bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual beliefs about temporal continuity explain variation of perceptual biases
Authors: Glasauer Stefan , Shi Zhuanghua 
Published: July 2021

AbstractPerception of magnitudes such as duration or distance is often found to be systematically biased. The biases, which result from incorporating prior knowledge in the perceptual process, can vary considerably between individuals. The variations are commonly attributed to differences in sensory precision and reliance on priors. However, another factor not considered so far is the implicit belief about how successive sensory stimuli are generated: independently from each other or with certain temporal continuity. The main types of explanatory models proposed so far – static or iterative – mirror this distinction but cannot adequately explain individual biases. Here we propose a new unifying model that explains individual variation as combination of sensory precision and beliefs about temporal continuity and predicts the experimentally found changes in biases when altering temporal continuity. Thus, according to the model, individual differences in perception depend on beliefs about how stimuli are generated in the world.
A Structure-based B-cell Epitope Prediction Model Through Combing Local and Global Features
Authors: Lu Shuai , Li Yuguang , Ma Qiang , Nan Xiaofei , Zhang Shoutao 
Published: July 2021

ABSTRACTB-cell epitopes (BCEs) are a set of specific sites on the surface of an antigen that binds to an antibody produced by B-cell. The recognition of BCEs is a major challenge for drug design and vaccines development. Compared with experimental methods, computational approaches have strong potential for BCEs prediction at much lower cost. Moreover, most of the currently methods focus on using local information around target residue without taking the global information of the whole antigen sequence into consideration. We propose a novel deep leaning method through combing local features and global features for BCEs prediction. In our model, two parallel modules are built to extract local and global features from the antigen separately. For local features, we use Graph Convolutional Networks(GCNs) to capture information of spatial neighbors of a target residue. For global features, Attention-Based Bidirectional Long Short-Term Memory(Att-BLSTM) networks are applied to extract information from the whole antigen sequence. Then the local and global features are combined to predict BCEs. The experiments show that the proposed method achieves superior performance over the state-of-the-art BCEs prediction methods on benchmark datasets. Also, we compare the performance differences between data with or without global features. The experimental results show that global features play an important role in BCEs prediction. Our detailed case study on the BCEs prediction for SARS-Cov-2 receptor binding domain confirms that our method is effective for predicting and clustering true BCEs.
Multiple lines of evidence combine to understand tree species coexistence
Authors: McNickle Gordon G. , Ritzi Morgan V. , Blackstone Kliffi M.S. , Couture John J. , Nelson Taylor , Hardiman Brady S. , Montague Madeline S. , Jacobs Douglass F. 
Published: July 2021

ABSTRACTUnderstanding drivers of species coexistence is a central challenge in ecology (1,2). Coexistence cannot be observed directly, and while species co-occurrence in time and space is necessary for coexistence, it is not sufficient to prove coexistence (3,4). Species exclusion from a region is potentially observable, but can take decades to occur, and still might just occur stochastically (5,6). Thus, ecologists generally use theory to identify indirect observations that are indicative of mechanisms driving coexistence or exclusion (7–9). Various methods have been developed to indirectly infer coexistence, each of which requires different data, none of which are usually conclusive on their own, and are not typically combined (e.g. (9–12)). Here, we combine three different approaches which are normally used in isolation to build a case about a lack of coexistence of multiple hardwood species. Importantly, though each method has its flaws, we find that all three point to the same conclusion which strengthens the case for a lack of coexistence. First, in an experimental planting of three mature tree species we found no relationship between productivity and species diversity, which has been hypothesized to occur due to a lack of niche differences among species. Second, we used modern coexistence theory to calculate niche and fitness differences for each pair of species, which confirmed the high niche overlap among species and competitive dominance of one species. Third, we used the United States Department of Agriculture Forest Inventory and Analysis data to examine co-occurrence patterns of our species across thousands of natural forest stands and found that, these three species were distributed randomly throughout the USA, and do not significantly co-occur as would be expected if coexistence occurred naturally. Given that these independent methods agree; we take this as strong evidence about a lack of coexistence.
Parallel processing by distinct classes of principal neurons in the olfactory cortex
Authors: Nagappan Shivathmihai , Franks Kevin M. 
Published: July 2021

