bluuebunny/crossref_metadata_2025_split huggingface dataset:
A computational model for individual differences in non-reinforced learning for individual items
Authors: Salomon Tom , Itzkovitch Alon , Daw Nathaniel D. , Schonberg Tom 
Published: March 2022

AbstractCue-Approach Training (CAT) is a paradigm that enhances preferences without external reinforcmeents, suggesting a potential role for internal learning processes. Here, we developed a novel Bayesian computational model to quantify anticipatory response patterns during the training phase of CAT. This phase includes individual items and thus this marker is potentially of internal learning signals at the item level. Our model, fitted to meta-analysis data from 29 prior CAT experiments, was able to predict individual differences in non-reinforced preference changes using a key computational marker. Crucially, two new experiments manipulated the training procedure to influence the model’s predicted learning marker. As predicted and preregistered, the manipulation successfully induced differential preference changes, supporting a causal role of our model. These findings demonstrate powerful potential of our computational framework for investigating intrinsic learning processes. This framework could be used to predict preference changes and opens new avenues for understanding intrinsic motivation and decision-making.TeaserBayesian modeling of response time predicts individual differences in non reinforced preference change.
Syrah, a Slide-seqV2 pipeline augmentation
Authors: Brewster C.E. , Mann F.G. , Benham-Pyle B.W. , Sánchez Alvarado A. 
Published: March 2022

AbstractSpatial transcriptomic techniques such as Slide-seqV2 uncover novel relationships and interactions between cell types by coupling gene expression and spatial data. Here we discuss two unexpected sources of error in Slide-seqV2 data, one physical and one computational. To address this we present an analysis pipeline augmentation, Syrah, which corrects for these errors and show that it improves both data quantity and quality over the standard pipeline alone or in combination with additional sequencing.
Planarians employ diverse and dynamic stem cell microenvironments to support whole-body regeneration
Authors: Benham-Pyle Blair W. , Mann Frederick G. , Brewster Carolyn E. , Dewars Enya R. , Vuu Dung M. , Nowotarski Stephanie H. , Guerrero-Hernández Carlos , Malloy Seth , Hall Kate E. , Maddera Lucinda E. , Chen Shiyuan , Morrison Jason A. , McKinney Sean A. , Slaughter Brian D. , Perera Anoja , Alvarado Alejandro Sánchez 
Published: March 2022

SUMMARYStem cells enable regeneration by self-renewing and differentiating as instructed by a local microenvironment called a niche1–3. In most cases, the repair or replacement of tissues is fueled by tissue-specific or lineage-restricted stem cells that proliferate in response to local injury and apoptosis4–11. However, in organisms that regenerate using abundant adult pluripotent stem cells, the stem cell niches that support tissue repair have not been identified or characterized. Since these adult pluripotent stem cells are often more widely distributed and plentiful than lineage-restricted stem cells of other organisms, defining their microenvironments may uncover alternative forms of stem cell regulation12–14. Here we used unbiased spatial transcriptomics to define the cellular and molecular environments that support pluripotency in the highly regenerative freshwater planarianSchmidtea mediterranea. We determined that stem cells associate with a diverse collection of differentiated cell types, and these associations are highly dynamic during regeneration. We explored associations with two distinct cell types: secretory cells we term ‘hecatonoblasts,’ and intestinal cells. While both cell types regulate stem cell proliferation, their spatial relationships to stem cells defy the concept of a single regenerative niche. Thus, the planarian stem cell pool is likely maintained by a dynamic collection of distinct microenvironments that cooperatively power whole-body regeneration.
Eusocial insect queens show costs of reproduction and transcriptomic signatures of reduced longevity
Authors: Collins David H. , Prince David C. , Donelan Jenny L. , Chapman Tracey , Bourke Andrew F. G. 
Published: March 2022

