bluuebunny/crossref_metadata_2025 huggingface dataset:
Trajectories of Pelvic Floor Symptoms and Support After Vaginal Delivery in Primiparous Women Between Third Trimester and 1 Year Postpartum
Authors: Hill Audra Jolyn , Yang Jingye , Martinez Liliana I. , Nygaard Ingrid , Egger Marlene J.
Published: August 2021

Objectives

The objectives of this study were to describe trajectories of pelvic floor symptoms and support from the third trimester to 1 year postpartum in primiparous women after vaginal delivery and to explore factors associated with their resolution between 8 weeks postpartum and 1 year postpartum.

Methods

Five hundred ninety-seven nulliparous women 18 years or older who gave birth vaginally at term completed the Epidemiology of Prolapse and Incontinence Questionnaire and the Pelvic Organ Prolapse Quantification examination at the third trimester, 8 weeks postpartum, and 1 year postpartum.

Results

At 1 year postpartum, 41%, 32%, and 23% of participants reported stress urinary incontinence, nocturia, and flatus incontinence, respectively, and 9% demonstrated maximal vaginal descent (MVD) ≥ 0 cm. For more common symptoms, incidence rates between the third trimester and 8 weeks postpartum ranged from 6% for urinary frequency to 22% for difficult bowel movements, and resolution rates between 8 weeks postpartum and 1 year postpartum ranged from 23% for stress urinary incontinence to 73% for pain. Between the third trimester and 8 weeks postpartum, 13% demonstrated de novo MVD ≥ 0 cm. For most symptoms, the presence of the same symptom before delivery decreased the probability of resolution between 8 weeks postpartum and 1 year. However, the sensitivities of predelivery vaginal bulge and MVD of 0 cm or greater for those outcomes at 1 year postpartum was overall low (10–12%).

Conclusions

One year postpartum, urinary and bowel symptoms are common in primiparous women who gave birth vaginally. A substantial portion of this burden is represented by symptoms present before delivery, while most of the prevalence of worse anatomic support is accounted for by de novo changes after delivery.
Personalized Early AAC Intervention to Build Language and Literacy Skills
Authors: Light Janice , Barwise Allison , Gardner Ann Marie , Flynn Molly
Published: August 2021

Personalized augmentative and alternative communication (AAC) intervention refers to an approach in which intervention is tailored to the individual's needs and skills, the needs and priorities of the individual's family and other social environments, the evidence base, and the individual's response to intervention. This approach is especially relevant to AAC intervention for young children with complex communication needs given their unique constellations of strengths and challenges, and the qualitative and quantitative changes that they experience over time as they develop, as well as the diversity of their families, schools, and communities. This article provides detailed documentation of personalized AAC intervention over a 6-month period for a 3-year-old girl with developmental delay and complex communication needs. The article describes (1) personalization of multimodal AAC supports to provide this child with the tools to communicate; (2) personalized intervention to build semantic and morphosyntactic skills; and (3) personalized instruction in literacy skills (i.e., letter sound correspondences, sound blending, decoding, sight word recognition, reading simple stories, reading comprehension, and encoding skills). Specific goals, instructional materials, and procedures are described; data on speech, language, and literacy outcomes are presented.
Electrocardiographic Findings Associated With Neurological Pathology and Other T-Wave Catastrophes
Authors: Davis Wesley D. , Goettl Bradley , Bowden Leah
Published: August 2021

An 87-year-old female patient presented with altered mental status. During the routine workup for altered mental status, an electrocardiogram (ECG) was obtained. The ECG showed T-wave morphology known to be consistent with myocardial infarction. Although the ECG is a crucial diagnostic tool to recognize myocardial ischemia and infarction promptly, it must be understood that T-wave abnormalities can represent noncardiac pathology. A case presentation illustrates a unique ECG change whose presence is associated with catastrophic central nervous system diseases that cause increased intracranial pressure.
Implementation of a Procainamide-Based Cardioversion Strategy for the Management of Recent-Onset Atrial Fibrillation
Authors: Matuskowitz Andrew J. , Weant Kyle A. , Gregory Haili , Field Michael E. , Calhoun Chara , Bushkar Brent J. , Hall Gregory A. , Caporossi Jeffrey
Published: August 2021

Atrial fibrillation/flutter (AF) remains the most common rhythm disturbance in adult patients presenting to emergency departments (EDs). Although pharmacologic cardioversion has been established as safe and effective in recent-onset AF, its use in U.S. EDs is uncommon. The purpose of this study was to assess the safety and efficacy of intravenous (IV) procainamide for pharmacologic cardioversion in patients presenting to the ED with AF of <48-hr duration. Patients presenting to the ED with recent-onset AF (<48 hr) undergoing a cardioversion strategy with IV procainamide from 2017 to 2019 were reviewed. Clinical outcomes assessed included rates of cardioversion, hospital admission, stroke, and return ED visits for arrhythmia or serious adverse events. A total of 64 patients received procainamide therapy—60.9% achieved cardioversion and 35.9% were admitted to the hospital. The mean dose was 1062.4 mg (12.1 mg/kg). No patients returned to the ED secondary to stroke and 9.4% experienced complications attributed to procainamide, the most common being hypotension. Within 30 days of therapy, 20.3% of patients returned to the ED secondary to arrhythmia recurrence. Patients experiencing cardioversion with procainamide were less likely to be admitted to the hospital (25.6% vs. 52.0%; p = 0.04) or receive a rate control agent (17.9% vs. 64.0%; p = 0.001). There was no significant difference in the rate of 30-day return between those who experienced pharmacologic cardioversion and those who did not (p = 0.220). The implementation of a procainamide-based acute cardioversion strategy for patients presenting to the ED with recent-onset AF resulted in a 60% cardioversion rate, which was associated with a significantly higher rate of discharge from the ED. Transient hypotension was the most common adverse event. Further investigation into ED-based protocols for management of recent-onset AF is necessary to better understand their safety and efficacy.
Improving Communication Between Hospital and Outpatient Psychiatric Providers
Authors: Sietsma Alexandra C. , Brennan-Cook Jill M. , Malak Lawrence T. , Lauzon Vanessa L.
Published: August 2021

