bluuebunny/crossref_metadata_2025 huggingface dataset:
The ensemble of gene regulatory networks at mutation–selection balance
Authors: Yang Chia-Hung , Scarpino Samuel V.
Published: January 2023

The evolution of diverse phenotypes both involves and is constrained by molecular interaction networks. When these networks influence patterns of expression, we refer to them as gene regulatory networks (GRNs). Here, we develop a model of GRN evolution analogous to work from quasi-species theory, which is itself essentially the mutation–selection balance model from classical population genetics extended to multiple loci. With this GRN model, we prove that—across a broad spectrum of selection pressures—the dynamics converge to a stationary distribution over GRNs. Next, we show from first principles how the frequency of GRNs at equilibrium is related to the topology of the genotype network, in particular, via a specific network centrality measure termed the eigenvector centrality. Finally, we determine the structural characteristics of GRNs that are favoured in response to a range of selective environments and mutational constraints. Our work connects GRN evolution to quasi-species theory—and thus to classical populations genetics—providing a mechanistic explanation for the observed distribution of GRNs evolving in response to various evolutionary forces, and shows how complex fitness landscapes can emerge from simple evolutionary rules.
The cells of Robert Hooke: pores, fibres, diaphragms and the cell theory that wasn't
Authors: Peters Winfried S.
Published: January 2023

The early microscopist Robert Hooke (1653–1703) is commonly credited with the discovery and naming of biological cells in the course of his studies of plant tissues. Surprisingly, the theoretical context of this apparent discovery is rarely evaluated when Hooke's contribution to the development of modern biology is discussed. Hooke worked within the conceptual framework of the developing fibre doctrine, and consequently interpreted plant and animal structures as solid yet porous materials that directed and regulated the movements of fluids. The strength of his theory-derived expectations is exemplified by his postulate of valve-like passages in plant cell walls despite his admitted inability to detect any. Neglecting Hooke's theoretical background, modern commentators regularly misread important parts of his anatomical works. This shows, for instance, in the common assertion that Hooke used
pore
and
cell
interchangeably when in fact they represented the whole and its part, or in the claim that his cells were closed structures. Here I present a reconstruction of what Hooke and contemporary scholars meant when they spoke of cells in plant materials, namely elements of continuous pipes for fluid transport, and evaluate alternative interpretations.
Octadecabacter algicola sp. nov. and Octadecabacter dasysiphoniae sp. nov., isolated from a marine red alga and emended description of the genus Octadecabacter
Authors: Jin Myeong Seo , Kim Kyung Hyun , Baek Ju Hye , Kim Jeong Min , Jeon Che Ok
Published: January 2023

Two Gram-stain-negative, strictly aerobic, catalase- and oxidase-positive and non-motile rod-shaped bacteria, strains D2-3T and G9-8T, were isolated from a marine red alga. Both strains contained ubiquinone-10 as the sole isoprenoid quinone. As the major cellular fatty acids (>5.0 %), D2-3T contained C16 : 0, 11-methyl-C18 : 1ω7c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), whereas G9-8T contained C16 : 0, 11-methyl-C18 : 1ω7c, C12 : 1 3-OH, and summed feature 8. The DNA G+C contents of D2-3T and G9-8T were 54.4 % and 56.0 %, respectively. As the major polar lipids, phosphatidylglycerol, diphosphatidylglycerol and unidentified phospholipid, aminolipid and lipid were identified from both strains, and phosphatidylcholine was additionally detected from G9-8T only. The 16S rRNA gene sequence similarity of D2-3T and G9-8T was 98.5 % and their digital DNA–DNA hybridization (DDH) value was 19.1 %. Phylogenetic analyses based on 16S rRNA gene and genome sequences revealed that D2-3T and G9-8T formed respectively distinct phylogenetic lineages within the genus

Octadecabacter

. D2-3T and G9-8T were most closely related to

Octadecabacter ascidiaceicola

RA1-3T and

Octadecabacter antarcticus

307T, with 98.9 % and 98.5 % 16S rRNA gene sequence similarities, respectively, and digital DDH values between D2-3T and

O. ascidiaceicola

and between G9-8T and

O. antarcticus

were 18.3 % and 19.5 %, respectively. Phenotypic, chemotaxonomic and molecular features support the hypothesis that D2-3T and G9-8T represent two novel species of the genus

Octadecabacter

, for which the names Octadecabacter algicola sp. nov. and Octadecabacter dasysiphoniae sp. nov. are proposed. The type strains of O. algicola and O. dasysiphoniae are D2-3T (=KACC 22493T =JCM 34969T) and G9-8T (=KACC 22488T =JCM 34973T), respectively.
ICTV Virus Taxonomy Profile: Hadakaviridae 2023
Authors: Sato Yukiyo , Turina Massimo , Chiba Sotaro , Okada Ryo , Bhatti Muhammad F. , Kotta-Loizou Ioly , Coutts Robert H. A. , Kondo Hideki , Sabanadzovic Sead , Suzuki Nobuhiro ,   ICTV Report Consortium
Published: January 2023

