bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the impacts of microbial activity and species interactions on passive bioremediation of a coastal acid sulfate soil (CASS) ecosystem
Authors: Ling Yu-Chen , Moreau John W.
Published: July 2020

Microbial iron and sulfate reduction are the primary drivers of coastal acid sulfate soil (CASS) passive bioremediation schemes. Microbial sulfate reduction is the limiting step for pyrite formation, a desirable endpoint for CASS remediation. Little is known, however, about the impacts of microbial activity or species interaction on long-term iron and sulfur cycling in CASS ecosystems. Using a combination of molecular biology, geochemical speciation and artificial intelligence-powered computational modeling, we deduced from microbial activity patterns (RNA-based) and geochemical measurements a best-fit equation for predicting biogeochemical pyrite formation in a model CASS ecosystem. In addition to the time-dependent activities of key sulfate-reducing prokaryotic taxa (e.g.Desulfobacteraceae), this equation required methylotrophs (Methylobacteriaceae) and bacterial predators (Bacteriovorax) for best-fitting, suggesting that specific microbial interactions exert meaningful influences on CASS bioremediation efficiency. Our findings confirmed that CASS microorganisms act as an assemblage in response to rewetting by tidewater. Accurate predictions of long-term CASS bioremediation efficiency require modelling of complex and interdependent relationships between geochemical speciation and microbial activity.

Highlights

Coastal acid sulfate soil (CASS) is a global environmental issue.

Microbial activity can be modelled quantitatively to predict CASS remediation.

Sulfate-reducing prokaryotes (SRP) play a key role in CASS remediation.

Predation on SRP with cultured representatives occurred during early wet-up.

The above mechanism leads to increased activity among uncultured SRP.
Co-expressed subunits of dual genetic origin define a conserved supercomplex mediating essential protein import into chloroplasts
Authors: Ramundo Silvia , Asakura Yukari , Salomé Patrice A. , Strenkert Daniela , Boone Morgane , Mackinder Luke C. M. , Takafuji Kazuaki , Dinc Emine , Rahire Michèle , Crèvecoeur Michèle , Magneschi Leonardo , Schaad Olivier , Hippler Michael , Jonikas Martin C. , Merchant Sabeeha , Nakai Masato , Rochaix Jean-David , Walter Peter
Published: July 2020

In photosynthetic eukaryotes, thousands of proteins are translated in the cytosol and imported into the chloroplast through the concerted action of two translocons — termed TOC and TIC — located in the outer and inner membranes of the chloroplast envelope, respectively. The degree to which the molecular composition of the TOC and TIC complexes is conserved over phylogenetic distances has remained controversial. Here, we combine transcriptomic, biochemical, and genetic tools in the green alga Chlamydomonas (Chlamydomonas reinhardtii) to demonstrate that, despite a lack of evident sequence conservation for some of its components, the algal TIC complex mirrors the molecular composition of a TIC complex fromArabidopsis thaliana.The Chlamydomonas TIC complex contains three nuclear-encoded subunits, Tic20, Tic56 and Tic100, and one chloroplast-encoded subunit, Tic214, and interacts with the TOC complex, as well as with several uncharacterized proteins to form a stable supercomplex (TicToc), indicating that protein import across both envelope membranes is mechanistically coupled. Expression of the nuclear and chloroplast genes encoding both known and the here newly identified TicToc components is highly coordinated, suggesting that a mechanism for regulating its biogenesis across compartmental boundaries must exist. Conditional repression of Tic214, the only chloroplast-encoded subunit in the TicToc complex, impairs the import of chloroplast proteins with essential roles in chloroplast ribosome biogenesis and protein folding and induces a pleiotropic stress response, including several proteins involved in the chloroplast unfolded protein response. These findings underscore the functional importance of the TicToc supercomplex in maintaining chloroplast proteostasis.
Semantic relatedness emerges in deep convolutional neural networks designed for object recognition
Authors: Huang Taicheng , Zhen Zonglei , Liu Jia
Published: July 2020

Human not only can effortlessly recognize objects, but also characterize object categories into semantic concepts and construct nested hierarchical structures. Similarly, deep convolutional neural networks (DCNNs) can learn to recognize objects as perfectly as human; yet it is unclear whether they can learn semantic relatedness among objects that is not provided in the learning dataset. This is important because it may shed light on how human acquire semantic knowledge on objects without top-down conceptual guidance. To do this, we explored the relation among object categories, indexed by representational similarity, in two typical DCNNs (AlexNet and VGG11). We found that representations of object categories were organized in a hierarchical fashion, suggesting that the relatedness among objects emerged automatically when learning to recognize them. Critically, the emerged relatedness of objects in the DCNNs was highly similar to the WordNet in human, implying that top-down conceptual guidance may not be a prerequisite for human learning the relatedness among objects. Finally, the developmental trajectory of the relatedness among objects during training revealed that the hierarchical structure was constructed in a coarse-to-fine fashion, and evolved into maturity before the establishment of object recognition ability. Taken together, our study provides the first empirical evidence that semantic relatedness of objects emerged as a by-product of object recognition, implying that human may acquire semantic knowledge on objects without explicit top-down conceptual guidance.