SUMMARYUnderstanding the specific roles that different neuron types play within a neural circuit is essential for understanding what that circuit does and how it does it. Primary olfactory (piriform, PCx) cortex contains two main types of principal neurons: semilunar (SL) and pyramidal (PYR). SLs and PYRs have different morphologies, connectivity, biophysical properties, and downstream projections, predicting distinct roles in cortical odor processing. The prevailing model is that odor processing in PCx occurs in two stages, where SLs are the primary recipients of olfactory bulb (OB) input, and PYRs receive and transform information from SLs. Here we recorded from opto-genetically-identified SLs and PYRs in awake, head-fixed mice. We found differences in SL and PYR odor-evoked activity that reflect their different connectivity profiles. But SL responses did not precede PYR responses and suppressing SL activity had little effect on PYR odor responses. These results suggest that SLs and PYRs form parallel odor processing channels.
Consistent coordination patterns provide near perfect behavior decoding in a comprehensive motor program for insect flight
Authors: Putney Joy , Angjelichinoski Marko , Ravier Robert , Ferrari Silvia , Tarokh Vahid , Sponberg Simon 
Published: July 2021

AbstractPatterns of motor activity can be used to decode behavior state. Precise spike timing encoding is present in many motor systems, but is not frequently utilized to decode behavior or to examine how coordination is achieved across many motor units. Testing whether the same coordinated sets of muscles control different movements is difficult without a complete motor representation at the level of the currency of control – action potentials. Here, we demonstrate nearly perfect decoding of six hawk moth flight behaviors elicited in response to wide-field drifting visual stimuli about the flight axes – pitch, roll, and yaw – using a comprehensive, spike-resolved motor program and a simple linear decoding pipeline. A complex decoding scheme is not necessary, even if the functional patterns of control are nonlinear. We show that muscle covariation present in one pair of visual stimulus conditions can be used to decode behavior in a different pair of visual stimulus conditions, indicating the presence of conserved muscle coordination patterns at the level of motor neuronal timings in functionally distinct behaviors. We also demonstrate that as few as half the muscles can be used to retain decoding performance, linking coordination to redundancy in encoding, if not function, across the entire moth flight motor program.
Structural insight into the dual function of LbpB in mediating Neisserial pathogenesis
Authors: Yadav Ravi , Govindan Srinivas , Daczkowski Courtney , Mesecar Andrew , Chakravarthy Srinivas , Noinaj Nicholas 
Published: July 2021

AbstractLactoferrin binding protein B (LbpB) is a lipoprotein present on the surface of Neisseria that has been postulated to serve dual functions during pathogenesis in both iron acquisition from lactoferrin, and in providing protection against the cationic antimicrobial peptide lactoferricin. Here, we present the structures of LbpB from N. meningitidis and N. gonorrhoeae in complex with human holo-lactoferrin, forming a 1:1 complex and confirmed by SEC-SAXS. LbpB consists of N- and C-lobes with the N-lobe interacting extensively with the C-lobe of lactoferrin. Our structures provides insight into LbpB’s preference towards holo-lactoferrin, and our mutagenesis and binding studies show that lactoferrin and lactoferricin bind independently. Our studies provide the molecular details for how LbpB serves to capture and preserve lactoferrin in an iron-bound state for delivery to the membrane transporter LbpA for iron piracy, and as an antimicrobial peptide sink to evade host immune defenses.
Conformational dynamics during misincorporation and mismatch extension defined using a DNA polymerase with a fluorescent artificial amino acid
Authors: Dangerfield Tyler L. , Kirmizialtin Serdal , Johnson Kenneth A. 
Published: July 2021