Patients suffering from mental illness are often less likely to engage in treatment at an outpatient level. Lack of communication and coordination of care between providers has negative results for the health system and the patient. Improved communication has shown improved satisfaction of providers in health care. Using prior research, an electronic reminder and standardized documentation of communication was added to the health system's electronic health record. The aim of this quality improvement (QI) project was to compare pre-/postintervention communication and satisfaction between emergency department and outpatient psychiatric providers. The QI project was conducted on a convenience sample of 13 outpatient psychiatric providers at a large academic medical center. Using a pre-/postintervention design, QI project data were collected via chart reviews and pre-/postsurveys. The chart review results revealed the communication rate increased significantly from pre (22%) to post (85%), p < .001. The survey results revealed overall satisfaction had statistically significant increase from pre- (Mdn = 3, neutral) to postintervention (Mdn = 5, very satisfied), Z = −2.21, p =.027. The survey results revealed a statistically significant increase in frequency of direct communication from pre- (21%–40%) to postintervention (81%–100%), Z = −2.06, p = .039. The QI project documents an increase in both provider satisfaction and communication post-intervention.
Comparing Performance of Different Predictive Models in Estimating Disease Progression in Alzheimer Disease
Authors: Ezzati Ali , Zammit Andrea R. , Lipton Richard B.
Published: August 2021

Background:

Automatic classification techniques provide tools to analyze complex data and predict disease progression.

Methods:

A total of 305 cognitively normal; 475 patients with amnestic mild cognitive impairment (aMCI); and 162 patients with dementia were included in this study. We compared the performance of 3 different methods in predicting progression from aMCI to dementia: (1) index-based model; (2) logistic regression (LR); and (3) ensemble linear discriminant (ELD) machine learning models. LR and ELD models were trained using data from cognitively normal and dementia subgroups, and subsequently were applied to aMCI subgroup to predict their disease progression.

Results:

Performance of ELD models were better than LR models in prediction of conversion from aMCI to Alzheimer dementia at all time frames. ELD models performed better when a larger number of features were used for prediction.

Conclusion:

Machine learning models have substantial potential to improve the predictive ability for cognitive outcomes.
Industrial applications of digital twins
Authors: Jiang Yuchen , Yin Shen , Li Kuan , Luo Hao , Kaynak Okyay
Published: August 2021

A digital twin (DT) is classically defined as the virtual replica of a real-world product, system, being, communities, even cities that are continuously updated with data from its physical counterpart, as well as its environment. It bridges the virtual cyberspace with the physical entities and, as such, is considered to be the pillar of Industry 4.0 and the innovation backbone of the future. A DT is created and used throughout the whole life cycle of the entity it replicates, from cradle to grave, so to speak. This article focuses on the present state of the art of DTs, concentrating on the use of DTs in industry in the context of smart manufacturing, especially from the point of view of plantwide optimization. The main capabilities of DTs (mirroring, shadowing and threading) are discussed in this context. The article concludes with a perspective on the future.

This article is part of the theme issue ‘Towards symbiotic autonomous systems’.
The personal digital twin, ethical considerations
Authors: de Kerckhove Derrick
Published: August 2021

The personal digital twin extends to individual persons, a concept that originated in engineering to twin complex machines with a digital simulation containing a model of its functions to monitor its past and present behaviour, and repair, correct, improve or otherwise ensure its optimal operation. Several independent trends in technological developments are seen to converge towards the elaboration of the digital replication of individual human data and life history, notably in health industries. Among the main ones, we consider the ubiquitous distribution of digital assistants, the rapid progress of machine learning concurrent with the exponential growth of ‘personal’ Big Data and the incipient interest in developing lifelogs. The core hypothesis here is that among the psychological effects of the digital transformation, the externalization of cognitive faculties such as memory, planning and judgement, the decision-making processes located within the human person are also emigrating to digital functions, perhaps as a prelude to a later re-integration within the person via brain–computer interfaces. The paper concludes with ethical considerations about these ongoing developments.