ABSTRACTEusocial insect queens have been suggested to be counter-examples to the standard evolutionary theory of ageing through lacking costs of reproduction. Using the bumblebee (Bombus terrestris), we tested this hypothesis experimentally against the alternative that costs of reproduction exist in eusocial insect queens, but are latent, resulting in the positive fecundity-longevity relationship typically found in unmanipulated queens. We experimentally increased queens’ costs of reproduction by removing their eggs, which causes queens to increase their egg-laying rate. Treatment queens had significantly reduced longevity relative to control queens whose egg-laying rate was not increased. In addition, treatment and control queens differed in age-related gene expression based on mRNA-seq in both their overall expression profiles and the expression of ageing-related genes. Remarkably, this occurred principally with respect to relative age, not chronological age. These results provide the first simultaneously phenotypic and transcriptomic experimental evidence of costs of reproduction in queens of eusocial insects and suggest how the genetic pathways underpinning ageing might become remodelled during eusocial evolution.
A Tailored Approach To Study Legionella Infection Using Lattice Light Sheet Microscope (LLSM)
Authors: Yi Xiyu , Miao Haichao , Lo Jacky Kai-Yin , Elsheikh Maher M. , Lee Tek Hyung , Jiang Chenfanfu , Zhang Yuliang , Segelke Brent W. , Overton K. Wesley , Bremer Peer-Timo , Laurence Ted A. 
Published: March 2022

AbstractLegionella is a genus of ubiquitous environmental pathogens found in freshwater systems, moist soil, and composted materials. More than four decades of Legionella research has provided important insights into Legionella pathogenesis [1]. Although standard commercial microscopes have led to significant advances in understanding Legionella pathogenesis [2,3], great potential exists in the deployment of more advanced imaging techniques to provide additional insights. The Lattice Light Sheet Microscope (LLSM) is a recently developed microscope for 4D live cell imaging with high resolution and minimum photo-damage [4]. We built a LLSM with an improved version for the optical layout with two path-stretching mirror sets and a novel Reconfigurable Galvanometer Scanner (RGS) module to improve the reproducibility and reliability of the alignment and maintenance of the LLSM. We commissioned this LLSM to study Legionella pneumophila infection with a tailored workflow designed over instrumentation, experiments, and data processing methods. Our results indicate that Legionella pneumophila infection is correlated with a series of morphological signatures such as smoothness, migration pattern and polarity both statistically and dynamically. Our work demonstrates the benefits of using LLSM for studying long-term questions in bacterial infection. Our free-for-use modifications and workflow designs on the use of LLSM system contributes to the adoption and promotion of the state-of-the-art LLSM technology for both academic and commercial applications.
Cost-effectiveness of antigen testing for ending COVID-19 isolation
Authors: Maya Sigal , Kahn James G. 
Published: March 2022

AbstractBackgroundThe Omicron variant of SARS-CoV-2 led to a steep rise in transmissions. Recently, as public tolerance for isolation abated, CDC guidance on duration of at-home isolation of COVID-19 cases was shortened to five days if no symptoms, with no lab test requirement, despite more cautious approaches advocated by other federal experts.MethodsWe conducted a decision tree analysis of alternative protocols for ending COVID-19 isolation, estimating net costs (direct and productivity), secondary infections, and incremental cost-effectiveness ratios. Sensitivity analyses assessed the impact of input uncertainty.ResultsPer 100 individuals, five-day isolation had 23 predicted secondary infections and a net cost of $33,000. Symptom check on day five (CDC guidance) yielded a 23% decrease in secondary infections (to 17.8), with a net cost of $45,000. Antigen testing on day six yielded 2.9 secondary infections and $63,000 in net costs. This protocol, compared to the next best protocol of antigen testing on day five of a maximum eight-day isolation, cost an additional $1,300 per secondary infection averted. Antigen or polymerase chain reaction testing on day five were dominated (more expensive and less effective) versus antigen testing on day six. Results were qualitatively robust to uncertainty in key inputs.ConclusionsA six-day isolation with antigen testing to confirm the absence of contagious virus appears the most effective and cost-effective de-isolation protocol to shorten at-home isolation of individuals with COVID-19.
Social information-mediated population dynamics in non-grouping prey
Authors: Tóth Zoltán , Csöppü Gabriella 
Published: March 2022