AbstractHigh-fidelity DNA polymerases select the correct nucleotide over the structurally similar incorrect nucleotides with extremely high specificity while maintaining fast rates of incorporation. Previous analysis revealed the conformational dynamics and complete kinetic pathway governing correct nucleotide incorporation using a high-fidelity DNA polymerase variant containing a fluorescent unnatural amino acid. Here we extend this analysis to investigate the kinetics of nucleotide misincorporation and mismatch extension. We report the specificity constants for all possible misincorporations and characterize the conformational dynamics of the enzyme during misincorporation and mismatch extension. We present free energy profiles based on the kinetic measurements and discuss the effect of different steps on specificity. During mismatch incorporation and subsequent extension (with the correct nucleotide), the rates of the conformational change and chemistry are both greatly reduced. The nucleotide dissociation rate, however, increases to greatly exceed the rate of chemistry. To investigate the structural basis for discrimination against mismatched nucleotides, we performed all atom molecular dynamics simulations on complexes with either the correct or mismatched nucleotide bound at the polymerase active site. We show that the closed form of the enzyme with a mismatch bound is greatly destabilized due to weaker interactions with active site residues, non-ideal base pairing, and a large increase in the distance from the 3’-OH group of the primer strand to the α-phosphate of the incoming nucleotide, explaining the reduced rates of misincorporation. The observed kinetic and structural mechanisms governing nucleotide misincorporation reveal the general principles likely applicable to other high fidelity DNA polymerases.
A theoretical model of mitochondrial ATP synthase deficiencies. The role of mitochondrial carriers
Authors: Mazat Jean-Pierre , Devin Anne , Yoboue Edgar , Ransac Stéphane 
Published: July 2021

AbstractThe m.8993T>G mutation of the mitochondrialMT-ATP6gene is associated with NARP syndrome (Neuropathy, Ataxia and Retinitis Pigmentosa). The equivalent point mutation introduced in yeastSaccharomyces cerevisiaemitochondrial DNA considerably reduced the activity of ATP synthase and of cytochrome-c-oxidase preventing yeast growth on oxidative substrates. The over-expression of the mitochondrial oxodicarboxylate carrier (Odc1p) is able to rescue the growth on oxidative substrate by increasing the substrate-level phosphorylation of ADP coupled to conversion ofα-ketoglutarate (AKG) into succinate with an increase in Complex IV activity. Previous studies showed that equivalent point mutations in ATP synthase behave similarly and can be rescued by Odc1p overexpression and/or uncoupler of OXPHOS from ATP synthesis. In order to better understand the mechanism of ATP synthase mutation bypass, we developed a core model of mitochondrial metabolism based on AKG as respiratory substrate. We describe the different possible metabolite output and the ATP/O ratio values as a function of ATP synthase inhibition.
Host-symbiont population genomics provide insights into partner fidelity, transmission mode and habitat adaptation in deep-sea hydrothermal vent snails
Authors: Breusing Corinna , Genetti Maximilian , Russell Shelbi L. , Corbett-Detig Russell B. , Beinart Roxanne A. 
Published: July 2021

AbstractSymbiont specificity, both at the phylotype and strain level, can have profound consequences for host ecology and evolution. However, except for insights from a few model symbiosis systems, the degree of partner fidelity and the influence of host versus environmental factors on symbiont composition are still poorly understood. Nutritional symbioses between invertebrate animals and chemosynthetic bacteria at deep-sea hydrothermal vents are examples of relatively selective associations, where hosts affiliate only with particular, environmentally acquired phylotypes of gammaproteobacterial or campylobacterial symbionts. In hydrothermal vent snails of the sister genera Alviniconcha and Ifremeria this phylotype specificity has been shown to play a role in habitat distribution and partitioning among different holobiont species. However, it is currently unknown if fidelity goes beyond species level associations that might influence genetic structuring, connectivity and habitat adaptation of holobiont populations. We used metagenomic analyses to assess sequence variation in hosts and symbionts and identify correlations with geographic and environmental factors. Our analyses indicate that host populations are not differentiated across a ~800 km gradient, while symbiont populations are clearly structured between vent locations due to a combination of neutral and selective processes. Overall, these results suggest that host individuals flexibly associate with locally adapted strains of their specific symbiont phylotypes, which supports a long-standing but untested paradigm of the benefits of horizontal transmission. Strain flexibility in these snails likely enables host populations to exploit a range of habitat conditions, which might favor wide-spread genetic connectivity and ecological resilience unless physical dispersal barriers are present.Significance StatementSymbiont composition in horizontally transmitted symbioses is influenced by a combination of host genetics, environmental conditions and geographic barriers. Yet the relative importance of these factors and the effects of adaptive versus neutral evolutionary forces on symbiont population structure remain unknown in the majority of marine symbioses. To address these questions, we applied population genomic approaches in four species of deep-sea hydrothermal vent snails that live in obligate association with chemosynthetic bacteria. Our analyses show that host genetics plays a minor role compared to environment for symbiont strain composition despite specificity to symbiont species and corroborate a long-standing hypothesis that vent invertebrates affiliate with locally adapted symbiont strains to cope with the variable habitat conditions characterizing hydrothermal vents.
Divergence in dimerization and activity of primate APOBEC3C
Authors: Gaba Amit , Hix Mark A. , Suhail Sana , Flath Ben , Boysan Brock , Williams Danielle R. , Pelletier Tomas , Emerman Michael , Morcos Faruck , Cisneros G. Andrés , Chelico Linda 
Published: July 2021

