bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are we really Bayesian? Probabilistic inference shows sub-optimal knowledge transfer
Authors: Lin Chin-Hsuan Sophie , Do Trang Thuy , Unsworth Lee , Garrido Marta I. 
Published: April 2023

AbstractNumerous studies have found that the Bayesian framework, which formulates the optimal integration of the knowledge of the world (i.e. prior) and current sensory evidence (i.e. likelihood), captures human behaviours sufficiently well. However, there are debates regarding whether humans use precise but cognitively demanding Bayesian computations for behaviours. Across two studies, we trained participants to estimate hidden locations of a target drawn from priors with different levels of uncertainty. In each trial, scattered dots provided noisy likelihood information about the target location. Participants showed that they learned the priors and combined prior and likelihood information to infer target locations in a Bayes fashion. We then introduced a transfer condition presenting a trained prior and a likelihood that has never been put together during training. How well participants integrate this novel likelihood with their learned prior is an indicator of whether participants perform Bayesian computations. In one study, participants experienced the newly introduced likelihood, which was paired with a different prior, during training. Participants changed likelihood weighting following expected directions although the degrees of change were significantly lower than Bayes-optimal predictions. In another group, the novel likelihoods were never used during training. We found people integrated a new likelihood within (interpolation) better than the one outside (extrapolation) the range of their previous learning experience and they were quantitatively Bayes-suboptimal in both. We replicated the findings of both studies in a validation dataset. Our results showed that Bayesian behaviours may not always be achieved by a full Bayesian computation. Future studies can apply our approach to different tasks to enhance the understanding of decision-making mechanisms.Author summaryBayesian decision theory has emerged as a unified approach for capturing a wide range of behaviours under uncertainty. However, behavioural evidence supporting that humans use explicit Bayesian computation is scarce. While it has been argued that knowledge generalization should be treated as hard evidence of the use of Bayesian strategies, results from previous work were inconclusive. Here, we develop a marker that effectively quantifies how well humans transfer learned priors to a new scenario. Our marker can be applied to various tasks and thus can provide a path forwarding the understanding of psychological and biological underpinnings of inferential behaviours.
Global Marine Cold Seep Metagenomes Reveal Diversity of Taxonomy, Metabolic Function, and Natural Products
Authors: Yu Tao , Luo Yingfeng , Tan Xinyu , Zhao Dahe , Bi Xiaochun , Li Chenji , Zheng Yanning , Xiang Hua , Hu Songnian 
Published: April 2023

AbstractCold seeps in the deep sea are closely linked to energy exploration as well as global climate change. The alkane-dominated chemical energy-driven model makes cold seeps an oasis of deep-sea life, showcasing an unparalleled reservoir of microbial genetic diversity. By analyzing 113 metagenomes collected from 14 global sites across 5 cold seep types, we present a comprehensive Cold Seep Microbiomic Database (CSMD) to archive the genomic and functional diversity of cold seep microbiome. The CSMD includes over 49 million non-redundant genes and 3175 metagenome-assembled genomes (MAGs), which represent 1897 species spanning 106 phyla. In addition, beta diversity analysis indicates that both sampling site and cold seep type have substantial impact on the prokaryotic microbiome community composition. Heterotrophic and anaerobic metabolisms are prevalent in microbial communities, accompanied by considerable mixotrophs and facultative anaerobes, indicating the versatile metabolic potential in cold seeps. Furthermore, secondary metabolic gene cluster analysis indicates that at least 98.81% of the sequences encode potentially novel natural products. These natural products are dominated by ribosomal processing peptides, which are widely distributed in archaea and bacteria. Overall, the CSMD represents a valuable resource which would enhance the understanding and utilization of global cold seep microbiomes.
Hunger- and thirst-sensing neurons modulate a neuroendocrine network to coordinate sugar and water ingestion
Authors: González-Segarra Amanda J. , Pontes Gina , Jourjine Nicholas , Toro Alexander Del , Scott Kristin 
Published: April 2023

