Miracle-dz/UniFAR-FTUs huggingface dataset:
Alteration of (Frequency-Dependent) Fitness in Time-Shift Experiments Reveals Cryptic Coevolution and Uncoordinated Stasis in a Virtual Jurassic Park

Among the major unresolved questions in ecosystem evolution are whether coevolving multispecies communities are dominated more by biotic or by abiotic factors, and whether evolutionary stasis affects performance as well as ecological profile; these issues remain difficult to address experimentally. Digital evolution, a computer-based instantiation of Darwinian evolution in which short self-replicating computer programs compete, mutate, and evolve, is an excellent platform for investigating such topics in a rigorous experimental manner. We evolved model communities with ecological interdependence among community members, which were subjected to two principal types of mass extinction: a pulse extinction that killed randomly, and a selective press extinction involving an alteration of the abiotic environment to which the communities had to adapt. These treatments were applied at two different strengths (Strong and Weak), along with unperturbed Control experiments. We performed several kinds of competition experiments using simplified versions of these communities to see whether long-term stability that was implied previously by ecological and phylogenetic metrics was also reflected in performance, namely, whether fitness was static over long periods of time. Results from Control and Weak treatment communities revealed almost completely transitive evolution, while Strong treatment communities showed higher incidences of temporal intransitivity, with pre-treatment ecotypes often able to displace some of their post-recovery successors. However, pre-treatment carryovers more often had lower fitness in mixed communities than in their own fully native conditions. Replacement and invasion experiments pitting single ecotypes against pre-treatment reference communities showed that many of the invading ecotypes could measurably alter the fitnesses of one or more residents, usually with depressive effects, and that the strength of these effects increased over time even in the most stable communities. However, invaders taken from Strong treatment communities often had little or no effect on resident performance. While we detected periods of time when the fitness of a particular evolving ecotype remained static, this stasis was not permanent and never affected an entire community at once. Our results lend support to the fitness-deterioration interpretation of the Red Queen hypothesis, and highlight community context dependence in determining fitness, the shaping of communities by both biotic factors and abiotic forcing, and the illusory nature of evolutionary stasis. Our results also demonstrate the potential of digital evolution studies to illuminate many aspects of evolution in interacting multispecies communities.
The mechanism of MICU-dependent gating of the mitochondrial Ca2+uniporter

Mitochondrial Ca2+ uniporter (MCU) mediates mitochondrial Ca2+ uptake, regulating ATP production and cell death. According to the existing paradigm, MCU is occluded at the resting cytosolic [Ca2+] and only opens above an ∼400 nM threshold. This Ca2+-dependent gating is putatively conferred by MICUs, EF hand-containing auxiliary subunits that block/unblock the MCU pore depending on cytosolic [Ca2+]. Here we provide the first direct, patch-clamp based analysis of the Ca2+-dependent MCU gating and the role played by MICUs. Surprisingly, MICUs do not occlude the MCU pore, and MCU is a constitutively active channel without cytosolic [Ca2+] activation threshold. Instead, MICUs potentiate MCU activity when cytosolic Ca2+ binds to their EF hands. MICUs cause this potentiation by increasing the probability of open state of the MCU channel. One Sentence Summary Auxiliary MICU subunits do not occlude the mitochondrial Ca2+ uniporter (MCU) but increase its activity as cytosolic Ca2+ is elevated.
Linking Activity in Human Superior Temporal Cortex to Perception of Noisy Audiovisual Speech

Regions of the human posterior superior temporal gyrus and sulcus (pSTG/S) respond to the visual mouth movements that constitute visual speech and the auditory vocalizations that constitute auditory speech. We hypothesized that these multisensory responses in pSTG/S underlie the observation that comprehension of noisy auditory speech is improved when it is accompanied by visual speech. To test this idea, we presented audiovisual sentences that contained either a clear auditory component or a noisy auditory component while measuring brain activity using BOLD fMRI. Participants reported the intelligibility of the speech on each trial with a button press. Perceptually, adding visual speech to noisy auditory sentences rendered them much more intelligible. Post-hoc trial sorting was used to examine brain activations during noisy sentences that were more or less intelligible, focusing on multisensory speech regions in the pSTG/S identified with an independent visual speech localizer. Univariate analysis showed that less intelligible noisy audiovisual sentences evoked a weaker BOLD response, while more intelligible sentences evoked a stronger BOLD response that was indistinguishable from clear sentences. To better understand these differences, we conducted a multivariate representational similarity analysis. The pattern of response for intelligible noisy audiovisual sentences was more similar to the pattern for clear sentences, while the response pattern for unintelligible noisy sentences was less similar. These results show that for both univariate and multivariate analyses, successful integration of visual and noisy auditory speech normalizes responses in pSTG/S, providing evidence that multisensory subregions of pSTG/S are responsible for the perceptual benefit of visual speech. Significance Statement Enabling social interactions, including the production and perception of speech, is a key function of the human brain. Speech perception is a complex computational problem that the brain solves using both visual information from the talker’s facial movements and auditory information from the talker’s voice. Visual speech information is particularly important under noisy listening conditions when auditory speech is difficult or impossible to understand alone Regions of the human cortex in posterior superior temporal lobe respond to the visual mouth movements that constitute visual speech and the auditory vocalizations that constitute auditory speech. We show that the pattern of activity in cortex reflects the successful multisensory integration of auditory and visual speech information in the service of perception.
SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles

SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.
α-Synuclein-112 Impairs Synaptic Vesicle Recycling Consistent With Its Enhanced Membrane Binding Properties

Synucleinopathies are neurological disorders associated with α-synuclein overexpression and aggregation. While it is well established that overexpression of wild type α-synuclein (α-syn-140) leads to cellular toxicity and neurodegeneration, much less is known about other naturally occurring α-synuclein splice isoforms. In this study we provide the first detailed examination of the synaptic effects caused by one of these splice isoforms, α-synuclein-112 (α-syn-112). α-Syn-112 is produced by an in-frame excision of exon 5, resulting in deletion of amino acids 103-130 in the C-terminal region. α-Syn-112 is upregulated in the substantia nigra, frontal cortex, and cerebellum of parkinsonian brains and is correlated with susceptibility to sporadic Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy (MSA). We report here that α-syn-112 binds strongly to anionic phospholipids when presented in highly-curved liposomes, similar to α-syn-140. However, α-syn-112 bound significantly stronger to all phospholipids tested, including the phosphoinositides. α-Syn-112 also dimerized and trimerized on isolated synaptic membranes, while α-syn-140 remained largely monomeric. When introduced acutely to lamprey synapses, α-syn-112 robustly inhibited synaptic vesicle recycling. Interestingly, α-syn-112 produced effects on the plasma membrane and clathrin-mediated synaptic vesicle endocytosis that were phenotypically intermediate between those caused by monomeric and dimeric α-syn-140. These findings indicate that α-syn-112 exhibits enhanced phospholipid binding and oligomerization in vitro and consequently interferes with synaptic vesicle recycling in vivo in ways that are consistent with its biochemical properties. This study provides additional evidence suggesting that impaired vesicle endocytosis is a cellular target of excess α-synuclein and advances our understanding of potential mechanisms underlying disease pathogenesis in the synucleinopathies.
In silico approach for designing of a multi-epitope based vaccine against novel Coronavirus (SARS-COV-2)

A novel Coronavirus (SARS-COV-2) has now become a global pandemic. Considering the severity of infection and the associated mortalities, there is an urgent need to develop an effective preventive measure against this virus. In this study, we have designed a novel vaccine construct using computational strategies. Spike (S) glycoprotein is the major antigenic component that trigger the host immune responses. Detailed investigation of S protein with various immunoinformatics tools enabled us to identify 5 MHC I and 5 MHC II B-cell derived T-cell epitopes with VaxiJen score > 1 and IC50 value < 100nM. These epitopes were joined with a suitable adjuvant and appropriate linkers to form a multi-epitope based vaccine construct. Further, in silico testing of the vaccine construct for its antigenicity, allergenicity, solubility, and other physicochemical properties showed it to be safe and immunogenic. Suitable tertiary structure of the vaccine protein was generated using 3Dpro of SCRATCH suite, refined with GalaxyRefine, and validated with ProSA, PROCHECK, and ERRAT server. Finally, molecular docking studies were performed to ensure a favorable binding affinity between the vaccine construct and TLR3 receptor. The designed multi-epitope vaccine showed potential to elicit specific immune responses against the SARS-COV-2. However, further wet lab validation is necessary to confirm the actual effectiveness, safety and immunogenic potency of the vaccine construct against derived in this study.
Conducting Natural Language Inference with Word-Pair-Dependency and Local Context