AbstractThe APOBEC3 (A3) family of single-stranded DNA cytidine deaminases are host restriction factors that inhibit lentiviruses, such as HIV-1, in the absence of the Vif protein that causes their degradation. Deamination of cytidine in HIV-1 (-)DNA forms uracil that causes inactivating mutations when uracil is used as a template for (+)DNA synthesis. For APOBEC3C (A3C), the chimpanzee and gorilla orthologues are more active than human A3C, and the Old World Monkey A3C from rhesus macaque (rh) is not active against HIV-1. Multiple integrated analyses determined why rhA3C was not active against HIV-1 and how to increase this activity. Biochemical, virological, and coevolutionary analyses combined with molecular dynamics simulations showed that the key amino acids needed to promote rhA3C antiviral activity also promoted dimerization. Although rhA3C shares a similar dimer interface with hominid A3C, the key amino acid contacts were different. Overall, our results determine the basis for why rhA3C is less active than human A3C, establish the amino acid network for dimerization and increased activity, and track the loss and gain of A3C antiviral activity in primates. The coevolutionary analysis of the A3C dimerization interface provides a basis from which to analyze dimerization interfaces of other A3 family members.
Substrate, temperature, and geographical patterns among nearly 2,000 natural yeast isolates
Authors: Spurley William J. , Fisher Kaitlin J. , Langdon Quinn K. , Buh Kelly V. , Jarzyna Martin , Haase Max A. B. , Sylvester Kayla , Moriarty Ryan V. , Rodriguez Daniel , Sheddan Angela , Wright Sarah , Sorlie Lisa , Hulfachor Amanda Beth , Opulente Dana A. , Hittinger Chris Todd 
Published: July 2021

AbstractYeasts have broad importance as industrially and clinically relevant microbes and as powerful models for fundamental research, but we are only beginning to understand the roles yeasts play in natural ecosystems. Yeast ecology is often more difficult to study compared to other, more abundant microbes, but growing collections of natural yeast isolates are beginning to shed light on fundamental ecological questions. Here we used environmental sampling and isolation to assemble a dataset of 1,962 isolates collected from throughout the contiguous United States of America (USA) and Alaska, which were then used to uncover geographic patterns, along with substrate and temperature associations among yeast taxa. We found some taxa, including the common yeasts Torulaspora delbrueckii and Saccharomyces paradoxus, to be repeatedly isolated from multiple sampled regions of the US, and we classify these as broadly distributed cosmopolitan yeasts. A number of yeast taxon - substrate associations were identified, some of which were novel and some of which support previously reported associations. Further, we found a strong effect of isolation temperature on the phyla of yeasts recovered, as well as for many species. We speculate that substrate and isolation temperature associations reflect the ecological diversity of and niche partitioning by yeast taxa.Take AwayAnalysis of environmental metadata of nearly 2,000 yeast isolates.Individual yeast taxa associate with specific substrates and plant genera.Optimal yeast isolation temperature differs depending on taxonomic rank.Substrate type and isolation temperatures affect isolated yeast diversity.
Predicting protein domain temperature adaptation across the prokaryote-eukaryote divide
Authors: Jensen Sarah E. , Johnson Lynn C. , Casstevens Terry , Buckler Edward S. 
Published: July 2021