ABSTRACTConsumption of food and water is tightly regulated by the nervous system to maintain internal nutrient homeostasis. Although generally considered independently, interactions between hunger and thirst drives are important to coordinate competing needs. InDrosophila, four neurons called the Interoceptive Subesophageal zone Neurons (ISNs) respond to intrinsic hunger and thirst signals to oppositely regulate sucrose and water ingestion. Here, we investigate the neural circuit downstream of the ISNs to examine how ingestion is regulated based on internal needs. Utilizing the recently available fly brain connectome, we find that the ISNs synapse with a novel cell type Bilateral T-shaped neuron (BiT) that projects to neuroendocrine centers.In vivoneural manipulations revealed that BiT oppositely regulates sugar and water ingestion. Neuroendocrine cells downstream of ISNs include several peptide-releasing and peptide-sensing neurons, including insulin producing cells (IPC), crustacean cardioactive peptide (CCAP) neurons, and CCHamide-2 receptor isoform RA (CCHa2R-RA) neurons. These neurons contribute differentially to ingestion of sugar and water, with IPCs and CCAP neurons oppositely regulating sugar and water ingestion, and CCHa2R-RA neurons modulating only water ingestion. Thus, the decision to consume sugar or water occurs via regulation of a broad peptidergic network that integrates internal signals of nutritional state to generate nutrient-specific ingestion.
Comparative analysis of noise-attenuation mechanisms in gene expression: From single cells to cell populations
Authors: Zhang Zhanhao , Nieto Cesar , Singh Abhyudai 
Published: April 2023

AbstractNegative feedback regulation is a well-known motif for suppressing deleterious fluctuations in gene product levels. We systematically compare two scenarios where negative feedback is either implemented in the protein production rate (regulated synthesis) or in the protein degradation rate (regulated degradation). Our results show that while in lownoise regimes both schemes are identical, they begin to show remarkable differences in high-noise regimes. Analytically solving for the probability distributions of the protein levels reveals that regulated synthesis is a better strategy to suppress random fluctuations while also minimizing protein levels dipping below a threshold. In contrast, regulated degradation is preferred if the goal is to minimize protein levels going beyond a threshold. Finally, we compare and contrast these distributions not only in a single cell over time but also in an expanding cell population where these effects can be buffered or exacerbated due to the coupling between expression and cell growth.
Differential Expression of Gluconeogenesis-Related Transcripts in a Freshwater Zooplankton Model Organism Suggests a Role of the Cori Cycle in Hypoxia Tolerance
Authors: Malek M. C. , Behera J.R. , Kilaru A. , Yampolsky L. Y. 
Published: April 2023

AbstractGluconeogenesis (GNG) is the process of regenerating glucose and NAD+ that allows continuing ATP synthesis by glycolysis during fasting or in hypoxia. Recent data fromC. elegansand crustaceans challenged with hypoxia show differential and tissue-specific expression of GNG-specific genes.Here we report differential expression of several GNG-specific genes in the head and body of a model organism,Daphnia magna,a planktonic crustacean, in normoxic and acute hypoxic conditions. We predict that GNG-specific transcripts will be enriched in the body, where most of the fat tissue is located, rather than in the head, where the tissues critical for survival in hypoxia, the central nervous system and locomotory muscles, are located. We measured the relative expression of GNG-specific transcripts in each body part by qRT-PCR and normalized them by either the expression of a reference gene or the rate-limiting glycolysis enzyme pyruvate kinase (PK).Our data show that of the three GNG-specific transcripts tested, pyruvate carboxylase (PC) showed no differential expression in either the head or body. Phosphoenolpyruvate carboxykinase (PEPCK-C), on the other hand, is upregulated in hypoxia in both body parts. Fructose-1,6-bisphosphatase (FBP) is upregulated in the body relative to the head and upregulated in hypoxia relative to normoxia, with a stronger body effect in hypoxia when normalized by PK expression.These results support our hypothesis thatDaphniacan survive hypoxic conditions by implementing the Cori cycle, where body tissues supply glucose and NAD+ to the brain and muscles, enabling them to continuously generate ATP by glycolysis.
Reply to Barton et al: signatures of natural selection during the Black Death
Authors: Vilgalys Tauras P. , Klunk Jennifer , Demeure Christian E. , Cheng Xiaoheng , Shiratori Mari , Madej Julien , Beau Rémi , Elli Derek , Patino Maria I. , Redfern Rebecca , DeWitte Sharon N. , Gamble Julia A. , Boldsen Jesper L. , Carmichael Ann , Varlik Nükhet , Eaton Katherine , Grenier Jean-Christophe , Golding G. Brian , Devault Alison , Rouillard Jean-Marie , Yotova Vania , Sindeaux Renata , Ye Chun Jimmie , Bikaran Matin , Dumaine Anne , Brinkworth Jessica F , Missiakas Dominique , Rouleau Guy A. , Steinrücken Matthias , Pizarro-Cerdá Javier , Poinar Hendrik N. , Barreiro Luis B. 
Published: April 2023

