

text: As an approach to determining the aetiology of chronic lymphocytic leukaemia (CLL), we searched for a virus expressed in human CLL B‐cells by combining high‐throughput sequencing and digital subtraction. Pooled B‐cell mRNA transcriptomes from five CLL patients and five healthy donors were sequenced with 454 Life Sciences technology. Human reads were excluded by BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST‐like alignment tool) searches. Remaining reads were screened with BLAST against viral databases. Purified B‐cells from two CLL patients, with and without stimulation by phorbol‐esters, were sequenced using Illumina technology to achieve depth of sequencing. Burrows‐Wheeler Aligner mapping and BLAST searches were used for the Illumina data. Pyrosequencing resulted in about 400 000 reads per sample. No viral candidate could be found. Illumina single‐end sequencing for 115 cycles yielded an average of 26 ± 2·5 million filtered reads per sample, of which 2·2 ± 0·6 million remained unmapped to human references. BLAST searches of these reads against viral and human databases assigned nine reads to an Epstein‐Barr virus origin, in one sample following phorbol‐ester stimulation. Other reads showing a putative viral origin were dismissed after further analysis. Despite an in‐depth analysis of the CLL transcriptome reaching more than 100 million sequences, we have not found evidence for a putative viral candidate in CLL.


title: Systems biology of pathogen‐host interaction: Networks of protein‐protein interaction within pathogens and pathogen‐human interactions in the post‐genomic era

text: Infectious diseases comprise some of the leading causes of death and disability worldwide. Interactions between pathogen and host proteins underlie the process of infection. Improved understanding of pathogen‐host molecular interactions will increase our knowledge of the mechanisms involved in infection, and allow novel therapeutic solutions to be devised. Complete genome sequences for a number of pathogenic microorganisms, as well as the human host, has led to the revelation of their protein‐protein interaction (PPI) networks. In this post‐genomic era, pathogen‐host interactions (PHIs) operating during infection can also be mapped. Detailed systematic analyses of PPI and PHI data together are required for a complete understanding of pathogenesis of infections. Here we review the striking results recently obtained during the construction and investigation of these networks. Emphasis is placed on studies producing large‐scale interaction data by high‐throughput experimental techniques.


title: Polyomavirus Models of Brain Infection and the Pathogenesis of Multiple Sclerosis

text: Multiple sclerosis (MS) is generally considered to be an autoimmune disorder with myelin as the target and with several unidentified viruses playing ancillary roles, possibly through molecular mimicry. Although this paradigm has led to important progress on potential mechanisms of myelin loss, neither a target antigen in myelin nor a triggering mechanism has yet been identified, leaving the etiology of MS still unknown. Animal models of viral demyelination and studies showing that JC virus (JCV), the polyomavirus which causes progressive multifocal leukoencephalopathy (PML), may be latent in some normal human brains suggest another possibility. A host immune response targeting proteins expressed at low levels from viral DNA latent in the central nervous system (CNS) might underlie a focal demyelinating disease such as MS. A shift from autoimmunity to a latent‐virus model is not a trivial substitution of target antigens. This shift would expand the search for a definitive laboratory test for MS and could lead to improved therapeutic and preventive approaches.


News from academia: Biotechnoloy Journal 3/2007


title: Fruit Characteristics of Species Dispersed by the Black Lemur (Eulemur macaco) in the Lokobe Forest, Madagascar

text: ABSTRACT: I describe the fruit characteristics of species closely associated with black lemur seed dispersal (i.e., species that are often dispersed by die black lemur and only dispersed by the black lemur in die Lokobe Forest). A black lemur group was habituated and observed during the day and night for all months of die year (total 1272 h). When fruits were eaten, die plant species was identified, die maturity of the fruit and treatment of the seeds noted, and the fruit described in terms of ripe fruit color, husk thickness, fruit length, and seed length and width. Black lemur feces were searched for seeds; these were identified and signs of damage noted. Other potential dispersers feeding on the fruits of species eaten by the black lemur were also noted. The black lemurs were seen eating die fruits of 70 species. Of these, 51 species were defined as closely associated with black lemur dispersal and 16 species had seeds that were either often preyed upon or wasted by the black lemur, or were seen being eaten by other potential seed dispersers. Fruits of species in the former group were often dull colored (94% of species); rarely less than 1 cm long (6%); rarely had seeds less than 0.1 cm long or less than 0.1 cm wide (2 and 4%, respectively); never had seeds more than 4 cm long or greater than 2 cm wide; and quite often had either thick husks (49%) or thin husks (51%). In contrast, the fruits of the latter group were often brightly colored (75% of species) and nearly always had a thin husk (94%). Also, this latter group included more small and very large fruits and seeds than the former group. Fruit characteristics significantly associated with the former group were: dull color, thick husk, fruit length greater than 2 cm, seed length 1–4 cm, and seed width 1–2 cm. The extent to which these traits are the result of coevolution between plants and the guild of lemur dispersers that includes the black lemur is not clear, but a coevolved lemur–fruit syndrome remains a possibility. RESUMES: Cette étude porte sur la description des caracteristiques des fruits appartenant aux espèces dont la dissemination des graines est étroitement liée au Eulemur macaco. Ces espèces sont definies comme étant souvent disséminees par E. macaco et uniquement disséminées par E. macaco dans la for○t de Lokobe. Dans le but d'identifier ces espéces, un groupe de E. macaco a été habituéà la présence humaine et observé jour et nuit pendant tous les mois de 1'année (en total 1272 h). Une fois le fruit consommé, I'espèce était identifyée, la maturityé du fruit ainsi que le traitement de la graine notés et le fruit était dàcrit en termé de couleur á maturityé, d'épaisseur de I'enveloppe, de longueur de fruit et de longueur et de largeur de graine. Par la suite, les féces sont recherchés afin d'identifier les graines qu'ils contiennent et routes signes d'endommagement de celles‐ci sont notés. Les autres agents de dissémination potentiels, consomma‐teurs des fruits appartenant aux espèces consommées par E. macaco, ont étéégalement notés. Les E. macaco ont été vu consommer les fruits de 70 espèces. De ces dernières, 51 espèces étaient définies comm.éaetant étroitement liées à la dissémination par E. macaco et les graines de 16 espèces sont soit consommées, soit gaspillées par E. macaco, soit ont été vu consommées par d'autres agents de dissémination potentiels. Les fruits des espèces appartenant au groupe précédent sont souvent d'une couleur sombre (94% des espèces), d'une longueur rarement < 1 cm (6%), avaient rarement des fruits < 0.1 cm de long ou < 0.1 cm de large (2 et 4% respectivement) et n'ont jamais des graines > 4 cm de long ou > 2 cm de large, et presque souvent avaient une enveloppe épaisse (49%) et presque souvent une enveloppe mince (51%). Par contre, les fruits du dernier groupe sont souvent d'une couleur claire (75% des espèces) 'et presque toujours ont une enveloppe mince (94%). De plus, ce groupe inclut plus de petits et de très larges fruits et graines que le premier groupe. Les classes des caractéristiques des fruits significativement associées au premier groupe sont: couleur sombre, enveloppe épaisse, longueur de fruit >2 cm, longueur de graine 1‐4 cm, et largeur de graine 1‐2 cm. Cependant, 1'importance du ro̧le joué par la coévolution entre les plantes et le groupe des lémuriens disséminateurs, comprennant Eulemur m., dans le développement des caractéristiques de ces fruits n'est pas connue.


title: Flavors of Flaviviral RNA Structure: towards an Integrated View of RNA Function from Translation through Encapsidation

text: For many viruses, RNA is the holder of genetic information and serves as the template for both replication and translation. While host and viral proteins play important roles in viral decision‐making, the extent to which viral RNA (vRNA) actively participates in translation and replication might be surprising. Here, the focus is on flaviviruses, which include common human scourges such as dengue, West Nile, and Zika viruses, from an RNA‐centric viewpoint. In reviewing more recent findings, an attempt is made to fill knowledge gaps and revisit some canonical views of vRNA structures involved in replication. In particular, alternative views are offered on the nature of the flaviviral promoter and genome cyclization, and the feasibility of refining in vitro‐derived models with modern RNA probing and sequencing methods is pointed out. By tracing vRNA structures from translation through encapsidation, a dynamic molecule closely involved in the self‐regulation of viral replication is revealed.


title: Phylogenetic relationships and molecular evolution in uropeltid snakes (Serpentes: Uropeltidae): allozymes and albumin immunology

text: Multilocus electrophoretic methods and microcomplement fixation comparisons of serum albumin are used to assess phylogenetic relationships among species of uropeltid snakes, to infer aspects of their population biology and biogeography, and to evaluate their relationships to other primitive snakes (Henophidia). There is very good agreement between phylogenetic inferences derived from the electrophoretic data and those derived from the albumin immunological data. Protein variation detected by electrophoresis is relatively high among 17 operational taxonomic units (OTUs) examined. The mean number of alleles per locus (5.1 across all OTUs), levels of polymorphism (25% of loci), and heterozygosity (4–6%), are typical of, or greater than, values reported for other snakes. Species of uropeltids are genetically highly differentiated, as measured by genetic distances (lowest interspecific Nei's unbiased genetic distances, 0.22‐0.27 among several Sri Lankan species; 2.3 between Teretrurus of India and other uropeltines). The phylogenetic tree most consistent with both the immunological and electrophoretic data shows uropeltines from Sri Lanka to be monophyletic, but the Indian species are paraphyletic with respect to those from Sri Lanka. Rhinophis travancoricus of India is inferred to be the sister taxon to the Sri Lankan radiation. As the genera are presently understood, neither Rhinophis nor Uropeltis appears to be monophyletic. A biogeographic scenario derived from the phylogenetic hypothesis suggests an early diversification of uropeltids in India, followed by a single invasion into the lowlands of Sri Lanka. Subsequent evolution on Sri Lanka resulted in occupation of montane biotopes. Cylindrophis is the sister group to uropeltines and is considered a member of the Uropeltidae. The immunological data indicate no phylogenetic association between uropeltids and other ‘anilioid’ taxa, specifically Anilius, Loxocemus or Xenopeltis, although we cannot rule out a very remote relationship. We specifically reject the hypothesis that uropeltines and scolecophidians form a clade relative to henophidians. High levels of genetic variation and a trend toward negative F(IS) values for polymorphic loci in three populations suggest generally large effective population sizes and outbreeding in these species. The niche‐width variation hypothesis for allozyme loci is not supported by the uropeltid data. In comparison to other vertebrates, the relationship between Nei's genetic distance and albumin immunological distance in uropeltids suggests either conservative albumin evolution or strong differentiation at electrophoretic loci.