AbstractProtein thermostability is important for fitness but difficult to measure across the proteome. Fortunately, protein thermostability is correlated with prokaryote optimal growth temperatures (OGTs), which can be predicted from genome features. Models that can predict temperature sensitivity across the prokaryote-eukaryote divide would help inform how eukaryotes adapt to elevated temperatures, such as those predicted by climate change models. In this study we test whether prediction models can cross the prokaryote-eukaryote divide to predict protein stability in both prokaryotes and eukaryotes. We compare models built using a) the whole proteome, b) Pfam domains, and c) individual amino acid residues. Proteome-wide models accurately predict prokaryote optimal growth temperatures (r2 up to 0.93), while site-specific models demonstrate that nearly half of the proteome is associated with optimal growth temperature in both Archaea and Bacteria. Comparisons with the small number of eukaryotes with temperature sensitivity data suggest that site-specific models are the most transferable across the prokaryote-eukaryote divide. Using the site-specific models, we evaluated temperature sensitivity for 323,850 amino acid residues in 2,088 Pfam domain clusters in Archaea and Bacteria species separately. 59.0% of tested residues are significantly associated with OGT in Archaea and 75.2% of tested residues are significantly associated with OGT in Bacteria species at a 5% false discovery rate. These models make it possible to identify which Pfam domains and amino acid residues are involved in temperature adaptation and facilitate future research questions about how species will fare in the face of increasing environmental temperatures.
Single Serine on TSC2 Exerts Biased Control over mTORC1 Activation by ERK1/2 but Not Akt
Authors: Dunkerly-Eyring Brittany L. , Pinilla-Vera Miguel , McKoy Desirae , Mishra Sumita , Grajeda Martinez Maria I. , Oeing Christian U. , Ranek Mark J. , Kass David A. 
Published: July 2021

SummaryThe mammalian target of rapamycin complex 1 (mTORC1) is tightly controlled by tuberous sclerosis complex-2 (TSC2) that is regulated by phosphorylation from kinases responding to environmental cues. Protein kinase G specifically modifies serine-1365 (S1364, human), and its phosphorylation (or phosphomimetic SE mutant) potently blocks mTORC1 co-activation by pathological stress, while a phospho-silenced (SA) mutation does the opposite. Neither alter basal mTORC1 activity. Here we show S1365 exerts biased control over mTORC1 activity (S6K phosphorylation) modifying ERK1/2 but not Akt-dependent stimulation. Whereas mTORC1 activation by endothelin-1 is potently modified by S1365 status, insulin or PDGF stimulation are unaltered. TSC2-S1365 is also phosphorylated upon ET-1 but not insulin stimulation in a PKG-dependent manner, revealing intrinsic bias. Neither energy or nutrient modulation of mTORC1 are impacted by S1365. Consistent with these results, knock-in mice with either TSC2 SA or SE mutations develop identical obesity, glucose intolerance, and fatty liver disease from a high fat diet. Thus, S1365 provides an ERK1/2-selective mTORC1 control mechanism and a genetic means to modify pathological versus physiological mTOR stimuli.
Tissue Specific Age Dependence of the Cell Receptors Involved in the SARS-CoV-2 Infection
Authors: Forst Christian V. , Zeng Lu , Wang Qian , Zhou Xianxiao , Vatansever Sezen , Tu Zhidong , Zhang Bin 
Published: July 2021

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has affected tens of millions of individuals and caused hundreds of thousands of deaths worldwide. Due to its rapid surge, there is a shortage of information on viral behavior and host response after SARS-CoV-2 infection. Here we present a comprehensive, multiscale network analysis of the transcriptional response to the virus. We particularly focus on key-regulators, cell-receptors, and host-processes that are hijacked by the virus for its advantage. ACE2-controlled processes involve a key-regulator CD300e (a TYROBP receptor) and the activation of IL-2 pro-inflammatory cytokine signaling. We further investigate the age-dependency of such receptors and identify the adipose and the brain as potentially contributing tissues for the disease’s severity in old patients. In contrast, several other tissues in the young population are more susceptible to SARS-CoV-2 infection. In summary, this present study provides novel insights into the gene regulatory organization during the SARS-CoV-2 infection and the tissue-specific age dependence of the cell receptors involved in COVID-19.