bluuebunny/crossref_metadata_2025 huggingface dataset:
An accessible infrastructure for artificial intelligence using a docker-based Jupyterlab in Galaxy
Authors: Kumar Anup , Cuccuru Gianmauro , Grüning Björn , Backofen Rolf
Published: July 2022

Artificial intelligence (AI) programs that train on a large amount of data require powerful compute infrastructure. Jupyterlab notebook provides an excellent framework for developing AI programs but it needs to be hosted on a powerful infrastructure to enable AI programs to train on large data. An open-source, docker-based, and GPU-enabled jupyterlab notebook infrastructure has been developed that runs on the public compute infrastructure of Galaxy Europe for rapid prototyping and developing end-to-end AI projects. Using such a notebook, long-running AI model training programs can be executed remotely. Trained models, represented in a standard open neural network exchange (ONNX) format, and other resulting datasets are created in Galaxy. Other features include GPU support for faster training, git integration for version control, the option of creating and executing pipelines of notebooks, and the availability of multiple dashboards for monitoring compute resources. These features make the jupyterlab notebook highly suitable for creating and managing AI projects. A recent scientific publication that predicts infected regions of COVID-19 CT scan images is reproduced using multiple features of this notebook. In addition, colabfold, a faster implementation of alphafold2, can also be accessed in this notebook to predict the 3D structure of protein sequences. Jupyterlab notebook is accessible in two ways - first as an interactive Galaxy tool and second by running the underlying docker container. In both ways, long-running training can be executed on Galaxy’s compute infrastructure. The scripts to create the docker container are available under MIT license at https://github.com/anuprulez/ml-jupyter-notebook.

Contact

kumara@informatik.uni-freiburg.de

anup.rulez@gmail.com
Evolution of SARS-CoV-2 during the first year of the COVID-19 pandemic in Northwestern Argentina
Authors: Zambrana Montaño Romina , Culasso Andrés Carlos Alberto , Fernández Franco , Marquez Nathalie , Debat Humberto , Salmerón Mariana , Zamora Ana María , Ruíz de Huidobro Gustavo , Costas Dardo , Alabarse Graciela , Charre Miguel Alejandro , Fridman Ariel David , Mamani Claudia , Vaca Fabiana , Maza Diaz Claudia , Raskovsky Viviana , Lavaque Esteban , Lesser Veronica , Cajal Pamela , Agüero Fernanda , Calvente Cintia , Torres Carolina , Viegas Mariana
Published: July 2022

Studies about the evolution of SARS-CoV-2 lineages in different backgrounds such as naive populations, are still scarce, especially from South America. The aim of this work was to study the introduction and diversification pattern of SARS-CoV-2 during the first year of the COVID-19 pandemic in the Northwestern Argentina (NWA) region and to analyze the evolutionary dynamics of the main lineages found. In this study, we analyzed a total of 260 SARS-CoV-2 whole-genome sequences from Argentina, belonging to the Provinces of Jujuy, Salta and Tucumán, from March 31st, 2020, to May 22nd, 2021, which covered the full first wave and the early second wave of the COVID-19 pandemic in Argentina. In the first wave, eight lineages were identified: B.1.499 (76.9%), followed by N.5 (10.2%), B.1.1.274 (3.7%), B.1.1.348 (3.7%), B.1 (2.8%), B.1.600 (0.9%), B.1.1.33 (0.9%) and N.3 (0.9%). During the early second wave, the first-wave lineages were displaced by the introduction of variants of concern (VOC) (Alpha, Gamma), or variants of interest (VOI) (Lambda, Zeta, Epsilon) and other lineages with more limited distribution. Phylodynamic analyses of the B.1.499 and N.5, the two most prevalent lineages in NWA, revealed that the substitution rate of lineage N.5 (7.9 × 10−4 substitutions per site per year, s/s/y) was a ∼40% faster than that of lineage B.1.499 (5.9 × 10−4 s/s/y), although both are in the same order of magnitude than other non-VOC lineages. No mutations associated with a biological characteristic of importance were observed as signatures markers of the phylogenetic groups established in Northwestern Argentina, however, single sequences in non-VOC lineages did present mutations of biological importance or associated with VOCs as sporadic events, showing that many of these mutations could emerge from circulation in the general population. This study contributed to the knowledge about the evolution of SARS-CoV-2 in a pre-vaccination and without post-exposure immunization period.
Unwilling or Unable? Using 3D tracking to evaluate dogs’ reactions to differing human intentions
Authors: Völter Christoph J. , Lonardo Lucrezia , Steinmann Maud G.G.M. , Ramos Carolina Frizzo , Gerwisch Karoline , Schranz Monique-Theres , Dobernig Iris , Huber Ludwig
Published: July 2022