Significance Statement

The origin of semantic concepts is in a long-standing debate, where top-down conceptual guidance is thought necessary to form the hierarchy structure of objects. Here we challenged this hypothesis by examining whether deep convolutional neural networks (DCNNs) for object recognition can emerge the semantic relatedness of objects with no relation information in training object datasets. We found that in the DCNNs representations of objects were organized in a hierarchical fashion, which was highly similar to WordNet in human. This finding suggests that top-down conceptual guidance may not be a prerequisite for human learning the relatedness among objects; rather, semantic relatedness of objects may emerge as a by-product of object recognition.
Dynamic transitions between neural states are associated with flexible task-switching during a memory task
Authors: Liu Wei , Kohn Nils , Fernández Guillén
Published: July 2020

Flexible behavior requires switching between different task conditions. It is known that such task- switching is associated with costs in terms of slowed reaction time, reduced accuracy, or both. The neural correlates of task-switching have usually been studied by requiring participants to switch between distinct task demands that recruit different brain networks. Here, we investigated the transition of neural states underlying switching between two opposite memory-related processes (i.e.,memory retrieval and memory suppression) in a memory task. We investigated 26 healthy participants who performed a Think/No-Think task while being in the fMRI scanner. Behaviorally, we show that it was more difficult for participants to suppress unwanted memories when a No-Think was preceded by a Think trial instead of another No- Think trial. Neurally, we demonstrate that Think-to-No-Think switches were associated with an increase in control-related and a decrease in memory-related brain activity. Neural representations of task demand, assessed by decoding accuracy, were lower immediately after task switching compared to the non-switch transitions, suggesting a switch-induced delay in the neural transition towards the required task condition. This suggestion is corroborated by an association between condition-specific representational strength and condition-specific performance in switch trials. Taken together, we provided neural evidence from the time-resolved decoding approach to support the notion that carry-over of the previous task-set activation is associated with the switching cost leading to less successful memory suppression.

Significance statement

Our brain can switch between multiple tasks but at the cost of less optimal performance during transition. One possible neuroscientific explanation is that the representation of the task condition is not easy to be updated immediately after switching. Thus, weak representations for the task at hand explain performance costs. To test this, we applied brain decoding approaches to human fMRI data when participants switched between successive trials of memory retrieval and suppression. We found that switching leads to a weaker representation of the current task. The remaining representation of the previous, opposite task is associated with inferior performance in the current task. Therefore, timely updating of task representations is critical for task switching in the service of flexible behaviors.
Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)
Authors: Gruber Conor , Patel Roosheel , Trachman Rebecca , Lepow Lauren , Amanat Fatima , Krammer Florian , Wilson Karen M. , Onel Kenan , Geanon Daniel , Tuballes Kevin , Patel Manishkumar , Mouskas Konstantinos , Simons Nicole , Barcessat Vanessa , Del Valle Diane , Udondem Samantha , Kang Gurpawan , Gangadharan Sandeep , Ofori-Amanfo George , Rahman Adeeb , Kim-Schulze Seunghee , Charney Alexander , Gnjatic Sacha , Gelb Bruce D. , Merad Miriam , Bogunovic Dusan
Published: July 2020

Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease have been reported in regions with ongoing SARS-CoV-2 epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome in Children (MIS-C) cases. We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28). Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T-lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcγR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti-IL6R antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.

One Sentence Summary

This study maps the cellular and serological immune dysfunction underlying a novel pediatric inflammatory syndrome associated with SARS-CoV-2.
Objective sensory testing methods reveal a higher prevalence of olfactory loss in COVID-19–positive patients compared to subjective methods: A systematic review and meta-analysis
Authors: Hannum Mackenzie E. , Ramirez Vicente A. , Lipson Sarah J. , Herriman Riley D. , Toskala Aurora K. , Lin Cailu , Joseph Paule V. , Reed Danielle R.
Published: July 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence, from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords “COVID-19,” “smell,” and/or “olfaction.” We included any study that quantified olfactory loss as a symptom of COVID-19. Studies were grouped and compared based on the type of method used to measure smell loss—subjective measures such as self-reported smell loss versus objective measures using rated stimuli—to determine if prevalence rate differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbance rates. We identified 34 articles quantifying anosmia as a symptom of COVID-19, collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4-89.2%) and 45% with subjective measurements (95% CI of 31.1-58.5%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2; the use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss.
Sample Pooling as an efficient strategy for SARS-COV-2 RT-PCR screening: a multicenter study in Spain
Authors: de Salazar Adolfo , Aguilera Antonio , Trastoy Rocio , Fuentes Ana , Alados Juan Carlos , Causse Manuel , Galán Juan Carlos , Moreno Antonio , Trigo Matilde , Pérez Mercedes , Roldán Carolina , Pena Ma José , Bernal Samuel , Serrano-Conde Esther , Barbeito Gema , Torres Eva , Riazzo Cristina , Cortes-Cuevas Jose Luis , Chueca Natalia , Coira Amparo , Sanchez-Calvo Juan M , Marfil Eduardo , Becerra Federico , Gude María José , Pallarés Ángeles , Del Molino María Luisa Pérez , García Federico
Published: July 2020

Importance

The actual demand on SARS-CoV-2 diagnosis is a current challenge for clinical laboratories. Sample pooling may help to ameliorate workload in clinical laboratories.

