Mapping the genetic and environmental aetiology of autistic traits in Sweden and the United Kingdom BackgroundAutistic traits are influenced by both genetic and environmental factors, and are known to vary geographically in prevalence. But to what extent does their aetiology also vary from place to place?

MethodsWe applied a novel spatial approach to data on autistic traits from two large twin studies, the Child and Adolescent Twin Study in Sweden (CATSS; N=16,677, including 8,307 twin pairs) and the Twins Early Development Study in the UK (TEDS; N=11,594, including 5,796 twin pairs), to explore how the influence of nature and nurture on autistic traits varies from place to place.

ResultsWe present maps of gene- and environment-by geography interactions in Sweden and the United Kingdom (UK), showing geographical variation in both genetic and environmental influences across the two countries. In Sweden genetic influences appear higher in the far south and in a band running across the centre of the country. Environmental influences appear greatest in the south and north, with reduced environmental influence across the central band. In the UK genetic influences appear greater in the south, particularly in more central southern areas and the southeast, the Midlands and the north of England. Environmental influences appear greatest in the south and east of the UK, with less influence in the north and the west.

ConclusionsWe hope this systematic approach to identifying aetiological interactions will inspire research to examine a wider range of previously unknown environmental influences on the aetiology of autistic traits. By doing so, we will gain greater understanding of how these environments draw out or mask genetic predisposition and interact with other environmental influences in the development of autistic traits.
From GWAS Variant to Function: a Study of ~148,000 Variants for Blood Cell Traits. Genome-wide association studies (GWAS) have identified hundreds of thousands of genetic variants associated with complex diseases and traits. However, most variants are noncoding and not clearly linked to genes, making it challenging to interpret these GWAS signals. We present a systematic variant-to-function study, prioritizing the most likely functional elements of the genome for experimental follow-up, for >148,000 variants identified for hematological traits. Specifically, we developed VAMPIRE: Variant Annotation Method Pointing to Interesting Regulatory Effects, an interactive web application implemented in R Shiny (http://shiny.bios.unc.edu/vampire/). This tool efficiently integrates and displays information from multiple complementary sources, including epigenomic signatures from blood cell relevant tissues or cells, functional and conservation summary scores, variant impact on protein and gene expression, chromatin conformation information, as well as publicly available GWAS and phenome-wide association study (PheWAS) results. Leveraging data generated from independently performed functional validation experiments, we demonstrate that our prioritized variants, genes, or variant-gene links are significantly more likely to be experimentally validated. This study not only has important implications for systematic and efficient revelation of functional mechanisms underlying GWAS variants for hematological traits, but also provides a prototype that can be adapted to many other complex traits, paving the path for efficient variant to function (V2F) analyses.
The spindle assembly checkpoint and the spatial activation of Polo kinase determine the duration of cell division and prevent neural stem cells tumor formation The maintenance of a restricted pool of asymmetrically dividing stem cells is essential for tissue homeostasis. This process requires the control of mitotic progression that ensures the accurate chromosome segregation. In addition, this event is coupled to the asymmetric distribution of cell fate determinants in order to prevent stem cell amplification. How this coupling is regulated remains poorly described. Here, using asymmetrically dividing Drosophila neural stem cells (NSCs), we show that Polo kinase activity levels determine the length of cell division, independent of the spindle assembly checkpoint (SAC). This event is mediated by the direct phosphorylation of Polo kinase by Aurora A at spindle poles and Aurora B kinases at centromeres. Furthermore, we show that Aurora A-dependent activation of Polo is the major event that promotes NSC polarization and together with the SAC prevents brain tumor growth. Altogether, our results show that an Aurora/Polo kinase module couples NSC mitotic progression and polarization for tissue homeostasis. 