Sensitivity to the slope (α) of the amplitude spectrum is dependent on the α of Recently Viewed Environments: A visual adaptation study in modified reality Scenes contain many statistical regularities that could benefit visual processing if accounted for by the visual system. One such statistic is the orientation-averaged slope () of the amplitude spectrum of natural scenes. Human observers show different discrimination sensitivity to : sensitivity is highest for  values between 1.0 and 1.2 and decreases as  is steepened or shallowed. The range of  for peak discrimination sensitivity is concordant with the average  of natural scenes, which may indicate that visual mechanisms are optimized to process information at  values commonly encountered in the environment. Here we explore the association between peak discrimination sensitivity and the most viewed s in natural environments. Specifically, we verified whether discrimination sensitivity depends on the recently viewed environments. Observers were immersed, using a Head-Mounted Display, in an environment that was either unaltered or had its average  steepened or shallowed by 0.4. Discrimination thresholds were affected by the average shift in , but this effect was most prominent following adaptation to a shallowed environment. We modeled these data with a Bayesian observer and explored whether a change in the prior or a change in the likelihood best explained the psychophysical effects. Change in discrimination thresholds following adaptation could be explained by a shift in the central tendency of the prior concordant with the shift of the environment, in addition to a change in the likelihood. Our findings suggest that expectations on the occurrence of  that result from a lifetime of exposure remain plastic and able to accommodate for the statistical structure of recently viewed environments.
Age-associated changes to neuronal dynamics involve a disruption of excitatory/inhibitory balance in C. elegans In the aging brain, many of the alterations underlying cognitive and behavioral decline remain opaque. C. elegans offers a powerful model for aging research, with a simple, well-studied nervous system to further our understanding of the cellular modifications and functional alterations accompanying senescence. We perform multi-neuronal functional imaging across the aged C. elegans nervous system, measuring an age-associated breakdown in system-wide functional organization. At single-cell resolution, we detect shifts in activity dynamics toward higher frequencies. In addition, we measure a specific loss of inhibitory signaling that occurs early in the aging process and alters the systems critical excitatory/inhibitory balance. These effects are recapitulated with mutation of the calcium channel subunit UNC-2/CaV2. We find that manipulation of inhibitory GABA signaling can partially ameliorate or accelerate the effects of aging. The effects of aging are also partially mitigated by disruption of the insulin signaling pathway, known to increase longevity, or by a reduction of caspase activation. Data from mammals are consistent with our findings, suggesting a conserved shift in the balance of excitatory/inhibitory signaling with age that leads to breakdown in global neuronal dynamics and functional decline.
Widespread redundancy in -omics profiles of cancer mutation states In studies of cellular function in cancer, researchers are increasingly able to choose from many -omics assays as functional readouts. Choosing the correct readout for a given study can be difficult, and which layer of cellular function is most suitable to capture the relevant signal may be unclear. In this study, we consider prediction of cancer mutation status (presence or absence) from functional -omics data as a representative problem. Since functional signatures of cancer mutation have been identified across many data types, this problem presents an opportunity to quantify and compare the ability of different -omics readouts to capture signals of dysregulation in cancer. The TCGA Pan-Cancer Atlas contains genetic alteration data including somatic mutations and copy number variants (CNVs), as well as several -omics data types. From TCGA, we focus on RNA sequencing, DNA methylation arrays, reverse phase protein arrays (RPPA), microRNA, and somatic mutational signatures as -omics readouts.