AbstractInadvertent social information (ISI) use, i.e., the exploitation of social cues including the presence and behaviour of others, has been predicted to mediate population-level processes even in the absence of cohesive grouping. However, we know little about how such effects may arise when the prey population lacks social structure beyond the spatiotemporal autocorrelation originating from the random movement of individuals. In this study, we built an individual-based model where predator avoidance behaviour could spread among randomly moving prey through the network of nearby observers. We qualitatively assessed how ISI use may affect prey population size when cue detection was associated with different probabilities and fitness costs, and characterised the structural properties of the emerging detection networks that would provide pathways for information spread in prey. We found that ISI use was among the most influential model parameters affecting prey abundance and increased equilibrium population sizes in most examined scenarios. Moreover, it could substantially contribute to population survival under high predation pressure, but this effect strongly depended on the level of predator detection ability. When prey exploited social cues in the presence of high predation risk, the observed detection networks consisted of a large number of connected components with small sizes and small ego networks; this resulted in efficient information spread among connected individuals in the detection networks. Our study provides hypothetical mechanisms about how temporary local densities may allow information diffusion about predation threats among conspecifics and facilitate population stability and persistence in non-grouping animals.Significance StatementThe exploitation of inadvertently produced social cues may not only modify individual behaviour but also fundamentally influence population dynamics and species interactions. Using an individual-based model, we investigated how the detection and spread of adaptive antipredator behaviour may cascade to changes in the demographic performance of randomly moving (i.e., non-grouping) prey. We found that social information use contributed to population stability and persistence by reducing predation-related per capita mortality and raising equilibrium population sizes when predator detection ability reached a sufficient level. We also showed that temporary detection networks had structural properties that allowed efficient information spread among prey under high predation pressure. Our work represents a general modelling approach that could be adapted to specific predator-prey systems and scrutinize how temporary local densities allow dynamic information diffusion about predation threats and facilitate population stability in non-grouping animals.
Estimating the time structure of descending activation that generates movements at different speeds
Authors: Ramadan Rachid , Hummert Cora , Jokeit Jean-Stephane , Schöner Gregor 
Published: March 2022

In targeted movements of the hand, descending activation patterns must not only generate muscle activation, but must also adjust spinal reflexes from stabilizing the initial to stabilizing the final postural state. We estimate descending activation patterns that change minimally while generating a targeted movement within a given movement time based on a model of the biomechanics, muscle dynamics, and the stretch reflex. The estimated descending activation patterns predict human movement trajectories quite well. Their temporal structure varies across workspace and with movement speed, from monotonic profiles for slow movements to non-monotonic profiles for fast movements. Descending activation patterns at different speeds thus do not result from a not mere rescaling of invariant templates, but reflect varying needs to compensate for interaction torques and muscle dynamics. The virtual attractor trajectories, on which active muscle torques are zero, lie within reachable workspace and are largely invariant movements when represented in end-effector coordinates. Their temporal structure along movement direction changes from linear ramps to ''N-shaped'' profiles with increasing movement speed.
The S. cerevisiae m6A-reader Pho92 impacts meiotic recombination by controlling key methylated transcripts
Authors: Scutenaire Jérémy , Plassard Damien , Matelot Mélody , Villa Tommaso , Zumsteg Julie , Libri Domenico , Séraphin Bertrand 
Published: March 2022

SUMMARYN6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNAs, participates in the post-transcriptional control of gene expression. In Saccharomyces cerevisiae, m6A is only found during meiosis. Although the deletion of the m6A- methyltransferase Ime4 impairs this process, the molecular impact of m6A on gene expression remains ill defined. Here we investigated the function of the budding yeast m6A reader Pho92. We found that Pho92 is specifically expressed during meiosis and impacts meiotic progression. We used high-throughput RNA sequencing and mapping of Pho92-binding sites following UV-crosslinking to show that Pho92 is recruited to specific mRNAs in an m6A-dependent manner during the meiotic prophase, preceding their down-regulation. Strikingly, point mutations altering m6A sites in mRNAs targeted by Pho92 are sufficient to delay their down-regulation and, in one case, to impact meiotic progression. Altogether, our results indicate that Pho92 facilitate the meiotic progression by accelerating the down-regulation of timely-regulated mRNAs during meiotic recombination.
Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits
Authors: Li Ziru , Bowers Emily , Zhu Junxiong , Yu Hui , Hardij Julie , Bagchi Devika P. , Mori Hiroyuki , Lewis Kenneth T. , Granger Katrina , Schill Rebecca L. , Romanelli Steven M. , Abrishami Simin , Hankenson Kurt D. , Singer Kanakadurga , Rosen Clifford J. , MacDougald Ormond A. 
Published: March 2022