title: Protein trafficking along the exocytotic pathway

text: Proteins of the exocytotic (secretory) pathway are initially targeted to the endoplasmic reticulum (ER) and then translocated across and/or inserted into the membrane of the ER. During their anterograde transport with the bulk of the membrane flow along the exocytotic pathway, some proteins are selectively retained in various intracellular compartments, while others are sorted to different branches of the pathway. The signals or structural motifs that are involved in these selective targeting processes are being revealed and investigations into the mechanistic nature of these processes are actively underway.


title: Disturbance regimes, gap‐demanding trees and seed mass related to tree height in warm temperate rain forests worldwide

text: For tropical lowland rain forests, Denslow (1987) hypothesized that in areas with large‐scale disturbances tree species with a high demand for light make up a larger proportion of the flora; results of tests have been inconsistent. There has been no test for warm temperate rain forests (WTRFs), but they offer a promising testing ground because they differ widely in the extent of disturbance. WTRF is dominated by microphylls sensu Raunkiaer and has a simpler structure and range of physiognomy than tropical or subtropical rain forests. It occurs in six parts of the world: eastern Asia, New Zealand, Chile, South Africa, SE Australia and the Azores. On the Azores it has been mostly destroyed, so we studied instead the subtropical montane rain forest (STMRF) on the Canary Islands which also represents a relict of the kind of WTRF that once stretched across southern Eurasia. We sought to find whether in these six regions the proportion of tree species needing canopy gaps for establishment reflects the frequency and/or extent of canopy disturbance by wind, landslide, volcanic eruptions (lava flow and ash fall), flood or fire. We used standard floras and ecological accounts to draw up lists of core tree species commonly reaching 5 m height. We excluded species which are very rare, very localized in distribution, or confined to special habitats, e.g. coastal forests or rocky sites. We used published accounts and our own experience to classify species into three groups: (1) needing canopy gaps for establishment; (2) needing either light shade throughout or a canopy gap relatively soon (a few months or years) after establishment; and (3) variously more shade‐tolerant. Group 1 species were divided according the kind of canopy opening needed: tree‐fall gap, landslide, lava flow, flood or fire. Only some of the significant differences in proportion of Group 1 species were consistent with differences in the extent of disturbance; even in some of those cases other factors seem likely to have had a major determining influence during evolution. We also sought to determine whether the species that are at least ‘short‐term persistent’ in the soil seed bank (lasting 2–4 years) are all species needing canopy gaps for establishment. The answer was negative; large numbers of seeds of some shade‐tolerants accumulate in the soil, and these species are able to benefit from soil disturbance in deep shade. We found a significant and strong positive relationship in Japan between mean seed mass and mature tree height, a weak positive relationship in New Zealand and no relationship in any of the other four regions. When comparing the seed mass values of Group 1 and Group 3 species we obtained different answers depending on whether or not we confined ourselves to taxonomically controlled contrasts. In only two of the four regions with an appreciable number of species in Group 1 is the mean seed mass of such species significantly lower than that of Group 3 species when taxonomic relatedness is ignored.


title: Distinct Patterns of Multiple Sclerosis Pathology Indicates Heterogeneity in Pathogenesis

text: Multiple sclerosis is an inflammatory demyeli‐nating disease of the central nervous system. The hallmark of its pathology is the demyelinated plaque with reactive glial scar formation. However, a detailed analysis of the patterns of demyelination, oligodendroglia cell pathology and the reaction of other tissue components suggests that the pathogenesis of myelin destruction in this disease may be heterogeneous. In this review we present a new classification scheme of lesional activity on the basis of the molecular composition of myelin degradation products in macrophages. When these criteria are used, different patterns of demyelination can be distinguished, including demyelination with relative preservation of oligodendrocytes, myelin destruction with concomitant and complete destruction of oligodendrocytes or primary destruction or disturbance of myelinating cells with secondary demyelination. Furthermore, in some cases a primary selective demyelination may be followed by secondary oligodendrocyte loss in the established lesions. Finally, some extraordinarily severe conditions may result in destructive lesions with loss of myelin, oligodendrocytes, axons and astro‐cytes. This heterogeneity of plaque pathology is discussed in the context of recent experimental models of inflammatory demyelination, which show that different immunological pathways may lead to the formation of demyelinated plaques that reveal the diverse structural aspects described above. Our data indicate, that the demyelinated plaques of multiple sclerosis may reflect a common pathological end point of a variety of different immunological mechanisms of myelin destruction in this disease.


Advances in experimental medicine and biology. Volumes 138–142: Published by Plenum Press, New York. Vol 138, $49.50; Vol 139, $59.50; Vol 140, $35; Vol 142, $49.50


title: Taxonomy of the Peperomia species (Piperaceae) with pseudo‐epiphyllous inflorescences, including four new species

text: Twelve of the estimated 1500–1700 taxa in Peperomia show a particular feature: their terminal inflorescences seem to originate from the base of a leaf blade as a result of the presence of a sessile leaf at the base of these inflorescences. Three of these 12 taxa occur in Ecuador and four species are reported from Colombia. From Peru, two species are known from historical herbarium collections, and three other species are new to science. One new species is described from Bolivia. Collections of all 12 species are quite rare and, in the past, their identification seems to have been rather problematic. Previous authors have referred to these inflorescences as epiphyllous but, as shown here, this is not a correct description. To make a clear distinction from genuine epiphyllous inflorescences, the term ‘pseudo‐epiphyllous’ is proposed. In addition to the publication of four new species of Peperomia, emended descriptions are provided for the other species, synonymy is treated, and lectotypes are designated. The architecture of the plants is discussed and a key to the 12 species is provided. © 2008 The Linnean Society of London, Botanical Journal of the Linnean Society, 2008, 157, 177–196.


title: AVP‐IC(50)Pred: Multiple machine learning techniques‐based prediction of peptide antiviral activity in terms of half maximal inhibitory concentration (IC(50))

text: Peptide‐based antiviral therapeutics has gradually paved their way into mainstream drug discovery research. Experimental determination of peptides' antiviral activity as expressed by their IC(50) values involves a lot of effort. Therefore, we have developed “AVP‐IC(50)Pred,” a regression‐based algorithm to predict the antiviral activity in terms of IC(50) values (μM). A total of 759 non‐redundant peptides from AVPdb and HIPdb were divided into a training/test set having 683 peptides (T(683)) and a validation set with 76 independent peptides (V(76)) for evaluation. We utilized important peptide sequence features like amino‐acid compositions, binary profile of N8‐C8 residues, physicochemical properties and their hybrids. Four different machine learning techniques (MLTs) namely Support vector machine, Random Forest, Instance‐based classifier, and K‐Star were employed. During 10‐fold cross validation, we achieved maximum Pearson correlation coefficients (PCCs) of 0.66, 0.64, 0.56, 0.55, respectively, for the above MLTs using the best combination of feature sets. All the predictive models also performed well on the independent validation dataset and achieved maximum PCCs of 0.74, 0.68, 0.59, 0.57, respectively, on the best combination of feature sets. The AVP‐IC(50)Pred web server is anticipated to assist the researchers working on antiviral therapeutics by enabling them to computationally screen many compounds and focus experimental validation on the most promising set of peptides, thus reducing cost and time efforts. The server is available at http://crdd.osdd.net/servers/ic50avp. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 753–763, 2015.


title: The loss‐bet paradox: Actuaries, accountants, and other numerate people rate numerically inferior gambles as superior

text: Psychologists have convincingly demonstrated that preferences are not always stable and, instead, are often “constructed” based on information available in the judgment or decision context. In 4 studies with experts (accountants and actuaries in Studies 1 and 2, respectively) and a diverse lay population (Studies 3 and 4), the evidence was consistent with the highly numerate being more likely than the less numerate to construct their preferences by rating a numerically inferior bet as superior (i.e., the bets effect). Thus, the effect generalizes beyond a college student sample, and preference construction differs by numeracy. Contrary to prior thinking about preference construction, however, high expertise and high ability (rather than low) consistently related to the paradoxical phenomenon. Results across studies including Study 3's experimental modifications of the task supported the hypothesized number comparison process (and not a lack of expertise with monetary outcomes and probabilities or numeracy‐related differences in attention to numbers) as the effect's underlying cause. The bets effect was not attenuated by Study 4's instructions to think about what would be purchased with bet winnings. Task results combined with free‐response coding supported the notion that highly numerate participants have a systematic and persistent inclination for doing simple and complex number operations that drive their judgments (even after controlling for nonnumeric intelligence). Implications for 3 types of dual‐process theories are discussed. The results were inconsistent with default‐interventionist theories, consistent or unclear with respect to fuzzy trace theory, and consistent with interactive theories.