Across a collection of genes recurrently mutated in cancer, RNA sequencing tends to be the most effective predictor of mutation state. Surprisingly, we found that for many of the genes we considered, one or more other data types are approximately equally effective predictors. Performance was more variable between mutations than it was between data types for the same mutation, and there was often little difference between the top data types. We also found that combining data types into a single multi-omics model provided little or no improvement in predictive ability over the best individual data type. Based on our results, for the design of studies focused on the functional outcomes of cancer mutations, there are often multiple -omics types that can serve as effective readouts, although gene expression seems to be a reasonable default option. Is a Ring-arranged Vascular Pattern Unique to Stems? A Three Dimensional Reconstruction of Anaxagorea (Annonaceae) Carpel Vasculature and its Evolutionary Implications Elucidating the origin of carpel has been a challenge in botany for a long time. The Unifying Theory suggested that the carpel originate from a composite organ comprising an ovule-bearing shoot and a foliar part enclosing the shoot. A logical inference from this theory is that placenta in angiosperms should have radiosymmetrical vasculature, just like that in a young branch. Anaxagorea is the most basal genus of the primitive angiosperm family, Annonaceae. The conspicuous carpel stipe makes it an ideal material for exploring the carpel vasculature. In this study, serial sections of flower and carpel were delineated in Anaxagorea luzonensis and A. javanica, and a three-dimensional model of the carpel vasculature was reconstructed. The results show that (1) vascular bundles at both the carpel stipe and the ovule/placenta are in a radiosymmetrical pattern, (2) the amphicribral bundles would develop into ring-arranged bundle complex with the carpel maturation, (3) the ovule/placenta bundles were separated from the bundles of the carpel wall, and, (4) all the radiosymmetrical vasculature (including amphicribral bundles and ring-arranged bundle complexes) in the carpel were fed by a larger radiosymmetrical bundle system. These results suggest that the radiosymmetrical pattern of carpel vasculature are in line with the Unifying Theory. Expansion of mutation-driven haematopoietic clones is associated with insulin resistance and low HDL-cholesterol in individuals with obesity AimsHaematopoietic clones caused by somatic mutations with [&ge;]2% variant allele frequency (VAF), known as clonal haematopoiesis of indeterminate potential (CHIP), increase with age and have been linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones are also associated with adverse clinical outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes, and to examine the development of clones over time in relation to age and metabolic dysregulation over up to 20 years in individuals with obesity.

Methods and ResultsWe used an ultrasensitive single-molecule molecular inversion probe sequencing assay to identify clonal haematopoiesis driver mutations (CHDMs) in blood samples from individuals with obesity from the Swedish Obese Subjects study. In a single-timepoint dataset with samples from 1050 individuals, we identified 273 candidate CHDMs in 216 individuals, with VAF ranging from 0.01% to 31.15% and CHDM prevalence and clone sizes increasing with age. Longitudinal analysis over 20 years in CHDM-positive samples from 40 individuals showed that small clones can grow over time and become CHIP. VAF increased on average by 7% (range -4% to 27%) per year. Rate of clone growth was positively associated with insulin resistance (R=0.40, P=0.025) and low circulating levels of high-density lipoprotein-cholesterol (HDL-C) (R=-0.68, P=1.74E-05).

ConclusionOur results show that haematopoietic clones can be detected and monitored before they become CHIP and indicate that insulin resistance and low HDL-C, well-established cardiovascular risk factors, are associated with clonal expansion in individuals with obesity.

Translational perspectivesClonal haematopoiesis-driver mutations are somatic mutations in haematopoietic stem cells that lead to clones detectable in peripheral blood. Haematopoietic clones with a variant allele frequency (VAF) [&ge;]2%, known as clonal haematopoiesis of indeterminate potential (CHIP), are recognized as an independent cardiovascular risk factor. Here, we show that smaller clones are prevalent, and also correlate with age. Our longitudinal observations in individuals with obesity over 20 years showed that more than half of all clone-positive individuals show growing clones and clones with VAF <2% can grow and become CHIP. Importantly, clone growth was accelerated in individuals with insulin resistance and low high-density lipoprotein-cholesterol (HDL-C).

Translational outlook 1: Haematopoietic clones can be detected and monitored before they become CHIP.

Translational outlook 2: The association between insulin resistance and low HDL-C with growth of haematopoietic clones opens the possibility that treatments improving metabolism, such as weight loss, may reduce growth of clones and thereby cardiovascular risk.