Objective

to evaluate the efficacy of sample pooling compared to the individual analysis for the diagnosis of CoVID-19, by using different commercial platforms for nucleic acid extraction and amplification.

Design and settings

observational, prospective, multicentre study across 9 Spanish clinical microbiology laboratories including SARS-CoV-2 RNA testing performed in April 2020, during the first three days after acceptance to participate.

Participants and Methods

3519 naso-oro-pharyngeal samples received at the participating laboratories were processed individually and in pools (351 pools) according to the existing methodology in each of the centres.

Results

We found that 253 pools (2519 samples) were negative, and 99 pools (990 samples) were positive; with 241 positive samples (6.85%), our pooling strategy would have saved 2167 PCR tests. For 29 pools (made out of 290 samples) we found discordant results when compared to their correspondent individual samples: in 24/29 pools (30 samples), minor discordances were found; for five pools (5 samples), we found major discordances. Sensitivity, specificity, positive and negative predictive values for pooling were 97.93%, 100%, 100% and 99.85% respectively; accuracy was 99.86% and kappa concordant coefficient was 0.988. As a result of the sample dilution effect of pooling, a loss of 2-3 Cts was observed for E, N or RdRP genes.

Conclusion

we show a high efficiency of pooling strategies for SARS-CoV-2 RNA testing, across different RNA extraction and amplification platforms, with excellent performance in terms of sensitivity, specificity, and positive and negative predictive values. We believe that our results may help clinical laboratories to respond to the actual demand and clinical need on SARS-CoV-2 testing, especially for the screening of low prevalence populations.

Key points

Question

May clinical laboratories implement sample pooling as an efficient and safe strategy for SARS-COV-2 RT-PCR screening?

Findings

Sensitivity, specificity, positive and negative predictive values for pooling were 97.93%, 100%, 100% and 99.85% respectively; accuracy was 99.86% and kappa concordant coefficient was 0.988.

Meaning

Sample pooling can be used safely at clinical laboratories, especially for the screening of low prevalence populations.
DETECTION OF AUTOLOGOUS BLOOD DOPING
Authors: Malm Christer , Granlund Irene , Hall Michael , Lindén Pernilla , Ericsson Magnus , Langridge James I. , Gethings Lee A. , Hughes Chris , Khoo Nelson
Published: July 2020

Abstract

Objectives

Autologous blood transfusion (ABT) enhances athlete’s performance, is banned as doping by the World Anti-Doping Agency (WADA). Currently, there is no implemented detection method for ABT. Transfusion of one’s own, long-term cryopreserved red blood cells (cryo-RBC) immediately increases circulating RBC count, hemoglobin mass, blood volume and oxygen carrying capacity, resulting in enhanced physical performance. Functional viablity of cryo-RBC are maintained for decades, but storage lesions lead to removal of damaged RBC from circulation days after transfusion, with remaining circulating cryo-RBC displaying normal half-life.

Methods

The cytosolic RBC peptidome from 22 human subjects (12 men and 10 women) was analyzed by UHPLC-MS/MS before and after ABT with cryo-RBC. As a control group and for investigation of confounders, 14 elite athletes and 5 recreational subjects were sampled multiple times, also at high altitude.

Results

Here we report alteration in the cytosolic peptidome of circulating RBC weeks after ABT, discriminating doped from non-doped human subjects. A valid discriminating multivariate model (OPLS-DA) based on <200 peptides was accomplished (R2/Q2= 0.88/0.59, P CV-ANOVA < 0.0001, ROC AUC = 0.97). Models did not show bias for sex, high altitude or elite endurance training and racing.