title: Budding of enveloped viruses from the plasma membrane

text: Many enveloped viruses are released from infected cells by maturing and budding at the plasma membrane. During this process, viral core components are incorporated into membrane vesicles that contain viral transmembrane proteins, termed ‘spike’ proteins. For many years these spike proteins, which are required for infectivity, were believed to be incorporated into virions via a direct interaction between their cytoplasmic domains and viral core components. More recent evidence shows that, while such direct interactions drive budding of alphaviruses, this may not be the case for negative strand RNA viruses and retroviruses. These viruses can bud particles in the absence of spike proteins, using only viral core components to drive the process. In some cases the spike proteins, without the viral core, can be released as virus‐like particles. Optimal budding and release may, therefore, depend on a ‘push‐and‐pull’ concerted action of core and spike, where oligomerization of both components plays a crucial role.


title: Development and Testing of an Abbreviated Numeracy Scale: A Rasch Analysis Approach

text: Research has demonstrated that individual differences in numeracy may have important consequences for decision making. In the present paper, we develop a shorter, psychometrically improved measure of numeracy—the ability to understand, manipulate, and use numerical information, including probabilities. Across two large independent samples that varied widely in age and educational level, participants completed 18 items from existing numeracy measures. In Study 1, we conducted a Rasch analysis on the item pool and created an eight‐item numeracy scale that assesses a broader range of difficulty than previous scales. In Study 2, we replicated this eight‐item scale in a separate Rasch analysis using data from an independent sample. We also found that the new Rasch‐based numeracy scale, compared with previous measures, could predict decision‐making preferences obtained in past studies, supporting its predictive validity. In Study, 3, we further established the predictive validity of the Rasch‐based numeracy scale. Specifically, we examined the associations between numeracy and risk judgments, compared with previous scales. Overall, we found that the Rasch‐based scale was a better linear predictor of risk judgments than prior measures. Moreover, this study is the first to present the psychometric properties of several popular numeracy measures across a diverse sample of ages and educational level. We discuss the usefulness and the advantages of the new scale, which we feel can be used in a wide range of subject populations, allowing for a more clear understanding of how numeracy is associated with decision processes. Copyright © 2012 John Wiley & Sons, Ltd.


title: Molluscum contagiosum and the acquired immunodeficiency syndrome: clinical and immunological details of two cases

text: We report here the clinical and immunological findings in two patients with molluscum contagiosum poxvirus infection and the acquired immunodeficiency syndrome (AIDS). These cases support earlier evidence that the molluscum contagiosum virus may act as an opportunistic pathogen. There is now evidence that members of all five families of double stranded DNA‐containing human viruses have been associated with unusual clinical manifestations in AIDS patients, and the significance of DNA virus infections in patients with AIDS is discussed.


title: Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: results of a randomized controlled trial

text: Background The development of antibiotic resistance by microorganisms is an increasing problem in medicine. In chronic wounds, bacterial colonization is associated with impaired healing. Cold atmospheric plasma is an innovative promising tool to deal with these problems. Objectives The 5‐min argon plasma treatment has already demonstrated efficacy in reducing bacterial numbers in chronic infected wounds in vivo. In this study we investigated a 2‐min plasma treatment with the same device and the next‐generation device, to assess safety and reduction in bacterial load, regardless of the kind of bacteria and their resistance level in chronic wounds. Methods Twenty‐four patients with chronic infected wounds were treated in a prospective randomized controlled phase II study with 2 min of cold atmospheric argon plasma every day: 14 with MicroPlaSter alpha device, 10 with MicroPlaSter beta device (next‐generation device) in addition to standard wound care. The patient acted as his/her own control. Bacterial species were detected by standard bacterial swabs and bacterial load by semiquantitative count on nitrocellulose filters. The plasma settings were the same as in the previous phase II study in which wounds were exposed for 5 min to argon plasma. Results Analysis of 70 treatments in 14 patients with the MicroPlaSter alpha device revealed a significant (40%, P < 0·016) reduction in bacterial load in plasma‐treated wounds, regardless of the species of bacteria. Analysis of 137 treatments in 10 patients with the MicroPlaSter beta device showed a highly significant reduction (23·5%, P < 0·008) in bacterial load. No side‐effects occurred and the treatment was well tolerated. Conclusions A 2‐min treatment with either of two cold atmospheric argon plasma devices is a safe, painless and effective technique to decrease the bacterial load in chronic wounds.


title: Bioprocess Engineering Issues That Would Be Faced in Producing a DNA Vaccine at up to 100 m(3) Fermentation Scale for an Influenza Pandemic

text: The risk of a pandemic with a virulent form of influenza is acknowledged by the World Health Organization (WHO) and other agencies. Current vaccine production facilities would be unable to meet the global requirement for vaccine. As a possible supplement a DNA vaccine may be appropriate, and bioprocess engineering factors bearing on the use of existing biopharmaceutical and antibiotics plants to produce it are described. This approach addresses the uncertainty of timing of a pandemic that precludes purpose‐built facilities. The strengths and weaknesses of alternative downstream processing routes are analyzed, and several gaps in public domain information are addressed. The conclusion is that such processing would be challenging but feasible.


Abstracts of the 13th international symposium on bioluminescence and chemiluminescence


title: A comparative study of the distribution and density of stomata in the British flora

text: The distribution of stomata over both leaf surfaces may affect both the photosynthetic rate and water use efficiency of species, implying that species with different photosynthetic and water requirements may also have different stomatal distributions. A database containing data on the distribution of stomata on the leaves of 469 British plant species was used to look for relationships between stomatal distribution (including both location on the leaf and density) and both habitat and morphological variables. Statistical models were applied to the data that minimized any effects that phylogenetic constraints may have had on the data. Hypostomaty is common in woody species, species which typically occur in shaded habitats and species with large or glabrous leaves. Amphistomaty, however, predominates in species which occur in non‐shaded habitats, species with small, dissected or hairy leaves, and in annual species. Amphistomaty, therefore, tends to occur in species where CO(2) may be limiting photosynthesis (unshaded environments), or where there are structures to prevent water loss from the leaf (e.g. hairs). Hypostomaty, however, occurs in slow‐growing species (e.g. trees), species with leaves which have large boundary layers (large or entire leaves) and in species where CO(2) is unlikely to limit photosynthesis (shaded habitats).


title: The efficiency of surgical masks of varying design and composition

text: Five different types of surgical mask of varying design and composition of natural and synthetic fibres were tested for their efficiency in vivo by means of a special test chamber. Contaminated particles escaping through or around the mask during speech by the wearer could be collected and sized. Analysis of the data showed that the gross efficiency of all the masks was high, but that some masks were distinctly better at small particle “filtration” than others. There was a significant difference in efficiency between the best and worst masks. The best masks contained more fabric, were softer and were pleated, while the worst were stiffer, smaller and not pleated. Reusable cotton fabric masks were as effective as synthetic fabric masks when made to a good design.


title: Different applications of virus‐like particles in biology and medicine: Vaccination and delivery systems

text: Virus‐like particles (VLPs) mimic the whole construct of virus particles devoid of viral genome as used in subunit vaccine design. VLPs can elicit efficient protective immunity as direct immunogens compared to soluble antigens co‐administered with adjuvants in several booster injections. Up to now, several prokaryotic and eukaryotic systems such as insect, yeast, plant, and E. coli were used to express recombinant proteins, especially for VLP production. Recent studies are also generating VLPs in plants using different transient expression vectors for edible vaccines. VLPs and viral particles have been applied for different functions such as gene therapy, vaccination, nanotechnology, and diagnostics. Herein, we describe VLP production in different systems as well as its applications in biology and medicine. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 113–132, 2016.


The educational implications of biotechnology a report on the seminar held at the National University of Singapore on June 5, 1981 by the IUBS Commission for Biological Education


title: Autoimmunity and the microbiome: T‐cell receptor mimicry of “self” and microbial antigens mediates self tolerance in holobionts: The concepts of “holoimmunity” (TcR‐mediated tolerance for the holobiont) and “holoautoimmunity” (loss of tolerance for the holobiont) are introduced

text: I propose a T‐cell receptor (TcR)‐based mechanism by which immunity mediates both “genetic self” and “microbial self” thereby, connecting microbiome disease with autoimmunity. The hypothesis is based on simple principles. First, TcR are selected to avoid strong cross‐reactivity with “self,” resulting in selection for a TcR repertoire mimicking “genetic self.” Second, evolution has selected for a “microbial self” that mimics “genetic self” so as to share tolerance. In consequence, our TcR repertoire also mimics microbiome antigenicity, providing a novel mechanism for modulating tolerance to it. Also, the microbiome mimics the TcR repertoire, acting as a secondary immune system. I call this TcR‐microbiome mimicry “holoimmunity” to denote immune tolerance to the “holobiont self.” Logically, microbiome‐host mimicry means that autoimmunity directed at host antigens will also attack components of the microbiome, and conversely, an immunological attack on the microbiome may cross‐react with host antigens producing “holoautoimmunity.”


title: Reproduction and development in rats chronologically exposed to 60‐Hz electric fields

text: Previous studies have raised the possibility of reproductive and developmental changes in miniature swine chronically exposed to a strong 60‐Hz electric field. Two replicate experiments on rats were performed to determine if similar changes could be detected in animals exposed under a comparable regime, which was based on average, induced‐current densities and on the chronology of reproductive development, as dosimetrically and biologically scaled. Beginning at three months of age, female rats of the F(0) generation and their subsequent offspring were chronically exposed to a 60‐Hz electric field (100 kV/ m unperturbed) for 19 h/day for the duration of experimentation. After four weeks of exposure, F(0) female rats were mated to unexposed male rats during the field‐off period. No significant developmental effects were detected in their litters, confirming our previous results with swine and rats. The F(0) females were mated for a second time at 7.2 months of age, and the fetuses were evaluated shortly before term. In the first experiments, the incidence of intrauterine mortality was significantly less in exposed than in sham‐exposed litters, and there was a tendency (P = 0.12) for an increased incidence of malformed fetuses in exposed litters. Neither end point was significantly affected in the second experiment. Copulatory behavior of the female F(1) offspring, which were bred at three months of age, was not affected in either experiment. There was a statistically significant decrease in the fertility of F(1) exposed females and a significant increase in the fraction of exposed litters with malformed fetuses in the first experiment; both end points were essentially the same in the sham and exposed groups of the second experiment. That the significant effects detected in the first experiment were not seen in the second may be attributed to random or biological variation. Alternatively, the finding may indicate that the response threshold for induction of malformations lies near 100 kV/m.