The family Hadakaviridae, including the genus Hadakavirus, accommodates capsidless viruses with a 10- or 11-segmented positive-sense (+) RNA genome. Currently known hosts are ascomycetous filamentous fungi. Although phylogenetically related to polymycovirids with a segmented double-stranded RNA genome and certain encapsidated picorna-like viruses, hadakavirids are distinct in their lack of a capsid (‘hadaka’ means naked in Japanese) and their consequent inability to be pelleted by conventional ultracentrifugation; they show ribonuclease susceptibility in host tissue homogenates. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hadakaviridae, which is available at ictv.global/report/hadakaviridae.
Leveraging open tools to realize the potential of self-archiving: A cohort study in clinical trials
Authors: Franzen Delwen L.
Published: January 2023

While Open Access (OA) is growing, many publications remain behind a paywall. This limits the impact of research and entrenches global inequalities by restricting access to knowledge to those that can afford it. Many journal policies allow researchers to make a version of their publication openly accessible through self-archiving in a repository, sometimes after an embargo period (green OA). Unpaywall and Shareyourpaper are open tools that help users find OA articles and support authors to legally self-archive their papers, respectively. This study leveraged these tools to assess the potential of green OA to increase discoverability in a cohort of clinical trial results publications from German university medical centers. Of the 1,897 publications in this cohort, 46% (n=871/1,897, 95% Confidence Interval (CI) 44% to 48%) were not openly accessible via a journal or a repository. Of these, 85% (n=736/871, 95% CI 82% to 87%) had a permission to self-archive the accepted or published version in an institutional repository. Thus, most of the closed-access clinical trial results in this cohort could be made openly accessible, in line with World Health Organization (WHO) recommendations. In addition to providing further evidence of the unrealized potential of green OA, this study demonstrates the use of open tools to obtain actionable information on self-archiving at scale, and empowers efforts to increase science discoverability.
Self-experience in MDMA assisted therapy of PTSD
Authors: van der Kolk Bessel A. , Wang Julie B. , Yehuda Rachel , Bedrosian Leah , Cooker Allison , Harrison Charlotte , Mithoefer Michael , Yazar-Klosinki Berra , Emerson Amy , Doblin Rick
Published: January 2023

In recent years there has been a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). This renaissance of psychedelic studies opens the door for a new paradigm in psychiatric medicine: drug-facilitated psychotherapy. In this study we report the findings of a randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial (NCT03537014) to test the effects of MDMA-assisted therapy (MDMA-AT) on patients with severe PTSD. The vast majority (85%) of individuals in this study reported having suffered early childhood trauma, which is strongly associated with deficits in emotional coping skills /altered self-capacities, which have been shown to constitute major obstacles to successful completion of currently available evidence-based treatments. Partcicipants were randomized 1:1 to receive manualized therapy with either MDMA or placebo with three preparatory and nine integrative therapy sessions. Symptoms were measured at baseline and at 2□ months after the last experimental session with the Clinician-Administered PTSD Scale for DSM-5, the Toronto Alexithymia Scale (TAS_20), the Self Compassion Scale (SCS) and the Inventory of Altered Self-Capacities (IASC). MDMA-AT, compared with psychotherapy alone, significantly altered the domains of alexithymia, self-compassion, and altered self-capacities. These findings suggest that MDMA-AT can substantially improve transdiagnostic mental processes associated with poor treatment response.
Decoding the relative contributions of extrinsic and intrinsic mechanisms in mediating heterogeneous spiking activities of sensory neurons in vivo using computational modeling
Authors: Akhshi Amin , Haggard Myriah , Marquez Mariana M. , Farjami Saeed , Chacron Maurice J. , Khadra Anmar
Published: January 2023

Neurons ubiquitously display heterogeneities in spiking activity even within a given cell type. To date, the relative contributions of extrinsic mechanisms (e.g., synaptic bombardment) and intrinsic mechanisms (e.g., conductances, cell morphology) towards determining spiking activity remain poorly understood. Here we address this important question using a novel approach that combines biophysical techniques, in which extracellular in vivo recordings of electrosensory pyramidal cells within weakly electric fish, are combined with computational modeling. Specifically, by varying parameters, a conductance-based computational model successfully reproduced the highly heterogeneous spiking activities seen experimentally. Model parameters that varied the most were then used to gauge the relative contributions of extrinsic vs. intrinsic mechanisms. Overall, extrinsic synaptic input was predicted to be the main factor accounting for spiking heterogeneities. We tested this prediction experimentally by performing two different manipulations: i) pharmacologically inactivating feedback; ii) applying the neuromodulator serotonin. Our model predicted that feedback inactivation should reduce while serotonin application should increase spiking heterogeneities. Experiments corroborated these predictions. Importantly, for serotonin application, increased heterogeneity occurred despite a strong reduction in intrinsic membrane conductance, further demonstrating that extrinsic synaptic input is the primary determinant of spiking heterogeneities in vivo. Taken together, our results demonstrate that devising a computational model to capture spiking heterogeneities in vivo and assessing which parameters are responsible can successfully determine the relative contributions of extrinsic vs. intrinsic inputs. We expect this approach to be generalizable to other systems and species.
Multi-Omics Atlas-Assisted Discovery of Transcription Factors for Selective T Cell State Programming
Authors: Chung H. Kay , Liu Cong , Jambor Alexander N. , Riesenberg Brian P. , Sun Ming , Casillas Eduardo , Chick Brent , Wang Audrey , Wang Jun , Ma Shixin , Mcdonald Bryan , He Peixiang , Yang Qiyuan , Chen Timothy , Varanasi Siva Karthik , LaPorte Michael , Mann Thomas H. , Chen Dan , Hoffmann Filipe , Tripple Victoria , Ho Josephine , Modliszewski Jennifer , Williams April , Cho Ukrae H. , Liu Longwei , Wang Yingxiao , Hargreaves Diana C. , Thaxton Jessica E. , Kaech Susan M. , Wang Wei
Published: January 2023