Conclusion

Identified peptides with low intra- and inter-individual variation, and high multivariate model weight and probability scores, create a direct method for the detection of autologous blood doping.
The UK Covid-19 lockdown weakened in April and May 2020: implications for the size of the epidemic and for outcomes had lockdown been earlier
Authors: Lander Anthony
Published: July 2020

The number of active cases in the UK Covid-19 epidemic, the case fatality rate, the susceptible proportion of the population, and how well the lockdown was maintained during April–May 2020 are unknown. These four have a relationship with the shape of the daily mortality curve once one considers the intervals from infection to death or recovery. Without an understanding of this relationship we cannot say that an earlier lockdown would have saved lives. Using a small stochastic model, the lockdown had to be weakened, in April and May, for simulated deaths to match ongoing actual daily deaths. Google mobility data was found to be consistent with the weakening required in the model with similar changes from baseline in time and magnitude. If in an earlier lockdown, mobility and interactions would have followed a similar course, then with a large epidemic curve an earlier lockdown might be associated with many more deaths than some currently believe. This was confirmed in the stochastic model and in two modified SIR models of epidemics of various sizes. The first SIR model had a fixed period to recovery and the second used random periods, both models had random periods to death. Weakening of the mitigations was required to tune the output in large but not in small epidemics. This gives weight to the epidemic having affected many more individuals than some reports currently suggest. In both one and two-week earlier lockdowns, total deaths were found to depend on the size of the epidemic and to vary from 2,000–49,000 deaths. There was a linear relationship between the peak proportion of the population infected and the reciprocal of the case fatality rate. This work questions the low prevalence of < 0.1%, reported by the Office for National Statistics in May and June 2020, since to accommodate a weakening lockdown, the shape of the daily mortality curve, and an acceptable case fatality rate a much larger epidemic curve is required.
Distinct Diurnal and Day of Week Online Search Patterns Related to Common Eye Conditions
Authors: Deiner Michael S. , McLeod Stephen D. , Schallhorn Julie M. , Chodosh James , Hwang Daniel H. , Lietman Thomas M. , Porco Travis C.
Published: July 2020

Importance

Studies suggest diurnal patterns of some eye conditions. Leveraging new information sources such as online search data to learn more about such patterns could improve understanding of patient eye-related conditions and well-being and improve timing of clinical and remote eye care.

Objective

To investigate our hypothesis that the public is likely to consistently search about different eye conditions at different hours of the day or days of week, we conducted an observational study using search data for terms related to eye conditions such as conjunctivitis. We asked if search volumes reflected diurnal or day-of-week patterns and if those patterns were distinct from each other.

Design

Hourly search data for eye-related and control search terms for 2018 were analyzed and compared.

Setting

Data from 10 USA states.

Exposure

Internet search.

Participants

Populations that searched Google’s search engine using our chosen study terms.

Main Outcome Measures

Cyclical hourly and weekly online search patterns.

Results

Distinct diurnal (p<0.001 for all search terms) and day-of-week search patterns for eye-related terms were observed but with differing peak time periods and cyclic strengths. Some diurnal patterns represented reported clinical patterns. Of the eye related terms, “conjunctivitis” and “pink eye” had the strongest diurnal cyclic patterns based on peak-to-trough ratios. Stronger signal was restricted to and peaked in mornings, and amplitude was higher on weekdays. In contrast, “dry eyes” had a higher amplitude diurnal pattern on weekends, with stronger signal occurring over a broader evening to morning period and peaking in early morning.

Conclusions and Relevance

The frequency of online searches for various eye conditions can show cyclic patterns according to time of day or week. Further studies to understand the reasons for these variations may help supplement current clinical understanding of eye symptom presentation and improve the timeliness of patient messaging and care interventions.

Key Points

Question

Do online public search engine queries for different eye-health terms follow hourly or daily patterns and do the patterns differ from each other or reflect what is known clinically?

Findings

Unique hourly and day of week eye health related search patterns appear diurnal and can reflect what has been observed clinically.

Meaning

Online search data may reflect timing of eye conditions and could improve clinical understanding of eye-related symptom occurrence, including outside of clinics. Knowing precisely when patient’s eye condition interests increase holds promise -for example to optimize timing and availability of local or remote eye care resources.
Probabilistic divergence of a TBM methodology from the ideal protocol
Authors: Runthala Ashish
Published: July 2020

Protein structural information is essential for the detailed mapping of a functional protein network. For a higher modelling accuracy and quicker implementation, template based algorithms have been extensively deployed and redefined. The methods only assess the predicted structure against its native state/template, and do not estimate the accuracy for each modelling step. A divergence measure is postulated to estimate the modelling accuracy against its theoretical optimal benchmark. By freezing the domain boundaries, the divergence measures are predicted for the most crucial steps of a modelling algorithm. To precisely refine the score using weighting constants, big data analysis could further be deployed.
Self-incompatibility limits sexual reproduction rather than environmental conditions in an invasive aquatic plant
Authors: Portillo Lemus Luis O. , Bozec Michel , Harang Marilyne , Coudreuse Julie , Haury Jacques , Stoeckel Solenn , Barloy Dominique
Published: July 2020

Fruitfulness and fertility are important components of sexual reproductive success in plants, and often depends on environmental conditions and reproductive systems. For invasive plants, fruitfulness and fertility control their ecological success and adaptation in invaded ecosystems. We studied which factors bring about fruitfulness and fertility in invasive populations of the aquatic plantLudwigia grandiflorasubsp.hexapetala.