One Sentence SummaryIn obesity, the growth rate of mutation-driven haematopoietic clones increased with insulin resistance and low HDL-C, both known risk factors for cardiovascular disease. Predicting the re-distribution of antibiotic molecules caused byinter-species interactions in microbial communities Microbes associate in nature forming complex communities, but they are often studied in purified form. Here I show that differences in antibiotic sensitivity between co-existing bacterial species can modify the diffusion of antibiotic molecules, and alter the drug efficacy measured in conventional in vitro assays. I developed a model, validated experimentally using an artificial two-species community, showing antibiotic molecules re-distribute evenly across all species if they have similar drug sensitivity. The result is lower drug efficacy with respect to conventional in vitro assays. However, when species have different sensitivities, the re-distribution of antibiotic is uneven and most sensitive species accumulate more drug. The result is increased drug efficacy against these species. Despite this discrepancy with conventional laboratory assays, my data suggests the changes in drug efficacy are predictable and provides insight into how communities can affect the diffusion of other molecules in the environment. Effect of sublethal prenatal endotoxaemia on murine placental transport systems and lipid homeostasis Infection alters the expression of transporters that mediate the placental exchange of xenobiotics, lipids and cytokines. We hypothesized that lipopolysaccharide (LPS) modifies the expression of placental transport systems and lipid homeostasis. LPS (150 g/kg; i.p.) treatments were administered for 4 h or 24 h, animals were euthanized at gestational days (GD) 15.5 or 18.5, and maternal blood, foetuses and placentae were collected. Increased rates of foetal demise were observed at GD15.5 following LPS treatment, whereas at GD18.5, high rates of early labour occurred and were associated with distinct proinflammatory responses. LPS did not alter ABC transporter mRNA expression but decreased Fabppm at GD15.5 (LPS-4 h) and increased Fat/Cd36 lipid transporter mRNA at GD18.5 (LPS-4 h). At the protein level, breast cancer-related protein (BCRP) and Abcg1 levels were decreased in the placental labyrinth zone (Lz) at GD15.5, whereas P-glycoprotein (P-gp) and Bcrp Lz-immunostaining was decreased at GD18.5. In the placental junctional zone (Jz), P-gp, Bcrp and Abcg1 levels were higher at GD18.5. Specific maternal plasma and placental changes in triacylglycerol, free fatty acid, cholesterol, cholesterol ester and monoacylglycerol levels were detected in a gestational age-dependent manner. In conclusion, LPS-induced foetal death and early labour were associated with altered placental ABC and lipid transporter expression and deranged maternal plasma and placental lipid homeostasis. These changes likely modify foetal xenobiotic exposure and placental lipid exchange in cases of bacterial infection. LPS-TLR4 pathway exaggerates alcohol-induced acute-on-chronic liver failure via provoking NETs formation Backgrounds: Intrahepatic infiltration of neutrophils is a character of alcoholic acute-on-chronic liver failure (AACLF) and neutrophil extracellular traps (NETs) are an important strategy for neutrophils to fix and kill invading microorganisms. Intestinal bacteria and the gut-liver axis have been thought to play a key role in many liver diseases also including AACLF. However, whether NETs appear in AACLF and play a role in AACLF is still unsure. Methods: WT, NE KO, and TLR4 KO mice were used to build the AACLF model, and the intestinal bacteria were eliminated at the same time and LPS was given. Then the formation of NETs and AACLF related markers were detected. Results: The serum MPO-DNA and LPS concentration was increased in AACLF patients and a correlation was revealed between these two indexes. More intrahepatic NETs formed in AACLF mice by testing MPO-DNA, Cit H3, and NE. These markers decreased with gut detergent and restored markers with gut detergent plus LPS supplement. While NETs formation failed to change with gut microbiome or combine LPS supplement in TLR4 KO mice. As we tested AACLF related characters, liver injury, intrahepatic fat deposition, inflammation, and fibrosis alleviated with depletion of NE. These related marks were also attenuated with gut sterilization by antibiotics and recovered with combined treatment with antibiotics plus LPS. But the liver injury, intrahepatic fat, fibro deposition, and liver inflammation-related markers did show a significant difference in TLR4 KO mice when they received the same treatment. Conclusion: Intestinal-derived LPS promotes NETs formation in AACLF through the TLR4 pathway and further accelerates the AACLF process by NETs. A tRNA processing enzyme is a central regulator of the mitochondrial unfolded protein response The mitochondrial unfolded protein response (UPRmt) has emerged as a predominant mechanism that preserves mitochondrial function. Consequently, multiple pathways likely exist to modulate UPRmt. We unexpectedly discovered that the tRNA processing enzyme, homolog of ELAC2 (HOE-1), is central to UPRmt regulation in Caenorhabditis elegans. We find that nuclear HOE-1 is necessary and sufficient to robustly activate UPRmt. We show that HOE-1 acts via transcription factors ATFS-1 and DVE-1 that are crucial for UPRmt. Mechanistically, we show that HOE-1 likely mediates its effects via tRNAs, as blocking tRNA export prevents HOE-1-induced UPRmt. Interestingly, we find that HOE-1 does not act via the integrated stress response, which can be activated by uncharged tRNAs, pointing towards its reliance on a new mechanism. Finally, we show that the subcellular localization of HOE-1 is responsive to mitochondrial stress and is subject to negative regulation via ATFS-1. Together, we have discovered a novel RNA-based cellular pathway that modulates UPRmt. Effect of urbanization and its environmental stressors on the intraspecific variation of flight functional traits in two bumblebee species The way urbanization shapes the intraspecific variation of pollinator functional traits is little understood. However, this topic is relevant for investigating ecosystem services and pollinator health. Here, we studied how urbanization affects the functional traits of workers in two bumblebee species (Bombus terrestris and B. pascuorum) sampled in 37 sites along a gradient of urbanization in North Italy (an area of 1800 km2 including the metropolitan context of Milan and other surrounding capital districts). Namely, we investigated the role played by land-use composition, configuration, temperature, flower resource abundance, and air pollutants on the variation of traits related to flight performance (i.e., body size, wing shape and size fluctuating asymmetry). These traits are relevant because they are commonly used as indicators of stress during insect development. The functional traits of the two bumblebees responded idiosyncratically to urbanization. Urban temperatures were associated with smaller wing sizes in B. pascuorum and with more accentuated fluctuating asymmetry of wing size in B. terrestris. Moreover, flower abundance correlated with bigger wings in B. terrestris and with less asymmetric wing sizes in B. pascuorum. Other traits did not vary significantly and other urban variables played minor effects. These patterns highlight that environmental stressors linked to urbanization negatively impact traits related to flight performance and development stability of these species with possible consequences on the pollination service they provide.