AbstractBartonet al.1raise several statistical concerns regarding our original analyses2that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high FSTvalues at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant nearERAP2continues to emerge as the strongest candidate for selection (p = 1.2×10−5), falling below the Bonferroni-corrected significance threshold recommended by Bartonet al. Importantly, the evidence for selection onERAP2is further supported by functional data demonstrating the impact of theERAP2genotype on the immune response toY. pestisand by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.
Determining the Statistical Significance of the Difference Between Arbitrary Curves: A Spreadsheet Method
Authors: Hristova Kalina , Wimley William C. 
Published: April 2023

ABSTRACTWe present a simple, spreadsheet-based method to determine the statistical significance of the difference between any two arbitrary curves. This modified Chi-squared method addresses two scenarios: A single measurement at each point with known standard deviation, or multiple measurements at each point averaged to produce a mean and standard error. The method includes an essential correction for the deviation from normality in measurements with small sample size, which are typical in biomedical sciences. Statistical significance is determined without regard to the functionality of the curves, or the signs of the differences. Numerical simulations are used to validate the procedure. Example experimental data are used to demonstrate its application. An Excel spreadsheet is provided for performing the calculations for either scenario.
Insulin-like peptides regulate oogenesis by stimulating ovarian ecdysteroid production in the Indian malaria mosquitoAnopheles stephensi
Authors: Phipps Benjamin L. , Brown Mark R. , Strand Michael R. 
Published: April 2023

AbstractFemales of many mosquito species feed on vertebrate blood to produce eggs, making them effective disease vectors. In the dengue vectorAedes aegypti, blood feeding signals the brain to release ovary ecdysteroidogenic hormone (OEH) and insulin-like peptides (ILPs) that trigger ecdysteroid production by the ovaries. These ecdysteroids regulate synthesis of the yolk protein vitellogenin (Vg) that is packaged into eggs. Less is known about the reproductive biology ofAnophelesmosquitoes, which pose a greater public health threat thanAedesspp. because they are competent to transmit mammalian malaria. ILPs can triggerAn. stephensiovaries to secrete ecdysteroids. UnlikeAe. aegypti,Anophelesalso transfer ecdysteroids fromAnophelesmales to females during mating. To elucidate the role of OEH and ILPs inAn. stephensi, we decapitated blood-fed females to ablate the source of these peptides and injected them with each hormone. Yolk deposition into oocytes was abolished in decapitated females and rescued by ILP injection. ILP activity was dependent on blood feeding and little change in triglyceride and glycogen stores was observed in response to blood-feeding, suggesting this species requires nutrients from blood to form eggs. We also measured egg maturation, ecdysteroid titers, and yolk protein expression in mated and virgin females. Although yolk deposition into developing oocytes was significantly reduced in virgins compared to mated females, no differences in ecdysteroid titers or Vg transcript abundance were detected between these groups. 20-hydroxyecdysone (20E) stimulated Vg expression in female fat bodies in primary culture. Given these results, we conclude that ILPs control egg formation by regulating ecdysteroid production in the ovaries.
Shifts in the coral microbiome in response toin situexperimental deoxygenation
Authors: Howard Rachel D. , Schul Monica , Rodriguez Bravo Lucia M. , Altieri Andrew , Meyer Julie L. 
Published: April 2023