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. Engineered bacteria detect tumor DNA Advances in bacterial engineering have catalysed the development of living cell diagnostics and therapeutics1-3, including microbes that respond to diseases such as gut inflammation4, intestinal bleeding5, pathogens6 and hypoxic tumors7. Bacteria can easily access the entire gastrointestinal tract via oral administration8, and they can produce outputs that can be noninvasively measured in stool4 or urine7. Cellular memory, such as bistable switches4,9,10 or genomic rearrangement11, has been used to allow bacteria to store information over time. However, living biosensors have not yet been engineered to detect specific DNA sequences or mutations from outside the cell. Here, we engineer naturally competent Acinetobacter baylyi to detect donor DNA from the genomes of colorectal cancer (CRC) cells and organoids. We characterize the functionality of the biosensors in vitro with co-culture assays and then validate in vivo with sensor bacteria delivered orally or rectally into mice injected with orthotopic donor CRC organoids. We observe horizontal gene transfer from the tumor to the sensor bacteria in vivo, allowing their detection in stool. The sensor bacteria achieved 100% discrimination between mice with and without CRC using both delivery methods. Our findings establish a framework for biosensing applications that require the detection of mutations or organisms within environments that are difficult to sample. In addition, the platform can be readily expanded to include in situ production and delivery of therapeutic payloads at the detection site. Can single-component protein condensates form multiphase architectures? Phase-separated biomolecular condensates that contain multiple coexisting phases are widespread in vitro and in cells. Multiphase condensates emerge readily within multi-component mixtures of biomolecules (e.g. proteins and nucleic acids) when the different components present sufficient physicochemical diversity (e.g. in inter-molecular forces, structure, and chemical composition) to sustain separate coexisting phases. Because such diversity is highly coupled to the solution conditions (e.g. temperature, pH, salt, composition), it can manifest itself immediately from the nucleation and growth stages of condensate formation, develop spontaneously due to external stimuli, or progressively as the condensates age. Here, we investigate thermodynamic factors that can explain the intrinsic transformation of single-component condensates into multiphase architectures during the nonequilibrium process of ageing. We develop a multiscale model that integrates atomistic simulations of proteins, sequence-dependent coarse-grained simulations of condensates, and a minimal model of dynamically ageing condensates with non-conservative inter-molecular forces. Our nonequilibrium simulations of condensate ageing predict that single-component condensates that are initially homogeneous and liquid-like can transform into gel-core/liquid-shell or liquid-core/gel-shell multiphase condensates as they age, due to gradual and irreversible enhancement of inter-protein interactions. The type of multiphase architecture is determined by the ageing mechanism, the molecular organization of the gel and liquid phases, and the chemical make up of the protein. Notably, we predict that inter-protein disorder-to-order transitions within the prion-like domains of intracellular proteins could lead to the required non-conservative enhancement of inter-molecular interactions. Our study, therefore, predicts a potential mechanism

Significance StatementBiomolecular condensates are highly diverse systems spanning not only homogeneous liquid droplets, but also gels, glasses, and even multiphase architectures that contain various coexisting liquid-like and/or gel-like inner phases. Multiphase architectures form when the different biomolecular components in a multi-component condensate establish sufficiently imbalanced inter-molecular forces to sustain different coexisting phases. While such a requirement seems, at first glance, impossible to fulfil for a condensate formed exclusively of chemically-identical proteins (i.e., single-component), our simulations predict conditions under which this may be possible. During condensate ageing, a sufficiently large imbalance in inter-molecular interactions can emerge intrinsically from the accumulation of protein structural transitions--driving even single-component condensates into nonequilibrium liquid-core/gel-shell or gel-core/liquid-shell multiphase architectures. Hydrophobic mismatch is a key factor in protein transport on the Tat pathway The twin-arginine translocation (Tat) pathway transports folded proteins across membranes in bacteria, thylakoid, plant mitochondria, and archaea. In most species, the active Tat machinery consists of three independent subunits, TatA, TatB and TatC. TatA and TatB from all bacterial species possess short transmembrane alpha-helices (TMHs), both of which are only fifteen residues long in E. coli. Such short TMHs cause a hydrophobic mismatch between Tat subunits and the membrane bilayer. Here, by modifying the length of the TMHs of E. coli TatA and TatB, we assess the functional importance of the hydrophobic mismatch in the Tat transport mechanism. Surprisingly, both TatA and TatB with as few as 11 residues