This article proposes to conduct natural language inference with novel Enhanced-Relation-Head-Dependent triplets (RHD triplets), which are constructed via enhancing each word in the RHD triplet with its associated local context. Most previous approaches based on deep neural network (DNN) for this task either perform token alignment without considering syntactic dependency among words, or directly use tree- LSTM to generate passage representation with irrelevant information. To improve token alignment and inference judgment with word-pair-dependency, the RHD triplet structure is first proposed. To avoid incorporating irrelevant information, this proposed approach performs comparison directly on each triplet-pair of the given passage-pair (instead of comparing each triplet in a passage with the content merged from the whole opposite passage). Furthermore, to take local context into consideration while conducting token alignment and inference judgment, we also enhance the words of the triplets with their associated local context to improve the performance. Experimental results show that the proposed approach is better than most previous approaches that adopt tree structures, and its performance is comparable to other state-of-the-art approaches (however, our approach is more human comprehensible).
Effectiveness of active learning for ecology teaching: the perspective of students vs their grades

We evaluated the effectiveness of active learning for ecology teaching by comparing the perspective of students to their grades in exams. We estimated the perspective of the students through anonymous survey; we used students’ exam grades to estimate their ecology learning, and their effort and performance in the active learning tasks through their grades and proportion of intermediate steps for each active learning task. Active learning involved teachers’ stimuli for students’ active involvement, extra-class group task, individual online writing assessments, redoing exam in pairs, and classroom writing group assessments. We also evaluated the impact, unto the effectiveness of active learning, of several student characteristics, such as sex, age, individual study effort, and previous basic knowledge. We found that self-evaluated learning increased linearly with teachers’ attempts to stimulate students’ active involvement (P = 0.0003), extra-class group task (P = 0.0003), and previous basic knowledge (P = 0.02), while students’ grades increased asymptotically with extra-class group task (P < 2−16), and increased linearly with online writing assessments (P = 9.3−8) and classroom-based writing group assessments (P = 0.03). Our results showed that students perceive most part of the effectiveness of active-learning tasks and of teachers’ efforts. We showed that active learning tasks are complementary, so we recommend that teachers in both college and high school should implement simultaneous active-learning tasks, that include extra-class work in group, individual and group writing assessments, and should stimulate students’ engagement through respectful and non-authoritarian behavior of the teacher. Our results also showed that previous basic knowledge also plays a central role in driving effective learning, evidencing the importance of students instruction outside college. The applied teaching methodology is cheap and feasible for large classes. In these times of rising intolerance, prejudice, dismiss of environmental issues and disregard of science itself, we need an effective, pluralistic, respectful, and student-centred education, that fosters critical thinking, tolerance and respect for differing points of view.
miRNAs and neural alternative polyadenylation specify the virgin behavioral state

How are diverse regulatory strategies integrated to impose appropriately patterned gene expression that underlie in vivo phenotypes? Here, we reveal how coordinated miRNA regulation and neural-specific alternative polyadenylation (APA) of a single locus controls complex behaviors. Our entry was the unexpected observation that deletion of Bithorax-Complex (BX-C) miRNAs converts virgin female flies into a subjective post-mated behavioral state, normally induced by seminal proteins following copulation. Strikingly, this behavioral switch is directly attributable to misregulation of homothorax (hth). We localize specific CNS abdominal neurons where de-repressed Hth compromises virgin behavior in BX-C miRNA mutants. Moreover, we use genome engineering to demonstrate that precise mutation of hth 3’UTR sites for BX-C miRNAs, or deletion of its neural 3’ UTR extension containing most of these sites, both induce post-mated behaviors in virgins. Thus, facilitation of miRNA-mediated repression by neural APA is required for virgin females to execute behaviors appropriate to their internal state.
Alignment free identification of clones in B cell receptor repertoires

Following pathogenic challenge, activated B cells rapidly expand and undergo somatic hypermutation, yielding groups of clonally related B-cells with diversified immunoglobulin receptors. Inference of clonal relationships based on the receptor sequence is an essential step in many adaptive immune receptor repertoire sequencing studies. These relationships are typically identified by a multi-step process that involves: (1) grouping sequences based on shared V and J gene assignments, and junction lengths, and (2) clustering these sequences using a junction-based distance. However, this approach is sensitive to the initial V(D)J gene assignments, which are error-prone, and fails to identify clonal relatives whose junction length has changed through accumulation of indels. Through defining a translation-invariant feature space in which we cluster the sequences, we develop an alignment-free clonal identification method that does not require gene assignments and is not restricted to a fixed junction length. This alignment-free approach has higher sensitivity compared to a typical junction-based distance method without loss of specificity and PPV. While the alignment-free procedure identifies clones that are broadly consistent with the junction-based distance method, it also identifies clones with characteristics (multiple V or J gene assignments or junction lengths) that are not detectable with the junction based distance method.
Structure of intact human MCU supercomplex with the auxiliary MICU subunits

