nils-herrmann/clean_scirepeval huggingface dataset:
The World Coral Conservatory (WCC): A Noah's ark for corals to support survival of reef ecosystems
Venue: PLoS biology

Global change causes widespread decline of coral reefs. In order to counter the anticipated disappearance of coral reefs by the end of this century, many initiatives are emerging, including creation of marine protected areas (MPAs), reef restoration projects, and assisted evolution initiatives. Such efforts, although critically important, are locally constrained. We propose to build a “Noah's Ark” biological repository for corals that taps into the network of the world’s public aquaria and coral reef scientists. Public aquaria will serve not only as a reservoir for the purpose of conservation, restoration, and research of reef-building corals but also as a laboratory for the implementation of operations for the selection of stress-resilient and resistant genotypes. The proposed project will provide a global dimension to coral reef education and protection as a result of the involvement of a network of public and private aquaria.
Controlling control—A primer in open-source experimental control systems
Venue: PLoS biology

Biological systems are composed of countless interlocking feedback loops. Reactor control systems—such as Chi-Bio (https://chi.bio/), recently published in PLOS Biology—enable biologists to drive multiple processes within living biological samples, using a single experimental framework. Consequently, the dynamic relationships between many biological variables can be explored simultaneously in situ. Similar multivariable experimental reactors are employed beyond biology in the study of active matter and non-equilibrium chemical reactions, in which physical systems are maintained far from equilibrium through the continuous introduction of energy or matter. Inexpensive state-of-the-art components enable open-source implementation of such multiparameter architectures, which represent a move away from expensive systems optimised for single measurements, towards affordable and reconfigurable multi-measurement systems. The transfer of well-understood engineering knowledge into the hands of biological and chemical specialists via open-source channels allows rapid cycles of experimental development and heralds a change in experimental capability that is driving increased theoretical and practical understanding of out-of-equilibrium systems across a wide range of scientific fields.
Selective enhancement of low-gamma activity by tACS improves phonemic processing and reading accuracy in dyslexia
Venue: PLoS biology

The phonological deficit in dyslexia is associated with altered low-gamma oscillatory function in left auditory cortex, but a causal relationship between oscillatory function and phonemic processing has never been established. After confirming a deficit at 30 Hz with electroencephalography (EEG), we applied 20 minutes of transcranial alternating current stimulation (tACS) to transiently restore this activity in adults with dyslexia. The intervention significantly improved phonological processing and reading accuracy as measured immediately after tACS. The effect occurred selectively for a 30-Hz stimulation in the dyslexia group. Importantly, we observed that the focal intervention over the left auditory cortex also decreased 30-Hz activity in the right superior temporal cortex, resulting in reinstating a left dominance for the oscillatory response. These findings establish a causal role of neural oscillations in phonological processing and offer solid neurophysiological grounds for a potential correction of low-gamma anomalies and for alleviating the phonological deficit in dyslexia.
Delay-period activity in frontal, parietal, and occipital cortex tracks noise and biases in visual working memory
Venue: PLoS biology

Working memory is imprecise, and these imprecisions can be explained by the combined influences of random diffusive error and systematic drift toward a set of stable states (“attractors”). However, the neural correlates of diffusion and drift remain unknown. Here, we investigated how delay-period activity in frontal and parietal cortex, which is known to correlate with the decline in behavioral memory precision observed with increasing memory load, might relate to diffusion and drift. We analyzed data from an existing experiment in which subjects performed delayed recall for line orientation, at different loads, during functional magnetic resonance imaging (fMRI) scanning. To quantify the influence of drift and diffusion, we modeled subjects’ behavior using a discrete attractor model and calculated within-subject correlation between frontal and parietal delay-period activity and whole-trial estimates of drift and diffusion. We found that although increases in frontal and parietal activity were associated with increases in both diffusion and drift, diffusion explained the most variance in frontal and parietal delay-period activity. In comparison, a subsequent whole-brain regression analysis showed that drift, rather than diffusion, explained the most variance in delay-period activity in lateral occipital cortex. These results are consistent with a model of the differential recruitment of general frontoparietal mechanisms in response to diffusive noise and of stimulus-specific biases in occipital cortex.
In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age
Venue: PLoS biology

Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles of nasopharyngeal (NP) swabs from 430 individuals with PCR-confirmed SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong antiviral response with up-regulation of antiviral factors such as OAS1-3 and IFIT1-3 and T helper type 1 (Th1) chemokines CXCL9/10/11, as well as a reduction in transcription of ribosomal proteins. SARS-CoV-2 culture in human airway epithelial (HAE) cultures replicated the in vivo antiviral host response 7 days post infection, with no induction of interferon-stimulated genes after 3 days. Patient-matched longitudinal specimens (mean elapsed time = 6.3 days) demonstrated reduction in interferon-induced transcription, recovery of transcription of ribosomal proteins, and initiation of wound healing and humoral immune responses. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load, while transcripts for B cell–specific proteins and neutrophil chemokines were elevated in patients with lower viral load. Older individuals had reduced expression of the Th1 chemokines CXCL9/10/11 and their cognate receptor CXCR3, as well as CD8A and granzyme B, suggesting deficiencies in trafficking and/or function of cytotoxic T cells and natural killer (NK) cells. Relative to females, males had reduced B cell–specific and NK cell–specific transcripts and an increase in inhibitors of nuclear factor kappa-B (NF-κB) signaling, possibly inappropriately throttling antiviral responses. Collectively, our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time course, with observed differences due to age and sex that may contribute to disease severity.
Leiomodin creates a leaky cap at the pointed end of actin-thin filaments
Venue: PLoS biology

Improper lengths of actin-thin filaments are associated with altered contractile activity and lethal myopathies. Leiomodin, a member of the tropomodulin family of proteins, is critical in thin filament assembly and maintenance; however, its role is under dispute. Using nuclear magnetic resonance data and molecular dynamics simulations, we generated the first atomic structural model of the binding interface between the tropomyosin-binding site of cardiac leiomodin and the N-terminus of striated muscle tropomyosin. Our structural data indicate that the leiomodin/tropomyosin complex only forms at the pointed end of thin filaments, where the tropomyosin N-terminus is not blocked by an adjacent tropomyosin protomer. This discovery provides evidence supporting the debated mechanism where leiomodin and tropomodulin regulate thin filament lengths by competing for thin filament binding. Data from experiments performed in cardiomyocytes provide additional support for the competition model; specifically, expression of a leiomodin mutant that is unable to interact with tropomyosin fails to displace tropomodulin at thin filament pointed ends and fails to elongate thin filaments. Together with previous structural and biochemical data, we now propose a molecular mechanism of actin polymerization at the pointed end in the presence of bound leiomodin. In the proposed model, the N-terminal actin-binding site of leiomodin can act as a “swinging gate” allowing limited actin polymerization, thus making leiomodin a leaky pointed-end cap. Results presented in this work answer long-standing questions about the role of leiomodin in thin filament length regulation and maintenance.
Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFβ-dependent Smad/YAP/TAZ signaling
Venue: PLoS biology

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-β (TGFβ)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial–mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFβ through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFβ axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.
Isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies
Venue: PLoS biology

As a novel alternative to established surface display or combinatorial chemistry approaches for the discovery of therapeutic peptides, we present a method for the isolation of small, cysteine-rich domains from bovine antibody ultralong complementarity-determining regions (CDRs). We show for the first time that isolated bovine antibody knob domains can function as autonomous entities by binding antigen outside the confines of the antibody scaffold. This yields antibody fragments so small as to be considered peptides, each stabilised by an intricate, bespoke arrangement of disulphide bonds. For drug discovery, cow immunisations harness the immune system to generate knob domains with affinities in the picomolar to low nanomolar range, orders of magnitude higher than unoptimized peptides from naïve library screening. Using this approach, knob domain peptides that tightly bound Complement component C5 were obtained, at scale, using conventional antibody discovery and peptide purification techniques.
Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling
Venue: PLoS biology

The small GTPase RhoA is a central signaling enzyme that is involved in various cellular processes such as cytoskeletal dynamics, transcription, and cell cycle progression. Many signal transduction pathways activate RhoA—for instance, Gαq-coupled Histamine 1 Receptor signaling via Gαq-dependent activation of RhoGEFs such as p63. Although multiple upstream regulators of RhoA have been identified, the temporal regulation of RhoA and the coordination of different upstream components in its regulation have not been well characterized. In this study, live-cell measurement of RhoA activation revealed a biphasic increase of RhoA activity upon histamine stimulation. We showed that the first and second phase of RhoA activity are dependent on p63 and Ca2+/PKC, respectively, and further identified phosphorylation of serine 240 on p115 RhoGEF by PKC to be the mechanistic link between PKC and RhoA. Combined approaches of computational modeling and quantitative measurement revealed that the second phase of RhoA activation is insensitive to rapid turning off of the receptor and is required for maintaining RhoA-mediated transcription after the termination of the receptor signaling. Thus, two divergent pathways enable both rapid activation and persistent signaling in receptor-mediated RhoA signaling via intricate temporal regulation.
Spastin depletion increases tubulin polyglutamylation and impairs kinesin-mediated neuronal transport, leading to working and associative memory deficits
Venue: PLoS biology

Mutations in the gene encoding the microtubule-severing protein spastin (spastic paraplegia 4 [SPG4]) cause hereditary spastic paraplegia (HSP), associated with neurodegeneration, spasticity, and motor impairment. Complicated forms (complicated HSP [cHSP]) further include cognitive deficits and dementia; however, the etiology and dysfunctional mechanisms of cHSP have remained unknown. Here, we report specific working and associative memory deficits upon spastin depletion in mice. Loss of spastin-mediated severing leads to reduced synapse numbers, accompanied by lower miniature excitatory postsynaptic current (mEPSC) frequencies. At the subcellular level, mutant neurons are characterized by longer microtubules with increased tubulin polyglutamylation levels. Notably, these conditions reduce kinesin-microtubule binding, impair the processivity of kinesin family protein (KIF) 5, and reduce the delivery of presynaptic vesicles and postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Rescue experiments confirm the specificity of these results by showing that wild-type spastin, but not the severing-deficient and disease-associated K388R mutant, normalizes the effects at the synaptic, microtubule, and transport levels. In addition, short hairpin RNA (shRNA)-mediated reduction of tubulin polyglutamylation on spastin knockout background normalizes KIF5 transport deficits and attenuates the loss of excitatory synapses. Our data provide a mechanism that connects spastin dysfunction with the regulation of kinesin-mediated cargo transport, synapse integrity, and cognition.
Estimating the risk of species interaction loss in mutualistic communities
Venue: PLoS biology

Interactions between species generate the functions on which ecosystems and humans depend. However, we lack an understanding of the risk that interaction loss poses to ecological communities. Here, we quantify the risk of interaction loss for 4,330 species interactions from 41 empirical pollination and seed dispersal networks across 6 continents. We estimate risk as a function of interaction vulnerability to extinction (likelihood of loss) and contribution to network feasibility, a measure of how much an interaction helps a community tolerate environmental perturbations. Remarkably, we find that more vulnerable interactions have higher contributions to network feasibility. Furthermore, interactions tend to have more similar vulnerability and contribution to feasibility across networks than expected by chance, suggesting that vulnerability and feasibility contribution may be intrinsic properties of interactions, rather than only a function of ecological context. These results may provide a starting point for prioritising interactions for conservation in species interaction networks in the future.
Recommendations for future university pandemic responses: What the first COVID-19 shutdown taught us
Venue: PLoS biology

The SARS-CoV-2 epidemic challenged universities and other academic institutions to rapidly adapt to urgent and life-threatening situations. It forced most institutions to shut down nearly every aspect of their research and educational enterprises. In doing so, university leaders were thrust into unchartered waters and forced them to make unprecedented decisions. Successes and failures along the way highlighted how the autonomous nature of the American academic research enterprise and skillsets normally required of university leaders were ill-suited to mounting an emergency response. Here, as faculty from medical centers in the United States, we draw lessons from these experiences and apply them as we plan for the next possible COVID-19-induced shutdown as well as other large-scale pandemics and emergencies at universities in the United States and throughout the world.
Cortical tracking of speech in noise accounts for reading strategies in children
Venue: PLoS biology

Humans’ propensity to acquire literacy relates to several factors, including the ability to understand speech in noise (SiN). Still, the nature of the relation between reading and SiN perception abilities remains poorly understood. Here, we dissect the interplay between (1) reading abilities, (2) classical behavioral predictors of reading (phonological awareness, phonological memory, and rapid automatized naming), and (3) electrophysiological markers of SiN perception in 99 elementary school children (26 with dyslexia). We demonstrate that, in typical readers, cortical representation of the phrasal content of SiN relates to the degree of development of the lexical (but not sublexical) reading strategy. In contrast, classical behavioral predictors of reading abilities and the ability to benefit from visual speech to represent the syllabic content of SiN account for global reading performance (i.e., speed and accuracy of lexical and sublexical reading). In individuals with dyslexia, we found preserved integration of visual speech information to optimize processing of syntactic information but not to sustain acoustic/phonemic processing. Finally, within children with dyslexia, measures of cortical representation of the phrasal content of SiN were negatively related to reading speed and positively related to the compromise between reading precision and reading speed, potentially owing to compensatory attentional mechanisms. These results clarify the nature of the relation between SiN perception and reading abilities in typical child readers and children with dyslexia and identify novel electrophysiological markers of emergent literacy.
Glycan cross-feeding supports mutualism between Fusobacterium and the vaginal microbiota
Venue: PLoS biology

Women with bacterial vaginosis (BV), an imbalance of the vaginal microbiome, are more likely to be colonized by potential pathogens such as Fusobacterium nucleatum, a bacterium linked with intrauterine infection and preterm birth. However, the conditions and mechanisms supporting pathogen colonization during vaginal dysbiosis remain obscure. We demonstrate that sialidase activity, a diagnostic feature of BV, promoted F. nucleatum foraging and growth on mammalian sialoglycans, a nutrient resource that was otherwise inaccessible because of the lack of endogenous F. nucleatum sialidase. In mice with sialidase-producing vaginal microbiotas, mutant F. nucleatum unable to consume sialic acids was impaired in vaginal colonization. These experiments in mice also led to the discovery that F. nucleatum may also “give back” to the community by reinforcing sialidase activity, a biochemical feature of human dysbiosis. Using human vaginal bacterial communities, we show that F. nucleatum supported robust outgrowth of Gardnerella vaginalis, a major sialidase producer and one of the most abundant organisms in BV. These results illustrate that mutually beneficial relationships between vaginal bacteria support pathogen colonization and may help maintain features of dysbiosis. These findings challenge the simplistic dogma that the mere absence of “healthy” lactobacilli is the sole mechanism that creates a permissive environment for pathogens during vaginal dysbiosis. Given the ubiquity of F. nucleatum in the human mouth, these studies also suggest a possible mechanism underlying links between vaginal dysbiosis and oral sex.
Choosing fast and simply: Construction of preferences by starlings through parallel option valuation
Venue: PLoS biology

The integration of normative and descriptive analyses of decision processes in humans struggles with the fact that measuring preferences by different procedures yields different rankings and that humans appear irrationally impulsive (namely, show maladaptive preference for immediacy). Failure of procedure invariance has led to the widespread hypothesis that preferences are constructed “on the spot” by cognitive evaluations performed at choice time, implying that choices should take extra time in order to perform the necessary comparisons. We examine this issue in experiments with starlings (Sturnus vulgaris) and show that integrating normative and descriptive arguments is possible and may help reinterpreting human decision results. Our main findings are that (1) ranking alternatives through direct rating (response time) accurately predicts preference in choice, overcoming failures of procedure invariance; (2) preference is not constructed at choice time nor does it involve extra time (we show that the opposite is true); and (3) starlings’ choices are not irrationally impulsive but are instead directly interpretable in terms of profitability ranking. Like all nonhuman research, our protocols examine decisions by experience rather than by description, and hence support the conjecture that irrationalities that prevail in research with humans may not be observed in decisions by experience protocols.
Metabolic excretion associated with nutrient–growth dysregulation promotes the rapid evolution of an overt metabolic defect
Venue: PLoS biology

In eukaryotes, conserved mechanisms ensure that cell growth is coordinated with nutrient availability. Overactive growth during nutrient limitation (“nutrient–growth dysregulation”) can lead to rapid cell death. Here, we demonstrate that cells can adapt to nutrient–growth dysregulation by evolving major metabolic defects. Specifically, when yeast lysine-auxotrophic mutant lys− encountered lysine limitation, an evolutionarily novel stress, cells suffered nutrient–growth dysregulation. A subpopulation repeatedly evolved to lose the ability to synthesize organosulfurs (lys−orgS−). Organosulfurs, mainly reduced glutathione (GSH) and GSH conjugates, were released by lys− cells during lysine limitation when growth was dysregulated, but not during glucose limitation when growth was regulated. Limiting organosulfurs conferred a frequency-dependent fitness advantage to lys−orgS− by eliciting a proper slow growth program, including autophagy. Thus, nutrient–growth dysregulation is associated with rapid organosulfur release, which enables the selection of organosulfur auxotrophy to better tune cell growth to the metabolic environment. We speculate that evolutionarily novel stresses can trigger atypical release of certain metabolites, setting the stage for the evolution of new ecological interactions.