in their respective TMHs are still able to insert into the membrane bilayer, albeit with a decline in membrane integrity. Three different assays, both qualitative and quantitative, were conducted to evaluate the Tat activity of the TMH length mutants. Our experiments indicate that the TMHs of TatA and TatB appear to be evolutionarily tuned to 15 amino acids, with activity dropping off with any modification of this length. We believe our study supports a model of Tat transport utilizing localized toroidal pores that form when the membrane bilayer is thinned to a critical threshold. In this context, the 15-residue length of the TatA and TatB TMHs can be seen as a compromise between the need for some hydrophobic mismatch to allow the membrane to reversibly reach the threshold thinness required for toroidal pore formation, and the permanently destabilizing effect of placing even shorter helices into these energy-transducing membranes. Polycystins are upregulated in fibrotic kidneys and promote renal fibrosis Autosomal polycystic kidney disease (ADPKD) is caused by mutations in PKD1or PKD2 gene, which encodes polycystin-1 or polycystin-2 respectively. Paradoxically, polycystins are up-regulated in human ADPKD kidneys and overexpression of polycystin-1 even induced renal cyst formation in mice, suggesting that up-regulation of polycystin is pathogenic. In this study, we determined the role of polycystin in renal fibrosis and explored its underlying mechanisms. We found that the expression of polycystin-1 or polycystin-2 was positively correlated with the expression of collagen-I in the kidney of three different fibrotic mouse models. Pharmaceutical inhibition or genetic knockout of polycystin-2 reduced the expression of pro-fibrotic markers in fibrotic kidneys of two animal models. Moreover, conditional knockout of Pkd1 gene attenuated renal fibrosis in two mouse models. Enhancer of Zeste homolog 2 (EZH2) is a methyltransferase which plays important role in renal fibrosis. We found that EZH2 was positively correlated with the expression of polycystins in fibrotic kidneys. Conditional knockout of the Ezh2 attenuated the anti-fibrotic responses induced by Pkd1 deletion in fibrotic kidneys.

In conclusion, polycystins are up-regulated in injured kidneys and polycystins promote renal fibrosis through up-regulation of EZH2 in fibrotic kidneys, suggesting that renal fibrosis in polycystic kidneys is not the direct effect of PKD gene mutations.

SignificanceMutations of polycystins cause autosomal polycystic kidney disease (ADPKD) which is associated with increased renal fibrosis in cystic kidneys. However, the role of polycystin in renal fibrosis remains unclear. Here, we showed that the expression of polycystins is positively correlated with the development of renal fibrosis in injured kidneys. Pharmaceutical inhibition or genetic deletion of polycystin-2 attenuated renal fibrosis in fibrotic kidneys. Moreover, genetic deletion of polycystin-1 inhibited renal fibrosis in two different animal models. Finally, we showed that ablation of the methyltransferase EZH2 mitigated the anti-fibrotic effect of polycystin-1 deletion in fibrotic kidneys. We conclude that polycystin promotes through EZH2 and renal fibrosis in cystic kidney is not the direct effect of PKD gene mutations. Multi-omic analysis of the Arabidopsis clock activator mutant rve 4 6 8 reveals connections to carbohydrate metabolism and proteasome regulation Plants are able to sense changes in their light environments, such as the onset of day and night, as well as anticipate these changes in order to adapt and survive. Central to this ability is the plant circadian clock, a molecular circuit that precisely orchestrates plant cell processes over the course of a day. REVEILLE proteins (RVEs) are recently discovered members of the plant circadian circuitry that activate the evening complex and PRR genes to maintain regular circadian oscillation. The RVE 8 protein and its two homologs, RVE 4 and 6, have been shown to limit the length of the circadian period, with rve 4 6 8 triple-knockout plants possessing an elongated period along with increased leaf surface area, biomass, cell size and delayed flowering relative to wild-type Col-0 plants. Here, using a multi-omics approach consisting of phenomics, transcriptomics, proteomics, and metabolomics we draw novel connections between RVE8-like proteins and a number of core plant cell processes. In particular, we reveal that loss of RVE8-like proteins results in altered carbohydrate, organic acid and lipid metabolism, including a starch excess phenotype at dawn. We further demonstrate that rve 4 6 8 plants have lower levels of 20S proteasome subunits and possess significantly reduced proteasome activity, potentially explaining the increase in cell-size observed in RVE8-like mutants. Overall, this robust, multi-omic dataset, provides substantial new insights into the far reaching impact RVE8-like proteins have on the diel plant cell environment. Principles of mRNA targeting via the Arabidopsism6A-binding protein