This article is part of the theme issue ‘Towards symbiotic autonomous systems’.
Stochastic model predictive control framework for resilient cyber-physical systems: review and perspectives
Authors: Chen Jicheng , Shi Yang
Published: August 2021

In the era of Industrial 4.0, the next-generation control system regards the cyber-physical system (CPS) as the core ingredient thanks to the comprehensive integration of physical systems, online computation, networking and control. A reliable, stable and resilient CPS should pledge robustness and safety. A significant concern in CPS development arises from security issues since the CPS is vulnerable to physical constraints, ubiquitous uncertainties and malicious cyber attacks. The integration of the stochastic model predictive control (MPC) framework and the resilient mechanism is a possible approach to guarantee robustness in the presence of stochastic uncertainties and enable resilience against cyber attacks. This review paper aims to offer a detailed overview of existing stochastic MPC algorithms and their CPS applications. More specifically, we first review existing stochastic MPC algorithms for both linear and nonlinear systems subject to probabilistic constraints. We then discuss how to extend the stochastic MPC framework to incorporate resilience mechanisms for constrained CPS under various malicious attacks. Finally, we present an architectural stochastic MPC-based framework for resilient CPS and identify future research challenges.

This article is part of the theme issue ‘Towards symbiotic autonomous systems’.
Sediminihaliea albiluteola gen. nov., sp. nov., a new member of the family Halieaceae, isolated from marine sediment
Authors: Jiang Shan , Lian Feng-Bai , Sun You-Yang , Zhang Xiao-Kui , Du Zong-Jun
Published: August 2021

A Gram-stain-negative, rod-shaped and facultatively aerobic bacterial strain, designated F7430T, was isolated from coastal sediment collected at Jingzi Wharf in Weihai, PR China. Cells of strain F7430T were 0.3–0.4 µm wide, 2.0–2.6 µm long, non-flagellated, non-motile and formed pale-beige colonies. Growth was observed at 4–40 °C (optimum, 30 °C), pH 6.0–9.0 (optimum, pH 7.5–8.0) and at NaCl concentrations of 1.0–10.0 % (w/v; optimum, 1.0 %). The sole respiratory quinone of strain F7430T was ubiquinone 8 and the predominant cellular fatty acids were summed feature 8 (C18 : 1
 ω7c / C18 : 1
 ω6c; 60.7 %), summed feature 3 (C16 : 1
 ω7c/C16 : 1
 ω6c; 30.2 %) and C15 : 0 iso (13.9 %). The polar lipids of strain F7430T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid and three unidentified lipids. Results of 16S rRNA gene sequences analyses indicated that this strain belonged to the family

Halieaceae

and had high sequence similarities to

Parahaliea aestuarii

JCM 51547T (95.3 %) and

Halioglobus pacificus

DSM 27932T (95.2 %) followed by 92.9–95.0 % sequence similarities to other type species within the aforementioned family. The rpoB gene sequences analyses indicated that the novel strain had the highest sequence similarities to

Parahaliea aestuarii

JCM 51547T (82.2 %) and

Parahaliea mediterranea

DSM 21924T (82.2 %) followed by 75.2–80.5 % sequence similarities to other type species within this family. Phylogenetic analyses showed that strain F7430T constituted a monophyletic branch clearly separated from the other genera of family

Halieaceae

. Whole-genome sequencing of strain F7430T revealed a 3.3 Mbp genome size with a DNA G+C content of 52.6 mol%. The genome encoded diverse metabolic pathways including the Entner–Doudoroff pathway, assimilatory sulphate reduction and biosynthesis of dTDP-l-rhamnose. Based on results from the current polyphasic study, strain F7430T is proposed to represent a novel species of a new genus within the family

Halieaceae

, for which the name Sediminihaliea albiluteola gen. nov., sp. nov. is proposed. The type strain of the type species is F7430T (=KCTC 72873T=MCCC 1H00420T).
Genetic parameters of colostrum and calf serum antibodies in Swedish dairy cattle
Authors: Cordero-Solorzano Juan , de Koning Dirk-Jan , Tråvén Madeleine , de Haan Therese , Jouffroy Mathilde , Larsson Andrea , Myrthe Aline , Arts Joop A.J. , Parmentier Henk K. , Bovenhuis Henk , Wensman Jonas Johansson
Published: August 2021

Background

Colostrum with sufficient IgG content is essential for the newborn calf, as it provides passive immunity which substantially affects the probability of survival during rearing. Failure of passive transfer occurs when a calf does not absorb enough antibodies from the colostrum as indicated by less than 10 g/L of IgG in calf serum. Besides delayed access to colostrum, this can be due to low IgG production of the mother or poor IgG absorption by the calf. The aim of this study was to estimate the genetic background of antibody levels and indicator traits for antibodies in colostrum and calf serum, and their correlation with milk production and health.

Results

Colostrum data were available from 1340 cows with at least one calving and calf serum data were available from 886 calves from these cows. Antibody concentrations were estimated using refractometry (digital Brix refractometer for colostrum and optical refractometer for serum) as indicator traits and established using ELISAs to determine total IgG and natural antibodies [NAb] of various antibody isotypes in colostrum and serum. Colostrum traits had heritabilities ranging from 0.16 to 0.31 with repeatabilities from 0.21 to 0.55. Brix had positive genetic correlations with all colostrum antibody traits including total IgG (0.68). Calf serum antibody concentrations had heritabilities ranging from 0.25 to 0.59, with a significant maternal effect accounting for 17 to 27% of the variance. When calves later in life produced their first lactation, lactation-average somatic cell score was found to be negatively correlated with NAb in calf serum.