ABSTRACTGlobal climate change impacts ocean communities through rising surface temperatures, ocean acidification, and deoxygenation. While the response of the coral holobiont to the first two effects has been relatively well studied, little is known about the response of the coral microbiome to deoxygenation. In this study, we investigated the response of the microbiome to hypoxia in two coral species that differ in their relative tolerance to hypoxia. We conductedin situoxygen manipulations on a coral reef in Bahía Almirante, Panama, which has previously experienced episodes of low dissolved oxygen concentrations. Naïve coral colonies (previously unexposed to hypoxia) of massive starlet coral (Siderastrea siderea) and Lamarck’s sheet coral (Agaricia lamarcki) were transplanted to a reef and either enclosed in chambers that created hypoxic conditions or left at ambient oxygen levels. We collected samples of surface mucus and tissue after 48 hours of exposure and characterized the microbiome by sequencing 16S rRNA genes. We found that the microbiomes of the two coral species were distinct from one another and remained so after exhibiting similar shifts in microbiome composition in response to hypoxia. There was an increase in both abundance and number of taxa of anaerobic microbes after exposure to hypoxia. Some of these taxa may play beneficial roles in the coral holobiont by detoxifying the surrounding environment during hypoxic stress. This work describes the first characterization of the coral microbiome under hypoxia and is an initial step toward identifying potential beneficial bacteria for corals facing this environmental stressor.ImportanceMarine hypoxia is a threat for corals but has remained understudied in tropical regions where coral reefs are abundant. Deoxygenation on coral reefs will worsen with ongoing climate change, acidification, and eutrophication. We do not yet understand the response of the coral microbiome to hypoxia, and whether this reaction may have a beneficial or harmful role in the coral holobiont. To understand how the coral microbial community structure responds during hypoxic stress, we experimentally lowered the oxygen levels around corals in the field to observe changes in the composition of the coral microbiome. We documented the increase of anaerobic and pathogenic bacteria in the microbiomes of the massive starlet coral (Siderastrea siderea) and Lamarck’s sheet coral (Agaricia lamarcki) in 48 hours. This work provides fundamental knowledge of the microbial response in the coral holobiont during hypoxia and may provide insight to holobiont function during stress.
Insight into the genetic diversity, resistance, and virulence ofListeriafrom the marine environment: reveal the risk of hypervirulent isolates
Authors: Pan Mao , Yan Wang , Lingling Li , Shunshi Ji , Peijing Li , Lingyun Liu , Jinni Chen , Hui Sun , Xia Luo , Changyun Ye 
Published: April 2023

AbstractListeria monocytogenes is a major human foodborne pathogen and a ubiquitous environmental saprophyte. In this study, we investigated the prevalence and characteristics ofListeria spp. from beach sand in the coastal environment. Three differentListeria spp.,Listeria monocytogenes(n=16),Listeria fleishmanii(n=7), andListeria aquatica(n=3) were isolated from 769 beach sand samples and demonstrated diverse biofilm forming capacity. TheL. monocytogenesisolates belonged to four distinct sequence types (ST87, ST121, ST35, and ST85) and contained the majority of virulence genes, some isolates were hypervirulent clones or had close phylogenetic relatedness with clinical cases. The ST87 isolates showed higher ability of biofilm formation in seawater than other STs strains. As a reservoir of microbes from marine environments and human/animal excrement, coastal sand would play an important role in the spread ofL. monocytogenes and is an environmental risk for human listeriosis.
Stepwise design of pseudosymmetric protein hetero-oligomers
Authors: Kibler Ryan D. , Lee Sangmin , Kennedy Madison A. , Wicky Basile I. M. , Lai Stella M. , Kostelic Marius M. , Li Xinting , Chow Cameron M. , Carter Lauren , Wysocki Vicki H. , Stoddard Barry L. , Baker David 
Published: April 2023