Transcription factors (TFs) regulate the differentiation of T cells into diverse states with distinct functionalities. To precisely program desired T cell states in viral infections and cancers, we generated a comprehensive transcriptional and epigenetic atlas of nine CD8+T cell differentiation states for TF activity prediction. Our analysis catalogued TF activity fingerprints of each state, uncovering new regulatory mechanisms that govern selective cell state differentiation. Leveraging this platform, we focused on two critical T cell states in tumor and virus control: terminally exhausted T cells (TEXterm), which are dysfunctional, and tissue-resident memory T cells (TRM), which are protective. Despite their functional differences, these states share significant transcriptional and anatomical similarities, making it both challenging and essential to engineer T cells that avoid TEXtermdifferentiation while preserving beneficial TRMcharacteristics. Throughin vivoCRISPR screening combined with single-cell RNA sequencing (Perturb-seq), we validated the specific TFs driving the TEXtermstate and confirmed the accuracy of TF specificity predictions. Importantly, we discovered novel TEXterm-specific TFs such as ZSCAN20, JDP2, and ZFP324. The deletion of these TEXterm-specific TFs in T cells enhanced tumor control and synergized with immune checkpoint blockade. Additionally, this study identified multi-state TFs like HIC1 and GFI1, which are vital for both TEXtermand TRMstates. Furthermore, our global TF community analysis and Perturb-seq experiments revealed how TFs differentially regulate key processes in TRMand TEXtermcells, uncovering new biological pathways like protein catabolism that are specifically linked to TEXtermdifferentiation. In summary, our platform systematically identifies TF programs across diverse T cell states, facilitating the engineering of specific T cell states to improve tumor control and providing insights into the cellular mechanisms underlying their functional disparities.
Evolution of explorative and exploitative search strategies in collective foraging
Authors: Garg Ketika , Smaldino Paul E. , Kello Christopher T.
Published: January 2023

Evolutionary theories of foraging hypothesize that foraging strategies evolve to maximize search efficiency. Many studies have investigated the central trade-off between explore-exploit and how individual foragers manage it under various conditions. For foragers in groups, this trade-off can be affected by the social environment, influencing the evolution of individual search strategies. Previous work has shown that when learning socially, explorative search strategies can optimize group search efficiency. However, social learning can cause discrepancies in strategies that benefit the group vs. an individual. We model the evolution of explorative and exploitative strategies using Lévy exponents under different levels of social learning and investigate their effect on individual and group search efficiencies. We show that reliance on social learning can lead to the evolution of mixed groups that are not optimally efficient. Exploiters can have a selective advantage in scrounging findings by explorers, but too many exploiters can diminish group efficiencies. However, greater opportunities for social learning can increase the benefits of explorative strategies. Finally, we show that area-restricted search can help individuals balance exploration and exploitation, and make groups more efficient. Our results demonstrate how exploration and exploitation must be balanced at both individual and collective levels for efficient search.
GolpHCat (TMEM87A): a unique voltage-gated and pH-sensitive cation channel in the Golgi
Authors: Kang Hyunji , Jeong Heejin , Han Ah-reum , Koh Wuhyun , Lee Jung Moo , Jo Heeyoung , Lee Hayeon , Bhalla Mridula , Roh Woo Suk , Jang Hyun Jun , Lee Boyoung , Kim Ho Min , An Hyun Joo , Lee C. Justin
Published: January 2023

