bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating risk-taking behaviors in Lycosidae: are the nutritional benefits of sugar water worth the risk of predation?
Authors: Woyak Lauren , McCullagh Elizabeth , Wiggins Will 
Published: May 2022

AbstractThe risk-taking tendencies and addiction in small vertebrates are often used to understand the processes of larger vertebrates, such as humans. We set out to find whether certain risk-taking behaviors characteristic of addiction remain consistent between vertebrates and invertebrates. Different animals will gorge on sugar water, and addiction-like tendencies are often associated with the overconsumption of sucrose. The goal of my study was to evaluate those risk-taking behaviors and compare invertebrate risk-taking behaviors to vertebrate risk-taking behaviors. The risk-taking behavior we observed was the process of relieving cravings while the risk of predation was present. Through this study we document evidence of wolf spiders feeding on a 25% sucrose solution and explain the wolf spiders’ preference to a sugar water solution over filtered tap water. To evaluate if wolf spiders exhibit addiction like behaviors associated with sucrose, we placed a green-colored, sugar water-soaked cotton ball on the silk of a large, predatory Tigrosa helluo wolf spider and a regular, filtered water-soaked cotton ball on the “safe” side of a plastic trial arena and then evaluated the behaviors of the prey spiders. We used a mixture of Pardosa milvina and Rabidosa rabida as test spiders, with one group given a sugar-water treatment beforehand and the other group was given a green colored control cotton ball with filtered tap water (n=14 for both the sugar water treatment and control groups). The wolf spiders who were predisposed to the sugar water treatment were more likely to cross through their predator’s silk in order to gain access to the sugar water cotton ball than their counterparts who were not given a sugar water treatment prior. These results suggest the risk for predation of the wolf spider is not worth the benefits of the sugar water, unless a wolf spider has been allowed unlimited access to sugar water in advance. When a wolf spider who was allowed unlimited access to sugar water beforehand is presented with a risky situation, they will increase their risk-taking behaviors via crossing through a predator’s silk in order indulge in the sugar water. These results suggest the addictive properties of sugar spans across vertebrates and invertebrates, and potentially opens the door for a cost-efficient and ethically acceptable invertebrate model-organism for examining the risk-taking behaviors associated with addiction.
Divergent acute versus prolonged pharmacological GLP-1R responses in adult beta cell-selective β-arrestin 2 knockout mice
Authors: Bitsi Stavroula , Manchanda Yusman , ElEid Liliane , Mohamed Nimco , Hansen Ben , Suba Kinga , Rutter Guy A. , Salem Victoria , Jones Ben , Tomas Alejandra 
Published: May 2022

AbstractThe glucagon-like peptide-1 receptor (GLP-1R) is a major therapeutic target in type 2 diabetes (T2D) and obesity. Following activation, GLP-1Rs are rapidly desensitised by β-arrestins, scaffolding proteins that terminate G protein interactions but also act as independent signalling mediators. While GLP-1R interacts with β-arrestins 1 and 2, expression of the latter is greatly enhanced in beta cells, making this the most relevant isoform. Here, we have assessed in vivo glycaemic responses to the pharmacological GLP-1R agonist exendin-4 in adult beta cell-selective β-arrestin 2 knockout (KO) mice. Lean female and high-fat, high-sucrose-fed KO mice of both sexes displayed worse acute responses versus control littermates, an effect that was inverted 6 hours post-agonist injection, resulting in prolonged in vivo cell-cell connectivity in KO islets implanted in mouse eyes. Similar effects were observed for the clinically relevant semaglutide and tirzepatide but not with exendin-phe1, an agonist biased away from β-arrestin recruitment. Ex vivo acute cAMP was impaired, but overnight desensitisation was reduced in KO islets. The acute signalling defect was attributed to enhanced β-arrestin 1 and phosphodiesterase (PDE) 4 activity in the absence of β-arrestin 2, while the reduced desensitisation correlated with altered GLP-1R trafficking, involving impaired recycling and lysosomal targeting and increased trans-Golgi network (TGN) localisation and signalling, as well as reduced GLP-1R ubiquitination by the E3 ubiquitin ligase NEDD4. This study has unveiled fundamental aspects of the role of β-arrestin 2 in regulating pharmacological GLP-1R responses with direct application to the rational design of improved GLP-1R-targeting therapeutics.
Secondary reversion to sexual monomorphism associated with tissue-specific loss of doublesex expression
Authors: Gao Jian-jun , Barmina Olga , Thompson Ammon , Kim Bernard , Suvorov Anton , Tanaka Kohtaro , Watabe Hideaki , Toda Masanori J. , Chen Ji-Min , Katoh Takehiro K. , Kopp Artyom 
Published: May 2022