Conclusions

Our results suggest that antibody levels in colostrum and calf serum can be increased by means of selection.
A Driven Disordered Systems Approach to Biological Evolution in Changing Environments
Authors: Das Suman G , Krug Joachim , Mungan Muhittin
Published: August 2021

Biological evolution of a population is governed by the fitness landscape, which is a map from genotype to fitness. However, a fitness landscape depends on the organisms environment, and evolution in changing environments is still poorly understood. We study a particular model of antibiotic resistance evolution in bacteria where the antibiotic concentration is an environmental parameter and the fitness landscapes incorporate tradeoffs between adaptation to low and high antibiotic concentration. With evolutionary dynamics that follow fitness gradients, the evolution of the system under slowly changing antibiotic concentration resembles the athermal dynamics of disordered physical systems under quasistatic external drives. Specifically, our model can be described as a system with interacting hysteretic elements, and it exhibits effects such as hysteresis loops and memory formation under antibiotic concentration cycling. Using methods familiar from studies in this field, we derive a number of analytical and numerical results. Our approach provides a general framework for studying motifs of evolutionary dynamics in biological systems in a changing environment.
scAgeCom: a murine atlas of age-related changes in intercellular communication inferred with the package scDiffCom
Authors: Lagger Cyril , Ursu Eugen , Equey Anaïs , Avelar Roberto A. , Pisco Angela O. , Tacutu Robi , de Magalhães João Pedro
Published: August 2021

Dysregulation of intercellular communication is a well-established hallmark of aging. To better understand how this process contributes to the aging phenotype, we built scAgeCom, a comprehensive atlas presenting how cell-type to cell-type interactions vary with age in 23 mouse tissues. We first created an R package, scDiffCom, designed to perform differential intercellular communication analysis between two conditions of interest in any mouse or human single-cell RNA-seq dataset. The package relies on its own list of curated ligand-receptor interactions compiled from seven established studies. We applied this tool to single-cell transcriptomics data from the Tabula Muris Senis consortium and the Calico murine aging cell atlas. All the results can be accessed online, using a user-friendly, interactive web application (https://scagecom.org). The most widespread changes we observed include upregulation of immune system processes, inflammation and lipid metabolism, and downregulation of extracellular matrix organization, growth, development and angiogenesis. More specific interpretations are also provided.
AngioPlate – Biofabrication of perfusable complex tissues in multi-well plates with 4D subtractive manufacturing
Authors: Rajasekar Shravanthi , Lin Dawn S. Y. , Zhang Feng , Sotra Alexander , Boshart Alex , Clotet-Freixas Sergi , Liu Amy , Hirota Jeremy A. , Ogawa Shinichiro , Konvalinka Ana , Zhang Boyang
Published: August 2021

Organ-on-a-chip systems that recapitulate tissue-level functions have been proposed to improve in vitro–in vivo correlation in drug development. Significant progress has been made to control the cellular microenvironment with mechanical stimulation and fluid flow. However, it has been challenging to introduce complex 3D tissue structures due to the physical constraints of microfluidic channels or membranes in organ-on-a-chip systems. Although this problem could be addressed with the integration of 3D bioprinting, it is not an easy task because the two technologies have fundamentally different fabrication processes. Inspired by 4D bioprinting, we develop a 4D subtractive manufacturing technique where a flexible sacrificial material can be patterned on a 2D surface, change shape when exposed to aqueous hydrogel, and subsequently degrade to produce perfusable networks in a natural hydrogel matrix that can be populated with cells. The technique is applied to fabricate organ-specific vascular networks, vascularized kidney proximal tubules, and terminal lung alveoli in a customized 384-well plate and then further scaled to a 24-well plate format to make a large vascular network, vascularized liver tissues, and for integration with ultrasound imaging. This biofabrication method eliminates the physical constraints in organ-on-a-chip systems to incorporate complex ready-to-perfuse tissue structures in an open-well design.
The rs1421085 variant within FTO promotes but not inhibits thermogenesis and is potentially associated with human migration
Authors: Zhang Zhiyin , Chen Na , Liu Ruixin , Yin Nan , He Yang , Li Danjie , Tong Muye , Gao Aibo , Lu Peng , Li Huabing , Zhang Dan , Gu Weiqiong , Hong Jie , Wang Weiqing , Qi Lu , Wang Jiqiu , Ning Guang
Published: August 2021

Disease-associated GWAS loci are predominantly scattered among noncoding regions of the human genome, which impedes causality estimation. One lead risk signal of obesity–rs1421085 T>C within the FTO gene–is reported to functional in vitro but lack of organismal evidence. Here, we established global and the brown-adipocyte specific locus-knock-in mice to recapitulate this homologous variant in humans, and discovered the minor allele (C-allele) as one candidate thermogenic locus. Mice carrying the C-alleles showed increased thermogenic capacity and a resistance to high-fat diet-induced adiposity. In terms of mechanism, the knock-in models showed enhanced FTO expression, while FTO knockdown or inhibition effectively eliminated the increased thermogenic ability of brown adipocytes. In humans, the C-allele was associated with lower birthweight, and its allele frequency increases following the environmental temperature decreases. Cumulatively, these findings demonstrated rs1421085 T>C as a functional variant regulating whole-body thermogenesis, and this variation was possibly related to early human migration from hot to cold environments.
ImputeCoVNet: 2D ResNet Autoencoder for Imputation of SARS-CoV-2 Sequences
Authors: Pesaranghader Ahmad , Pelletier Justin , Grenier Jean-Christophe , Poujol Raphaёl , Hussin Julie
Published: August 2021