BOARD OF DIRECTORS NOMINATIONS


title: Reflexive Modernization at the Source: Local Media Coverage of Bovine Spongiform Encephalopathy in Rural Alberta

text: The potential for reflexive modernization is defined by multiple factors, but the acknowledgment of risk is crucial, particularly among social groups that play a key role in risk minimization. This study offers an examination of the role of local media in response to the outbreak of bovine spongiform encephalopathy (BSE) in beef‐producing communities in rural Alberta. BSE is one of several global risk issues that reflexive modernization theorists argue have the potential to trigger a transformation toward a critically reflexive society in which such risks are minimized. Content analysis of newspapers in beef‐producing regions in Alberta, however, shows how local media framed BSE in a manner that maximized community cohesion and protection of local culture. This selective coverage of BSE in rural Alberta is quite likely to have contributed to, or at least reinforced, support for the current institutional structure of Canadian agriculture in beef‐producing regions, through the constriction of discourse.


European Symposium of Bio‐Organic Chemistry 2003 (ESBOC): The Evolution of Catalysis


title: Synthetic peptides from the N‐domains of CEACAMs activate neutrophils

text: Abstract: Four members of the carcinoembryonic antigen family, CEACAM1, CEACAM8, CEACAM6 and CEACAM3, recognized by CD66a, CD66b, CD66c and CD66d monoclonal antibodies (mAb), respectively, are expressed on human neutrophils. CD66a, CD66b, CD66c and CD66d mAb binding to neutrophils triggers an activation signal that regulates the adhesive activity of CD11/CD18, resulting in an increase in neutrophil adhesion to human umbilical vein endothelial cells. Molecular modeling of CEACAM1 using IgG and CD4 as models has been performed, and three peptides from the N‐terminal domain were found to increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. The peptides were 14 amino acids in length and were predicted to be present at loops and turns between β‐sheets. To better understand the amino acid sequences critical for this biological activity, in the present study we examined the other neutrophil CEACAMs and the highly homologous CEACAM, CEA. Molecular modeling of the N‐terminal domains of human CEACAM8, ‐6, ‐3 and CEA was performed. Twenty peptides, each 14 amino acids in length, that were homologous to the previously reported peptides from the N‐domains of CEACAM1, were synthesized and tested for their ability to alter neutrophil adhesion. Only one new peptide, from the N‐domain of CEA, was found to increase neutrophil adhesion, and this peptide differed from the corresponding CEACAM1 peptide by only a single conservative amino acid substitution. Importantly, minor amino acid differences between active and inactive homologous peptides suggest regions of these peptides that are critical for biological activity. The data suggest that the regions SMPF of peptide CD66a‐1, QLFG of peptide CD66a‐2 and NRQIV of peptide CD66a‐3 are critical for the activities of these peptides, and for the native CEACAMs.


Abstracts from the International Symposium on Frontiers in Life Sciences: Molecular Basis of Disease, Prevention and Treatment


The Human Gene Map 1 December 1984


title: Viruses as precipitants of asthma symptoms. I. Epidemiology

text: Christopher Robin had wheezles and sneezles, they bundled him into his bed. They gave him what goes with a cold in the nose, and some more for a cold in the head. They wondered if wheezles could turn into measles, if measles would turn into mumps; They examined his chest for a rash, and the rest of his body for swellings and lumps. They sent for some doctors in sneezles and wheezles, to tell them what ought to be done. All sorts and conditions of famous physicians came hurrying round at a run. They all made a note of the state of his throat, they asked if he suffered from thirst; They asked if the sneezles came after the wheezles, or if the first sneezle came first. They said, ‘If you teazle a sneezle or wheezle, a measle may easily grow. But humour or pleazle the wheezle or sneezle, the measle will certainly go.’ They expounded the reazles for sneezles and wheezles, the manner of measles when new. They said ‘If he freezles in draughts and in breezles, then PHTHEEZLES may even ensue.’ Christopher Robin got up in the morning, the sneezles had vanished away. And the look in his eye seemed to say to the sky, ‘Now, how to amuse them today?’ A. A. Milne, Now We Are Six, 1927.


title: Group 2 Promoted Hydrogen Release from NMe(2)H⋅BH(3): Intermediates and Catalysis

text: Both homo‐ and heteroleptic alkyl and amide complexes of the Group 2 elements Mg and Ca are shown to be active for the catalytic dehydrocoupling of Me(2)NH⋅BH(3). Reactions of either magnesium dialkyls or the β‐diketiminate complex [HC{(Me)CN(Dipp)}(2)MgnBu] with four or two equivalents of Me(2)NHBH(3), respectively, produce compounds containing the [H(3)BNMe(2)BH(2)Me(2)N](−) ion, which coordinates to the magnesium centers through Mg—N and Mg⋅⋅⋅HB interactions in both the solution and solid states. Thermolysis of these compounds at 60 °C produces the cyclic product [(H(2)BNMe(2))(2)] and, it is proposed, magnesium hydrido species by an unprecedented δ‐hydride elimination process. Calcium‐based species, although less reactive than their magnesium‐based counterparts, are found to engage in similar dehydrocoupling reactivity and to produce a similar distribution of products under thermally promoted catalytic conditions. A mechanism for these observations is presented that involves initial production and insertion of H(2)B=NMe(2) into polarized M—N bonds as the major B—N bond‐forming step. The efficacy of this insertion and subsequent β‐ or δ‐hydride elimination steps is proposed to be dependent upon the charge density and polarizing capability of the participating Group 2 center, providing a rationale for the observed differences in reactivity between magnesium and calcium.


Viruses as precipitants of asthma symptoms II. Physiology and mechanisms


title: Synthesis and Antiviral Properties of Spirocyclic [1,2,3]‐Triazolooxazine Nucleosides

text: An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of β‐d‐psicofuranose to the corresponding azido‐derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides, obtained by Sonogashira chemistry. The products of these reactions underwent 1,3‐dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity using MHV (mouse hepatitis virus) as a model wherein derivative 3 f showed the most promising activity and tolerability.


Mechanisms of asthma exacerbation


The Human Gene Map 15 November 1983


MERS outbreak


title: Decreased FEV (1)% in asthmatic adults in Scottish homes with high Environmental Relative Moldiness Index values

text: BACKGROUND: Exposures to indoor biological contaminants have been implicated in asthma's aetiology but their effect on lung function is not well quantified. OBJECTIVE: The aim of this cross‐sectional study of non‐smoking, asthmatic adults in Scotland was to determine the correlation between the results from a standard spirometry test, forced expiratory volume in one‐second percent (FEV (1)%), and quantitative estimates of some biological exposures. METHODS: A population (n = 55) of non‐smoking, adult asthmatics in Scotland was included in this study and each completed a questionnaire that allowed the determination of the Asthma Control Questionnaire scores (ACQ) and St. George's Respiratory Questionnaire scores (SGRQ), as well as corticosteroid use. Spirometry testing was completed and the pre‐bronchodilator FEV (1)% value calculated. At about the same time, floor dust samples were collected in the living room and in the bedroom. These dust samples were analysed for mould contamination, as described by the Environmental Relative Moldiness Index (ERMI) values and by (1, 3)‐β‐D‐glucan concentrations, for endotoxin, and for dust mite, cat, and dog allergen concentrations. The asthmatics' FEV (1)% values were tested for correlation (Pearson) to questionnaire‐based estimates of health. Also, each biological exposure was tested for correlation (Pearson) to the FEV (1)% values. RESULTS: FEV (1)% results were correlated with ACQ scores (ρ −0.586, P < 0.001), SGRQ scores (ρ −0.313, P = 0.020), and weakly with corticosteroid use (ρ −0.221, P = 0.105). The ERMI values in the homes (average 5.3) were significantly correlated with FEV (1)% values (ρ −0.378, P = 0.004). There was no correlation between FEV (1)% and concentrations of endotoxin, (1, 3)‐β‐D‐glucan, or any of the allergens. CONCLUSION AND CLINICAL RELEVANCE: Although these results do not prove that mould exposures caused the deficit in lung function observed in this study, it might be advisable for asthmatics to avoid high ERMI environments.