ECT2 Specific recognition of N6-methyladenosine (m6A) in mRNA by RNA-binding proteins containing a YT521-B homology (YTH) domain is important in eukaryotic gene regulation. The Arabidopsis YTH-domain protein ECT2 is thought to bind to mRNA at URU(m6A)Y sites, yet RR(m6A)CH is the canonical m6A consensus site in all eukaryotes and ECT2 functions require m6A binding activity. Here, we apply iCLIP (individual-nucleotide resolution cross-linking and immunoprecipitation) and HyperTRIBE (targets of RNA-binding proteins identified by editing) to define high-quality target sets of ECT2, and analyze the patterns of enriched sequence motifs around ECT2 crosslink sites. Our analyses show that ECT2 does in fact bind to RR(m6A)CH. Pyrimidine-rich motifs are enriched around, but not at m6A-sites, reflecting a preference for N6-adenosine methylation of RRACH/GGAU islands in pyrimidine-rich regions. Such motifs, particularly oligo-U and UNUNU upstream of m6A sites, are also implicated in ECT2 binding via its intrinsically disordered region (IDR). Finally, URUAY-type motifs are enriched at ECT2 crosslink sites, but their distinct properties suggest function as sites of competition between binding of ECT2 and as yet unidentified RNA-binding proteins. Our study provides coherence between genetic and molecular studies of m6A-YTH function in plants, and reveals new insight into the mode of RNA recognition by YTH-domain-containing proteins. Bispecific antibody neutralizes circulating SARS-CoV-2 variants, prevents escape and protects mice from disease Neutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19)1,2. We developed a bispecific, IgG1-like molecule (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C1353. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 neutralizes SARS-CoV-2 and its variants of concern, as well as the escape mutants generated by the parental monoclonals. In a novel animal model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails. Marburg and Ebola virus infections elicit a complex, muted inflammatory state in bats The Marburg and Ebola filoviruses cause a severe, often fatal, disease in humans and nonhuman primates but have only subclinical effects in bats, including Egyptian rousettes, which are a natural reservoir of Marburg virus. A fundamental question is why these viruses are highly pathogenic in humans but fail to cause disease in bats. To understand how bats resist the disease caused by filoviruses, we infected one cohort of Egyptian rousette bats with Marburg virus and another cohort with Ebola virus and harvested multiple tissues for mRNA expression analysis. While virus transcripts were found primarily in the liver, Principal component analysis (PCA) revealed coordinated changes across multiple tissues. Gene signatures in kidney and liver pointed at induction of vasodilation, reduction of coagulation and changes in the regulation of iron metabolism. Signatures of immune response detected in spleen and liver indicated a robust anti-inflammatory state signified by macrophages in the M2 state and an active T cell response. Many of the responsive genes were found to be evolutionarily divergent, providing a framework for understanding the differences in outcomes of filovirus infections between bats and humans. In this study, we outline multiple interconnected pathways that respond to infection by MARV and EBOV, providing insights into the complexity of the mechanisms that enable bats to resist the disease caused by filoviral infections. The results have the potential to aid in the development of new strategies to effectively mitigate and treat the disease caused by these viruses in humans. Transfer learning framework for cell segmentation with incorporation of geometric features With recent advances in multiplexed imaging and spatial transcriptomic and proteomic technologies, cell segmentation is becoming a crucial step in biomedical image analysis. In recent years, Fully Convolutional Networks (FCN) have achieved great success in nuclei segmentation in in vitro imaging. Nevertheless, it remains challenging to perform similar tasks on in situ tissue images with more cluttered cells of diverse shapes. To address this issue, we propose a novel transfer learning, cell segmentation framework incorporating shape-aware features in a deep learning model, with multi-level watershed and morphological post-processing steps. Our results show that incorporation of geometric features improves generalizability to segmenting cells in in situ tissue images, using solely in vitro images as training data. Transcriptional and Functional Activity of Hemangiosarcoma Support Bone Marrow Nurse Cell Ontogeny Hemangiosarcoma and angiosarcoma are soft tissue sarcomas of malignant blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs that support the niche, enabling progression of canine hemangiosarcoma and human angiosarcoma. Here, we show that the transcriptional landscape of canine hemangiosarcoma and human angiosarcoma included comparable angiogenic and inflammatory programs. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells, a trait that was not observed in xenografts from canine osteosarcoma and lymphoma. In some cases, the xenografted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. We did not uncover a definitive transmissible etiology, but our data indicate that transcriptional programs of hemangiosarcoma cells resemble those of hematopoietic nurse cells, and these malignant cells support expansion and differentiation of human hematopoietic progenitors. We conclude that canine hemangiosarcoma, and possibly human angiosarcoma, originate from nurse cells that make up the stromal bone marrow niche, and that these cells may also support the growth of hematopoietic tumors. Effects of substrate on shrimp growth, water quality and bacterial community in the biofloc system nursing Penaeus vannamei postlarvae This study aimed to investigate the effects of substrate on water quality, shrimp growth and bacterial community in the biofloc system with a salinity of 5{per thousand}. Two treatments, biofloc system with (sB) or without (nB) addition of elastic solid packing filler (nylon) as substrate, were set up. Penaeus vannamei postlarvae (PL, [~] stage 15) were stocked at a density of 4000 PL m-3 in each treatment with triplicates for a 28-days culture experiment, taking glucose as carbon source (C:N 15:1). Results showed that the survival rate (96.3{+/-}3.6%), FCR (0.76{+/-}0.06) and productivity (1.54{+/-}0.12 kg m-3) in sB treatment were significantly better than those in nB treatment (81.0{+/-}7.1%, 0.98{+/-}0.08 and 1.14{+/-}0.09 kg m-3, P<0.05). All water parameters were in the recommended ranges. Substrate showed significant effect on TAN, TSS, turbidity, biofloc volume, pH and carbonate alkalinity (P < 0.05). Actinobacteria (4.0-22.7%), Bacteroidetes (10.4-33.5%), Firmicutes (0.2-11.2%), Planctomycetes (4.0-14.9%) and Proteobacteria (29.4-59.0%) were the most dominant phyla for both treatments. However, the bacterial community in sB treatment showed to be significantly different from that in nB treatment (Jaccard distance 0.94{+/-}0.01, P=0.001). Substrate showed significant effects on Shannon, Heip, Pielou and Simpson index, as well as relative abundances of Actinobacteria, Bacteroidetes and Planctomycetes (P < 0.05). The results suggested that addition of substrate affected the shrimp growth, water quality and bacterial community in the biofloc system nursing P. vannamei PL with a 5{per thousand} salinity. Pupil diameter tracked during motor adaptation in humans Pupil diameter, under constant illumination, is known to reflect individuals internal states, such as surprise about observation and environmental uncertainty. Despite the growing use of pupillometry in cognitive learning studies as an additional measure for examining internal states, few studies have used pupillometry in human motor learning studies. Here we provide the first detailed characterization of pupil diameter changes in a short-term reach adaptation paradigm. We measured pupil changes in 91 human participants while they adapted to abrupt, gradual, or switching force field conditions. Sudden increases in movement error caused by the introduction/reversal of the force field resulted in strong phasic pupil dilation during movement accompanied by a transient increase in tonic pre-movement baseline pupil diameter in subsequent trials. In contrast, clear changes in pupil responses were absent when the force field was gradually introduced, indicating that error drove the changes in pupil responses. Nevertheless, we found an association between baseline pupil diameter and awareness of the gradually-introduced perturbation assessed post-experimentally. In all experiments, we also found a strong co-occurrence of larger baseline pupil diameter and slower reaction and movement time after each set break. Interestingly, error-induced pupil responses gradually became insensitive after experiencing multiple reversals. Collectively, these results suggest that tonic baseline pupil diameter reflects ones belief about environmental uncertainty, whereas phasic pupil dilation during movement reflects surprise about a sensory outcome (i.e., movement error), and both effects are modulated by novelty. Our results provide a new approach for non-verbally assessing participants internal states during motor learning. Navigating the amino acid sequence space between functional proteins using a deep learning framework MotivationShedding light on the relationships between protein se-quences and functions is a challenging task with many implications in protein evolution, diseases understanding, and protein design. Protein sequence / function space is however hard to comprehend due to its com-plexity. Generative models help to decipher complex systems thanks to their abilities to learn and recreate data specificity. Applied to protein sequences, they can point out relationships between protein positions and functions capture the sequence patterns associated with functions or navigate through uncharted area of molecular evolution.