The extent to which dogs (Canis familiaris) as a domesticated species understand human intentions is still a matter of debate. The unwilling-unable paradigm has been developed to examine whether nonhuman animals are sensitive to intentions underlying human actions. In this paradigm, subjects tended to show more patience toward a human that appears willing but unable to transfer food to them compared to an unwilling (teasing) human. In the present study, we conducted the unwilling-unable paradigm with dogs using a detailed behavioural analysis based on machine-learning driven 3D tracking. Throughout two preregistered experiments, we found evidence, in line with our prediction, that dogs reacted more impatiently to actions signalling unwillingness to transfer food rather than inability. These differences were consistent through two different samples of pet dogs (total N=96) and they were evident also in the machine-learning generated 3D tracking data. Our results, therefore, provide robust evidence that dogs distinguish between similar actions (leading to the same outcome) associated with different intentions. However, their reactions did not lead to any measurable preference for one experimenter over the other in a subsequent transfer phase. We discuss different cognitive mechanisms that might underlie dogs’ performance in this paradigm.
White matter connectivity in uncinate fasciculus accounts for visual attention span in developmental dyslexia
Authors: Zhao Jingjing , Song Zujun , Zhao Yueye , Thiebaut de Schotten Michel , Altarelli Irene , Ramus Franck
Published: July 2022

The present study aimed to investigate the role of connectivity disruptions in two fiber pathways, the uncinate fasciculus (UF) and the frontal aslant tract (FAT), in developmental dyslexia and determine the relationship between the connectivity of these pathways and behavioral performance in children with dyslexia. A total of 26 French children with dyslexia and 31 age-matched control children were included. Spherical deconvolution tractography was used to reconstruct the two fiber pathways. Hindrance-modulated oriented anisotropy (HMOA) was used to measure the connectivity of each fiber pathway in both hemispheres. The boys with dyslexia showed reduced HMOA in the UF compared to control boys, but this difference was not observed in girls. Furthermore, HMOA of the UF correlated with individual differences in the visual attention span in participants with dyslexia. All significant results found in HMOA of the UF were verified in fractional anisotropy (FA) of the UF using standard diffusion imaging model. This study suggests a differential sex effect on the connectivity disruption in the UF in developmental dyslexia. It also indicates that the UF may play an essential role in the visual attention span deficit in developmental dyslexia.

Significance Statement

This study presents the first account of connectivity disruption in the uncinate fasciculus in developmental dyslexia. In particular, this connectivity disruption only appears in boys with dyslexia but not in girls with dyslexia. We also show that the connectivity of the uncinate fasciculus accounts for individual differences in the visual attention span in children with dyslexia, expanding the current understanding of the function of the uncinate fasciculus.
Landscape of infection enhancing antibodies in COVID-19 and healthy donors
Authors: Ismanto Hendra S , Xu Zichang , Saputri Dianita S , Wilamowski Jan , Li Songling , Nugraha Dendi K , Horiguchi Yasuhiko , Okada Masato , Arase Hisashi , Standley Daron M
Published: July 2022

To assess the frequency of SARS-CoV-2 infection enhancing antibodies in the general population, we searched over 64 million heavy chain antibody sequences from healthy and COVID-19 patient repertoires for sequences similar to 11 previously reported enhancing antibodies. Although the distribution of sequence identities was similar in COVID-19 and healthy repertoires, the COVID-19 hits were significantly more clonally expanded than healthy hits. Furthermore, among the tested hits, 17 out of 94 from COVID-19, compared with 2 out of 96 from healthy, bound to the enhancing epitope. A total of 6 of the 19 epitope-binding antibodies enhanced ACE2 receptor binding to the spike protein. Together, this study revealed that enhancing antibodies are far more frequent in COVID-19 patients than in healthy donors, but a reservoir of potential enhancing antibodies exists in healthy donors that could potentially mature to actual enhancing antibodies upon infection.
Thick Filament Activation Is Different in Fast and Slow-Twitch Skeletal Muscle
Authors: Gong Henry M. , Ma Weikang , Regnier Michael , Irving Thomas C.
Published: July 2022