AbstractAnimal evolution is characterized by frequent turnover of sexually dimorphic traits – new sex- specific characters are gained, and some ancestral sex-specific characters are lost, in many lineages. In insects, sexual differentiation is predominantly cell-autonomous and depends on the expression of the doublesex (dsx) transcription factor. In most cases, cells that transcribe dsx have the potential to undergo sex-specific differentiation, while those that lack dsx expression do not. Consistent with this mode of development, comparative research has shown that the origin of new sex-specific traits can be associated with the origin of new spatial domains of dsx expression. In this report, we examine the opposite situation – a secondary loss of the sex comb, a male-specific grasping structure that develops on the front legs of some drosophilid species. We show that, while the origin of the sex comb is linked to an evolutionary gain of dsx expression in the leg, sex comb loss in a newly identified species of Lordiphosa (Drosophilidae) is associated with a secondary loss of dsx expression. We discuss how the developmental control of sexual dimorphism affects the mechanisms by which sex-specific traits can evolve.
enclone: precision clonotyping and analysis of immune receptors
Authors: Jaffe David B. , Shahi Payam , Adams Bruce A. , Chrisman Ashley M. , Finnegan Peter M. , Raman Nandhini , Royall Ariel E. , Tsai FuNien , Vollbrecht Thomas , Reyes Daniel S. , McDonnell Wyatt J. 
Published: May 2022

AbstractHalf a billion years of evolutionary battle forged the vertebrate adaptive immune system, an astonishingly versatile factory for molecules that can adapt to arbitrary attacks. The history of an individual encounter is chronicled within a clonotype: the descendants of a single fully rearranged adaptive immune cell. For B cells, reading this immune history for an individual remains a fundamental challenge of modern immunology. Identification of such clonotypes is a magnificently challenging problem for three reasons:The cell history is inferred rather than directly observed: the only available data are the sequences of V(D)J molecules occurring in a sample of cells.Each immune receptor is a pair of V(D)J molecules. Identifying these pairs at scale is a technological challenge and cannot be done with perfect accuracy—real samples are mixtures of cells and fragments thereof.These molecules can be intensely mutatedduring the optimization of the response to particular antigens, blurring distinctions between kindred molecules.It is thus impossible to determine clonotypes exactly. All solutions to this problem make a trade-off between sensitivity and specificity; useful solutions must address actual artifacts found in real data.We presentenclone1, a system for computing approximate clonotypes from single cell data, and demonstrate its use and value with the 10x Genomics Immune Profiling Solution. To test it, we generate data for 1.6 million individual B cells, from four humans, including deliberately enriched memory cells, to tax the algorithm and provide a resource for the community. We analytically determine the specificity ofenclone’s clonotyping algorithm, showing that on this dataset the probability of co-clonotyping two unrelated B cells is around 10−9. We prove that using only heavy chains increases the error rate by two orders of magnitude.enclonecomprises a comprehensive toolkit for the analysis and display of immune receptor data. It is ultra-fast, easy to install, has public source code, comes with public data, and is documented atbit.ly/enclone. It has three “flavors” of use: (1) as a command-line tool run from a terminal window, that yields visual output; (2) as a command-line tool that yields parseable output that can be fed to other programs; and (3) as a graphical version (GUI).
Why the architecture of environmental fluctuation matters for fitness
Authors: Park John S. , Felmy Anja 
Published: May 2022