AbstractPseudosymmetric hetero-oligomers with three or more unique subunits with overall structural (but not sequence) symmetry play key roles in biology, and systematic approaches for generating such proteinsde novowould provide new routes to controlling cell signaling and designing complex protein materials. However, thede novodesign of protein hetero-oligomers with three or more distinct chains with nearly identical structures is a challenging problem because it requires the accurate design of multiple protein-protein interfaces simultaneously. Here, we describe a divide-and-conquer approach that breaks the multiple-interface design challenge into a set of more tractable symmetric single-interface redesign problems, followed by structural recombination of the validated homo-oligomers into pseudosymmetric hetero-oligomers. Starting fromde novodesigned circular homo-oligomers composed of 9 or 24 tandemly repeated units, we redesigned the inter-subunit interfaces to generate 15 new homo-oligomers and recombined them to make 17 new hetero-oligomers, including ABC heterotrimers, A2B2 heterotetramers, and A3B3 and A2B2C2 heterohexamers which assemble with high structural specificity. The symmetric homo-oligomers and pseudosymmetric hetero-oligomers generated for each system share a common backbone, and hence are ideal building blocks for generating and functionalizing larger symmetric assemblies.Significance StatementProtein oligomers composed of multiple unique subunits are versatile building blocks for creating functional materials and controlling biological processes. However, designing robust hetero-oligomers with distinct subunits and precise structural symmetry remains a major challenge. Here, we present a general strategy for designing such complexes by breaking down the problem into simpler steps by first symmetrically re-designing the interfaces of homo-oligomeric proteins, and then recombining validated variants to form pseudosymmetric hetero-oligomers. Using this method, we generated 17 hetero-oligomers with up to three unique subunits that assemble with high specificity. Our approach can be extended to create a wide range of pseudosymmetric assemblies for manipulating cellular signaling and as building blocks for advanced protein materials. These pseudosymmeteric heterotrimers have already enabled the construction of a set of massive nanocages, including a T=4 icosahedral nanocage with a 70 nm diameter and 240 subunits.1
Targeting MCL1-driven anti-apoptotic pathways to overcome hypomethylating agent resistance inRAS-mutated chronic myelomonocytic leukemia
Authors: Montalban-Bravo Guillermo , Ma Feiyang , Thongon Natthakan , Yang Hui , Gomez Irene Ganan- , Rodriguez-Sevilla Juanjo Jose , Adema Vera , Wildeman Bethany , Lockyer Pamela , Kim Yi June , Tanaka Tomoyuki , Darbaniyan Faezeh , Pancholy Shivam , Zhang Geoffrey , Al-Atrash Gheath , Dwyer Karen , Takahashi Koichi , Garcia-Manero Guillermo , Kantarjian Hagop , Colla Simona 
Published: April 2023

ABSTRACTRASpathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Using single-cell, multi-omics technologies, we sought to dissect the biological mechanisms underlying the initiation and progression ofRASpathway–mutated CMML. We found thatRASpathway mutations induced the transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs), which underwent proliferation and monocytic differentiation in response to cell-intrinsic and -extrinsic inflammatory signaling that also impaired immune cells’ functions. HSPCs expanded at disease progression and relied on the NF-KB pathway effector MCL1 to maintain their survival, which explains why patients withRASpathway– mutated CMML do not benefit from BCL2 inhibitors such as venetoclax. Our study has implications for developing therapies to improve the survival of patients withRASpathway– mutated CMML.
L-Ascorbic acid restrictsVibrio choleraesurvival in various growth conditions
Authors: Sen Himanshu , Kaur Manpreet , Raychaudhuri Saumya 
Published: April 2023

AbstractCholera, a deadly diarrheal disease, continues to ravage various parts of the world. It is caused byVibrio cholerae, an important member of the gamma-proteobacteria. Based on certain genetic and phenotypic tests, the organism is classified into two major biotypes, namely classical and El Tor. The El Tor and its variants are majorly responsible for the ongoing seventh pandemic across the globe. Previously, we have shown that cross feeding of glucose metabolic acidic by products of gut commensal can severely affect viability of the biotypes. In this work, we examined the effect of L-ascorbic acid on the survival ofVibrio choleraestrains belonging to both biotypes and different serotypes. We observed that L-ascorbic acid is effective in restricting the growth of all strains under various conditions including strains adapted with acid stress.