Overall, this study found species-specific variation patterns in syntopic taxa, expanding our understanding about the effects of anthropic disturbance in shaping relevant functional traits of pollinator model species. DNA Strand Breaks and Gaps Direct Retroviral Integration Integration into a host genome is essential for retrovirus infection and is catalyzed by a nucleoprotein complex (Intasome) containing the viral integrase (IN) and reverse transcribed (RT) copy DNA (cDNA). Previous studies demonstrated DNA site recognition limited intasome integration. Using single molecule Forster resonance energy transfer (smFRET), we show Prototype Foamy Virus (PFV) intasomes pause at DNA strand breaks and gaps. The break/gap discontinuities are similar to base excision repair (BER) lesion-processing intermediates, which affect retrovirus integration in vivo. Pausing targeted site-directed integration at the break/gap without inducing intasome conformational alterations. An 8-oxo-guanine lesion normally processes by BER and a G/T mismatch or a +T nucleotide insertion that induce flexibility or a bend in the DNA backbone did not promote intasome pausing or targeted integration. These results suggest that repair intermediates can modulate dynamic intasome-DNA interactions which target retroviral integration. Integrative small and long RNA-omics analysis of human healing and non-healing wounds discovers cooperating microRNAs as therapeutic targets MicroRNAs (miR) are important posttranscriptional regulators and exhibit a high potential to be utilized in diagnosis and therapy. However, our insufficient knowledge of the miR-mediated gene regulation in human skin wound healing severely hinders the identification of clinically relevant miRs. Here, we performed paired small RNA and long RNA sequencing in human tissue samples, including matched skin and acute wounds collected at each healing stage and chronic non-healing venous ulcers (VU). With integrative small and long RNA-omics analysis, we developed a compendium (https://www.xulandenlab.com/humanwounds-mirna-mrna), which will be an open, comprehensive resource to broadly aid wound healing research. With this first clinical, wound-centric resource of miRs and mRNAs, we identified 17 pathologically relevant miRs that exhibited abnormal VU expression and displayed their targets enriched explicitly in the VU gene signature. Intermeshing regulatory networks controlled by these miRs revealed their high cooperativity in contributing to chronic wound pathology characterized by persistent inflammation and proliferative phase initiation failure. Furthermore, we demonstrated that miR-34a, miR-424, and miR-516, upregulated in VU, cooperatively suppressed keratinocyte growth while promoting inflammatory response. Collectively, our study opens the possibility of developing innovative wound treatment that targets pathologically relevant cooperating miRs to attain higher therapeutic efficacy and specificity. Coordination of genome replication and anaphase entry by rDNA copy number in S. cerevisiae Eukaryotes maintain hundreds of copies of ribosomal DNA (rDNA), many more than required for ribosome biogenesis, suggesting a yet undefined role for large rDNA arrays outside of ribosomal RNA synthesis. We demonstrate that reducing the Saccharomyces cerevisiae rDNA array to 35 copies, which is sufficient for ribosome function, shifts rDNA from being the latest replicating region in the genome to one of the earliest. This change in replication timing results in delayed genome-wide replication and classic replication defects. We present evidence that the requirement for rDNA to replicate late, which is conserved among eukaryotes, also coordinates the completion of genome replication with anaphase entry through the proper sequestration of the mitotic exit regulator Cdc14p in the rDNA-containing nucleolus. Our findings suggest that, instead of being a passive repetitive element, the large late-replicating rDNA array plays an active role in genome replication and cell cycle control. Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice Determining the forces that shape diversity in host-associated bacterial communities is critical to understanding the evolution and maintenance of metaorganisms. To gain deeper understanding of the role of host genetics in shaping gut microbial traits, we employed a powerful genetic mapping approach using inbred lines derived from the hybrid zone of two incipient house mouse species. Further, we uniquely performed our analysis on microbial traits measured at the gut mucosal interface, which is in more direct contact with host cells and the immune system. A high number of mucosa-associated bacterial taxa have significant heritability estimates; heritabilities are greater for 16S rRNA transcript-compared to gene copy-based traits, and interestingly, are positively correlated with cospeciation rate estimates. Genomewide association mapping identifies 443 loci influencing 123 taxa, with narrow genomic intervals pinpointing promising candidate genes and pathways. Importantly, we identified an enrichment of candidate genes associated with several human diseases, including inflammatory bowel disease, and functional categories