We analysed fruitfulness and fertility of 37 populations growing under variable climatic conditions in Western Europe, and sub-sampled fruitful and fruitless populations grown in common controlled conditions. We carried out self- and cross-pollinations and measured their floral biometrics.

Environmental conditions, and temperature in particular, did not affect fruitfulness and fertility in-situ or in common controlled environments. Hand-pollinations resulted in fruit production by individuals sampled from fruitless populations when pollen came from fruitful populations, and by individuals sampled from fruitful populations whatever the origin of pollen. Floral biometrics evidenced the existence of two floral morphs that overlapped with fruitfulness, and individual incompatibility.

Our results rebutted the hypothesis that environmental conditions control fruitfulness and fertility in these invasive populations. We instead found that fruit and seed production were controlled by a reproductive system involving a self-incompatible approach herkogamous morph and a self-compatible reverse herkogamous morph. We assessed the floral morphs distribution worldwide of fruitless and fruitful native and invasive populations that matched our results at larger scale. Our results may constitute the first evidence of a possible heteromorphic self-incompatible system inLudwigiapopulations and in Onagraceae phylogeny. It calls for further investigations on reproductive systems in this plant family. Finally, the observation that the self-incompatible morph seemed to be the world most invasive morph in this species tackles our understanding of biological and ecological conditions for invasiveness.

Synthesis. Our study showed that fruitfulness and fertility in the aquatic invasive plant,Ludwigia grandiflorasubsp.hexapetaladepend on a self-incompatibility system coinciding with two floral morphs, rather than environmental conditions and limitations. These new explanations on the sexual success ofLudwigiainvasive populations will help defining new predictions about its worldwide spreads and ecological success, and will help reappraising future management plans.
VIRIDIC – a novel tool to calculate the intergenomic similarities of prokaryote-infecting viruses
Authors: Moraru Cristina , Varsani Arvind , Kropinski Andrew M.
Published: July 2020

Nucleotide based intergenomic similarities are useful to understand how viruses are related with each other and to classify them. Here we have developed VIRIDIC, which implements the traditional algorithm used by the International Committee on Taxonomy of Viruses (ICTV), Bacterial and Archaeal Viruses Subcommittee, to calculate virus intergenomic similarities. When compared with other software, VIRIDIC gave the best agreement with the traditional algorithm. Furthermore, it proved best at estimating the relatedness between more distantly related phages, relatedness that other tools can significantly overestimate. In addition to the intergenomic similarities, VIRIDIC also calculates three indicators of the alignment ability to capture the relatedness between viruses: the aligned fractions for each genome in a pair and the length ratio between the two genomes. The main output of VIRIDIC is a heatmap integrating the intergenomic similarity values with information regarding the genome lengths and the aligned genome fraction. VIRIDIC is available at viridic.icbm.de, both as a web-service and a stand-alone tool. It allows fast analysis of large phage genome datasets, especially in the stand-alone version, which can be run on the user’s own servers and can be integrated in bioinformatics pipelines. VIRIDIC was developed having viruses ofBacteriaandArchaeain mind, however, it could potentially be used for eukaryotic viruses as well, as long as they are monopartite.
QUALIS: The journal ranking system undermining the impact of Brazilian science
Authors: Jaffé Rodolfo
Published: July 2020

A system called QUALIS was implemented in Brazil in 2009, intended to rank graduate programs from different subject areas and promote selected national journals. Since this system uses a complicated suit of criteria (differing among subject areas) to group journals into discrete categories, it could potentially create incentives to publish in low-impact journals ranked highly by QUALIS. Here I assess the influence of the QUALIS journal ranking system on the global impact of Brazilian science. Brazil shows a steeper decrease in the number of citations per document since the implementation of this QUALIS system, compared to the top Latin American countries publishing more scientific articles. All subject areas showed some degree of bias, with social sciences being usually more biased than natural sciences. Lastly, the decrease in the number of citations over time proved steeper in a more biased subject area, suggesting a faster shift towards low-impact journals. Overall, the findings documented here suggest that the QUALIS system has undermined the global impact of Brazilian science, and reinforce a recent recommendation from an official committee evaluating graduate programs to eliminate QUALIS. A system based on impact metrics could avoid introducing distorted incentives, and thereby boost the global impact of Brazilian science.
CHO/LY-B cell growth under limiting sphingolipid supply: correlation between lipid composition and biophysical properties of sphingolipid-restricted cell membranes+
Authors: Monasterio Bingen G. , Jiménez-Rojo Noemi , García-Arribas Aritz B. , Riezman Howard , Goñi Félix M. , Alonso Alicia
Published: July 2020