The Golgi apparatus is a critical intracellular organelle that is responsible for modifying, packaging, and transporting proteins to their destinations. Golgi homeostasis involving the acidic pH, ion concentration, and membrane potential, is critical for proper functions and morphology of the Golgi. Although transporters and anion channels that contribute to Golgi homeostasis have been identified, the molecular identity of cation channels remains unknown. Here we identify TMEM87A as a novel Golgi-resident cation channel that contributes to pH homeostasis and rename it as GolpHCat (GolgipH-sensitiveCation channel). The genetic ablation of GolpHCat exhibits an impaired resting pH in the Golgi. Heterologously expressed GolpHCat displays voltage- and pH-dependent, non-selective cationic, and inwardly rectifying currents, with potent inhibition by gluconate. Furthermore, reconstitution of purified GolpHCat in liposomes generates functional channel activities with unique voltage-dependent gating and ion permeation. GolpHCat is expressed in various cell types such as neurons and astrocytes in the brain. In the hippocampus, GolpHCat-knockout mice show dilated Golgi morphology and altered glycosylation and protein trafficking, leading to impaired spatial memory with significantly reduced long-term potentiation. We elucidate that GolpHCat, by maintaining Golgi membrane potential, regulates ionic and osmotic homeostasis, protein glycosylation/trafficking, and brain functions. Our results propose a new molecular target for Golgi-related diseases and cognitive impairment.
Phylogenetic comparative approach reveals evolutionary conservatism, ancestral composition, and integration of vertebrate gut microbiota
Authors: Perez-Lamarque Benoît , Sommeria-Klein Guilhem , Duret Loréna , Morlon Hélène
Published: January 2023

How host-associated microbial communities evolve as their hosts diversify remains equivocal: How conserved is their composition? What was the composition of ancestral microbiota? Do microbial taxa covary in abundance over millions of years? Multivariate phylogenetic models of trait evolution are key to answering similar questions for complex host phenotypes, yet they are not directly applicable to relative abundances, which usually characterize microbiota. Here, we extend these models in this context, thereby providing a powerful approach for estimating phylosymbiosis (the extent to which closely related host species harbor similar microbiota), ancestral microbiota composition, and integration (evolutionary covariations in bacterial abundances). We apply our model to the gut microbiota of mammals and birds. We find significant phylosymbiosis that is not entirely explained by diet and geographic location, indicating that other evolutionary-conserved traits shape microbiota composition. We identify main shifts in microbiota composition during the evolution of the two groups and infer an ancestral mammalian microbiota consistent with an insectivorous diet. We also find remarkably consistent evolutionary covariations among bacterial orders in mammals and birds. Surprisingly, despite the substantial variability of present-day gut microbiota, some aspects of their composition are conserved over millions of years of host evolutionary history.
Dissecting the respective roles of microbiota and host genetics in the susceptibility ofCard9-/-mice to colitis
Authors: Danne C. , Lamas B. , Lavelle A. , Michel M-L. , Da Costa G. , Pham Hang-Phuong , Lefevre A. , Bridonneau C. , Bredon M. , Planchais J. , Straube M. , Emond P. , Langella P. , Sokol H.
Published: January 2023

Background

The etiology of Inflammatory Bowel Disease (IBD) is unclear but involves both genetics and environmental factors, including the gut microbiota. Indeed, exacerbated activation of the gastrointestinal immune system toward the gut microbiota occurs in genetically susceptible hosts and under the influence of the environment. For instance, a majority of IBD susceptibility loci lie within genes involved in immune responses, such as caspase recruitment domain member 9 (Card9). However, the relative impacts of genotype versus microbiota on colitis susceptibility in the context of CARD9 deficiency remain unknown.

Results

Card9gene directly contributes to recovery from dextran sodium sulfate (DSS)-induced colitis by inducing the colonic expression of the cytokine IL-22 and the antimicrobial peptidesReg3βandReg3γindependently of the microbiota. On the other hand,Card9is required for regulating the microbiota capacity to produce AhR ligands, which leads to the production of IL-22 in the colon, promoting recovery after colitis. In addition, cross-fostering experiments showed that five weeks after weaning, the microbiota transmitted from the nursing mother before weaning had a stronger impact on the tryptophan metabolism of the pups than the pups’ own genotype.

Conclusions

These results show the role of CARD9 and its effector IL-22 in mediating recovery from DSS-induced colitis in both microbiota-independent and microbiota-dependent manners.Card9genotype modulates the microbiota metabolic capacity to produce AhR ligands, but this effect can be overridden by the implantation of a WT or “healthy” microbiota before weaning. It highlights the importance of the weaning reaction occurring between the immune system and microbiota for host metabolism and immune functions throughout life. A better understanding of the impact of genetics on microbiota metabolism is key to developing efficient therapeutic strategies for patients suffering from complex inflammatory disorders.
TOBF1 modulates mouse embryonic stem cell fate through co-transcriptional regulation of alternative splicing
Authors: Aich Meghali , Ansari Asgar Hussain , Ding Li , Iesmantavicius Vytautas , Paul Deepanjan , Choudhary Chunaram , Maiti Souvik , Buchholz Frank , Chakraborty Debojyoti
Published: January 2023