We describe a new deep learning approach for the imputation of SARS-CoV-2 variants. Our model, ImputeCoVNet, consists of a 2D ResNet Autoencoder that aims at imputing missing genetic variants in SARS-CoV-2 sequences in an efficient manner. We show that ImputeCoVNet leads to accurate results at minor allele frequencies as low as 0.0001. When compared with an approach based on Hamming distance, ImputeCoVNet achieved comparable results with significantly less computation time. We also present the provision of geographical metadata (e.g., exposed country) to decoder increases the imputation accuracy. Additionally, by visualizing the embedding results of SARS-CoV-2 variants, we show that the trained encoder of ImputeCoVNet, or the embedded results from it, recapitulates viral clade’s information, which means it could be used for predictive tasks using virus sequence analysis.
RAPPPID: Towards Generalisable Protein Interaction Prediction with AWD-LSTM Twin Networks
Authors: Szymborski Joseph , Emad Amin
Published: August 2021

Motivation

Computational methods for the prediction of protein-protein interactions, while important tools for researchers, are plagued by challenges in generalising to unseen proteins. Datasets used for modelling protein-protein predictions are particularly predisposed to information leakage and sampling biases.

Results

In this study, we introduce RAPPPID, a method for the Regularised Automatic Prediction of Protein-Protein Interactions using Deep Learning. RAPPPID is a twin AWD-LSTM network which employs multiple regularisation methods during training time to learn generalised weights. Testing on stringent interaction datasets composed of proteins not seen during training, RAPPPID outperforms state-of-the-art methods. Further experiments show that RAPPPID’s performance holds regardless of the particular proteins in the testing set and its performance is higher for biologically supported edges. This study serves to demonstrate that appropriate regularisation is an important component of overcoming the challenges of creating models for protein-protein interaction prediction that generalise to unseen proteins. Additionally, as part of this study, we provide datasets corresponding to several data splits of various strictness, in order to facilitate assessment of PPI reconstruction methods by others in the future. Availability and Implementation: Code and datasets are freely available at https://github.com/jszym/rapppid.

Contact

amin.emad@mcgill.ca

Supplementary Information

Online-only supplementary data is available at the journal’s website.
Point Mutations in SARS-CoV-2 Variants Induce Long-Range Dynamical Perturbations in Neutralizing Antibodies
Authors: Ray Dhiman , Quijano Riley Nicolas , Andricioaei Ioan
Published: August 2021

Monoclonal antibodies are emerging as a viable treatment for the coronavirus disease 19 (COVID-19). However, newly evolved variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can reduce the efficacy of currently available antibodies and can diminish vaccine-induced immunity. Here, we demonstrate that the microscopic dynamics of neutralizing monoclonal antibodies can be profoundly modified by the mutations present in the spike proteins of the SARS-COV-2 variants currently circulating in the world population. The dynamical perturbations within the antibody structure, which alter the thermodynamics of antigen recognition, are diverse and can depend both on the nature of the antibody and on the spatial location of the spike mutation. The correlation between the motion of the antibody and that of the spike receptor binding domain (RBD) can also be changed, modulating binding affinity. Using protein-graph-connectivity networks, we delineated the mutant-induced modifications in the information-flow along allosteric pathway throughout the antibody. Changes in the collective dynamics were spatially distributed both locally and across long-range distances within the antibody. On the receptor side, we identified an anchor-like structural element that prevents the detachment of the antibodies; individual mutations there can significantly affect the antibody binding propensity. Our study provides insight into how virus neutralization by monoclonal antibodies can be impacted by local mutations in the epitope via a change in dynamics. This realization adds a new layer of sophistication to the efforts for rational design of monoclonal antibodies against new variants of SARS-CoV2, taking the allostery in the antibody into consideration.
Deep graph learning of inter-protein contacts
Authors: Xie Ziwei , Xu Jinbo
Published: August 2021

Motivation

Inter-protein (interfacial) contact prediction is very useful for in silico structural characterization of protein-protein interactions. Although deep learning has been applied to this problem, its accuracy is not as good as intra-protein contact prediction.

Results

We propose a new deep learning method GLINTER (Graph Learning of INTER-protein contacts) for interfacial contact prediction of dimers, leveraging a rotational invariant representation of protein tertiary structures and a pretrained language model of multiple sequence alignments (MSAs). Tested on the 13th and 14th CASP-CAPRI datasets, the average top L/10 precision achieved by GLINTER is 54.35% on the homodimers and 51.56% on all the dimers, much higher than 30.43% obtained by the latest deep learning method DeepHomo on the homodimers and 14.69% obtained by BIPSPI on all the dimers. Our experiments show that GLINTER-predicted contacts help improve selection of docking decoys.