ResultsIn this study, an unsupervised generative approach based on adversarial auto-encoder (AAE) is proposed to generate and explore new sequences with respect to their functions thanks to the prior distribution allowing a continuous exploration of the latent space. AAEs are tested on three protein families known for their multiple functions. Clustering re-sults on the encoded sequences from the latent space computed by AAEs display high level of homogeneity regarding the protein sequence func-tions. The study also reports and analyzes for the first time two sampling strategies based on latent space interpolation and latent space arithmetic to generate intermediate protein sequences sharing sequential and functional properties of original sequences issued from different families and functions. Generated sequences by interpolation between latent space data points demonstrate the ability of the AAE to generalize and to pro-duce meaningful biological sequences from an evolutionary uncharted area of the biological sequence space. Finally, 3D structure models generated by comparative modelling between different combinations of structures of different sub-families and of generated sequences from latent space or sub-family sequences point out to the ability of the latent space arithmetic to successfully transfer functional properties between sub-families. All in all this study confirms the ability of deep learning frameworks to model biological complexity and bring new tools to explore amino acid sequence and functional spaces.

AvailabilityCode and data used for this study are freely available at https://github.com/T-B-F/aae4seq.

Contacttristan@bitardfeildel.fr

Supplementary informationSupplementary data are available at online. If Research is Not the Evidence, What is it? The Lack of Research Citations in Health Vlogs Doctor-influencers have the knowledge needed to understand scientific research, and they have the social media popularity to share it with large audiences. In this article, I explore the treatment of evidence in vlogs by Egyptian doctor-influencers: how they present it and what they use instead of it. I answer the following questions: 1) How do doctor-influencers present evidence on social media? 2) If evidence is not the research, then what is it? The data was collected through in-depth interviews with 12 Egyptian doctor-influencers from different specializations; two focus groups; and a critical discourse analysis of 48 of the influencers most popular and most engaging videos. I found that the doctor-influencers cited academic research only in the videos about medical controversies, new treatments, misinformation, or common medical mistakes. In most of their videos, the Egyptian doctor-influencers scarcely referred to medical research. This is because they believe that their audiences would not understand evidence due to their low educational attainment, weak research skills, and the language barrier (as most medical research is published in English rather than Arabic). These findings highlight the challenges of communicating science in societies with a low level of education. In these settings, communicators may need to move beyond mediating research studies on social media and instead focus on simplifying, translating, and connecting evidence-based information to the cultural context. Oxytocin promotes social grooming in bonobos Oxytocin has attracted research attention due to its role in promoting social bonding. One notable recent hypothesis is the biobehavioral feedback loop, which posits that the oxytocin system has evolved to support the formation and maintenance of social bonds through a positive feedback loop, where oxytocin promotes social behaviours which then cause oxytocin release themselves. In the two Pan species, humans closest relatives, oxytocin is known to be released following key behaviours related to social bonding, such as social grooming in chimpanzees and female-female sexual behaviour in bonobos. However, no experimental evidence has demonstrated that oxytocin promotes such socio-positive behaviours. To test this, we administered nebulized oxytocin or saline placebo to a group of female bonobos and subsequently observed the change in their gross behavior during free interaction. We found that bonobos groomed other group members significantly more frequently in the oxytocin compared to placebo condition. Other behavioural measures did not largely differ between conditions, except for a nonsignificant trend for reduction in abnormal regurgitation/reingestion behaviour. Overall, we found that oxytocin promoted socio-positive interaction in bonobos, providing support for the biobehavioural feedback loop hypothesis of oxytocin in bonobo social evolution. Impedance scaling for gold and platinum microelectrodes ObjectiveElectrical measurement of the activity of individual neurons is a primary goal for many invasive neural electrodes. Making these "single unit" measurements requires that we fabricate electrodes small enough so that only a few neurons contribute to the signal, but not so small that the impedance of the electrode creates overwhelming noise or signal attenuation. Thus, neuroelectrode design often must strike a balance between electrode size and electrode impedance, where the impedance is often assumed to scale linearly with electrode area.