SummaryTo investigate roles for bone marrow adipocyte (BMAd) lipolysis in bone homeostasis, we created a BMAd-specific Cre mouse model in which we knocked out adipose triglyceride lipase (ATGL, Pnpla2). BMAd-Pnpla2-/- mice have impaired BMAd lipolysis, and increased size and number of BMAds at baseline. Although energy from BMAd lipid stores is largely dispensable when mice are fed ad libitum, BMAd lipolysis is necessary to maintain myelopoiesis and bone mass under caloric restriction. BMAd-specific Pnpla2 deficiency compounds the effects of caloric restriction on loss of trabecular bone, likely due to impaired osteoblast expression of collagen genes and reduced osteoid synthesis. RNA sequencing analysis of bone marrow adipose tissue reveals that caloric restriction induces dramatic elevations in extracellular matrix organization and skeletal development genes, and energy from BMAd is required for these adaptations. BMAd-derived energy supply is also required for bone regeneration upon injury, and maintenance of bone mass with cold exposure.
Confrontation of AlphaFold2 models with cryo-EM and crystal structures enlightens alternate geometries of the CYP102A1 multidomain protein
Authors: Urban Philippe , Pompon Denis 
Published: March 2022

AbstractLarge range structural dynamics plays a critical role for the function of electron transfer proteins. This information is generally not available from crystallographic structures, while cryo-electron microscopy (cryo-EM) can provide some elements but frequently with a degraded spatial resolution. Recently, AlphaFold-based structural modelling was extended to the prediction of protein complexes. In this work, bacterial CYP102A1 from Priestia megaterium was used as a test case to evaluate the capability of AlphaFold2 to predict alternative structures critical for catalysis. CYP102A1 monooxygenase, a NADPH-supported fatty acid hydroxylase, works as a soluble homodimer, each monomer harboring two flavins (FAD and FMN) and one heme cofactors. Large conformational changes are required during catalytic cycle to allow successive electron transfers from FAD to FMN and finally heme iron. We used the recently released AlphaFold2_advanced notebook (AF2A), to predict the possible alternate conformations supporting electron transfers in CYP102A1 homodimer. Challenging AF2A-derived models with previously reported experimental data revealed an unforeseen domain connectivity of the diflavin reductase part of the enzyme. Intermolecular crossed complex constitutes a novel type of structural organization never previously described. The predicted formation within the dimer of a stable complex between the heme containing domains was challenged and found consistent with uninterpreted features of reported crystallographic structures and cryo-EM imaging. The particularly efficient CYP102A1 catalytic mechanism was revisited to the light of the new evidenced connectivity in which the FMN-binding domain of each monomer oscillates on themselves to alternatively receive and transfer electrons without needing large structural change in the dimer. Such model was found explanatory for previously contradictory reported biochemical data. Possibility to mimic CYP102A1 structural organization into bicomponent eukaryotic P450 systems was evaluated by designing and modeling in silico synthetic reductase domains built from composite sequence segments from P. megaterium and human origins. More generally, this work illustrates how the ability of AF2A to predict alternate complex structures can enlighten and explain conformational changes critical for bio-assemblies.
Stability and expression of SARS-CoV-2 spike-protein mutations
Authors: Bæk Kristoffer T. , Mehra Rukmankesh , Kepp Kasper P. 
Published: March 2022