including innate immunity and G-protein-coupled receptors. These results highlight key features of the genetic architecture of mammalian host-microbe interactions and how they diverge as new species form. A chemical screen based on an interruption of zebrafish gastrulation identifies the HTR2C inhibitor Pizotifen as a suppressor of EMT-mediated metastasis Metastasis is responsible for approximately 90% of cancer-associated mortality but few models exist that allow for rapid and effective screening of anti-metastasis drugs. Current mouse models of metastasis are too expensive and time consuming to use for rapid and high-throughput screening. Therefore, we created a unique screening concept utilizing conserved mechanisms between zebrafish gastrulation and cancer metastasis for identification of potential anti-metastatic drugs. We hypothesized that small chemicals that interrupt zebrafish gastrulation might also suppress metastatic progression of cancer cells and developed a phenotype-based chemical screen to test the hypothesis. The screen used epiboly, the first morphogenetic movement in gastrulation, as a marker and enabled 100 chemicals to be tested in five hours. The screen tested 1280 FDA-approved drugs and identified Pizotifen, an antagonist for serotonin receptor 2C (HTR2C) as an epiboly-interrupting drug. Pharmacologic and genetic inhibition of HTR2C suppressed metastatic progression in a mouse model. Blocking HTR2C with Pizotifen restored epithelial properties to metastatic cells through inhibition of Wnt-signaling. In contrast, HTR2C induced epithelial to mesenchymal transition (EMT) through activation of Wnt-signaling and promoted metastatic dissemination of human cancer cells in a zebrafish xenotransplantation model. Taken together, our concept offers a novel platform for discovery of anti-metastasis drugs. An environmentally responsive transcriptional state modulates cell identities during root development Roots are fundamental organs for plant development and response to their environment: they anchor the plant to its growth substrate, uptake nutrients and water vital to plant growth, and can sense and respond to a variety of biotic and abiotic stresses. The architecture of root systems and their growth are known to be strongly affected by the environmental conditions found in the soil. However, the acquisition of cell identities at the root meristem is still mainly viewed as ontogenetically driven, where a small number of stem cells generate all the cell types through stereotyped divisions followed by differentiation, along a simple developmental trajectory. The extent to which environmental cues precisely shape and affect these developmental trajectories remains an open question. We used single-cell RNA-seq, combined with spatial mapping, to deeply explore the trajectories of cell states at the tip of Arabidopsis roots, known to contain multiple developing lineages. Surprisingly, we found that most lineage trajectories exhibit a stereotyped bifid topology with two developmental trajectories rather than one. The formation of one of the trajectories is driven by a strong and specific activation of genes involved in the responses to various environmental stimuli, that affects only of a subset of the cells in multiple cell types simultaneously, revealing another layer of patterning of cell identities in the root that is independent of cell ontogeny. We demonstrate the robustness of this environmentally responsive transcriptional state by showing that it is present in a mutant where cell type identities are greatly perturbed, as well as in different Arabidopsis ecotypes. We also show that the root can adapt the proportion of cells that acquire this particular state in response to environmental signals such as nutrient availability. The discovery of this cell state reveals new layers of cell identity that may underpin the adaptive potential of plant development. Medium-throughput zebrafish optogenetic platform identifies deficits in subsequent neural activity following brief early exposure to cannabidiol and Δ-9-tetrahydrocannabinol In the light of legislative changes and the widespread use of cannabis as a recreational and medicinal drug, delayed effects of cannabis upon brief exposure during embryonic development are of high interest as early pregnancies often go undetected. Here, zebrafish embryos were exposed to cannabidiol (CBD) and {Delta}-9-tetrahydrocannabinol l (THC) until the end of gastrulation (1-10 hours post-fertilization) and analyzed later in development (4-5 days post-fertilization). In order to measure neural activity, we implemented CaMPARI (Calcium-Modulated Photoactivatable Ratiometric Integrator) and optimized the protocol for a 96-well format complemented by locomotor analysis. Our results revealed that neural activity was decreased by CBD more than THC. At higher doses, both cannabinoids could dramatically reduce neural activity and locomotor activity. Interestingly, the decrease was more pronounced when CBD and THC were combined. At the receptor level, CBD-mediated reduction of locomotor activity was partially prevented using cannabinoid type 1 and 2 receptor inhibitors. Overall, we report that CBD toxicity occurs via two