Approach and main resultsHere we study how impedance scales with neural electrode area and find that the 1 kHz impedance of Pt electrodes (but not Au electrodes) transitions from scaling with area (r-2) to scaling with perimeter (r-1) when the electrode radius falls below 10 microns. This effect can be explained by the transition from planar to spherical diffusion behavior previously reported for electrochemical microelectrodes. Significance: These results provide important intuition for designing small, single unit recording electrodes. Specifically, for materials where the impedance is dominated by a pseudo-capacitance that is associated with a diffusion limited process, the total impedance will scale with perimeter rather than area when the electrode size becomes comparable with the diffusion layer thickness. For Pt electrodes this transition occurs around 10 um radius electrodes. At even lower frequencies (1 Hz) impedance approaches a constant. This transition to r-1 scaling implies that electrodes with a pseudo-capacitance can be made smaller than one might expect before thermal noise or voltage division limits the ability to acquire high-quality single-unit recordings. Ecological correlates of gene family size in a pine-feeding sawfly genome and across Hymenoptera A central goal in evolutionary biology is to determine the predictability of adaptive genetic changes. Despite many documented cases of convergent evolution at individual loci, little is known about the repeatability of gene family expansions and contractions. To address this void, we examined gene family evolution in the redheaded pine sawfly Neodiprion lecontei, a non-eusocial hymenopteran and exemplar of a pine-specialized lineage evolved from angiosperm-feeding ancestors. After assembling and annotating a draft genome, we manually annotated multiple gene families with chemosensory, detoxification, or immunity functions and characterized their genomic distributions and evolutionary history. Our results suggest that expansions of bitter gustatory receptor (GR), clan 3 cytochrome P450 (CYP3), and antimicrobial peptide (AMP) subfamilies may have contributed to pine adaptation. By contrast, there was no evidence of recent gene family contraction via pseudogenization. Next, we compared the number of genes in these same families across insect taxa that vary in diet, dietary specialization, and social behavior. In Hymenoptera, herbivory was associated with small GR and olfactory receptor (OR) families, eusociality was associated with large OR and small AMP families, and--unlike investigations in more closely related taxa--ecological specialization was not related to gene family size. Overall, our results suggest that gene families that mediate ecological interactions may expand and contract predictably in response to particular selection pressures, however, the ecological drivers and temporal pace of gene gain and loss likely varies considerably across gene families. Ultrahigh-Throughput Ambient MS: Direct Analysis at 22 Samples per Second by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) mass spectrometry is an ambient-direct sampling method being developed for high-throughput, label-free, biochemical screening of large-scale compound libraries. Here, we report the development of an ultrahigh-throughput continuous motion IR-MALDESI sampling approach capable of acquiring data at rates up to 22.7 samples per second in a 384-well microtiter plate. At top speed, less than 1% analyte carryover is observed from well-to-well and signal intensity relative standard deviations (RSD) of 11.5% and 20.9% for 3 M 1-hydroxymidazolam and 12 M dextrorphan, respectively, are achieved. The ability to perform parallel kinetics studies on 384 samples with ~30s time resolution using an isocitrate dehydrogenase 1 (IDH1) enzyme assay is shown. Finally, we demonstrate the repeatability and throughput of our approach by measuring 115,200 samples from 300 microtiter plate reads consecutively over 5.54 hours with RSDs under 8.14% for each freshly introduced plate. Taken together, these results demonstrate the use of IR-MALDESI at sample acquisition rates that surpass other currently reported direct sampling mass spectrometry approaches used for high throughput compound screening.