The contractile properties of fast-twitch and slow-twitch skeletal muscles are primarily determined by the myosin isoform content and modulated by a variety of sarcomere proteins. X-ray diffraction studies of regulatory mechanisms in muscle contraction have focused predominately on fast-or mixed-fiber muscle with slow muscle being much less studied. Here, we used time-resolved x-ray diffraction to investigate the dynamic behavior of the myofilament proteins in relatively pure slow fiber rat soleus (SOL) and pure fast fiber rat extensor digitorum longus (EDL) muscle during twitch and tetanic contractions at optimal length. During twitch contractions the diffraction signatures indicating a transition in the myosin heads from ordered OFF states, where heads are held close to the thick filament backbone, to disordered ON states, where heads are free to bind to thin filaments, were found in EDL and not in SOL muscle. During tetanic contraction, changes in the disposition of myosin heads as active tension develops is a cooperative process in EDL muscle whereas in SOL muscle this relationship is less cooperative. The observed reduced extensibility of the thick filaments in SOL muscle as compared to EDL muscles indicate a molecular basis for this behavior. These data indicate that for the EDL thick filament activation is a cooperative strain-induced mechano-sensing mechanism, whereas for the SOL thick filament activation has a more graded response. These different approaches to thick filament regulation in fast- and slow-twitch muscles may be adaptations for short duration, strong contractions versus sustained, finely controlled contractions, respectively.

Key Points

Fast twitch muscle and slow-twitch muscle are optimized for strong, short duration contractions and sustained smaller movements respectively.

Structural events (OFF to ON transitions) in the myosin containing thick filaments in fast muscle help determine the timing and strength of contractions but these have not been studied in slow-twitch muscle.

The X-ray diffraction signatures of structural OFF to ON transitions are different in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle, being completely absent during twitches in soleus muscle and blunted during tetanic contractions SOL as compared to EDL

Cooperative thick filament structural OFF to ON transitions in fast twitch muscle may be an adaptation for rapid and ballistic movements whereas more graded OFF to ON structural transitions in slow-twitch muscle may be an adaptation for slower, finer motions.
Possible role of left–right asymmetry in the sensory system and behavior during adaptation to food-sparse cave environments
Authors: Fernandes Vânia Filipa Lima , Glaser Yannik , Iwashita Motoko , Yoshizawa Masato
Published: July 2022

Laterality in relation to behavior and sensory systems is found commonly in a variety of animal taxa. Despite the advantages conferred by laterality (e.g., the startle response and complex motor activities), little is known about the evolution of laterality and its plasticity in response to ecological demands. In the present study, a comparative study model, the Mexican tetra (Astyanax mexicanus), composed of two morphotypes, i.e., riverine surface fish and caved-welling cavefish, was used to address the relationship between environment and laterality. The use of a machine learning-based fish posture detection system and sensory ablation revealed that the left cranial lateral line significantly supports one type of foraging behavior, i.e., vibration attraction behavior, in one cave population. Additionally, left–right asymmetric approaches toward a vibrating rod became symmetrical after fasting in one cave population but not in the other populations. Based on these findings, we propose a model explaining how the observed sensory laterality and behavioral shift could help adaptations in terms of the tradeoff in energy gain and loss during foraging according to differences in food availability among caves.
A synthetic protein-level neural network in mammalian cells
Authors: Chen Zibo , Linton James M. , Zhu Ronghui , Elowitz Michael B.
Published: July 2022

Artificial neural networks provide a powerful paradigm for information processing that has transformed diverse fields. Within living cells, genetically encoded synthetic molecular networks could, in principle, harness principles of neural computation to classify molecular signals. Here, we combine de novo designed protein heterodimers and engineered viral proteases to implement a synthetic protein circuit that performs winner-take-all neural network computation. This “perceptein” circuit includes modules that compute weighted sums of input protein concentrations through reversible binding interactions, and allow for self-activation and mutual inhibition of protein components using irreversible proteolytic cleavage reactions. Altogether, these interactions comprise a network of 310 chemical reactions stemming from 8 expressed protein species. The complete system achieves signal classification with tunable decision boundaries in mammalian cells. These results demonstrate how engineered protein-based networks can enable programmable signal classification in living cells.