Sphingolipids (SL) are ubiquitous in mammalian cell membranes, yet there is little data on the behavior of cells under SL-restriction conditions. LY-B cells derive from a CHO line in which serine palmitoyl transferase (SPT), thusde novoSL synthesis, is suppressed, while maintaining the capacity of taking up and metabolizing exogenous sphingoid bases from the culture medium. In the present study LY-B cells were adapted to grow in a fetal bovine serum (FBS)-deficient medium to avoid external uptake of lipids. The lowest FBS concentration that allowed LY-B cell growth, though at a slow rate, under our conditions was 0.04%, i.e. 250-fold less than the standard (10%) concentration. Cells grown under limiting SL concentrations remained viable for at least 72 h. Enriching with sphingomyelin the SL-deficient medium allowed the recovery of control LY-B cell growth rates. Studies including whole cells, plasma membrane preparations, and derived lipid vesicles were carried out. Laurdan fluorescence was recorded to measure membrane molecular order, showing a significant decrease in the rigidity of LY-B cells, not only in plasma membrane but also in whole cell lipid extract, as a result of SL limitation in the growth medium. Plasma membrane preparations and whole cell lipid extracts were also studied using atomic force microscopy in the force spectroscopy mode. Force measurements demonstrated that lower breakthrough forces were required to penetrate samples obtained from SL-poor LY-B cells than those obtained from control cells. Mass-spectroscopic analysis was also a helpful tool to understand the rearrangement undergone by the LY-B cell lipid metabolism. The most abundant SL in LY-B cells, sphingomyelin, decreased by about 85% as a result of SL limitation in the medium, the bioactive lipid ceramide and the ganglioside precursor hexosylceramide decreased similarly, together with cholesterol. Quantitative SL analysis showed that a 250-fold reduction in sphingolipid supply to LY-B cells led to a 6-fold decrease in membrane sphingolipids, underlining the resistance to changes in composition of these cells. Plasma membrane compositions exhibited similar changes, at least qualitatively, as the whole cells with SL restriction. A linear correlation was observed between the sphingomyelin concentration in the membranes, the degree of lipid order as measured by laurdan fluorescence, and membrane breakthrough forces assessed by atomic force microscopy. Concomitant changes were detected in glycerophospholipids under SL-restriction conditions.
The Torsin/ NEP1R1-CTDNEP1/ Lipin axis regulates nuclear envelope lipid metabolism for nuclear pore complex insertion
Authors: Jacquemyn Julie , Foroozandeh Joyce , Vints Katlijn , Swerts Jef , Verstreken Patrik , Gounko Natalia V. , Gallego Sandra F. , Goodchild Rose
Published: July 2020

Torsin ATPases of the endoplasmic reticulum (ER) and nuclear envelope (NE) lumen inhibit Lipin-mediated phosphatidate (PA) to diacylglycerol (DAG) conversion by an unknown mechanism. This excess PA metabolism is implicated inTOR1A/TorsinA diseases, but it is unclear whether it explains why Torsin concomitantly affects nuclear structure, lipid droplets (LD), organelle and cell growth. Here a fly miniscreen identified that Torsins affect these events via the NEP1R1-CTDNEP1 phosphatase complex. Further, Torsin homo-oligomerization rather than ATPase activity was key to function. NEP1R1-CTDNEP1 activates Lipin by dephosphorylation. We show that Torsin prevents CTDNEP1 from accumulating in the NE and excludes Lipin from the nucleus. Moreover, this repression of nuclear PA metabolism is required for interphase nuclear pore biogenesis. We conclude that Torsin is an upstream regulator of the NEP1R1-CTDNEP1/ Lipin pathway. This connects the ER/NE lumen with PA metabolism, and affects numerous cellular events including it has a previously unrecognized role in nuclear pore biogenesis.

Highlights

Nuclear envelope PA-DAG-TAG synthesis is independently regulated by Torsin and Torip/LAP1

Torsin removes CTDNEP1 from the nuclear envelope and excludes Lipin from the nucleus

Excess nuclear envelope NEP1R1-CTDNEP1/ Lipin activity impairs multiple aspects of NPC biogenesis

NEP1R1-CTDNEP1/ Lipin inhibition prevents cellular defects associated withTOR1AandTOR1AIP1/ LAP1 disease
Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice
Authors: Botterill Justin J , Vinod K Yaragudri , Gerencer Kathleen J , Teixeira Cátia M , LaFrancois John J , Scharfman Helen E
Published: July 2020

The dentate gyrus (DG) of the hippocampus is important for cognitive and affective behaviors. However, the circuits underlying these behaviors are unclear. DG mossy cells (MCs) have been a focus of attention because of their excitatory synapses on the primary DG cell type, granule cells (GCs). However, MCs also activate DG GABAergic neurons which inhibit GCs. We took advantage of specific methods and a gain- and loss-of function strategy with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to study MCs in diverse behaviors. Using this approach, manipulations of MCs could bidirectionally regulate behavior. The results suggest that inhibiting MCs can reduce anxiety-like behavior and improve cognitive performance. However, not all cognitive or anxiety-related behaviors were influenced, suggesting specific roles of MCs in some but not all types of cognition and anxiety. Notably, several behaviors showed sex-specific effects, with females often showing more pronounced effects than the males. We also used the immediate early gene c-Fos to address whether DREADDs bidirectionally regulated MC or GC activity. We confirmed excitatory DREADDs increased MC c-Fos. However, there was no change in GC c-Fos, consistent with MC activation leading to GABAergic inhibition of GCs. In contrast, inhibitory DREADDs led to a large increase in GC c-Fos, consistent with a reduction in MC excitation of GABAergic neurons, and reduced inhibition of GCs. Taken together, these results suggest that MCs regulate anxiety and cognition in specific ways. We also raise the possibility that cognitive performance may be improved by reducing anxiety.