Embryonic stem (ES) cells retain the ability to undergo lineage-specific differentiation that can eventually give rise to different cell types that constitute an organism. Although stem cell specific biological networks of transcription factors and epigenetic modifiers are well established, how the ES cell specific transcriptional and alternative splicing (AS) machinery regulate their expression has not been sufficiently explored. In this study, we show that the lncRNA associated protein TOBF1 regulates the co-transcriptional alternative splicing of transcripts necessary for maintaining stem cell identity in mouse ES cells. Overlaying information derived from TOBF1 chromatin occupancy, the distribution of its pluripotency-associated OCT-SOX binding motifs, and transcripts undergoing differential expression and alternative splicing upon its disruption unmasked local nuclear territories where these distinct events converge, ultimately leading to the maintenance of mouse ES cell identity.
Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses
Authors: Jossi Siân E. , Arcuri Melissa , Alshayea Areej , Persaud Ruby R. , Marcial-Juárez Edith , Palmieri Elena , Di Benedetto Roberta , Pérez-Toledo Marisol , Pillaye Jamie , Channell Will M. , Schager Anna E. , Lamerton Rachel E. , Cook Charlotte N. , Goodall Margaret , Haneda Takeshi , Bäumler Andreas J. , Jackson-Jones Lucy H. , Toellner Kai-Michael , MacLennan Calman A. , Henderson Ian R. , Micoli Francesca , Cunningham Adam F.
Published: January 2023

Vaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults againstSalmonellaTyphi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood. Here, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressingSalmonellaTyphimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (>5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV. Therefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such asS. Typhi.
Metabolic rewiring of the probiotic bacteriumLacticaseibacillus rhamnosusGG contributes to cell-wall remodeling and antimicrobials production
Authors: Suissa Ronit , Olender Tsviya , Malitsky Sergey , Golani Ofra , Turjeman Sondra , Koren Omry , Meijler Michael M. , Kolodkin-Gal Ilana
Published: January 2023

Lacticaseibacillus rhamnosus GG(LGG) is a Gram-positive beneficial bacterium that resides in the human intestinal tract and belongs to the family of lactic acid bacteria (LAB). This bacterium is a widely used probiotic and was suggested to provide numerous benefits for human health. However, as in most LAB strains, the molecular mechanisms that mediate the competitiveness of probiotics under different diets remain unknown. Fermentation is a fundamental process in LAB, allowing the oxidation of simple carbohydrates (e.g., glucose, mannose) for energy production under conditions of oxygen limitation, as in the human gut. Our results indicate that fermentation reshapes the metabolome, volatilome, and proteome architecture in LGG. Furthermore, fermentation alters cell envelope remodeling and peptidoglycan biosynthesis, which leads to altered cell wall thickness, aggregation properties, and cell wall composition. In addition, fermentable sugars induced secretion of known and novel metabolites and proteins targeting the enteric pathogensEnterococcus faecalisandSalmonella Enterica serovar Typhimurium. Overall, our results link the common metabolic regulation of cell wall remodeling, aggregation to host tissues, biofilm formation in probiotic strains, and connect the production of antimicrobial effectors with metabolome reprogramming. These findings provide novel insights into the role of nutrition in the establishment of LGG in the gastrointestinal tract.
Foraging guild modulates insectivorous bat responses to habitat loss and insular fragmentation in peninsular Malaysia
Authors: Hazard Quentin C.K. , Froidevaux Jérémy S.P. , Yoh Natalie , Moore Jonathan , Senawi Juliana , Gibson Luke , Palmeirim Ana Filipa
Published: January 2023

Despite mounting evidence on the ecological impacts of damming for biodiversity, little is known regarding its consequences in the hyper-diverse Southeast Asian tropical forests. Here we assess the effects of habitat loss and fragmentation on the diversity and activity of insectivorous bats within the hydroelectric Kenyir Lake in peninsular Malaysia. We surveyed bat assemblages on 26 islands and two mainland continuous forest sites using passive acoustic monitoring. Echolocation calls were classified into sonotypes, each corresponding to either one or multiple species, and grouped into foraging guilds. We then examined bat overall assemblage (sonotype richness, activity, and composition), guild- and sonotype-specific activity. From 9360 hours of recordings, we identified 16 bat sonotypes, including 10 forest (2854 bat passes), three edge (13 703) and three open-space foragers (3651). Sonotype richness increased towards denser forest structures (higher Normalized Difference Vegetation Index - NDVI), while species composition varied across the gradient of forest area. Forest foragers were positively affected by NDVI and negatively affected by distance to the closest neighbour, whereas edge foragers’ activity increased in smaller islands. Of the six sonotypes analysed, the activity of one forest sonotype increased with forest area, while that of one edge sonotype decreased. Ensuring habitat quality within insular forest remnants, in addition to their functional connectivity, maximises bat diversity, including the persistence of forest foraging species. Future hydropower development should therefore avoid the creation of a myriad of small, isolated, and habitat-degraded islands further characterised by altered levels of bat diversity and guild-level activity.