The mitochondrial Ca2+ uniporter (MCU) supercomplex is essential for mitochondrial Ca2+ uptake. Here, we present high-resolution cryo-EM structures of human MCU-EMRE supercomplex (MES, 3.41 Å) and MCU-EMRE-MICU1-MICU2 supercomplex (MEMMS, 3.64 Å). MES adopts a V-shaped dimer architecture comprising two hetero-octamers, and a pair of MICU1-MICU2 hetero-dimers form a bridge across the two halves of MES to constitute an O-shaped architecture of MEMMS. The MES and MEMMS pore profiles are almost identical, with Ca2+ in the selectivity filters and no obstructions, indicating both channels are conductive. Contrary to the current model in which MICUs block the MCU pore, MICU1-MICU2 dimers are located on the periphery of the MCU pores and do not occlude them. However, MICU1-MICU2 dimers may modulate MCU gating by affecting the matrix gate through the EMRE lever.
A bacterial tragedy of the commons that masks the actual frequency of mutants

The frequency of mutants in a population is central to the understanding of evolution. Mutant frequency is usually assessed by plating a bacterial culture on selective medium in which only specific rare mutants can grow, assuming that all mutant cells present on the plate are able to form colonies. Here we show an exception to this rule. Wild-type Escherichia coli cells are unable to grow with glycerol-2-phosphate (G2P) as a carbon source. In contrast, PHO-constitutive mutants can hydrolyse G2P to glycerol and form colonies on plates having G2P as their sole carbon source. However, the frequency of PHO-constitutive colonies on the selective plate is exceptionally low. Here we show that such mutations occur at a relatively high rate, but the growth of the existing mutants is inhibited due to a competition with the surrounding wild-type cells for the limited amounts of glycerol produced by the mutants. This scenario in which neither the wild-type nor the majority of the mutants are able to grow constitutes an unavoidable case of the ‘tragedy of the commons’. Evidence shows that the few mutants that do form colonies derive from micro-clusters of mutants on the selective plate. In addition, a mathematical model describes the fate of the wild-type and mutant populations on the selective plate.
Core-periphery structure in mutualistic networks: an epitaph for nestedness?

The calculation of nestedness has become a routine analysis in the study of ecological networks, as it is commonly associated with community resilience, robustness and species persistence. While meaningful in species distributional patterns, for an interaction matrix to be nested, specialist species must interact with ordered subsets of subsequently more generalized species — not just with a lower number of species. However, after reviewing 419 papers on mutualistic networks published since nestedness was introduced for the study of species interactions in 2003, we have found that only two theoretical studies considered explicitly ordered subsets. Instead, most studies interpret nestedness as a core of densely connected generalist species, surrounded by a periphery of specialist species attached to this core — a so-called core-periphery structure. Such a topological feature is generally perceived as a core-periphery structure in network science. Here, we argue that the concept of core-periphery may be more relevant for studies on mutualistic networks than the concept of nestedness, as ecologists are usually not interested in exploring in detail the ordered subsets that characterize nestedness but instead use nestedness to describe a topology with a core of densely linked generalist species surrounded by a sparsely linked periphery of specialists. To illustrate our arguments and the quantification of core-periphery structures, we calculate core-periphery and nestedness in a large publicly available dataset of mutualistic networks. We also describe the calculation of core-periphery structures, its relationship with nestedness, and provide the code inside the R package econetwork for its calculation in mutualistic networks. We hope that our review will help ecologists to move beyond nestedness towards a more explicit representation of the structure of ecological networks.
A snapshot of SARS-CoV-2 genome availability up to 30th March, 2020 and its implications

The SARS-CoV-2 pandemic has been growing exponentially, affecting nearly 900 thousand people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies in countries with the highest toll of confirmed cases. Although number of-available full-genomes is growing daily, and the full dataset contains sufficient phylogenetic information that would allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 datasets still present severe limitations. Studies assessing within country spread or transmission clusters should be considered preliminary at best, or hypothesis generating. Hence the need for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic. Significance Statement Although genome sequences of SARS-CoV-2 are growing daily and contain sufficient phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution.