Miracle-dz/UniFAR-FTUs huggingface dataset:
Low rattling: A predictive principle for self-organization in active collectives

Shake, rattle, and help each other along In classical statistical mechanics, the deterministic dynamics of a many-body system are replaced by a probabilistic description. Chvykov et al. work toward a similar description for the nonequilibrium self-organization of collectives of active particles. In these systems, continuously input energy drives localized fluctuations, but larger-scale ordering can emerge, such as in the flight of a flock of birds. A key concept in their theory is the importance of rattling, whereby ordered patterns emerge through local collisions between neighbors at specific frequencies. The authors demonstrate this behavior using a set of flapping robots and produce related simulations of the robot behavior. Science, this issue p. 90 Long-range dynamic order in active systems is connected to the driving energy and particle response. Self-organization is frequently observed in active collectives as varied as ant rafts and molecular motor assemblies. General principles describing self-organization away from equilibrium have been challenging to identify. We offer a unifying framework that models the behavior of complex systems as largely random while capturing their configuration-dependent response to external forcing. This allows derivation of a Boltzmann-like principle for understanding and manipulating driven self-organization. We validate our predictions experimentally, with the use of shape-changing robotic active matter, and outline a methodology for controlling collective behavior. Our findings highlight how emergent order depends sensitively on the matching between external patterns of forcing and internal dynamical response properties, pointing toward future approaches for the design and control of active particle mixtures and metamaterials.
Imposex in Sublittoral and Littoral Gastropods from the Gulf of Thailand and Strait of Malacca in Relation to Shipping

The study aimed to survey the presence and extent of imposex in sublittoral gastropods in relation to shipping traffic in the Gulf of Thailand and the Strait of Malacca. Females of several species of meso- and neogastropods showed a high incidence (up to 100%) of imposex at several sites. These females had a penis of variable size and a vas deferens (sperm duct), two typically male characteristics. Imposex has been found to be caused by TBT from antifouling paints. The occurrence of imposex was related to the distance to the main shipping routes, but not to water depth or diet of the investigated gastropods. TBT remains active far away from the target area and influences non-target animals. Some gastropods affected by imposex were found within shellfish culture plots and on the fish markets.
Development of a Technology for Online Measurement of Total and Water-Soluble Copper (Cu) in PM2.5

A novel monitor for online, in situ measurement of copper (Cu) in ambient fine and ultrafine particulate matter (PM) was developed based on a recent published high flow rate aerosol-into-liquid collector. This aerosol-into-liquid collector operates at 200 L/min flow and collects particles directly as highly concentrated slurry samples. The Cu concentration in slurry samples is subsequently determined by a cupric ion selective electrode (ISE). Laboratory tests were conducted to evaluate the performance of the cupric ISE. The calibration curve of the cupric ISE was determined using Cu(NO3)2 standard solutions prepared by serial dilution. As part of the evaluation, the effects of ionic strength, temperature and pH of the aerosol slurry sample on the cupric ISE measurement were also evaluated. The Cu measurement system performance was evaluated by collecting and measuring samples of lab-generated Cu(NO3)2 aerosols with known mass concentration. Overall, very good agreement between the theoretical and measured Cu concentrations was obtained, corroborating the excellent high overall collection efficiency and measurement accuracy of the Cu measurement system. Field evaluations of the online Cu monitor demonstrated very good agreement for total and water-soluble Cu concentrations with measurements performed by inductively coupled plasma mass spectrometry (ICP-MS), suggesting that interferences from other components of particulate matter are minimal under real world sampling conditions. Moreover, the field tests indicated that the new online Cu monitor could achieve near-continuous collection and measurements (at 2–4 h intervals) for at least 4 to 7 days without any obvious shortcomings in its operation. Both laboratory and field evaluations of the online Cu monitor indicate that it is an effective and valuable technology for PM collection and characterization of Cu in ambient aerosols and provides the foundation for the wider use of ISE for metal analysis and speciation of aerosols. Copyright 2014 American Association for Aerosol Research
In Situ, Real-Time Observations of the Adsorption and Self-Assembly of Macromolecules from Aqueous Solution onto an Untreated, Natural Surface

Scanning force microscopy, SFM, was used to observe the attachment and arrangement of poly(acrylic acid), PAA, from a monodispersed solution to the surface of freshly cleaved muscovite. The purpose was to use model materials to investigate some of the dynamic processes that occur in natural aqueous environments in situ and in real-time. The method was effective, but the susceptibility of the adsorbed polymer layers to nanometer scale scratching allowed imaging only under a carefully selected range of instrument parameters. Nanometer scale observations under solution showed stages of roughening and flattening as sequential polymer layers adsorbed and became attached to the surface and to other polymer molecules. More concentrated solutions produced rougher surfaces, faster. Measurement of adhesion forces between the tip and sample showed that the polymer layer became stickier with increased solution concentration and with time.
mRNA vaccine CVnCoV protects non-human primates from SARS-CoV-2 challenge infection

The ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic necessitates the fast development of vaccines to meet a worldwide need. mRNA-based vaccines are the most promising technology for rapid and safe SARS-CoV-2 vaccine development and production. We have designed CVnCoV, a lipid-nanoparticle (LNP) encapsulated, sequence optimised mRNA-based SARS-CoV-2 vaccine that encodes for full length, pre-fusion stabilised Spike protein. Unlike other mRNA-based approaches, CVnCoV exclusively consists of non-chemically modified nucleotides and can be applied at comparatively low doses. Here we demonstrate that CVnCoV induces robust humoral and cellular responses in non-human primates (NHPs). Animals vaccinated with 8 μg of CVnCoV were protected from challenge infection with SARS-CoV-2. Comprehensive analyses of pathological changes in challenged animals via lung histopathology and Computed Tomography (CT) scans gave no indication of enhanced disease upon CVnCoV vaccination. These results demonstrate safety, immunogenicity, and protective efficacy of CVnCoV in NHPs that extend our previously published preclinical data and provide strong support for further clinical testing in ongoing phase 2b/3 efficacy studies.
Sting orchestrates the crosstalk between polyunsaturated fatty acids metabolism and inflammatory responses

Inflammatory disorders are major health issues in which immune function and metabolic homeostasis are concertedly altered. Yet, the molecular mechanisms coordinating innate and metabolic pathways in homeostatic conditions are poorly understood. Here, we unveil a negative regulatory feedback loop involving the Stimulator of interferon genes (Sting) and the Fatty acid desaturase 2 (Fads2). At steady state, Sting regulates FA metabolism by repressing the activity of the Fads2 enzyme responsible for the desaturation of polyunsaturated FAs (PUFAs). Importantly, Sting activation increased Fads2 activity, while antagonizing Fads2 enhanced Sting activation, promoting the establishment of an anti-viral state. Remarkably, the cross-regulation between Sting and Fads2 is mediated by the cyclic GMP-AMP (cGAMP) Sting agonist and PUFAs. Indeed, we found that PUFAs inhibit Sting activation, while Sting agonists bind Fads2. Thus, our study identifies Sting as a master regulator of FA metabolism, and PUFAs as modulators of Sting-dependent inflammation. The interplay between Fads2 and Sting determines the fine-tuning of inflammatory responses, but comes at the expense of metabolic alterations, which are critical to consider in human pathologies associated with aberrant Sting activation.
Genome-wide identification, characterization and expression analysis of the Bcl-2 associated athanogene (BAG) gene family in Physcomitrium patens

The Bcl-2-associated athanogene (BAG) family is an evolutionarily conserved, multifunctional group of co-chaperones regulators that modulate a number of diverse processes. Plant BAG genes were identified to play an extensive role in processes of programmed cell death (PCD) ranging from growth and development to stress responses. In this study, we identified BAG genes from different photosynthetic organisms in order to gather evolutionary insights on these proteins followed by an in silico characterization of the BAG family in the bryophyte Physcomitrium patens. Ten putative PpBAGs harbouring a characteristic BAG domain were grouped into two subfamilies based on the presence of additional conserved domains and phylogenetic distances. Group I consisted of PpBAG4 and PpBAG5, containing an additional ubiquitin-like domain, and PpBAG10 with only the BAG domain. Group II consisted of PpBAG1–3 and PpBAG6-9, containing a calmodulin-binding IQ motif, a novel feature associated with plant BAG proteins. Interestingly, PpBAG9 exhibits an EF-Hand domain, not reported to date in this class of proteins. Caspase cleavage sites in PpBAG1, PpBAG3, PpBAG4-5 and PpBAG9 were predicted. In silico analysis of BAG genes revealed the presence of stress responsive elements, and a stress-regulated expression pattern which appears to be dependent on specifically organized promoter regulatory elements. According to our analyses, the present data suggest that some members of P. patens BAG gene family may play a role in heat responses, autophagy and pathogen immunity. Further studies are required to unveil the role of specific members of this gene family in PCD and stress responses in P. patens. Key message Genome-wide identification and phylogenetic relationships combined with in silico gene-expression profiling and protein-interaction analysis of PpBAGs in Physcomitrium patens, highlight the importance of a particular set in stress tolerance.
Postural effects on arm movement variability are idiosyncratic and feedback-dependent

Reaching movements are subject to noise arising during the sensing, planning and execution phases of movement production, which contributes to movement variability. When vision of the moving hand is available, reaching variability appears to be strongly influenced by noise occurring during the specification and/or online updating of movement plans in visual coordinates. In contrast, when vision of the hand is unavailable, variability appears more dependent upon hand movement direction, suggesting a greater influence of execution noise. Given that execution noise acts in part at the muscular level, we hypothesized that reaching variability should depend not only on movement direction but initial arm posture as well. Moreover, given that the effects of execution noise are more apparent when movements are performed without vision of the hand, we reasoned that postural effects would be more evident when visual feedback was withheld. To test these hypotheses, subjects planned memory-guided reaching movements to three frontal plane targets, using either an “adducted” or “abducted” initial arm posture. Movements were then executed with and without hand vision. We found that the effects of initial arm posture on movement variability were idiosyncratic in both visual feedback conditions. In addition, without visual feedback, posture-dependent differences in variability varied with movement extent, growing abruptly larger in magnitude during the terminal phases of movement, and were moderately correlated with differences in mean endpoint positions. The results emphasize the role of factors other than noise (i.e. biomechanics and suboptimal sensorimotor integration) in constraining patterns of movement variability in 3D space.
Genetic architecture of transmission stage production and virulence in schistosome parasites

Both theory and experimental data from pathogens suggest that the production of transmission stages should be strongly associated with virulence, but the genetic bases of parasite transmission/virulence traits are poorly understood. The blood fluke Schistosoma mansoni shows extensive variation in numbers of cercariae larvae shed and in their virulence to infected snail hosts, consistent with expected trade-offs between parasite transmission and virulence. We crossed schistosomes from two populations that differ 8-fold in cercarial shedding and in their virulence to Biomphalaria glabrata snail hosts, and determined four-week cercarial shedding profiles in F0, F1 and 376 F2 progeny from two independent crosses in inbred snails. Sequencing and linkage analysis revealed that cercarial production is polygenic and controlled by five QTLs. These QTLs act additively, explaining 28.56% of the phenotypic variation. These results demonstrate that the genetic architecture of key traits relevant to schistosome ecology can be dissected using classical linkage mapping approaches.
No Evidence for Human Monocyte-Derived Macrophage Infection and Antibody-Mediated Enhancement of SARS-CoV-2 Infection

Vaccines are essential to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and to protect the vulnerable population. However, one safety concern of vaccination is the possible development of antibody-dependent enhancement (ADE) of SARS-CoV-2 infection. The potential infection of Fc receptor bearing cells such as macrophages, would support continued virus replication and inflammatory responses, and thereby potentially worsen the clinical outcome of COVID-19. Here we demonstrate that SARS-CoV-2 and SARS-CoV-1 neither infect human monocyte-derived macrophages nor induce inflammatory cytokines in these cells, in sharp contrast to Middle East respiratory syndrome (MERS) coronavirus and the common cold human coronavirus 229E. Furthermore, serum from convalescent COVID-19 patients neither induced enhancement of SARS-CoV-2 infection nor innate immune response in human macrophages. These results support the view that ADE may not be involved in the immunopathological processes associated with COVID-19, however, more studies are necessary to understand the potential contribution of antibodies-virus complexes with other cells expressing FcR receptors.
Evaluating performance of existing computational models in predicting CD8+ T cell pathogenic epitopes and cancer neoantigens