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org.highwire.dtl.DTLVardef@5f916corg.highwire.dtl.DTLVardef@4473b4org.highwire.dtl.DTLVardef@82e8forg.highwire.dtl.DTLVardef@128b57b_HPS_FORMAT_FIGEXP  M_FIG C_FIG A constraints-based theory of the primary cause of senescence: imbalance of epigenetic and non-epigenetic information in histone crosstalk Cellular aging has been progressively elucidated by science. However, the fundamental cause of senescence--i.e., why organisms age at the multicellular-individual level--remains unclear. A recent theory of individuated multicellularity describes the emergence and growth of crucial information content for cell differentiation. This information is mostly conveyed in the non-epigenetic (i.e., transcription uncorrelated) histone crosstalk near transcription start sites. According to this theory, the non-epigenetic content emerges and grows at the expense of the information capacity for epigenetic content. If this "reassignment" of information capacity continues after adulthood, it may explain the senescence phenomenon. Here, I present a novel, falsifiable theory describing an uninterrupted growth of capacity for non-epigenetic information at the expense of that for epigenetic information not only during ontogeny but also throughout adulthood. As a byproduct, this continuous "reassignment" of capacity effectively creates an information imbalance in histone crosstalk, which in turn overregulates transcriptional levels. This overregulation is to be understood as transcriptional levels becoming more and more accurate but also less and less precise with respect to the needs of the multicellular individual--up to the point of dysfunctionality. This epigenetic/non-epigenetic information imbalance is proposed to be the primary reason why individuated multicellular organisms senesce. Outer hair cell electro-mechanical power conversion Outer hair cells are the cellular motors in the mammalian inner ear responsible for sensitive high-frequency hearing. Motor function requires expression of the protein prestin in the OHC lateral membrane and mechano-electrical transduction in the apical hair bundle. In the present report, electrical power consumption and mechanical power output are determined using previously published voltage clamp data from isolated OHCs and membrane patches. Results reveal that power output by the prestin-motor complex peaks at a best frequency much higher than implied by the low-pass character of nonlinear capacitance, and much higher than the whole-cell resistive-capacitive corner frequency. High frequency power output is enabled by a -90{degrees} shift in the phase of prestin-dependent electrical charge displacement, manifested electrically as emergence of imaginary-valued nonlinear capacitance. Genome editing excisase origins illuminated by somatic genome of Blepharisma Massive DNA excision occurs regularly in ciliates, ubiquitous microbial eukaryotes with somatic and germline nuclei in the same cell. Tens of thousands of internally eliminated sequences (IESs) scattered throughout a copy of the ciliate germline genome are deleted during development of the streamlined somatic genome. Blepharisma represents one of the two earliest diverging ciliate classes, and, unusually, has dual pathways of somatic nuclear development, making it ideal for investigating the functioning and evolution of these processes. Here, we report the somatic genome assembly of Blepharisma stoltei strain ATCC 30299 (41 Mb), arranged as numerous alternative telomere-capped minichromosomes. This genome encodes eight PiggyBac transposase homologs liberated from transposons. All are subject to purifying selection, but just one, the putative IES excisase, has a complete catalytic triad. We propose PiggyBac homologs were ancestral excisases that enabled evolution of extensive, natural genome editing. ITS-based assessment of Madagascar's fungal diversity and arrival of ectomycorrhizal fungi to the island Madagascar is known for its high diversity and endemism of Fauna and Flora, which makes it particularly interesting for research on diversity and evolution. Fungi, however, have been largely overlooked, and whether fungi exhibit the same patterns as animals and plants has yet to be further examined.

We collected fungal sporocarps and ectomycorrhizal (EcM) roots during opportunistic surveys in five forests in Madagascar and generated a dataset of fungal Internal Transcribed Spacer (ITS) DNA sequences. We analysed them together with all publicly available fungal ITS DNA sequences. We identified 620 Operational Taxonomic Units (OTUs) from Madagascar, 10% of which contained only sequences from our surveys. We found 292 OTUs belonging to EcM species with /russula-lactarius, /boletus, /tomentella-telephora, /cortinarius and /amanita as the most abundant EcM lineages. Overall, sixty percent of all the fungi and 81% of the EcM species found are endemic to Madagascar. Lastly, we conducted a phylogenetic analysis using all the OTUs in Amanitaceae, Boletaceae and Russulaceae families to elucidate their relative timing of arrival in Madagascar. We found that the EcM species from Madagascar in the three families diverged recently (less than 34 mya), long after the separation of India and Madagascar (88 mya), which is consistent with a dispersal mediated process of arrival on the island. Our study provides the first comprehensive view of the current state of knowledge of EcM fungi in Madagascar represented by molecular data useful for ecological and evolutionary studies.