cannabinoid receptors and is synergistically enhanced by THC exposure to negatively impact neural activity late in larval development. Future studies are warranted to reveal other cannabinoids and receptors involved in this pathway to understand the subsequent health implications of cannabis consumption on fetal development. Spatio-temporal, optogenetic control of gene expression in organoids Organoids derived from stem cells become increasingly important to study human development and to model disease. However, methods are needed to control and study spatio-temporal patterns of gene expression in organoids. To this aim, we combined optogenetics and gene perturbation technologies to activate or knock-down RNA of target genes, at single-cell resolution and in programmable spatio-temporal patterns. To illustrate the usefulness of our approach, we locally activated Sonic Hedgehog (SHH) signaling in an organoid model for human neurodevelopment. High-resolution spatial transcriptomic and single-cell analyses showed that this local induction was sufficient to generate stereotypically patterned organoids in three dimensions and revealed new insights into SHHs contribution to gene regulation in neurodevelopment.

With this study, we propose optogenetic perturbations in combination with spatial transcriptomics as a powerful technology to reprogram and study cell fates and tissue patterning in organoids. A network approach to genetic circuit designs As genetic circuits become more sophisticated, the size and complexity of data about their designs increases. This data captured goes beyond monolithic genetic sequences and towards circuit modularity and functional details, which are beneficial for analyzing circuit performance and establishing design automation techniques. However, the accessibility, visualisation and usability of design data (and metadata) have received relatively little attention to date. Here, we present a method to turn circuit designs into networks and showcase its potential to enhance the utility of design data. Since networks are dynamic structures, initial graphs can be interactively shaped into sub-networks of relevant information based on requirements such as abstraction, hierarchy and protein interactions. Additionally, several visual changes can be applied, such as colouring or clustering nodes based on types (e.g., genes or promoters), resulting in easier comprehension from a user perspective. This approach allows circuit designs to be coupled to other networks, such as metabolic pathways or implementation protocols captured in graph-like formats. Therefore, we advocate using networks to structure, access and improve synthetic biology information. Microbial colonization of tannin-rich tropical plants: interplay between degradability, methane production and tannin disappearance in the rumen AO_SCPLOWBSTRACTC_SCPLOWCondensed tannins in plants are found free and attached to protein and fibre but it is not known whether these fractions influence rumen degradation and microbial colonization. This study explored the rumen degradation of tropical tannins-rich plants and the relationship between condensed tannins fractions disappearance and microbial communities colonising plant particles. Leaves from Calliandra calothyrsus, Gliricidia sepium, and Leucaena leucocephala, pods from Acacia nilotica and the leaves of two agricultural by-products: Manihot esculenta and Musa spp. were incubated in situ in the rumen of dairy cows. An in vitro approach was also used to assess the effects of these plants on rumen fermentation parameters. All plants contained more than 100 g/kg of condensed tannins with a large proportion (32 to 61%) bound to proteins. Calliandra calothyrsus had the highest concentration of condensed tannins at 361 g/kg, whereas Acacia nilotica was particularly rich in hydrolysable tannins (350 g/kg). Hydrolysable and free condensed tannins from all plants completely disappeared after 24 h incubation in the rumen. Disappearance of protein-bound condensed tannins was variable with values ranging from 93% for Gliricidia sepium to 21% for Acacia nilotica. In contrast, fibre-bound condensed tannins disappearance averaged ~82% and did not vary between plants. Disappearance of bound fractions of condensed tannins was not associated with degradability of plant fractions. The presence of tannins interfered with the microbial colonisation of plants. Each plant had distinct bacterial and archaeal communities after 3 and 12 h of incubation in the rumen and distinct protozoal communities at 3 h. Adherent communities in tannin-rich plants had a lower relative abundance of fibrolytic microbes, notably Fibrobacter spp. Whereas, archaea diversity was reduced in high tannin-containing Calliandra calothyrsus and Acacia nilotica at 12 h of incubation. Concurrently, in vitro methane production was lower for Calliandra calothyrsus, Acacia nilotica and Leucaena leucocephala although for the latter total volatile fatty acids production was not affected and was similar to control. Here we show that the total amount of hydrolysable and condensed tannins contained in a plant govern the interaction with rumen microbes affecting degradability and fermentation. The effect