AbstractThe physical environment provides the very stage upon which the eco-evolutionary play unfolds. How fluctuations in the environment affect demographic fitness is thus central to selection predictions, life history analyses, and viability of populations. Treatment of fluctuating environments typically leverages the mathematics of random variability. However, environmental fluctuations in nature are almost always combinations of random and non-random components. For example, some fluctuations contain feedbacks which generate autocorrelation (e.g.disturbances such as floods, fires, and hurricanes), while others are driven by geophysical forces that create fixed cyclicality (e.g.seasonal, tidal, and diel). Despite theoretical developments, the consideration of non-random characteristics of fluctuations is still rare in empirical work on natural populations, mostly due to convention and partially due to difficulties in measuring and analyzing timeseries of environmental fluctuations. We show why non-randomness matters for fitness. Using a simple demographic model, we systematically compare four major categories of fluctuating environments: stochastic, positively autoregressive, negatively autoregressive, and periodic with error (“Noisy Clock”). The architectures of fluctuations influence the fitness of structured populations even when the modelled environments only differ in the timing of fluctuations, and not in their overall frequency. Importantly, we highlight two quantitative mechanisms through which fitness depends on fluctuation architecture—the consecutiveness of deviations from the environmental mean, and Jensen’s Inequality acting on nonlinear biological parameters—both relevant features in virtually all populations inhabiting variable environments. Our goal is to argue that non-random structures of environmental variability should be more seriously considered in empirical work. Such an endeavor would tap into the rich diversity of variable environments in nature to expand our understanding of the commensurate diversity of population dynamics.
Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies
Authors: Bonatto Paese Christian Louis , Chang Ching-Fang , Kristeková Daniela , Brugmann Samantha A. 
Published: May 2022

AbstractCiliopathies represent a disease class characterized by a broad range of phenotypes including polycystic kidneys and skeletal anomalies. Ciliopathic skeletal phenotypes are among the most common and most difficult to treat due to a poor understanding of the pathological mechanisms leading to disease. Using an avian model (talpid2) for a human ciliopathy with skeletal anomalies (Orofaciodigital syndrome 14), we identified disruptions in the FGF23-PTH axis that resulted in reduced calcium uptake in the developing mandible and subsequent micrognathia. While pharmacological intervention with the FDA-approved pan-FGFR inhibitor AZD4547 alone rescued expression of the FGF target Sprouty2, it did not significantly rescue micrognathia. In contrast, treatment with a cocktail of AZD4547 and Teriparatide acetate, a PTH agonist and FDA-approved treatment for osteoporosis, resulted in a molecular, cellular, and phenotypic rescue of ciliopathic micrognathia in talpid2 mutants. Together, these data provide novel insight into pathological molecular mechanisms associated with ciliopathic skeletal phenotypes and a potential therapeutic strategy for a pleiotropic disease class with limited to no treatment options.Summary StatementTreatment options for ciliopathic phenotypes are very limited. Using an avian model, we report a novel molecular mechanism and potential therapeutic treatment for ciliopathic micrognathia.
Deceptive learning in histopathology
Authors: Shahamatdar Sahar , Saeed-Vafa Daryoush , Linsley Drew , Khalil Farah , Lovinger Katherine , Li Lester , McLeod Howard , Ramachandran Sohini , Serre Thomas 
Published: May 2022

AbstractDeep learning holds immense potential for histopathology, automating tasks that are simple for expert pathologists, and revealing novel biology for tasks that were previously considered difficult or impossible to solve by eye alone. However, the extent to which the visual strategies learned by deep learning models in histopathological analysis are trustworthy or not has yet to be systematically analyzed. In this work, we address this problem and discover new limits on the histopathological tasks for which deep learning models learn trustworthy versus deceptive solutions. While tasks that have been extensively studied in the field like tumor detection are reliable and trustworthy, recent advances demonstrating the ability to learn molecular profiling from hematoxylin and eosin (H&E) stained slides do not hold up to closer scrutiny. Our analysis framework represents a new approach in understanding the capabilities of deep learning models, which should be incorporated into the computational pathologists toolkit.
Formation of multiple flagella caused by a mutation of the flagellar rotor protein FliM inVibrio alginolyticus
Authors: Homma Michio , Takekawa Norihiro , Fujiwara Kazushi , Hao Yuxi , Onoue Yasuhiro , Kojima Seiji 
Published: May 2022