SIGNIFICANCE STATEMENT

The dentate gyrus (DG) has many important cognitive roles as well as being associated with affective behavior. This study addressed how a glutamatergic DG cell type called mossy cells (MCs) contributes to diverse behaviors, which is timely because it is known that MCs regulate the activity of the primary DG cell type, granule cells (GCs), but how MC activity influences behavior is unclear. We show, surprisingly, that activating MCs can lead to adverse behavioral outcomes, and inhibiting MCs have an opposite effect. Importantly, the results appeared to be task-dependent and showed that testing both sexes was important. Additional experiments indicated what MC and GC circuitry was involved. Taken together, the results suggest how MCs influence behaviors that involve the DG.
Crash landing ofVibrio choleraeby MSHA pili-assisted braking and anchoring in a viscoelastic environment
Authors: Zhang Wenchao , Luo Mei , Feng Chunying , Liu Huaqing , Zhang Hong , Bennett Rachel R. , Utada Andrew S. , Liu Zhi , Zhao Kun
Published: July 2020

Mannose-sensitive hemagglutinin (MSHA) pili and flagellum are critical for the surface attachment ofVibrio cholerae, the first step ofV. choleraecolonization on host surfaces. However, the cell landing mechanism remains largely unknown, particularly in viscoelastic environments such as the mucus layers of intestines. Here, combining the cysteine-substitution-based labelling method with single-cell tracking techniques, we quantitatively characterized the landing ofV. choleraeby directly observing both pili and flagellum of cells in a viscoelastic non-Newtonian solution consisting of 2% Luria-Bertani and 1% methylcellulose (LB+MC). The results show that MSHA pili are evenly distributed along the cell length and can stick to surfaces at any point along the filament. With such properties, MSHA pili are observed to act as a brake and anchor during cell landing which include three phases: running, lingering, and attaching. Importantly, loss of MSHA pili results in a more dramatic increase in mean path length in LB+MC than in 2% LB only or in 20% Ficoll solutions, indicating that the role of MSHA pili during cell landing is more apparent in viscoelastic non-Newtonian fluids than viscous Newtonian ones. Our work provides a detailed picture of the landing dynamics ofV. choleraeunder viscoelastic conditions, which can provide insights into ways to better controlV. choleraeinfections in real mucus-like environment.
Higher order thalamus encodes correct goal-directed action
Authors: LaTerra D. , Petryszyn S. , Rosier Marius , Palmer L.M.
Published: July 2020

The thalamus is the gateway to the cortex. Cortical encoding of sensory information can therefore only be understood by considering the influence of thalamic processing on sensory input. Despite modulating sensory processing, little is known about the role of the thalamus during sensory-based behavior, let alone goal-directed behavior. Here, we use two-photon Ca2+imaging, patch-clamp electrophysiology and optogenetics to investigate the role of axonal projections from the posteromedial nucleus of the thalamus (POm) to the forepaw area of the primary somatosensory cortex (forepaw S1) during sensory processing and goal-directed behavior. We demonstrate that POm axons are active during tactile stimulus and increase activity specifically during the response and, to a lesser extent, reward epochs of a tactile goal-directed task. Furthermore, POm axons in forepaw S1 preferentially signaled correct behavior, with greatest activity during HIT responses. This activity is important for behavioral performance, as photoinhibition of archaerhodopsin-expressing neurons in the POm decreased overall behavioral success. Direct juxtacelluar recordings in the awake state illustrates POm neurons fire sustained action potentials during tactile stimulus. This tactile-evoked POm firing pattern was used during ChR2 photoactivation of POm axons in forepaw S1, revealing that action potentials in layer 2/3 (L2/3) pyramidal neurons are inhibited during sustained POm input. Taken together, POm axonal projections in forepaw S1 encode correct goal-directed active behavior, leading to GABAA-mediated inhibition of L2/3 pyramidal neurons.
Machine learning dimensionality reduction for heart rate n-variability (HRnV) based risk stratification of chest pain patients in the emergency department
Authors: Liu Nan , Chee Marcel Lucas , Koh Zhi Xiong , Leow Su Li , Wah Ho Andrew Fu , Guo Dagang , Hock Ong Marcus Eng
Published: July 2020

Background

Chest pain is among the most common presenting complaints in the emergency department (ED). Swift and accurate risk stratification of chest pain patients in the ED may improve patient outcomes and reduce unnecessary costs. Traditional logistic regression with stepwise variable selection has been used to build risk prediction models for ED chest pain patients. In this study, we aimed to investigate if machine learning dimensionality reduction methods can achieve superior performance than the stepwise approach in deriving risk stratification models.