One-Sentence Summary

A synthetic protein circuit that performs winner-take-all neural network computation in mammalian cells
Cystathionine β-synthase gene inactivation dysregulates major urinary protein biogenesis and impairs sexual signaling in mice
Authors: Bretes Ewa , Wróblewski Jacek , Wyszczelska-Rokiel Monika , Jakubowski Hieronim
Published: July 2022

Reproductive success in mice depends on major urinary proteins (Mup) that facilitate sexual interactions between females and males. Deletion of cystathionine β-synthase (Cbs) gene, a metabolic gene important for homeostasis of one-carbon metabolism, impairs reproduction by causing female infertility in mice. Here we examined Mup biogenesis and sexual signaling inCbs−/−vs.Cbs+/−mice. We found that total urinary Mup protein was significantly reduced in male and femaleCbs−/−vs. Cbs+/−mice. SDS-PAGE/Western blot, ESIMS, and RT-qPCR analyses of the liver, plasma, and urinary proteins identified a male-specific Mup20 inCbs−/−, but notCbs+/−females. As other Mups were significantly reduced, the 18,893 Da Mup20 became the most abundand in urine ofCbs−/−females and males. Effects ofCbsgenotype on 18,645 Da, 18,693 Da, and 18,709 Da Mup species abundance were Mup and sex-specific.Cbs-dependent changes in hepatic Mups and Mup20 expression were similar at the protein and mRNA level. Changes in Mups, but not in Mup20, can be explained by downregulation of hepatic Zhx2 and Ghr receptors inCbs−/−mice. Behavioral testing showed thatCbs+/−females were attracted toCbs+/−but not toCbs−/−male urine.Cbs+/−males did not countermark urine ofCbs−/−males but countermarked urine of otherCbs+/−males and were attracted to urines ofCbs−/−as well asCbs+/−females.Cbs−/−males did not countermark urine ofCbs+/−males but were still attracted to urines ofCbs+/−females. Taken together, these findings show thatCbs, a metabolic gene, plays an important role in the regulation of Mup biogenesis and sexual signaling in mice.
Amplified cortical neural responses as animals learn to use novel activity patterns
Authors: Akitake Bradley , Douglas Hannah M. , LaFosse Paul K. , Beiran Manuel , Deveau Ciana E. , O’Rawe Jonathan , Li Anna J. , Ryan Lauren N. , Duffy Samuel P. , Zhou Zhishang , Deng Yanting , Rajan Kanaka , Histed Mark H.
Published: July 2022

Cerebral cortex supports representations of the world in patterns of neural activity, used by the brain to make decisions and guide behavior. Past work has found diverse, or limited, changes in the primary sensory cortex in response to learning, suggesting the key computations might occur in downstream regions. Alternatively, sensory cortical changes may be central to learning. We studied cortical learning by using controlled inputs we insert: we trained mice to recognize entirely novel, non-sensory patterns of cortical activity in the primary visual cortex (V1) created by optogenetic stimulation. As animals learned to use these novel patterns, we found their detection abilities improved by an order of magnitude or more. The behavioral change was accompanied by large increases in V1 neural responses to fixed optogenetic input. Neural response amplification to novel optogenetic inputs had little effect on existing visual sensory responses. A recurrent cortical model shows that this amplification can be achieved by a small mean shift in recurrent network synaptic strength. Amplification would seem to be desirable to improve decision-making in a detection task, and therefore these results suggest that adult recurrent cortical plasticity plays a significant role in improving behavioral performance during learning.
High-throughput Genetic Clustering of Type 2 Diabetes Loci Reveals Heterogeneous Mechanistic Pathways of Metabolic Disease
Authors: Kim Hyunkyung , Westerman Kenneth E. , Smith Kirk , Chiou Joshua , Cole Joanne B. , Majarian Timothy , von Grotthuss Marcin , Mercader Josep M. , Kwak Soo Heon , Kim Jaegil , Florez Jose C. , Gaulton Kyle , Manning Alisa K. , Udler Miriam S.
Published: July 2022

Aims/hypothesis

Type 2 diabetes (T2D) is highly polygenic and influenced by multiple biological pathways. Rapid expansion in the number of T2D loci can be leveraged to identify such pathways, thus facilitating improved disease management.

Methods

We developed a high-throughput pipeline to enable clustering of T2D loci based on variant-trait associations. Our pipeline extracted summary statistics from genome-wide association studies (GWAS) for T2D and related traits to generate a matrix of 324 variant x 64 trait associations and applied Bayesian Non-negative Factorization (bNMF) to identify genetic components of T2D. We generated cluster-specific polygenic scores and performed regression analysis in an independent cohort (N=25,419) to assess for clinical relevance.