AbstractThe marine bacteriumVibrio alginolyticusforms only a single flagellum at the cell pole. InVibrio, two proteins (GTPase FlhF and ATPase FlhG) regulate flagellar number at the cell pole. We previously isolated a mutant strain characterized as NMB155 that forms multiple flagella despite the absence of mutations inflhFandflhG. NMB155 also exhibited straight swimming without a directional change in flagellar rotation. Whole-genome sequencing of NMB155 identified an E9K mutation in FliM that is a component of the C-ring in the flagellar rotor. Mutations in FliM result in defects in flagellar formation (fla) and flagellar rotation (cheormot); however, there are few reports indicating that FliM mutations increase the number of flagella. Here, we determined that the E9K mutation confers the multi-flagellar phenotype and also thechephenotype. The co-expression of wild-type FliM and FliM-E9K indicated that they were competitive in regard to determining the flagellar number. It had been shown that the ATPase activity of FlhG corresponds to the flagellar number. We observed that the ATPase activity of FlhG was increased by the addition of FliM but not by the addition of FliM-E9K. This indicates that the N-terminal region of FliM that includes the E9 residue interacts with FlhG to increase its ATPase activity, and the E9K mutation may inhibit this interaction. We concluded that FliM downregulate FlhG activity to inhibit the formation of additional flagella.ImportanceThe flagellar rotor generates a driving force to rotate the flagellum and is not involved in controlling the number of flagella inVibrio. However, we observed that the E9K mutation in the rotor protein FliM confers multiple flagella. Our findings reveal a novel regulatory mechanism controlling flagellar number.
The Free Fatty Acid-Binding Pocket is a Conserved Hallmark in Pathogenic β-Coronavirus Spike Proteins from SARS-CoV to Omicron
Authors: Toelzer Christine , Gupta Kapil , Yadav Sathish K.N. , Hodgson Lorna , Williamson Maia Kavanagh , Buzas Dora , Borucu Ufuk , Powers Kyle , Stenner Richard , Vasileiou Kate , Garzoni Frederic , Fitzgerald Daniel , Payré Christine , Lambeau Gérard , Davidson Andrew D. , Verkade Paul , Frank Martin , Berger Imre , Schaffitzel Christiane 
Published: May 2022

AbstractAs COVID-19 persists, severe acquired respiratory syndrome coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor-binding domain (RBD) comprises a free fatty acid (FFA)-binding pocket. FFA-binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2 and VOCs bind the essential FFA linoleic acid (LA), while binding is abolished by one mutation in common cold-causing HCoV-HKU1. In the SARS-CoV S structure, LA stabilizes the locked conformation while the open, infectious conformation is LA-free. Electron tomography of SARS-CoV-2 infected cells reveals that LA-treatment inhibits viral replication, resulting in fewer, deformed virions. Our results establish FFA-binding as a hallmark of pathogenic β-CoV infection and replication, highlighting potential antiviral strategies.One-Sentence SummaryFree fatty acid-binding is conserved in pathogenic β-coronavirus S proteins and suppresses viral infection and replication.
Targeted single-cell genomics reveals novel host adaptation strategies of the symbiotic bacteria Endozoicomonas in Acropora tenuis coral
Authors: Ide Keigo , Nishikawa Yohei , Maruyama Toru , Tsukada Yuko , Kogawa Masato , Takeda Hiroki , Ito Haruka , Wagatsuma Ryota , Miyaoka Rimi , Nakano Yoshikatsu , Kinjo Koji , Ito Michihiro , Hosokawa Masahito , Yura Kei , Suda Shoichiro , Takeyama Haruko 
Published: May 2022