Contact

jinboxu@gmail.com
Arg1+ microglia are critical for shaping cognition in female mice
Authors: Stratoulias Vassilis , Ruiz Rocío , Kanatani Shigeaki , Osman Ahmed M. , Armengol Jose A. , Rodríguez-Moreno Antonio , Murgoci Adriana-Natalia , García-Domínguez Irene , Keane Lily , Vázquez-Cabrera Guillermo , Alonso-Bellido Isabel , Vernoux Nathalie , Tejera Dario , Grabert Kathleen , Cheray Mathilde , González-Rodríguez Patricia , Pérez-Villegas Eva M. , Martinez-Gallego Irene , Brodin David , Avila-Cariño Javier , Airavaara Mikko , Uhlén Per , Heneka Michael T. , Tremblay Marie-Ève , Blomgren Klas , Venero Jose L. , Joseph Bertrand
Published: August 2021

Diversity within microglia, the resident brain immune cells, is reported. Whether microglial subsets constitute different subtypes with intrinsic properties and unique functions has not been fully elucidated. Here, we describe a microglial subtype characterized by the expression of the enzyme Arginase-1, i.e. Arg1+microglia, which is found predominantly in the cholinergic neuron-rich forebrain region during early postnatal development. Arg1+ microglia are frequently observed in close apposition to neurons and exhibit a distinctive molecular signature reflecting a reactive profile. Arg1 deficiency in microglia results in impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, and cognitive behavioural deficiencies in female mice. Our results expand on microglia diversity and provide insights into distinctive spatiotemporal functions exerted by microglial subtypes.
Effects Of Video Games On Executive Control, Aggression and Gaming Motivation
Authors: Dixit Akshay , Sinha Divya , Ramachandran Hemalatha
Published: August 2021

With the advancements of computer technology and accessible internet, playing video games has become immensely popular across all age groups. Increasing research talks about the cognitive benefits of Video Games. At the same time, video games are stereotyped as an activity for the lazy and unproductive. Within this backdrop, our study aims to understand the effect of video games on Executive control (Visual Scanning and Visual Perception), Aggression, and Gaming Motivation.

Twenty non-gamers were selected and divided into two groups: Action Video Game Players (AVGP) and Non-Action Video Game Players NAVGP). We used two computerized tests: Gabor Orientation Identification Test and Visual Scanning Test (to assess visual perception and visual scanning, respectively) and two questionnaires (to assess aggression and gaming motivation). We found an improvement in visual perception as well as visual scanning following video game training in AVGPs. Interestingly, aggression did not increase with an increase in video game exposure. We also found insignificant changes in gaming motivation after the training, except for self-gratification motives.

Cognitive improvements do not relate to action video games alone, but non-action video games also show promising results to enhance cognition. With better timed and controlled training with video games, aggression as a prospective consequence of video game exposure can also be controlled. We propose targeted video game training as an approach to enhance cognition in non-gamers.
Reconfigurable asymmetric protein assemblies through implicit negative design
Authors: Sahtoe Danny D. , Praetorius Florian , Courbet Alexis , Hsia Yang , Wicky Basile I.M. , Edman Natasha I. , Miller Lauren M. , Timmermans Bart J. R. , Morris Hana M. , Kang Alex , Bera Asim K. , Baker David
Published: August 2021

Asymmetric multi-protein complexes that undergo subunit exchange play central roles in biology, but present a challenge for protein design. The individual components must contain interfaces enabling reversible addition to and dissociation from the complex, but be stable and well behaved in isolation. Here we employ a set of implicit negative design principles to generate beta sheet mediated heterodimers which enable the generation of a wide variety of structurally well defined asymmetric assemblies. Crystal structures of the heterodimers are very close to the design models, and unlike previously designed orthogonal heterodimer sets, the subunits are stable, folded and monomeric in isolation and rapidly assemble upon mixing. Rigid fusion of individual heterodimer halves to repeat proteins yields central assembly hubs that can bind two or three different proteins across different interfaces. We use these connectors to assemble linearly arranged hetero-oligomers with up to 6 unique components, branched hetero-oligomers, closed C4-symmetric two-component rings, and hetero-oligomers assembled on a cyclic homo-oligomeric central hub, and demonstrate such complexes can readily reconfigure through subunit exchange. Our approach provides a general route to designing asymmetric reconfigurable protein systems.
Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine
Authors: Kishi Koichiro E. , Kim Yoon Seok , Fukuda Masahiro , Kusakizako Tsukasa , Thadhani Elina , Byrne Eamon F.X. , Paggi Joseph M. , Ramakrishnan Charu , Matsui Toshiki E. , Yamashita Keitaro , Nagata Takashi , Konno Masae , Wang Peter Y. , Inoue Masatoshi , Benster Tyler , Uemura Tomoko , Liu Kehong , Shibata Mikihiro , Nomura Norimichi , Iwata So , Nureki Osamu , Dror Ron O. , Inoue Keiichi , Deisseroth Karl , Kato Hideaki E.
Published: August 2021