Dampness, indoor mould, fungal DNA and respiratory health – molecular methods in indoor epidemiology


The Human Gene Map 15 April 1986: The Morbid Anatomy of the Human Genome


News


title: Monoclonal Antibodies to Human Cell Surface Antigens

text: Many of the leukocyte cell surface molecules are known by “CD” numbers. In this Appendix, a short introduction describes the history and the use of CD nomenclature and provides a few key references to enable access to the wider literature. This is followed by a table that lists all human molecules with approved CD names, tabulating alternative names, key structural features, cellular expression, major known functions, and usefulness of the molecules or antibodies against them in research or clinical applications. Curr. Protoc. Immunol. 80:A.4A.1‐A.4A.73. © 2008 by John Wiley & Sons, Inc.


title: Electron microscopic observations on structures resembling myxovirus in human sarcomas

text: Human tumors of mesenchymal origin contain cytoplasmic structures resembling ribonucleoprotein strands of paramyxoviruses. Similar structures have previously been reported in collagen diseases. The nature and function of these structures remain unresolved.


title: Using Morpholinos to Control Gene Expression

text: Morpholino oligonucleotides are stable, uncharged, water‐soluble molecules used to block complementary sequences of RNA, preventing processing, read‐through, or protein binding at those sites. Morpholinos are typically used to block translation of mRNA and to block splicing of pre‐mRNA, though they can block other interactions between biological macromolecules and RNA. Morpholinos are effective, specific, and lack non‐antisense effects. They work in any cell that transcribes and translates RNA, but must be delivered into the nuclear/cytosolic compartment to be effective. Morpholinos form stable base pairs with complementary nucleic acid sequences but apparently do not bind to proteins to a significant extent. They are not recognized by any proteins and do not undergo protein‐mediated catalysis—nor do they mediate RNA cleavage by RNase H or the RISC complex. This work focuses on techniques and background for using Morpholinos. © 2017 by John Wiley & Sons, Inc.


text: Morpholino oligonucleotides are stable, uncharged, water‐soluble molecules used to block complementary sequences of RNA, preventing processing, read‐through, or protein binding at those sites. Morpholinos are typically used to block translation of mRNA and to block splicing of pre‐mRNA, though they can block other interactions between biological macromolecules and RNA. Morpholinos are effective, specific, and lack non‐antisense effects. They work in any cell that transcribes and translates RNA, but must be delivered into the nuclear/cytosolic compartment to be effective. Morpholinos form stable base pairs with complementary nucleic acid sequences but apparently do not bind to proteins to a significant extent. They are not recognized by any proteins and do not undergo protein‐mediated catalysis; nor do they mediate RNA cleavage by RNase H or the RISC complex. This work focuses on techniques and background for using Morpholinos.


Hospitalization of an oncology patient suspected of having severe acute respiratory syndrome: A setup for an infection control quagmire at a comprehensive cancer center


title: Prospective epidemiological study of common colds and secretory otitis media

text: To evaluate how often a common cold induces secretory otitis media (SOM) two groups of young children were studied. One comprised 373 children aged 9 months to 7 years who were being minded in institutions. The other group consisted of 210 children not minded in day institutions or private day care. This latter group was subdivided into children minded at home or in private day care attended by not more than 2 children (117 children), and the remainder (93 children). Common colds were defined as nasal discharge, and tympanometry was carried out 6 times at 2‐week intervals. Among the 1‐year‐olds common colds induced SOM in 83% of those minded in institutions and in 56% of those minded at home. At the age of 5 years this applied to 20% of both groups.


title: The aetiology and epidemiology of common colds, and the possibilities of prevention

text: The common cold syndrome and its causes are discussed and the feasibility of prophylaxis considered.


title: Diagnosis and treatment of community‐acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese Thoracic Society, Chinese Medical Association

text: Community‐acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline.


title: Tubular complexes of endoplasmic reticulum in lymphoblastic lymphoma: Case report

text: Distinctive intracytoplasmic tubular complexes have been identified occasionally by electron microscopy in a wide variety of hematologic and nonhematologic disorders. The mechanism of induction and significance of these tubular complexes are unknown. Tubular complexes were identified in the majority of bone marrow lymphoma‐leukemia cells in a patient with documented lymphoblastic lymphoma in lymph node. These complexes varied in size but in general ranged from 800–1500 mm, and consisted of masses of nonparallel, twisted, smooth, 40‐nm tubules. Continuity with adjacent endoplasmic reticulum was evident in some of the complexes. Cytochemical characteristics of the malignant cells included strong, focal, paranuclear acid phosphatase reactivity and strong, stippled nuclear terminal deoxynucleotidyl transferase positivity. Flow cytometric analysis showed a DNA‐RNA content pattern consistent with acute lymphoblastic leukemia and typical of T‐cell lymphoma. This represents the first report of such tubular complexes in a presumed T‐cell malignancy.


title: The multiple facets of HIV attachment to dendritic cell lectins

text: Entry of enveloped viruses into host cells depends on the interactions of viral surface proteins with cell surface receptors. Many enveloped viruses maximize the efficiency of receptor engagement by first binding to attachment‐promoting factors, which concentrate virions on target cells and thus increase the likelihood of subsequent receptor engagement. Cellular lectins can recognize glycans on viral surface proteins and mediate viral uptake into immune cells for subsequent antigen presentation. Paradoxically, many viral and non‐viral pathogens target lectins to attach to immune cells and to subvert cellular functions to promote their spread. Thus, it has been proposed that attachment of HIV to the dendritic cell lectin DC‐SIGN enables the virus to hijack cellular transport processes to ensure its transmission to adjacent T cells. However, recent studies show that the consequences of viral capture by immune cell lectins can be diverse, and can entail negative and positive regulation of viral spread. Here, we will describe key concepts proposed for the role of lectins in HIV attachment to host cells, and we will discuss recent findings in this rapidly evolving area of research.


What effect does isoflurane have upon ciliary beat pattern: an in vivo study The effect of anaesthetic gases given via laryngeal mask on nasal ciliary beat pattern and frequency has not been studied. Anaesthetic gases such as isoflurane, halothane and enflurane are known to reduce ciliary beat frequency, but it is unknown whether they also cause cilia to beat in a dyskinetic fashion. Brush biopsies of nasal mucosa were taken pre‐ and post‐anaesthesia with isoflurane, given via a laryngeal mask, from patients undergoing nasal surgery. The samples were observed by light microscopy, and high‐speed digital video recordings were made to determine ciliary beat frequency. Using slow‐motion playback, the ciliary beat pattern was scored for dysmotility, and the proportion of immotile cilia in the sample was determined. We found that ciliary beat frequency decreased significantly (P < 0.01) after exposure to isoflurane (10.24 Hz compared to 9.20 Hz). However, isoflurane did not alter the ciliary beat pattern or the proportion of immotile cilia.


title: Cytophotometric analysis of lytically and persistently infected tissue culture cells with measles virus

text: Lytically and persistently infected VERO and LUB cells were cytophotometrically characterized with the aid of computer analysis. Images scanned at 260 and 280 nm were processed by computer algorithms. With this approach, infected cells could be segmented and differentiated from uninfected cells. Lytically and persistently infected cells could be distinguished by distinct differences in nuclear and cytoplasmic optical densities. These findings are supported by biologic data based on the analysis of virus‐specific proteins and nucleic acids. The applied computer aided cytophotometry provides a new approach in the study of virus‐cell interaction.


title: CLADISTIC INFERENCE AND EVOLUTIONARY SCENARIOS: LOCOMOTORY STRUCTURE, FUNCTION, AND PERFORMANCE IN WATER STRIDERS

text: Abstract — A research methodology that aims to reveal how historical changes in environmental conditions (or selective regimes) have shaped the adaptive evolution of clades is applied to the adaptive evolution of water striders and their allies (Hemiptera‐Heteroptera, Gerromorpha), a group of semiaquatic insects which includes species that are conspicuously adapted to life on the surface film of water. Based upon reconstructed phylogenies for the higher gerromorphan taxa, the hypothesis that the hygropetric zone is the ancestral one is confirmed for the Mesoveliidae, Hebridae and the clade comprising the Paraphrynoveliidae, Macroveliidae and Hydrometridae, but not for the Hermatobatidae and Veliidae. There is no support for the hypothesis that the intersection zone was a sort of transitional zone during the ecological evolution of pleustonic bugs. It is shown that the unique morphological and behavioural traits of the most derived members of this group evolved after inferred historical changes in environmental conditions and therefore qualify as adaptations in the sense ofGould and Vrba (1982),Coddington (1988) andBaum and Larson (1991). Other predictions about the adaptive evolution of gerromorphan bugs do not pass the cladistic test. The study illustrates that cladistic inference is a valuable tool in clarifying and sharpening retrospective explanations of complex evolutionary scenarios.


title: Kaposi's sarcoma in renal transplant recipients ultrastructural and immunoperoxidase study of four cases

text: Tissues from four cases of Kaposi's sarcoma developing in renal transplant recipients were studied by light and electron microscopic examination and by immunoperoxidase staining for Factor‐VIII‐related antigen. Ultrastructurally, the tumors in all four cases contained a variable mixture of cells, including endothelial cells, pericytes, fibroblasts, and myofibroblasts. These findings support the origin of Kaposi's sarcoma from primitive vasoformative mesenchyme. Immunoperoxidase staining for Factor‐VIII‐related antigen was limited to endothelial cells. In one case intracytoplasmic virus‐like tubular complexes were seen. The significance of this finding is briefly discussed.


title: Biphasic regulation of RNA interference during rotavirus infection by modulation of Argonaute2

text: RNA interference (RNAi) is an evolutionary ancient innate immune response in plants, nematodes, and arthropods providing natural protection against viral infection. Viruses have also gained counter‐defensive measures by producing virulence determinants called viral‐suppressors‐of‐RNAi (VSRs). Interestingly, in spite of dominance of interferon‐based immunity over RNAi in somatic cells of higher vertebrates, recent reports are accumulating in favour of retention of the antiviral nature of RNAi in mammalian cells. The present study focuses on the modulation of intracellular RNAi during infection with rotavirus (RV), an enteric virus with double‐stranded RNA genome. Intriguingly, a time point‐dependent bimodal regulation of RNAi was observed in RV‐infected cells, where short interfering RNA (siRNA)‐based RNAi was rendered non‐functional during early hours of infection only to be reinstated fully beyond that early infection stage. Subsequent investigations revealed RV nonstructural protein 1 to serve as a putative VSR by associating with and triggering degradation of Argonaute2 (AGO2), the prime effector of siRNA‐mediated RNAi, via ubiquitin–proteasome pathway. The proviral significance of AGO2 degradation was further confirmed when ectopic overexpression of AGO2 significantly reduced RV infection. Cumulatively, the current study presents a unique modulation of host RNAi during RV infection, highlighting the importance of antiviral RNAi in mammalian cells.


title: Biosafety: Guidelines for Working with Pathogenic and Infectious Microorganisms

text: This unit, in conjunction with local and national guidelines and regulations (see appendix 1b), provides the basic biosafety information needed to perform the procedures detailed in this manual. Topics discussed include routine precautions when working with biohazards, disinfectants, disposal of biohazards, biosafety levels (as established by the U.S. National Institutes of Health and the U.S. Centers for Disease Control and Prevention), animal facilities, and clinical laboratories. In addition, resources for more information are provided in the Literature Cited and Key References sections and in URLs given within the text, as well as the Internet Resources section. Curr. Protoc. Microbiol. 13:1A.1.1‐1A.1.14. © 2009 by John Wiley & Sons, Inc.


title: Are point‐of‐care (POC) virological tests what is needed?

text: Point‐of‐care (POC) tests are becoming more available, although the way in which they should be used is currently undecided. Any ‘laboratory’‐based diagnosis of respiratory infections has three components: the specimen taken, the test used, and the interpretation of the results. Each of these components needs to be carefully addressed when using POC tests for the diagnosis of respiratory tract infections. Given the enthusiasm with which POC tests are being developed, it is likely that they will be used more and more widely. If so, the advantages and limitations of their use should be fully discussed and the implications recognised.