AbstractEndozoicomonas bacteria symbiose with various marine organisms and are known to be beneficial for coral health. However, genome analysis of coral-associated Endozoicomonas has been limited owing to the difficulty in cultivation and metagenomic approach by contamination of host-derived sequences. In this study, we applied a novel single-cell genomics technique using droplet microfluidics to obtain single-cell amplified genome (SAGs) for coral-associated Endozoicomonas spp. genome. We obtained seven novel Endozoicomonas genomes from Acropora tenuis coral. These genomes revealed that Endozoicomonas bacteria played host-associated functions in host corals and had undergone independent host-adaptive evolution in different clades. These adaptive evolutions were mediated by host-derived eukaryotic-like genes, some of which were speculated to influence host immune mechanisms. These genes are speculated to enhance coral tolerance to environmental stresses. This study suggests the possibility of host adaptation of Endozoicomonas spp. in symbiosis with corals and their contribution to coral bleaching tolerance.
An intrinsic oscillator underlies visual navigation in ants
Authors: Clement Leo , Schwarz Sebastian , Wystrach Antoine 
Published: May 2022

AbstractControlling behavior implies a constant balance between exploration – to gather information – and exploitation – to use this information to reach one’s goal. However, how this tradeoff is achieved in navigating animals is unclear. Here we recorded the paths of two phylogenetically distant visually navigating ant species (Myrmecia croslandi and Iridomyrmex purpureus) using a trackball-treadmill directly in their habitat. We show that both species continuously produce regular lateral oscillations with bursts of forward movement when facing the general direction of travel, providing a remarkable tradeoff between visual exploration across directions and movement areas. This dynamical signature is conserved across navigational contexts but requires certain visual cues to be fully expressed. Rotational feedback regulates the extent of turns, but is not required to produce them, indicating that oscillations are generated intrinsically. Learnt visual information modulates the oscillation’s amplitudes to fit the task at hand in a continuous manner: an unfamiliar panorama enhances the amplitude of oscillations in both naïve and experienced ants, favoring visual exploration; while a learnt familiar panorama reduces them, favoring exploitation through. The observed dynamical signature readily emerges from a simple neural-circuit model of the insect’s conserved pre-motor area known as the lateral accessory lobe, endorsing oscillations as a core, ancestral way of moving in insects. We discuss the importance and evolution of self-generated behaviors and how such an oscillator has been exapted to various modalities, behaviors and way of moving.
Metabolic size scaling reflects growth performance effects on age-size relationships in mussels (Mytilus galloprovincialis)
Authors: Ibarrola Irrintzi , Arranz Kristina , Markaide Pablo , Navarro Enrique 
Published: May 2022

AbstractBody-size scaling of metabolic rate in animals is typically allometric, with mass exponents that vary to reflect differences in the physiological status of organisms of both endogenous and environmental origin. Regarding the intraspecific analysis of this relationship in bivalve molluscs, one important source of metabolic variation comes from the large inter-individual differences in growth performance characteristic of this group. In the present study, we aimed to address the association of growth rate differences recorded among individual mussels (Mytilus galloprovincialis) with variable levels of the standard metabolic rate (SMR) resulting in growth-dependent shift in size scaling relationships. SMR was measured in mussels of different sizes and allometric functions fitting SMR vs. body-mass relationships were compared both inter- and intra-individually. The results revealed a metabolic component (the overhead of growth) attributable to the differential costs of maintenance of feeding and digestion structures between fast and slow growers; these costs were estimated to amount to a 3% increase in SMR per unit of increment in the weight specific growth rate. Scaling exponents computed for intraindividual SMR vs body-mass relationships had a common value b = 0.79 (~ ¾); however, when metabolic effects caused by differential growth were discounted, this value declined to 0.67 (= ⅔), characteristic of surface dependent processes. This last value of the scaling exponent was also recorded for the interindividual relationships of both SMR and RMR after long-lasting maintenance of mussels under optimal uniform conditions in the laboratory. The above results were interpreted based on the metabolic level boundary (MLB) hypothesis.