T cell recognition of a cognate peptide-MHC complex (pMHC) presented on the surface of infected or malignant cells, is of utmost importance for mediating robust and long-term immune responses. Accurate predictions of cognate pMHC targets for T Cell Receptors (TCR) would greatly facilitate identification of vaccine targets for both pathogenic diseases as well as personalized cancer immunotherapies. Predicting immunogenic peptides therefore has been at the centre of intensive research for the past decades but has proven challenging. Although numerous models have been proposed, performance of these models has not been systematically evaluated and their success rate in predicting epitopes in the context of human pathology, has not been measured and compared. In this study, we evaluated the performance of several publicly available models, in identifying immunogenic CD8+ T cell targets in the context of pathogens and cancers. We found that for predicting immunogenic peptides from an emerging virus such as SARS-CoV-2, none of the models perform substantially better than random or offer considerable improvement beyond HLA ligand prediction. We also observed suboptimal performance for predicting cancer neoantigens. Through investigation of potential factors associated with ill performance of models, we highlight several data- and model-associated issues. In particular, we observed that cross-HLA variation in the distribution of immunogenic and non-immunogenic peptides in training data of the models seem to substantially confound the predictions. We additionally compared key parameters associated with immunogenicity between pathogenic peptides and cancer neoantigens and observed evidence for differences in the thresholds of binding affinity and stability, which suggested the need to modulate different features in identifying immunogenic pathogen vs. cancer peptides. Overall, we demonstrate that accurate and reliable prediction of immunogenic CD8+ T cell targets remains unsolved, thus we hope our work will guide users and model developers regarding potential pitfalls and unsettled questions in existing immunogenicity predictors.
PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

HIV vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.
Fully autonomous mouse behavioral and optogenetic experiments in home-cage

Goal-directed behaviors involve distributed brain networks. The small size of the mouse brain makes it amenable to manipulations of neural activity dispersed across brain areas, but existing optogenetic methods serially test a few brain regions at a time, which slows comprehensive mapping of distributed networks. Laborious operant conditioning training required for most experimental paradigms exacerbates this bottleneck. We present an autonomous workflow to survey the involvement of brain regions at scale during operant behaviors in mice. Naïve mice living in a home-cage system learned voluntary head-fixation (>1 hour/day) and performed difficult decision-making tasks, including contingency reversals, for 2 months without human supervision. We incorporated an optogenetic approach to manipulate activity in deep brain regions through intact skull during home-cage behavior. To demonstrate the utility of this approach, we tested dozens of mice in parallel unsupervised optogenetic experiments, revealing multiple regions in cortex, striatum, and superior colliculus involved in tactile decision-making.
Microtubule Stutter: a Transient Dynamic Instability Phase that is Strongly Associated with Catastrophe

Microtubules (MT) are cytoskeletal fibers that undergo dynamic instability, a remarkable process involving phases of growth and shortening separated by approximately random transitions (catastrophe and rescue). Dissecting dynamic instability mechanism(s) requires first characterizing and quantifying these dynamics, a subjective process that often ignores complexity in MT behavior. Using a novel machine-learning based tool (STADIA), we show that microtubule behavior consists not only of growth and shortening, but also a transient intermediate phase we term ‘stutter. ’ Quantifying stutter and other behaviors with STADIA demonstrates that stutters precede most catastrophes in simulations and experiments. Moreover, we show that the anti-catastrophe factor CLASP2γ works by promoting stuttering MTs to return to growth. STADIA enables more comprehensive and objective analysis of MT dynamics compared to previous methods. The identification of stutters as a distinct and quantifiable phase of dynamic instability provides new opportunities for analyzing mechanisms of microtubule dynamics and their regulation by binding proteins.
Emerging SARS-CoV-2 Diversity Revealed by Rapid Whole-Genome Sequence Typing

Background Discrete classification of SARS-CoV-2 viral genotypes can identify emerging strains and detect geographic spread, viral diversity, and transmission events. Methods We developed a tool (GNUVID) that integrates whole genome multilocus sequence typing and a supervised machine learning random forest-based classifier. We used GNUVID to assign sequence type (ST) profiles to each of 69,686 SARS-CoV-2 complete, high-quality genomes available from GISAID as of October 20th 2020. STs were then clustered into clonal complexes (CCs), and then used to train a machine learning classifier. We used this tool to detect potential introduction and exportation events, and to estimate effective viral diversity across locations and over time in 16 US states. Results GNUVID is a scalable tool for viral genotype classification (available at https://github.com/ahmedmagds/GNUVID) that can be used to quickly process tens of thousands of genomes. Our genotyping ST/CC analysis uncovered dynamic local changes in ST/CC prevalence and diversity with multiple replacement events in different states. We detected an average of 20.6 putative introductions and 7.5 exportations for each state. Effective viral diversity dropped in all states as shelter-in-place travel-restrictions went into effect and increased as restrictions were lifted. Interestingly, our analysis showed correlation between effective diversity and the date that state-wide mask mandates were imposed. Conclusions Our classification tool uncovered multiple introduction and exportation events, as well as waves of expansion and replacement of SARS-CoV-2 genotypes in different states. Combined with future genomic sampling the GNUVID system could be used to track circulating viral diversity and identify emerging clones and hotspots.