Bracing for disaster: Specialists step up their preparations for emerging and evolving infectious disease threats


title: Shaping the flavivirus replication complex: It is curvaceous!

text: Flavivirus replication is intimately involved with remodelled membrane organelles that are compartmentalised for different functions during their life cycle. Recent advances in lipid analyses and gene depletion have identified a number of host components that enable efficient virus replication in infected cells. Here, we describe the current understanding on the role and contribution of host lipids and membrane bending proteins to flavivirus replication, with a particular focus on the components that bend and shape the membrane bilayer to induce the flavivirus‐induced organelles characteristic of infection.


title: Morphologic study of virus‐like particles in a case of acute leukemia

text: Virus‐like particles, grouped in clusters not bound by a membrane, were seen in electron micrographs of fresh leucoblasts of an acute leukemic patient. They consisted of large (100‐nm diameter), round particles apparently composed of subunits. Tubular structures (30–50‐nm diameter) were also seen in leucoblasts of the same patient. The two types of structures were never seen simultaneously in the same cell. The authors review the literature pertaining to the morphology of virus‐like particles associated with malignant hematologic disease.


text: Morpholino oligonucleotides are stable, uncharged, water‐soluble molecules that bind to complementary sequences of RNA, thereby inhibiting mRNA processing, read‐through, and protein binding at those sites. Morpholinos are typically used to inhibit translation of mRNA, splicing of pre‐mRNA, and maturation of miRNA, although they can also inhibit other interactions between biological macromolecules and RNA. Morpholinos are effective, specific, and lack non‐antisense effects. They work in any cell that transcribes and translates RNA. However, unmodified Morpholinos do not pass well through plasma membranes and must therefore be delivered into the nuclear or cytosolic compartment to be effective. Morpholinos form stable base pairs with complementary nucleic acid sequences but apparently do not bind to proteins to a significant extent. They are not recognized by proteins and do not undergo protein‐mediated catalysis; nor do they mediate RNA cleavage by RNase H or the RISC complex. This work focuses on techniques and background for using Morpholinos. Curr. Protoc. Mol. Biol. 83:26.8.1‐26.8.29. © 2008 by John Wiley & Sons, Inc.


title: Clinical features of Chlamydia pneumoniae acute respiratory infection

text: Chlamydia pneumoniae is a worldwide respiratory pathogen involved in 6–20% of community-acquired pneumonias and in about 5% of acute exacerbations of chronic bronchitis. Preliminary data also indicate a possible association between Chlamydia pneumoniae infection and asthma. Further studies are needed to elucidate whether Chlamydia pneumoniae is merely a precipitant of asthma symptoms or is actually one of the causes of asthma.


title: Introduction to virus‐caused cancers

text: Members of four different groups of animal viruses are known to cause cancer in animals. (Only two of them, the leukoviruses and herpesviruses, cause cancer in nonlaboratory situations.) All the members of these groups of viruses form integrated viral DNA in infected cells. However, the efficiencies with which they cause cancer vary by over a dozen orders of magnitude. These differences in efficiency are a result of differences in efficiency of formation and expression of the genes for neoplastic transformation. Four models of mechanisms for formation of the genes for neoplastic transformation are presented. Two involve the formation of new DNA sequences. No efficient human cancer‐causing viruses are known. Therefore, it is proposed that human cancer is a result of formation of the genes for neoplastic transformation by misevolution of a normal cellular information transferring process. This misevolution is caused by chemicals, physical agents, or viruses.


title: Overview of Protein Structural and Functional Folds

text: This overview provides an illustrated, comprehensive survey of some commonly observed protein‐fold families and structural motifs, chosen for their functional significance. It opens with descriptions and definitions of the various elements of protein structure and associated terminology. Following is an introduction into web‐based structural bioinformatics that includes surveys of interactive web servers for protein fold or domain annotation, protein‐structure databases, protein‐structure‐classification databases, structural alignments of proteins, and molecular graphics programs available for personal computers. The rest of the overview describes selected families of protein folds in terms of their secondary, tertiary, and quaternary structural arrangements, including ribbon‐diagram examples, tables of representative structures with references, and brief explanations pointing out their respective biological and functional significance.


title: Nowcasting by Bayesian Smoothing: A flexible, generalizable model for real-time epidemic tracking

text: Achieving accurate, real-time estimates of disease activity is challenged by delays in case reporting. “Nowcast” approaches attempt to estimate the complete case counts for a given reporting date, using a time series of case reports that is known to be incomplete due to reporting delays. Modeling the reporting delay distribution is a common feature of nowcast approaches. However, many nowcast approaches ignore a crucial feature of infectious disease transmission—that future cases are intrinsically linked to past reported cases—and are optimized to one or two applications, which may limit generalizability. Here, we present a Bayesian approach, NobBS (Nowcasting by Bayesian Smoothing) capable of producing smooth and accurate nowcasts in multiple disease settings. We test NobBS on dengue in Puerto Rico and influenza-like illness (ILI) in the United States to examine performance and robustness across settings exhibiting a range of common reporting delay characteristics (from stable to time-varying), and compare this approach with a published nowcasting software package while investigating the features of each approach that contribute to good or poor performance. We show that introducing a temporal relationship between cases considerably improves performance when the reporting delay distribution is time-varying, and we identify trade-offs in the role of moving windows to accurately capture changes in the delay. We present software implementing this new approach (R package “NobBS”) for widespread application and provide practical guidance on implementation.


Unity amidst uncertainty: COVID-19 pandemic fosters collaboration in rheumatology community


COVID-19 in the USA: a question of time


Strengthening accountability of the global health metrics enterprise


Sustaining containment of COVID-19 in China


title: Relative transmissibility of shigellosis among male and female individuals: a modeling study in Hubei Province, China

text: BACKGROUND: Developing countries exhibit a high disease burden from shigellosis. Owing to the different incidences in males and females, this study aims to analyze the features involved in the transmission of shigellosis among male (subscript m) and female (subscript f) individuals using a newly developed sex-based model. METHODS: The data of reported shigellosis cases were collected from the China Information System for Disease Control and Prevention in Hubei Province from 2005 to 2017. A sex-based Susceptible–Exposed–Infectious/Asymptomatic–Recovered (SEIAR) model was applied to explore the dataset, and a sex-age-based SEIAR model was applied in 2010 to explore the sex- and age-specific transmissions. RESULTS: From 2005 to 2017, 130 770 shigellosis cases (including 73 981 male and 56 789 female cases) were reported in Hubei Province. The SEIAR model exhibited a significant fitting effect with the shigellosis data (P < 0.001). The median values of the shigellosis transmission were 2.3225 × 10(8) for SAR(mm) (secondary attack rate from male to male), 2.5729 × 10(8) for SAR(mf), 2.7630 × 10(-8) for SAR(fm), and 2.1061 × 10(-8) for SAR(ff). The top five mean values of the transmission relative rate in 2010 (where the subscript 1 was defined as male and age ≤ 5 years, 2 was male and age 6 to 59 years, 3 was male and age ≥ 60 years, 4 was female and age ≤ 5 years, 5 was female and age 6 to 59 years, and 6 was male and age ≥ 60 years) were 5.76 × 10(-8) for β(61), 5.32 × 10(-8) for β(31), 4.01 × 10(-8) for β(34), 7.52 × 10(-9) for β(62), and 6.04 × 10(-9) for β(64). CONCLUSIONS: The transmissibility of shigellosis differed among male and female individuals. The transmissibility between the genders was higher than that within the genders, particularly female-to-male transmission. The most important route in children (age ≤ 5 years) was transmission from the elderly (age ≥ 60 years). Therefore, the greatest interventions should be applied in females and the elderly.