Highlights

We assessed the diversity of insectivorous bats in dam-induced islands in Malaysia

Species persistence was modulated by island size and habitat quality

Forest foragers were negatively affected by island isolation and degradation

Edge foragers benefited from fragmentation, increasing in activity on smaller islands

By creating multiple small, isolated, degraded islands, damming erodes bat diversity
Ancient loss of catalytic selenocysteine spurred convergent adaptation in a mammalian oxidoreductase
Authors: Rees Jasmin , Sarangi Gaurab , Cheng Qing , Floor Martin , Andrés Aida M , Miguel Baldomero Oliva , Villà-Freixa Jordi , Arnér Elias SJ , Castellano Sergi
Published: January 2023

Selenocysteine (Sec), the 21stamino acid specified by the genetic code, is a rare selenium-containing residue found in the catalytic site of selenoprotein oxidoreductases. Sec is analogous to the common cysteine (Cys) amino acid but its selenium atom offers physicalchemical properties not provided by the corresponding sulfur atom in Cys. Catalytic sites with Sec in selenoproteins of vertebrates are under strong purifying selection but one enzyme, Glutathione Peroxidase 6 (GPX6), independently exchanged Sec for Cys less than one hundred million years ago in several mammalian lineages. We reconstructed and assayed these ancient enzymes before and after Sec was lost and up to today, and found them to have lost their classic ability to reduce hydroperoxides using glutathione (GSH). This loss of function, however, was accompanied by bursts of amino acid changes in the catalytic domain, with protein sites concertedly changing under positive selection across distant lineages abandoning Sec in GPX6. This demonstrates that when sulfur in Cys impairs catalysis a narrow evolutionary path is followed, with epistasis and pleiotropy leading to convergent evolution and triggering enzymatic properties likely beyond those in classic GPXs. These findings are an unusual example of adaptive convergence towards unexplored oxidoreductase functions during mammalian evolution.
Fluctuating landscapes and heavy tails in animal behavior
Authors: Costa Antonio Carlos , Vergassola Massimo
Published: January 2023

Animal behavior is shaped by a myriad of mechanisms acting on a wide range of scales. This immense variability hampers quantitative reasoning and renders the identification of universal principles elusive. Through data analysis and theory, we here show that slow non-ergodic drives generally give rise to heavy-tailed statistics in behaving animals. We leverage high-resolution recordings ofC. eleganslocomotion to extract a self-consistent reduced order model for an inferred reaction coordinate, bridging from sub-second chaotic dynamics to long-lived stochastic transitions among metastable states. The slow mode dynamics exhibits heavy-tailed first passage time distributions and correlation functions, and we show that such heavy tails can be explained by dynamics on a time-dependent potential landscape. Inspired by these results, we introduce a generic model in which we separate faster mixing modes that evolve on a quasi-stationary potential, from slower non-ergodic modes that drive the potential landscape, and reflect slowly varying internal states. We show that, even for simple potential landscapes, heavy tails emerge when barrier heights fluctuate slowly and strongly enough. In particular, the distribution of first passage times and the correlation function can asymptote to a power law, with related exponents that depend on the strength and nature of the fluctuations. We support our theoretical findings through direct numerical simulations.
Crosstalk between chromatin and the transcription factor Shavenbaby defines transcriptional output along theDrosophilaintestinal stem cell lineage
Authors: Mancheno-Ferris Alexandra , Immarigeon Clément , Rivero Alexia , Depierre David , Chanard Nicolas , Fosseprez Olivier , Aughey Gabriel , Lhoumaud Priscilla , Anglade Julien , Southall Tony , Plaza Serge , Cuvier Olivier , Payre François , Polesello Cédric
Published: January 2023

The transcription factor Shavenbaby (Svb), the only member of the OvoL family inDrosophila, controls intestinal stem cell differentiation. Post-translational modification of Svb produces two protein isoforms, Svb-ACT and Svb-REP, which promote intestinal stem cell renewal or differentiation, respectively. Using engineered cell lines, we express either isoform to define their mode of action, and develop an unbiased method to identify Svb target genes in intestinal cells. Within a given cell type, Svb-ACT and Svb-REP antagonistically regulate the expression of a set of target genes, binding specific enhancers whose accessibility is constrained by. During intestinal differentiation, the set of target genes progressively changes, together with chromatin accessibility. Moreover, Svb-REP binding stabilizes three-dimensional enhancer-promoter loops, while influencing the local chromatin landscape to repress target genes. We propose that SvbACT-to-REP switch promotes enterocyte differentiation of intestinal stem cells through direct gene regulation and chromatin remodeling.
A defined community of core gut microbiota members promotes cognitive performance in honey bees
Authors: Cabirol Amélie , Schafer Julie , Neuschwander Nicolas , Kesner Lucie , Liberti Joanito , Engel Philipp
Published: January 2023

The composition of the gut microbiota has recently been identified as a cause of cognitive variability in humans and animals. Germ-free individuals and individuals exposed to an antibiotic treatment show severe alteration of their learning and memory performance measured in various cognitive tasks. While different species of bacteria are known to interact in the gut, their cumulative or synergistic effects on cognitive performance remain elusive. Here we established a defined bacterial community - composed of core members of the corbiculate bee microbiota - which enhances honey bees’ cognitive capacities. Honey bees colonized with this reconstituted community discriminated better two odours based on the presence or absence of a sucrose reward compared to germ-free individuals. They also memorized better these odour-food associations in the short-term. These cognitive improvements seem to constitute an emergent property of the community, because they could not be recapitulated by any of the community members when mono-associated in gnotobiotic bees and they were not explained by the total biomass in the gut. The identification of this community and its effect on bees open new avenues of research in neuroscience, microbiology, and ecology. Future research should help understanding how interactions between bacterial species in the community promote the host’s associative learning and memory performance.
Hypersensitivity to distractors in Fragile X syndrome from loss of modulation of cortical VIP interneurons
Authors: Rahmatullah Noorhan , Schmitt Lauren M. , De Stefano Lisa , Post Sam , Robledo Jessica , Chaudhari Gunvant R. , Pedapati Ernest , Erickson Craig A. , Portera-Cailliau Carlos , Goel Anubhuti
Published: January 2023

Attention deficit is one of the most prominent and disabling symptoms in Fragile X Syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention difficulties by overwhelming and/or distracting affected individuals, which disrupts activities of daily living at home and learning at school. We find that auditory or visual distractors selectively impair visual discrimination performance in both humans and mice with FXS, but not their typically developing controls. Vasoactive intestinal polypeptide (VIP) neurons were significantly modulated by incorrect responses in the post-stimulus period during early distractor trials in WT mice, consistent with their known role as ‘error’ signals. Strikingly, however, VIP cells fromFmr1-/-mice showed little modulation in error trials, and this correlated with their poor performance on the distractor task. Thus, VIP interneurons and their reduced modulatory influence on pyramidal cells, could be a potential therapeutic target for attentional difficulties in FXS.
Evidence forin vitroextensive proliferation of adult hepatocytes and biliary epithelial cells
Authors: Katsuda Takeshi , Li Jinyang , Merrell Allyson J , Sussman Jonathan , Matsuzaki Juntaro , Ochiya Takahiro , Stanger Ben Z
Published: January 2023

Over the last several years, a method has emerged which endows adult hepatocytes within vitroproliferative capacity, producing chemically-induced liver progenitors (CLiPs). However, a recent study questioned the origin of these cells, suggesting that resident liver progenitor cells, but not hepatocytes, proliferate. Here, we provide lineage tracing-based evidence that adult hepatocytes acquire proliferative capacityin vitro. Unexpectedly, we also found that the CLiP method allows biliary epithelial cells to acquire extensive proliferative capacity. Interestingly, after long-term culture, hepatocyte-derived cells (hepCLiPs) and biliary-derived cells (bilCLiPs) become similar in their gene expression patterns, and they both exhibit differentiation capacity to form hepatocyte-like cells. Finally, we provide evidence that hepCLiPs can repopulate chronically injured mouse livers, reinforcing our earlier argument that CLiPs can be a cell source for liver regenerative medicine. Moreover, this study offers bilCLiPs as a potential cell source for liver regenerative medicine.
A multiprotein signaling complex sustains AKT and mTOR/S6K activity necessary for the survival of cancer cells undergoing stress
Authors: Teran Pumar Oriana Y. , Zanotelli Matthew R. , Lin Miao-chong Joy , Schmitt Rebecca R. , Green Kai Su , Rojas Katherine S. , Hwang Irene Y. , Cerione Richard A. , Wilson Kristin F.
Published: January 2023

The ability of cancer cells to survive microenvironmental stresses is critical for tumor progression and metastasis; however, how they survive these challenges is not fully understood. Here, we describe a novel multiprotein complex (DockTOR) essential for the survival of cancer cells under stress, triggered by the GTPase Cdc42 and a signaling partner Dock7, which includes AKT, mTOR, and the mTOR regulators TSC1, TSC2, and Rheb. DockTOR enables cancer cells to maintain a low but critical mTORC2-dependent phosphorylation of AKT during serum deprivation by preventing AKT dephosphorylation through an interaction between phospho-AKT and the Dock7 DHR1 domain. This activity stimulates a Raptor-independent but Rapamycin-sensitive mTOR/S6K activity necessary for survival. These findings address long-standing questions of how Cdc42 signals result in mTOR activation and demonstrate how cancer cells survive conditions when growth factor-dependent activation of mTORC1 is off. Determining how cancer cells survive stress conditions could identify vulnerabilities that lead to new therapeutic strategies.
Representational geometry explains puzzling error distributions in behavioral tasks
Authors: Wei Xue-Xin , Woodford Michael
Published: January 2023