of protein- and fibre-bound condensed tannins on degradability is less important. Analysis of science journalism reveals gender and regional disparities in coverage Science journalism is a critical way in which the public can remain informed and benefit from new scientific findings. Such journalism also shapes the publics view of the current state of scientific findings and legitimizes experts. Those covering science can only cite and quote a limited number of sources. Sources may be identified by the journalists research or by recommendations by other scientists. In both cases, biases may influence who is identified and ultimately included as an expert. To analyze possible biases in science journalism, we analyzed 22,001 non-research articles published by Nature. We chose to analyze Nature non-research articles since its research articles provide a natural comparator. Our analysis considered two possible sources of disparity: gender and name origin. To explore these sources of disparity, we extracted cited authors names as well as extracted names of quoted speakers. While citations and quotations within a piece do not reflect the entire information-gathering process, they can provide insight into the demographics of visible sources. We then used the extracted names to predict gender and name origin of the cited authors and speakers.

In order to appropriately quantify the level of difference, we must identify a suitable reference set for comparison. We chose first and last authors within primary research articles in Nature and a subset of Springer Nature articles in the same time period as our comparator. In our analysis, we found a skew towards male quotation in Nature science journalism-related articles. However, quotation is trending toward equal representation at a faster rate than first and last authorship in academic publishing. Interestingly, we found that the gender disparity in Nature quotes was column-dependent, with the "Career Features" column reaching gender parity. Our name origin analysis found a significant over-representation of names with predicted Celtic/English origin and under-representation of names with a predicted East Asian origin. This finding was observed both in extracted quotes and journal citations, but dampened in citations. Coil-to-Helix Transition at the Nup358-BicD2 Interface Activates BicD2 for Dynein Recruitment Nup358, a nuclear pore protein, facilitates a nuclear positioning pathway that is essential for many biological processes, including neuromuscular and brain development. Nup358 binds and activates the auto-inhibited dynein adaptor Bicaudal D2 (BicD2), which in turn recruits and activates the dynein machinery to position the nucleus. However, the molecular details of the Nup358/BicD2 interaction remain poorly understood. Here, we show that a minimal Nup358 domain activates dynein/dynactin/BicD2 for processive motility on microtubules. Using nuclear magnetic resonance (NMR) titration and chemical exchange saturation transfer (CEST), a Nup358 helix encompassing residues 2162-2184 was identified, which transitioned from random coil to an -helix upon BicD2-binding and formed the core of the Nup358-BicD2 interface. Mutations in this region of Nup358 decreased the Nup358/BicD2 interaction, resulting in decreased dynein recruitment and impaired motility. BicD2 thus recognizes the cargo adaptor Nup358 though a "cargo recognition -helix", a structural feature that may stabilize BicD2 in its activated state and promote processive dynein motility. β-glucan imprinting remodels macrophage function in response to environmental cues In vitro, exposure of human primary monocytes to the fungal {beta}-glucan enhances their pro-inflammatory responsiveness towards several pathogens. Yet, the role of environmental condition of this process remains unclear. Here we found that {beta}-glucan-induced innate immune memory counteract the anti-inflammatory status of the macrophages. In response to {beta}-glucan imprinting, M-CSF-(M2-like-) macrophages increase their pro-inflammatory responsiveness to secondary stimuli associated with decrease of the M-CSF differentiation hallmarks. In contrast, in GM-CSF-(M1-like-) environment, {beta}-glucan imprinting reduced the pro-inflammatory canonical feature of the macrophages, together with their terminal differentiation marks. Comparing M-CSF and GM-CSF environment, we observed that {beta}-glucan-imprinted macrophages present comparable functions in terms of cytokine responses, phagocytosis, oxidative burst, and angiogenesis. This effect is mediated through Dectin-1 and associated with altered expression of the master regulators of macrophage terminal differentiation, IRF5 and IRF3. {beta}-glucan-induced innate immune memory skews the commitment of the macrophages in complex environment towards similar and less terminally differentiated cells. Together, these observations suggest a potential therapeutic role for {beta}-glucan-induced modulation of innate memory in different pathological contexts. The addition of FAIMS Increases Targeted Proteomics Sensitivity from FFPE Tumor Biopsies Mass spectrometry-based targeted proteomics allows objective protein quantitation of clinical biomarkers from a single