A changing world


title: Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles

text: Effective analysis of pathogens causing human and veterinary diseases demands rapid, specific and sensitive detection methods which can be applied in research laboratory setups and in field for routine diagnosis. Paper lateral flow biosensors (LFBs) have been established as attractive tools for such analytical applications. In the present study a prototype LFB was designed for whole particles (virions) detection of nodavirus or fish nervous necrosis virus. Nodavirus is an important threat in the aquaculture industry, causing severe economic losses and environmental problems. The LFB was based on polyclonal antibodies conjugated on gold nanoparticles for signal visualization. Brain and retinas from fish samples were homogenized, centrifuged and the supernatant was directly applied on the LFB. Formation of a red test line was indicative of nodavirus virions presence. Nodavirus visual detection was completed in short time (30 min). Key factors of the LFB development influencing the assays’ detection limit were characterized and the optimum parameters were determined, enabling increased efficiency, excluding non-specific interactions. Therefore, the proposed LFB assay consists a robust, simple, low cost and accurate method for detection of nodavirus virions in fish samples. The proposed biosensor is ideal for development of a commercial kit to be used on aquaculture facilities by fish farmers. It is anticipated that disease monitoring and environmental safety will benefit from the simplification of time consuming and costly procedures.


title: Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer

text: Helicobacter pylori (HP) colonizes the human stomach and induces acute gastritis, peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Increased virulence in HP isolates derives from harboring the cag (cytotoxin-associated genes) pathogenicity island (cagPAI). We analyzed the microvariants in cagPAI genes with the hypothesis that they may play an important role in determining HP virulence. We tested DNAs from cagA positive patients HP isolates; a total of 74 patients with chronic gastritis (CG, N = 37), intestinal metaplasia (IM, N = 21) or gastric cancer (GC, N = 16) from Mexico and Colombia. We selected 520 non-synonymous variants with at least 7.5% frequency in the original sequence outputs or with a minimum of 5 isolates with minor allele. After adjustment for multiple comparisons, no variants were statistically significantly associated with IM or GC. However, 19 non-synonymous showed conventional P-values < 0.05 comparing the frequency of the alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC; 12 of these showed a significant correlation with the severity of the disease. The present study revealed that several cagPAI genes from Latin American Western HP strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. However, none of the associations remained statistically significant after adjustment for multiple comparison.


NOW!: protection for obstetrical providers and patients


Review of equine Cryptosporidium infection


Opinion of the Scientific Panel on Animal Health and Welfare (AHAW) on a request from the Commission related with the risks of poor welfare in intensive calf farming systems


title: The major histocompatibility complex influences myelin basic protein 63‐88‐induced T cell cytokine profile and experimental autoimmune encephalomyelitis

text: Polymorphism of the major histocompatibility complex (MHC) influences susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP) in rats. Current concepts relate such influences to the capacity of class II molecules to present relevant peptides to autoreactive T cells. We have here analyzed the MHC influence on the immune response and the development of EAE after immunization with the immunodominant peptide MBP‐63–88. Analysis of MHC‐congenic LEWIS strains showed that RT1(a), RT1(c) and RT1(l) haplotypes are permissive for disease induction, whereas RT1(d) and RT1(u) are resistant. All EAE responding strains showed peptide‐specific proliferation and interferon (IFN)‐γ secretion, but no early significant tendency to express interleukin (IL‐4) or transforming growth factor (TGF)‐β mRNA in lymphocytes in response to the MBP 63–88, 7 days post immunization (p.i.). Later, 14 days p.i., peptide‐specific induction of IL‐4 and TGF‐β occurred in RT1(l) rats. Among the EAE non‐responders strains, only the RT1(u) rats showed an immune response to MBP 63‐88. This response, however, was qualitatively different from the immune response in the EAE‐susceptible strains. Thus, there was no proliferation and only moderate IFN‐γ production in response to peptide, but in contrast, a significant and early peptide‐induced IL‐4 and TGF‐β response was observed. The data suggest that the MHC‐associated susceptibility to EAE is partly related to the ability to mount a TH1‐like immune response while the MHC‐associated EAE resistance may either be related to MBP peptide non‐responsiveness or to peptide recognition and induction of a qualitatively different and disease down‐regulatory immune response.


II Joint Meeting of the German Society for Immunology (DGfl) and the Italian Society of Immunology, Clinical Immunology and Allergology (SIICA), 10–13 September, 2019, Munich, Germany


Role of absolute lymphocyte count in the screening of patients with suspected SARS


Opinion of the Scientific Panel on Animal Health and Welfare (AHAW) on a request from the Commission related to the probability of transmission of Porcine Reproductive and Respiratory Syndrome virus (PRRSv) to naive pigs via fresh meat


Opinion of the Scientific Panel on Animal Health and Welfare (AHAW) on a request from the Commission related with animal health and welfare risks associated with the import of wild birds other than poultry into the European Union


title: Natural variability of biochemical biomarkers in the macro‐zoobenthos: Dependence on life stage and environmental factors

text: Biomarkers are widely used in ecotoxicology as indicators of exposure to toxicants. However, their ability to provide ecologically relevant information remains controversial. One of the major problems is understanding whether the measured responses are determined by stress factors or lie within the natural variability range. In a previous work, the natural variability of enzymatic levels in invertebrates sampled in pristine rivers was proven to be relevant across both space and time. In the present study, the experimental design was improved by considering different life stages of the selected taxa and by measuring more environmental parameters. The experimental design considered sampling sites in 2 different rivers, 8 sampling dates covering the whole seasonal cycle, 4 species from 3 different taxonomic groups (Plecoptera, Perla grandis; Ephemeroptera, Baetis alpinus and Epeorus alpicula; Tricoptera, Hydropsyche pellucidula), different life stages for each species, and 4 enzymes (acetylcholinesterase, glutathione S‐transferase, alkaline phosphatase, and catalase). Biomarker levels were related to environmental (physicochemical) parameters to verify any kind of dependence. Data were statistically elaborated using hierarchical multilevel Bayesian models. Natural variability was found to be relevant across both space and time. The results of the present study proved that care should be paid when interpreting biomarker results. Further research is needed to better understand the dependence of the natural variability on environmental parameters. Environ Toxicol Chem 2017;36:3158–3167. © 2017 SETAC


title: Late‐onset Pneumocystis jirovecii pneumonia post–fludarabine, cyclophosphamide and rituximab: implications for prophylaxis

text: OBJECTIVE: Fludarabine, cyclophosphamide and rituximab (FCR) therapy for lymphoid malignancies has historically been associated with a low reported incidence of Pneumocystis jirovecii pneumonia (PJP). However, prophylaxis was routinely used in early studies, and molecular diagnostic tools were not employed. The objective of this study was to review the incidence of PJP during and post‐FCR in the era of highly sensitive molecular diagnostics and (18)F‐fluorodeoxyglucose (FDG) positron emission tomography (PET)–computerised tomography (CT). METHODS: All patients treated with standard FCR at the Peter MacCallum Cancer Centre (March 2009 to June 2012) were identified from a medications management database. Laboratory‐confirmed PJP cases during this time were identified from an electronic database. RESULTS: Overall, 66 patients were treated with a median of 5.5 FCR cycles. Eight PJP cases were identified, 6 of whom had received chemotherapy prior to FCR. In 5 cases, (18)F‐FDG PET demonstrated bilateral ground‐glass infiltrates. Median CD4(+) lymphocyte counts at time of PJP diagnosis and 9–12 months following FCR were 123 and 400 cells/μL, respectively. In patients receiving no prophylaxis, 9.1% developed PJP during FCR. The rate following FCR was 18.4%, with median onset at 6 months (2.4–24 months). CONCLUSION: Given the high rate of late‐onset PJP, consideration should be given for extended PJP prophylaxis for up to 12 months post‐FCR, particularly in pretreated patients. Further evaluation of the role of CD4(+) monitoring is warranted to quantify risk of disease development and to guide duration of prophylaxis.


title: Guidelines for the Control of Equine Viral Infections

text: SUMMARY: Twelve DNA viruses and forty‐three RNA viruses are known to infect horses. In addition, there are three unclassified viruses and, at least, three alleged viruses infecting horses. Differential diagnosis is difficult. At least twenty‐eight of the fifty‐eight viruses induce clinical disease but the range of syndromes is limited; eleven provoke respiratory symptoms and eleven cause encephalitis. Thirty‐four equine viruses with a limited geographical distribution are transmitted by arthropod vectors. Twenty viruses are spread by contact and their distribution, in general, is global. The vector‐transmitted virus diseases are best controlled by prophylactic vaccination. The viral contagions are not, in general, well controlled by vaccination and it is likely that prophylactic chemotherapy will become increasingly important in the future. RÉSUMÉ: On sait que douze virus ADN et quarante trois virus ARN sont responsables d'infections chez le cheval. En outre trois virus non classés et trois autres agents de type viral au moins sont également infectants pour cette espèce. Le diagnostic différentiel est difficile. Vingt huit au moins des cinquante trois virus provoquent des maladies cliniques mais la gamme des syndromes est restreinte: Onze virus engendrent des symptomes respiratoires, onze déterminent des encéphalites. Trente quatre virus dont la distribution géographique est limitée sont transmis par des arthropodes vecteurs. Vingt virus sont disséminés par contact et leur répartition est en général à l'échelle du globe. Les maladies provoquées par des virus à propagation vectorielle sont mieux controlées par une vaccination préventive. Les contagions virales ne sont pas, en général, efficacement controlées par la vaccination et l'on peut penser que la chimiothérapie préventive de ces affections connaitra une importance croissante à l'avenir. ZUSAMMENFASSUNG: Zwölf DNS‐Viren und 43 RNS‐Viren vermögen das Pferd zu infizieren. Dazu kommen drei unklassierte Viren und zum mindesten drei Erreger, die angeblich Viruscharakter haben. Die Differentialdiagnose ist schwierig. Mindestens 28 der 58 Viren verursachen klinisch manifeste Krankheiten, aber die Eigenart der Syndrome ist limitiert; elf davon provozieren respiratorische Symptome und elf rufen Encephalitis hervor. 34 equine Viren benötigen als Vektoren Arthropoden; ihre geographische Ausbreitung ist beschränkt. 20 Viren werden durch Kontakt übertragen; sie werden in der Regel auf der ganzen Welt angetroffen. Die durch Vektoren übertragenen Viruskrankheiten können am besten durch prophylaktische Impfungen kontrolliert werden. Die übrigen können im allgemeinen durch Impfungen nicht gut kontrolliert werden und es scheint wahrscheinlich, dass die prophylaktische Chemotherapie in Zukunft an Bedeutung gewinnen wird. SUMARIO: VIRUS EQUINOS Doce DNA virus y cuarenta y tres RNA virus son reconcodios como infectantes al caballo. En adicion hay tres no clasidicados virus y por lo menos tres tipos de virus muy se mejantes que afectan el caballo. El diagnostico diferencial es dificultoso. Aproximadamente 28 de los 28 virus inducen enfermedades clinicas con y espectro de sindromes limitado. 11 provocan sintomas respiratorios y 11 causan encefalitis. 34 virus equinos con limitacion en su distribucion geografica son transmitidos por vectores artropodos. Veinte virus son diseminados por contacto y su distribucion en general es global. Es controlada la enfermeead de estos vectiores per medio de vacunacion. Los contagio del virus no son bien controlados por lo general mediante vacunacion y solo una terapia profilactica que havenido tomando aunge en el futuro.