Methods

A retrospective analysis was conducted on the data of patients >20 years old who presented to the ED of Singapore General Hospital with chest pain between September 2010 and July 2015. Variables used included demographics, medical history, laboratory findings, heart rate variability (HRV), and HRnV parameters calculated from five to six-minute electrocardiograms (ECGs). The primary outcome was 30-day major adverse cardiac events (MACE), which included death, acute myocardial infarction, and revascularization. Candidate variables identified using univariable analysis were then used to generate the stepwise logistic regression model and eight machine learning dimensionality reduction prediction models. A separate set of models was derived by excluding troponin. Receiver operating characteristic (ROC) and calibration analysis was used to compare model performance.

Results

795 patients were included in the analysis, of which 247 (31%) met the primary outcome of 30-day MACE. Patients with MACE were older and more likely to be male. All eight dimensionality reduction methods marginally but non-significantly outperformed stepwise variable selection; The multidimensional scaling algorithm performed the best with an area under the curve (AUC) of 0.901. All HRnV-based models generated in this study outperformed several existing clinical scores in ROC analysis.

Conclusions

HRnV-based models using stepwise logistic regression performed better than existing chest pain scores for predicting MACE, with only marginal improvements using machine learning dimensionality reduction. Moreover, traditional stepwise approach benefits from model transparency and interpretability; in comparison, machine learning dimensionality reduction models are black boxes, making them difficult to explain in clinical practice.
Signatures of introgression across the allele frequency spectrum
Authors: Martin Simon H. , Amos William
Published: July 2020

ABSTRCT

The detection of introgression from genomic data is transforming our view of species and the origins of adaptive variation. Among the most widely used approaches to detect introgression is the so-called ABBA BABA test orDstatistic, which identifies excess allele sharing between non-sister taxa. Part of the appeal ofDis its simplicity, but this also limits its informativeness, particularly about the timing and direction of introgression. Here we present a simple extension,Dfrequency spectrum orDFS, in whichDis partitioned according to the frequencies of derived alleles. We use simulations over a large parameter space to show howDFScaries information about various factors. In particular, recent introgression reliably leads to a peak inDFSamong low-frequency derived alleles, whereas violation of model assumptions can lead to a lack of signal at low-frequencies. We also reanalyse published empirical data from six different animal and plant taxa, and interpret the results in the light of our simulations, showing howDFSprovides novel insights. We currently seeDFSas a descriptive tool that will augment both simple and sophisticated tests for introgression, but in the future it may be usefully incorporated into probabilistic inference frameworks.
Characterization of colibactin-associated mutational signature in an Asian oral squamous cell carcinoma and in other mucosal tumor types
Authors: Boot Arnoud , Ng Alvin W.T. , Chong Fui Teen , Ho Szu-Chi , Yu Willie , Tan Daniel S.W. , Iyer N. Gopalakrishna , Rozen Steven G.
Published: July 2020

Mutational signatures can reveal the history of mutagenic processes that cells were exposed to before and during tumorigenesis. We expect that as-yet-undiscovered mutational processes will shed further light on mutagenesis leading to carcinogenesis. With this in mind, we analyzed the mutational spectra of 36 Asian oral squamous cell carcinomas. The mutational spectra of two samples from patients who presented with oral bacterial infections showed novel mutational signatures. One of these novel signatures, SBS_AnT, is characterized by a preponderance of thymine mutations, strong transcriptional strand bias, and enrichment for adenines in the 4 bp 5′ of mutation sites. The mutational signature described in this manuscript was shown to be caused by colibactin, a bacterial mutagen produced by E. coli carrying the pks-island. Examination of publicly available sequencing data revealed SBS_AnT in 25 tumors from several mucosal tissue types, expanding the list of tissues in which this mutational signature is observed.
Simple and efficient profiling of transcription initiation and transcript levels with STRIPE-seq
Authors: Policastro Robert A. , Raborn R. Taylor , Brendel Volker P. , Zentner Gabriel E.
Published: July 2020

Accurate mapping of transcription start sites (TSSs) is key for understanding transcriptional regulation. However, current protocols for genome-wide TSS profiling are laborious and/or expensive. We present Survey of TRanscription Initiation at Promoter Elements with high-throughput sequencing (STRIPE-seq), a simple, rapid, and cost-effective protocol for sequencing capped RNA 5′ ends from as little as 50 ng total RNA. Including depletion of uncapped RNA and reaction cleanups, a STRIPE-seq library can be constructed in about 5 h. We show application of STRIPE-seq to TSS profiling in yeast and human cells and show that it can also be effectively used for quantification of transcript levels and analysis of differential gene expression. In conjunction with our ready-to-use computational workflows, STRIPE-seq is a straightforward, efficient means by which to probe the landscape of transcriptional initiation.