Results

We identified ten clusters, replicating the five from our prior analysis as well as novel clusters related to beta-cell dysfunction, pronounced insulin secretion, and levels of alkaline phosphatase, lipoprotein-A, and sex hormone-binding globulin. Four clusters related to mechanisms of insulin deficiency, five to insulin resistance, and one had an unclear mechanism. The clusters displayed tissue-specific epigenomic enrichment, notably with the two beta-cell clusters differentially enriched in functional and stressed pancreatic beta-cell states. Additionally, cluster-specific polygenic scores were differentially associated with patient clinical characteristics and outcomes. The pipeline was applied to coronary artery disease and chronic kidney disease, identifying multiple shared genetic pathways with T2D.

Conclusions/interpretation

Our approach stratifies T2D loci into physiologically meaningful genetic clusters associated with distinct tissues and clinical outcomes. The pipeline allows for efficient updating as additional GWAS become available and can be readily applied to other conditions, facilitating clinical translation of GWAS findings. Software to perform this clustering pipeline is freely available.
Protection of SARS-CoV-2 natural infection against reinfection with the Omicron BA.4 or BA.5 subvariants
Authors: Altarawneh Heba N. , Chemaitelly Hiam , Ayoub Houssein H. , Hasan Mohammad R. , Coyle Peter , Yassine Hadi M. , Al-Khatib Hebah A. , Benslimane Fatiha M. , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed Ghaith , Butt Adeel A. , Al-Romaihi Hamad Eid , Al-Thani Mohamed H. , Al-Khal Abdullatif , Bertollini Roberto , Tang Patrick , Abu-Raddad Laith J.
Published: July 2022

This study estimates the effectiveness of previous infection with SARS-CoV-2 in preventing reinfection with Omicron BA.4/BA.5 subvariants using a test-negative, case–control study design. Cases (SARS-CoV-2-positive test results) and controls (SARS-CoV-2-negative test results) were matched according to sex, 10-year age group, nationality, comorbid condition count, calendar week of testing, method of testing, and reason for testing. Effectiveness was estimated using the S-gene “target failure” (SGTF) infections between May 7, 2022-July 4, 2022. SGTF status provides a proxy for BA.4/BA.5 infections, considering the negligible incidence of other SGTF variants during the study. Effectiveness was also estimated using all diagnosed infections between June 8, 2022-July 4, 2022, when BA.4/BA.5 dominated incidence. Effectiveness of a previous pre-Omicron infection against symptomatic BA.4/BA.5 reinfection was 15.1% (95% CI: -47.1-50.9%), and against any BA.4/BA.5 reinfection irrespective of symptoms was 28.3% (95% CI: 11.4-41.9%). Effectiveness of a previous Omicron infection against symptomatic BA.4/BA.5 reinfection was 76.1% (95% CI: 54.9-87.3%), and against any BA.4/BA.5 reinfection was 79.7% (95% CI: 74.3-83.9%). Results using all diagnosed infections when BA.4/BA.5 dominated incidence confirmed the same findings. Sensitivity analyses adjusting for vaccination status confirmed study results. Protection of a previous infection against BA.4/BA.5 reinfection was modest when the previous infection involved a pre-Omicron variant, but strong when the previous infection involved the Omicron BA.1 or BA.2 subvariants. Protection of a previous infection against BA.4/BA.5 was lower than that against BA.1/BA.2, consistent with BA.4/BA.5’s greater capacity for immune-system evasion than that of BA.1/BA.2.
Longitudinal decline in striatal dopamine transporter binding in Parkinson’s disease: Associations with apathy and anhedonia
Authors: Costello Harry , Yamamori Yumeya , Reeves Suzanne , Schrag Anette , Howard Robert , Roiser Jonathan P.
Published: July 2022

Background

Motivational symptoms such as apathy and anhedonia are common in Parkinson’s disease, respond poorly to treatment, and have been hypothesised to share underlying neural mechanisms. Striatal dopaminergic dysfunction is considered central to motivational symptoms in Parkinson’s disease, but the association has never been examined longitudinally. We investigated whether the progression of dopaminergic neurodegeneration was associated with emergent apathy and anhedonia symptoms in Parkinson’s disease.

Methods

Longitudinal cohort study of 412 newly diagnosed Parkinson’s disease patients followed over five years as part of the Parkinson’s Progression Markers Initiative (PPMI) cohort. Apathy and anhedonia were measured using a composite score derived from relevant items of the 15-item geriatric depression scale (GDS-15) and part I of the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Dopaminergic neurodegeneration was measured using repeated ioflupane [123-I] single photon emission computed tomography imaging of striatal dopamine transporters (DAT).