ChRmine1, a recently-discovered bacteriorhodopsin-like cation-conducting channelrhodopsin1, 2, exhibits puzzling properties (unusually-large photocurrents, exceptional red-shift in action spectrum, and extreme light-sensitivity) that have opened up new opportunities in optogenetics1, 3–5. ChRmine and its homologs function as light-gated ion channels, but by primary sequence more closely resemble ion pump rhodopsins; the molecular mechanisms for passive channel conduction in this family of proteins, as well as the unusual properties of ChRmine itself, have remained mysterious. Here we present the cryo-electron microscopy structure of ChRmine at 2.0 Å resolution. The structure reveals striking architectural features never seen before in channelrhodopsins including trimeric assembly, a short transmembrane-helix 3 unwound in the middle of the membrane, a prominently-twisting extracellular-loop 1, remarkably-large intracellular cavities and extracellular vestibule, and an unprecedented hydrophilic pore that extends through the center of the trimer, separate from the three individual monomer pores. Electrophysiological, spectroscopic, and computational analyses provide insight into conduction and gating of light-gated channels with these distinct design features, and point the way toward structure-guided creation of novel channelrhodopsins for optogenetic applications in biology.
Hyperactive chemotaxis contributes to anti-TNFα treatment resistance in inflammatory bowel disease
Authors: Yau Tung On , Vadakekolathu Jayakumar , Foulds Gemma Ann , Du Guodong , Polytarchou Christos , Dickins Benjamin , Rutella Sergio
Published: August 2021

Background & Aims

Anti-tumour necrosis factor-alpha (anti-TNFα) agents have been used for inflammatory bowel disease (IBD), however, it has up to 30% non-response rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient response to anti-TNFα treatment are clearly needed.

Methods

Publicly available transcriptomic data from IBD patients receiving anti-TNFα therapy was systemically collected and integrated.In silicoflow cytometry approaches and MetaScape were applied to evaluate immune cell populations and to perform gene enrichment analysis, respectively. Genes identified within enrichment pathways validated in neutrophils were tracked in an anti-TNFα-treated animal model (with lipopolysaccharide (LPS)-induced inflammation). The receiver operating characteristic (ROC) curve was applied to all genes to identify the best prediction biomarkers.

Results

A total of 449 samples were retrieved from control, baseline and after primary anti-TNFα therapy or placebo. No statistically significant differences were observed between anti-TNFα treatment responders and non-responders at baseline in immune microenvironment scores. Neutrophils, endothelial and B cell populations were higher in baseline non-responders and chemotaxis pathways may contribute to the treatment resistance. Genes related to chemotaxis pathways were significantly up-regulated in LPS-induced neutrophils but no statistically significant changes were observed in neutrophils treated with anti-TNFα. Interleukin 13 receptor subunit alpha 2 (IL13RA2) is the best predictor (ROC: 80.7%, 95% CI: 73.8% - 87.5%) with a sensitivity of 68.13% and specificity of 84.93%, and significantly higher in non-responders compared to responders (p< 0.0001).

Conclusions

Hyperactive chemotaxis influences responses to anti-TNFα treatment andIL13RA2is a potential biomarker to predict anti-TNFα treatment response.
Citrus Huanglongbing is an immune-mediated disease that can be treated by mitigating reactive oxygen species triggered cell death of the phloem tissues caused by Candidatus Liberibacter asiaticus
Authors: Ma Wenxiu , Pang Zhiqian , Huang Xiaoen , Pandey Sheo Shankar , Li Jinyun , Xu Jin , Achor Diann S. , Vasconcelos Fernanda N.C. , Hendrich Connor , Huang Yixiao , Wang Wenting , Lee Donghwan , Wang Nian
Published: August 2021

The immune system is critical for keeping animals and plants healthy from pathogens. However, immune-mediated diseases are also common for human. Immune-mediated diseases have not been reported for plants. Here, we present evidence that citrus Huanglongbing (HLB), caused by phloem-colonizing Candidatus Liberibacter asiaticus (CLas), is an immune-mediated disease. CLas infection of Citrus sinensis stimulated systemic and chronic immune response in the phloem tissues including reactive oxygen species (ROS) production as indicated by H2O2, callose deposition, and induction of immune related genes. Systemic cell death of companion and sieve element cells, but not surrounding parenchyma cells, was observed following ROS production triggered by CLas. ROS production triggered by CLas localized in phloem tissues. The H2O2 concentration in exudates extracted from phloem enriched bark tissue of CLas infected plants reached a threshold of killing citrus protoplast cells, which was suppressed by uric acid (a ROS scavenger) and gibberellin. Foliar spray of HLB positive citrus with antioxidants (uric acid and rutin) and gibberellin significantly reduced both H2O2 concentrations and cell death in phloem tissues induced by CLas and reduced HLB symptoms. RNA-seq analyses of CLas infected and health C. sinensis support that CLas causes oxidative stress. In sum, HLB is an immune-mediated disease and both mitigating ROS via antioxidants and promoting plant growth can reduce cell death of the phloem tissues caused by CLas, thus controlling HLB.
On the interpretation of transcriptome-wide association studies
Authors: de Leeuw Christiaan , Werme Josefin , Savage Jeanne E. , Peyrot Wouter J. , Posthuma Danielle
Published: August 2021