title: Plant domestication disrupts biodiversity effects across major crop types

text: Plant diversity fosters productivity in natural ecosystems. Biodiversity effects might increase agricultural yields at no cost in additional inputs. However, the effects of diversity on crop assemblages are inconsistent, probably because crops and wild plants differ in a range of traits relevant to plant–plant interactions. We tested whether domestication has changed the potential of crop mixtures to over‐yield by comparing the performance and traits of major crop species and those of their wild progenitors under varying levels of diversity. We found stronger biodiversity effects in mixtures of wild progenitors, due to larger selection effects. Variation in selection effects was partly explained by within‐mixture differences in leaf size. Our results indicate that domestication might disrupt the ability of crops to benefit from diverse neighbourhoods via reduced trait variance. These results highlight potential limitations of current crop mixtures to over‐yield and the potential of breeding to re‐establish variance and increase mixture performance.


title: ALCOHOL TOLERANCE, ADH ACTIVITY, AND ECOLOGICAL NICHE OF DROSOPHILA SPECIES

text: In vitro alcohol dehydrogenase (ADH) activity was measured in adults of species belonging to Drosophila and to the related genus Zaprionus. Data were analyzed according to the known breeding sites and the level of ethanol tolerance of these species. Alcohol dehydrogenase activity was assayed with both ethanol (E) and isopropanol (I). Our results show a very broad range of activities among the 71 species investigated, the ratio of the highest value observed (D. melanogaster) to the lowest (D. pruinosa) being 65:1. A general positive correlation was found between the level of ADH activity and the capacity to detoxify ethanol. Nevertheless, many species show exceptions to this rule. Contrary to a logical expectation, adaptation to high alcoholic resources, which has been a recurrent evolutionary event, was not mediated by a more efficient use of ethanol, that is, an increase of the E/I ratio. This ratio seems to be quite variable according to the phylogeny and is especially low in the subgenus Sophophora as well as in Zaprionus. Alcohol tolerance clearly is related to the larval habitat of the species and shows that adaptation to alcoholic resources has been a major evolutionary challenge in drosophilids. This adaptation is not related to phylogeny, having occurred independently several times during the evolution of the group. Finally, it should be borne in mind that, besides metabolization and detoxification, other physiological processes such as nervous‐system tolerance or ethanol excretion may be involved in ethanol tolerance, and such functions also should be investigated. Environmental ethanol, which is certainly a major ecological parameter for many drosophilids, has selected a diversity of physiological adaptations, all related to the Adh locus, but presumably much more complicated than was previously believed.


title: Primary and secondary hemophagocytic lymphohistiocytosis have different patterns of T‐cell activation, differentiation and repertoire

text: Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening inflammatory syndrome characterized by hyperactivation of lymphocytes and histiocytes. T cells play a key role in HLH pathogenesis, but their differentiation pattern is not well characterized in patients with active HLH. We compared T‐cell activation patterns between patients with familial HLH (1°HLH), 2°HLH without apparent infectious trigger (2°HLH) and 2°HLH induced by a viral infection (2°V‐HLH). Polyclonal CD8(+) T cells are highly activated in 1°HLH and 2°V‐HLH, but less in 2°HLH as assessed by HLA‐DR expression and marker combination with CD45RA, CCR7, CD127, PD‐1 and CD57. Absence of increased HLA‐DR expression on T cells excluded active 1° HLH with high sensitivity and specificity. A high proportion of polyclonal CD127(−)CD4(+) T cells expressing HLA‐DR, CD57, and perforin is a signature of infants with 1°HLH, much less prominent in virus‐associated 2°HLH. The similar pattern and extent of CD8(+) T‐cell activation compared to 2° V‐HLH is compatible with a viral trigger of 1°HLH. However, in most 1°HLH patients no triggering infection was documented and the unique activation of cytotoxic CD4(+) T cells indicates that the overall T‐cell response in 1°HLH is different. This may reflect different pathways of pathogenesis of these two HLH variants.


title: Homologous collagen‐induced arthritis in ratg and mice are associated with structurally different major histocompatibility complex DQ‐like molecules

text: Collagen‐induced arthritis (CIA) in rats, induced with homologous type II collagen (CII), is a genetically more restricted disease and has better resemblance to rheumatoid arthritis by its chronic disease course, than CIA induced with heterologous CII. The DA strain is highly susceptible to CIA induced with homologous CII, while the Lewis strain is resistant. (DAxLew)F(1) is susceptible and backcrossing to Lewis reveals a close, but not complete, association of both arthritis and CII responsiveness to the RT1(a) haplotype. Analyses of congenic strains on DA and Lewis backgrounds suggest that expression of a major histocompatibility complex class II B(a) molecule, encoded from the RT1B(a) locus, is associated with arthritis susceptibility and CII responsiveness. The second exons coding for the first domains of the α and β chains of both the RT1(a) and RT1(1) haplotypes were sequenced and the deduced amino acid sequences compared with the corresponding molecule associated with susceptibility to CIA in the mouse (H‐2 A(q)). The sequences of the respective alleles revealed no obvious structural homology explaining the extensive similarities in the development of chronic autoimmune arthritis. Instead, this finding implies that different trimolecular constituents (i.e. class II,T cell receptor, and CII peptides) may yield an antigen presentation event that is able to trigger a similar autoaggressiveness in the two rodent species.


title: Lymphocyte Recruitment Following Spinal Cord Injury in Mice is Altered by Prior Viral Exposure

text: The inflammatory response induced by mechanical lesion of the spinal cord is known to include the recruitment of neutrophils and macrophages, while the involvement of lymphocytes has been largely ignored. We have studied the pattern of lymphocyte recruitment following partial transection of the mouse spinal cord. Using immunohistochemical techniques, all three types of lymphocytes (CD4‐positive T‐cells, CD8‐ positive T‐cells and B‐cells) were found in the vicinity of the lesion site within hours and persisted for up to 7 days. There was a predominance of B‐lymphocytes during the first 3 days. A second, late phase of cell infiltration, dominated by CD8‐positive T‐lymphocytes, occurred in mice that had been raised in a conventional breeding unit and had acquired antibody titres to a common murine virus (mouse hepatitis virus). In contrast, mice kept in specific pathogen‐free facilities did not show this late‐phase response. These findings suggest a possible role for lymphocytes in secondary tissue loss, local demyelination, scar formation, cytokine‐mediated inflammatory responses or trophic processes. They also provide evidence that a virus infection can significantly enhance the reaction of T‐cells to a spinal cord lesion.


Global Public Health Security: Inequality, Vulnerability and Public Health System Capabilities


title: The ecology of a beech forest on Mt. Sanpoiwadake, Hakusan National Park, Japan I. Braun‐Blanquet, TWINSPAN and DCA analysis

text: The Lindero membranaceae‐Fagetum crenatae association on Mt. Sanpoiwadake, Hakusan National Park, Japan, has been classified using traditional Braun‐Blanquet methods. The association was floristically sub‐divided into six communities, all of which had been included as four subassociations by Hukusima (1982). The resulting table was compared with an analogous community table derived using computer‐based TWINSPAN analysis. This dual approach was shown to provide a fully objective classification by method, the subjective element in the Braun‐Blanquet method thus being substantiated TWINSPAN. Subsequent ordination of the data using DCA then provided a further degree of objective evaluation allowing any misclassified stand or species to be re‐examined, and at the same time displaying the detailed inter‐relationships between all species or stands.


title: Identification of cross‐reactive antibodies for the detection of lymphocytes, myeloid cells and haematopoietic precursors in the naked mole rat

text: The naked mole rat (Heterocephalus glaber, NMR) is a rodent with exceptional longevity, low rates of age‐related diseases and spontaneous carcinogenesis. The NMR represents an attractive animal model in longevity and cancer research, but there are no NMR‐specific antibodies available to study its immune system with respect to age‐ and cancer‐related questions. Substantial homology of major NMR immune cell markers with those of Guinea pig, human and, to a lesser extent, mouse and rat origin are implicated for the existence of immunological cross‐reactivity. We identified 10 antibodies recognising eight immunophenotypic markers expressed on the NMR's T and B lymphocytes, macrophages/monocytes and putative haematopoietic precursors and used them for an immunophenotyping of leukocyte subsets of peripheral blood, spleen and bone marrow samples. Overall, we found that the leukocyte composition of NMR peripheral blood is comparable to that of mice. Notably, the frequency of cytotoxic T cells was found to be lower in the NMR compared to corresponding mouse tissues and human blood. Antibodies used in the present paper are available either commercially or from the scientific community and will provide new opportunities for the NMR as a model system in ageing‐ and cancer‐related research areas.


DISCONTINUOUS DNA VARIATION IN THE EVOLUTION OF PLANT SPECIES: THE GENUS LATHYRUS