section of formalin-fixed, paraffin-embedded (FFPE) tumor tissue biopsies. We combined high-field asymmetric waveform ion mobility spectrometry (FAIMS) and parallel reaction monitoring (PRM) to increase assay sensitivity. The modular nature of the FAIMS source allowed direct comparison of the performance of FAIMS-PRM to PRM. Limits of quantitation were determined by spiking synthetic peptides into a human spleen matrix. In addition, 20 clinical samples were analyzed using FAIMS-PRM and the quantitation of HER2 was compared with that obtained with the Ventana immunohistochemistry assay. FAIMS-PRM improved the overall signal-to-noise ratio over that from PRM and increased assay sensitivity in FFPE tissue analysis for four (HER2, EGFR, cMET, and KRAS) of five proteins of clinical interest. FAIMS-PRM enabled sensitive quantitation of basal HER2 expression in breast cancer samples classified as HER2 negative by immunohistochemistry. Furthermore, we determined the degree of FAIMS-dependent background reduction and showed that this correlated with an improved lower limit of quantitation with FAIMS. FAIMS-PRM is anticipated to benefit clinical trials in which multiple biomarker questions must be addressed and the availability of tumor biopsy samples is limited. Interactions and information: Exploring task allocation in ant colonies using network analysis In animal societies, individuals may take on different roles to fulfil their own needs and the needs of their groups. Ant colonies display high levels of organisational complexity, with ants fulfilling different roles at different timescales (what is known as task allocation). Factors affecting task allocation can be at the individual level (e.g., physiology), or at the group level (e.g., the network of interactions). We focus on group level processes by exploring the relationship between interaction networks, task allocation and task switching using a previously published dataset (Mersch et al., 2013) tracking the behaviour of six Camponotus fellah colonies over 41 days. In our new analyses, our goal was to better explain the noisy process of task switching beyond simple age polyethism. First, we investigated the architecture of interaction networks using node (individual) level network measures and their relation to the individuals task - foraging, cleaning or nursing - and whether or not the ant switched tasks. We then explored how noisy information propagation was among ants, as a function of the colony composition (how many ants carried out which tasks), through the information-theoretic metric of Effective Information. Our results show that interaction history was tied to task allocation: ants who switched to a task are more likely to have interacted with other ants carrying out that task. The degree to which interactions related to task allocation, as well as the noise in those interactions, depended on which groups of ants were interacting. Overall, we showed that colony cohesion was stable even as ant-level network measures varied more for ants when they switched functional groups; thus, ant colonies maintained a high level of information flow as determined by network analysis, and ant functional groups played different roles in maintaining colony cohesion through varied information flows.

HighlightsO_LIWe analysed the interaction networks of six Camponotus fellah colonies
C_LIO_LIWe tested how centrality and information flow were tied to task switching
C_LIO_LINode-level network metrics and the information theoretic measure of Effective Information explained differences among functional groups
C_LIO_LIInteractions were correlated with task switching, but the strength of the correlation differed across functional groups
C_LI Diverse stem-chondrichthyan oral structures and evidence for an independently acquired acanthodid dentition The teeth of sharks famously form a series of transversely-organised files with conveyor-belt replacement that are borne directly on the jaw cartilages, in contrast to the dermal plate-borne dentition of bony fishes that undergoes site-specific replacement. A major obstacle in understanding how this system evolved is the poorly understood relationships of the earliest chondrichthyans and the profusion of morphologically and terminologically diverse bones, cartilages, splints and whorls that they possess. Here we use tomographic methods to investigate mandibular structures in several early branching  acanthodian-grade stem-chondrichthyans. We show that the dentigerous jaw bones of disparate genera of ischnacanthids are united by a common construction, being growing bones with non-shedding dentition. Mandibular splints, which support the ventro-lateral edge of the Meckels cartilage in some taxa, are formed from dermal bone and may be an acanthodid synapomorphy. We demonstrate that the teeth of Acanthodopsis are borne directly on the mandibular cartilage and that this taxon is deeply nested within an edentulous radiation, representing an unexpected independent origin of teeth. Many or even all of the range of unusual oral structures may be apomorphic, but they should nonetheless be considered when building hypotheses of tooth and jaw evolution, both in chondrichthyans and more broadly.