Measuring and interpreting errors in behavioral tasks is critical for understanding cognition. Conventional wisdom assumes that encoding/decoding errors for continuous variables in behavioral tasks should naturally have Gaussian distributions, so that deviations from normality in the empirical data indicate the presence of more complex sources of noise. This line of reasoning has been central for prior research on working memory. Here we re-assess this assumption, and find that even in ideal observer models with Gaussian encoding noise, the error distribution is generally non-Gaussian, contrary to the commonly held belief. Critically, we find that the shape of the error distribution is determined by the geometrical structure of the encoding manifold via a simple rule. In the case of a high-dimensional geometry, the error distributions naturally exhibit flat tails. Using this novel insight, we apply our theory to visual short-term memory tasks, and find that it can account for a large array of experimental data with only two free parameters. Our results call attention to the geometry of the representation as a critically important, yet underappreciated factor in determining the character of errors in human behavior.
Tool-sensed object information effectively supports vision for multisensory grasping
Authors: Camponogara Ivan , Farnè Alessandro , Volcic Robert
Published: January 2023

Tools enable humans to extend their sensing abilities beyond the natural limits of their hands, allowing them to sense objects as if they were using their hands directly. The similarities between tool-mediated and hand-based sensing entail the existence of comparable processes for integrating tool- and hand-sensed information with vision, raising the intriguing question of whether tools can support vision in bimanual object manipulations. Here we investigated this question by measuring participants’ performance while reaching for and grasping objects either held with a tool or with their hand. We found that tool-mediated sensing effectively supports vision in multisensory grasping. Even more intriguingly, tool-mediated sensing resembled hand-based sensing. In addition, by manipulating the object features (availability of position and size versus position only), we found that both tool- and hand-mediated action performance was not hindered by the absence of size information. Thus, integrating the tool-sensed position of the object with its vision is sufficient to promote a multisensory advantage in grasping. In sum, our findings indicate that multisensory integration mechanisms significantly improve grasping actions, fine-tuning contralateral hand movements even when object information is only indirectly sensed through the hand operating a tool.

Significance statement

Tools allow extending the hands sensing capabilities beyond their anatomical limits. Here we show that object information sensed through a tool can guide bimanual object manipulations as effectively as when directly sensed by the hand. Both tool and hand sensing provide relevant object positional information that are merged with vision to improve action performance. Our findings provide evidence about the interchangeable use of tools and hands for skilled actions and open new perspectives for prosthetic applications and rehabilitative plans.
An effective sanitizer for fresh produce production:In situplasma activated water treatment inactivates pathogenic bacteria and maintains the quality of cucurbit fruit
Authors: Rothwell Joanna G. , Hong Jungmi , Morrison Stuart J. , Vyas Heema Kumari Nilesh , Xia Binbin , Mai-Prochnow Anne , McConchie Robyn , Phan-Thien Kim-Yen , Cullen Patrick J. , Carter Dee A.
Published: January 2023

The effect of plasma activated water (PAW) generated with a dielectric barrier discharge diffusor (DBDD) system on microbial load and organoleptic quality of cucamelons was investigated and compared to the established sanitizer, sodium hypochlorite (NaOCl). Pathogenic serotypes ofEscherichia coli,Salmonella enterica, andListeria monocytogeneswere inoculated onto the surface of cucamelons (6.5 log CFU g−1) and into the wash water (6 log CFU mL−1). PAW treatment involved 2 minutesin situwith water activated at 1500 Hz and 120 V, and air as the feed gas; NaOCl treatment was a wash with 100 ppm total chlorine; and the control treatment was a wash with tap water. PAW treatment produced a 3 log CFU g−1reduction of pathogens on the cucamelon surface without negatively impacting quality or shelf life. NaOCl treatment reduced the pathogenic bacteria on the cucamelon surface by 3-4 log CFU g−1, however, this treatment also reduced fruit shelf life and quality. Both systems reduced 6 log CFU ml−1pathogens in the wash water to below detectable limits. The critical role of superoxide anion radical (·O2−) in the antimicrobial power of DBDD-PAW was demonstrated through a scavenger assay, and chemistry modelling confirmed that ·O2−generation readily occurs in DBDD-PAW generated with the employed settings. Modelling of the physical forces produced during plasma treatment showed that bacteria likely experience strong local electric fields and polarization. We hypothesize that these physical effects synergise with reactive chemical species to produce the acute antimicrobial activity seen with thein situPAW system.

Importance

Plasma activated water (PAW) is an emerging sanitizer in the fresh food industry, where food safety must be achieved without a thermal kill step. Here we demonstrate PAW generatedin situto be a competitive sanitizer technology, providing a significant reduction of pathogenic and spoilage micro-organisms while maintaining the quality and shelf life of the produce item. Our experimental results are supported by modelling of the plasma chemistry and applied physical forces, which show that the system can generate highly reactive superoxide radicals and strong electric fields that combine to produce potent antimicrobial power.In situPAW has promise in industrial applications as it only requires low power (12 W), tap water and air. Moreover, it does not produce toxic by-products or hazardous effluent waste, making it a sustainable solution for fresh food safety.