AbstractProtein fold stability likely plays a role in SARS-CoV-2 S-protein evolution, together with ACE2 binding and antibody evasion. While few thermodynamic stability data are available for S-protein mutants, many systematic experimental data exist for their expression. In this paper, we explore whether such expression levels relate to the thermodynamic stability of the mutants. We studied mutation-induced SARS-CoV-2 S-protein fold stability, as computed by three very distinct methods and eight different protein structures to account for method- and structure-dependencies. For all methods and structures used (24 comparisons), computed stability changes correlate significantly (99% confidence level) with experimental yeast expression from the literature, such that higher expression is associated with relatively higher fold stability. Also significant, albeit weaker, correlations were seen for ACE2 binding. The effect of thermodynamic fold stability may be direct or a correlate of amino acid or site properties, notably the solvent exposure of the site. Correlation between computed stability and experimental expression and ACE2 binding suggests that functional properties of the SARS-CoV-2 S-protein mutant space are largely determined by a few simple features, due to underlying correlations. Our study lends promise to the development of computational tools that may ideally aid in understanding and predicting SARS-CoV-2 S-protein evolution.
The permeation of potassium ions through the lipid scrambling path of the membrane protein nhTMEM16
Authors: Cheng Xiaolu , Khelashvili George , Weinstein Harel 
Published: March 2022

AbstractThe TMEM16 family of transmembrane proteins includes Ca2+-activated phospholipid scramblases (PLS) that can also function as non-selective ion channels. Extensive structural and functional studies have established that a membrane-exposed hydrophilic groove in TMEM16 PLS can serve as a translocation pathway for lipids. However, it is still unclear how the TMEM16 PLS conduct ions. A “protein-delimited pore” model suggests that ions are translocated through a narrow opening of the groove region, which is not sufficiently wide to allow lipid movement, whereas a “proteolipid pore” model envisions ions and lipids translocating through an open conformation of the groove. We investigated the dynamic path of potassium ion (K+) translocation that occurs when an open groove state of nhTMEM16 is obtained from long atomistic molecular dynamics (MD) simulations and calculated the free energy profile of the ion movement through the groove with umbrella sampling methodology. The free energy profile identifies effects of specific interactions along the K+ permeation path. The same calculations were performed to investigate ion permeation through a groove closed to lipid permeation in the nhTMEM16 L302A mutant which exhibits a stable conformation of the groove that does not permit lipid scrambling. Our results identify structural and energy parameters that enable K+ permeation and suggest that the presence of lipids in the nhTMEM16 groove observed in the simulations during scrambling or in/out diffusion, affect the efficiency of K+ permeation to various extents.
Metagenomics Study of Bacterial Communities from Yamuna River water of city of Taj, Agra
Authors: Raghav Nupur , Saraswat Pooja , Srivastava Janendra Nath , Ranjan Rajiv 
Published: March 2022

ABSTRACTYamuna river water of Agra city is heavily contaminated with toxic pollutants including heavy metal that causes severe damage to ecological and social aspects. At present, the direct use of river water for the purpose of drinking causes severe hazards due to anthropogenic activities causing environmental pollution in rivers. In present study, Yamuna River water was collected from three different sites of Agra city. Various physico-chemical parameters were estimated by following the standard methods of APHA and the concentration of heavy metals were measured using Atomic Absorption Spectrophotometer (AAS). In case of physico-chemical parameters characterization, the obtained values were extremely above the permissible limits. On account of the research work; the Yamuna river water samples contains heavy metal concentrations (Cadmium, Chromium, Copper, Lead and Nickel) above the desirable and admissible levels except for Zinc. During analysis of non-culturable bacteria a substantial bacterial diversity was observed in the Yamuna river water samples collected from different sites. The water samples were subjected to metagenomic analysis using Illumina platform which revealed that Proteobacteria (phylum), Betaproteobacteria (class), Burkholderiales (order), Comamonadaceae (family),Hydrogenophaga(genus) andChloroflexi bacterium OLB 14(species) were found as the most dominant bacterial taxonomic abundance in the river water samples. The presence of such bacterial communities in water indicates the availability of pollutants and suggests the futuristic use in the field of bioremediation.