Transcriptome-wide association studies (TWAS) aim to detect relationships between gene expression and a phenotype, and are commonly used for secondary analysis of genome-wide association study (GWAS) results. Results from TWAS analyses are often interpreted as indicating a geneticrelationship between gene expression and a phenotype, but this interpretation is not consistent with the null hypothesis that is evaluated in the traditional TWAS framework. In this study we provide a mathematical outline of this TWAS framework, and elucidate what interpretations are warrantedgiven the null hypothesis it actually tests. We then use both simulations and real data analysis to assess the implications of misinterpreting TWAS results as indicative of a genetic relationship between gene expression and the phenotype. Our simulation results show considerably inflated type 1 error rates for TWAS when interpreted this way, with 41% of significant TWAS associations detected in the real data analysis found to have insufficient statistical evidence to infer such a relationship. This demonstrates that in current implementations, TWAS cannot reliably be used to investigate genetic relationships between gene expression and a phenotype, but that local genetic correlation analysis can serve as a potential alternative.
Long-term effects of moderate concussive brain injury during adolescence on synaptic and tonic GABA currents in dentate projection neurons
Authors: Gupta Akshay , Proddutur Archana , Elgammal Fatima S. , Santhakumar Vijayalakshmi
Published: August 2021

Progressive physiological changes in the hippocampal dentate gyrus circuits following traumatic brain injury contribute to temporal evolution of neurological sequelae. Although early posttraumatic changes in dentate synaptic and extrasynaptic GABA currents have been reported, whether they evolve over time and remain distinct between the two projection neuron classes, granule cells and semilunar granule cells, has not been evaluated. We examined changes in tonic GABA currents and spontaneous inhibitory postsynaptic currents (sIPSCs) and in dentate projection neurons one and three month after moderate concussive fluid percussion injury (FPI) in adolescent rats. Granule cell tonic GABA current amplitude remained elevated up to one month after FPI, but decreased to levels comparable to age-matched controls by three months postinjury. Granule cell sIPSC frequency, which we previously reported to be increased one week after FPI, remained higher than in age-matched controls at one month and was significantly reduced three months after FPI. In contrast to the early decrease, tonic GABA current amplitude and sIPSC frequency in semilunar granule cell was not different from controls three months after FPI. The switch in granule cell inhibitory inputs from early increase to subsequent decrease could contribute to the delayed emergence of cognitive deficits and seizure susceptibility after brain injury.
Nos2-/-mice infected withM. tuberculosisdevelop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis
Authors: Poh Xuan Ying , Hong Jia Mei , Bai Chen , Miow Qing Hao , Thong Pei Min , Wang Yu , Rajarethinam Ravisankar , Ding Cristine S.L. , Ong Catherine W.M.
Published: August 2021

Background

Understanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB.

Methods

We injected twoMycobacterium tuberculosis(M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ andNos2-/-mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains.

Results

Intra-cerebroventricular infection ofNos2-/-mice withM.tbled to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551M.tb, H37RvM.tbinfection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection ofNos2-/-mice withM.tbresembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice.

Conclusions

Intra-cerebroventricular infection ofNos2-/-mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB.
Orchestrated Restructuring Events During Secretory Granule Maturation Mediate Intragranular Cargo Segregation
Authors: Syed Zulfeqhar A. , Zhang Liping , Tran Duy T. , Bleck Christopher K. E. , Ten Hagen Kelly G.
Published: August 2021

Regulated secretion is an essential process where proteins are packaged into membranous secretory vesicles. However, the details of cargo packaging and secretory granule maturation are largely unknown. Here, we demonstrate that multiple distinct proteins undergo intragranular restructuring during secretory granule maturation in vivo, resulting in spatial segregation of distinct protein components within the same granule. Furthermore, through a combination of genetics and multimodality imaging, we demonstrate the molecular identity of each distinct intragranular structure. We further identify temporally-regulated genes that are essential for the restructuring events, including those controlling pH (Vha16-1), Cl− ions (Clic and ClC-c) and Ca2+ ions (fwe). Finally, we show that altered cargo glycosylation influences dimensions of these structures, thereby affecting secretory granule morphology. This study elucidates key steps and factors involved in intragranular, rather than intergranular segregation of cargo through regulated restructuring events during secretory granule maturation. Understanding how multiple distinct proteins are efficiently packaged into and secreted from the same secretory granule may provide insight into diseases resulting from defects in secretion.
A time irreversible model of nucleotide substitution for the SARS-CoV-2 evolution
Authors: Misawa Kazuharu
Published: August 2021

SARS-CoV-2 is the cause of the worldwide epidemic of severe acute respiratory syndrome. Evolutionary studies of the virus genome will provide a predictor of the fate of COVID-19 in the near future. Recent studies of the virus genomes have shown that C to U substitutions are overrepresented in the genome sequences of SARS-CoV-2. Traditional time-reversible substitution models cannot be applied to the evolution of SARS-CoV-2 sequences. Therefore, in this study, I propose a new time-irreversible model and a new method for estimating the nucleotide substitution rate of SARS-CoV-2. Computer simulations showed that that the new method gives good estimates. I applied the new method to estimate nucleotide substitution rates of SARS-CoV-2 sequences. The result suggests that the rate of C to U substitution of SARS-Cov-2 is ten times higher than other types of substitutions.