Results

Linear mixed-effects modelling across all contemporaneous data points identified a significant negative relationship between striatal DAT specific binding ratio(SBR) and apathy/anhedonia symptoms, which emerged as Parkinson’s disease progressed (interaction: β=-0.09, 95%CI[-0.15 -0.03], p=0.002). Appearance and subsequent worsening of apathy/anhedonia symptoms began on average two years after diagnosis and below a threshold striatal DAT SBR level. The interaction between striatal DAT SBR and time was specific to apathy/anhedonia symptoms, with no evidence of a similar interaction for general depressive symptoms from the GDS-15 (excluding apathy/anhedonia items) (β=-0.06, 95%CI[-0.13 0.01]) or motor symptoms indexed by the MDS-UPDRS part III (β=0.20, 95%CI[-0.25 0.65]).

Conclusion

The relationship between the progression of dopaminergic neurodegeneration and emergent apathy/anhedonia symptoms supports a central role for dopaminergic dysfunction in motivational symptoms in Parkinson’s disease. Striatal DAT imaging may be a useful indicator of apathy/anhedonia risk that could inform intervention strategies.
Assessment of Rational Use of Antibiotics: A Nationwide Cross-Sectional Study among People of Nepal
Authors: Khadka Sitaram , Khadka Sulochana , Yadav Gopal Kumar , Giri Santoshi , Sharma Arun , Joshi Rinku , Amgain Kapil
Published: July 2022

Introduction

This research was conducted with the objective to accentuate antimicrobial misuse across knowledge, behaviour and practice domains among general people of Nepal.

Materials and Methods

It was a nationwide cross-sectional survey conducted among 385 participants in Nepal from February 2022 to May 2022. Statistical analysis was done through SPSS® v21 and MedCalc for Windows v12.3.0. Modified Bloom’s cut-off point was utilized to categorize the participants’ overall knowledge, behaviour, and practice. The chi-square test and odds ratio (OR) using binary logistic regression at 95% CI, and Spearman’s rank correlation coefficient test (r) was calculated wherever appropriate.

Results

More than three-fifths of the participants (248, 64.42%) demonstrated good behaviour, whereas less than half of the participants showed good knowledge (137, 35.58%) and practice (161, 41.82%) about rational use of antibiotics. Health professionals had higher knowledge (OR: 1.07, 95% CI: 0.70-1.62) and good behaviour (OR: 0.42, 95% CI: 0.27-0.64) than other professions (P-value< 0.05). Those with higher income (≥ 50,000 NRs) had good behaviour (OR: 3.37, 95% CI: 1.65-6.87) and good practice (OR: 2.58, 95% CI: 1.47-4.50) scores than those with less monthly income (P-value< 0.05). Similarly, higher educational degrees viz., master and/or above had good behaviour (OR: 4.13, 95% CI: 2.62-6.49) and good practice scores (OR: 2.55, 95% CI: 1.68-3.87). Additionally, there were significant positive correlations between knowledge (K), behaviour (B) and practice (P) scores (r = 0.331 for K & B, r = 0.259 for K & P, and r = 0.618 for B & P respectively; P-value< 0.05).

Conclusions

Our findings imply the demand of effective legislature, strict enforcement of the drug act and proper implementation of plans and policies to curb the antibiotic misuse. Lack of execution of existing laws and unawareness of the public lead to extravagant use of antibiotics.
Hands are frequently contaminated with fecal bacteria and enteric pathogens globally: A systematic review and meta-analysis
Authors: Cantrell Molly E. , Sylvestre Émile , Wharton Hannah , Scheidegger Rahel , Curchod Lou , Gute David M. , Griffiths Jeffrey , Julian Timothy R , Pickering Amy J.
Published: July 2022

Enteric pathogen infections are a leading cause of morbidity and mortality globally, with the highest disease burden in low-income countries. Hands act as intermediaries in enteric pathogen transmission, transferring enteric pathogens between people and the environment through contact with fomites, food, water, and soil. In this study, we conducted a systematic review of prevalence and concentrations of fecal indicator microorganisms (i.e.,E. coli, fecal coliform) and enteric pathogens on hands. We identified eighty-four studies, reporting 35,440 observations of hand contamination of people in community or household settings. The studies investigated 44 unique microorganisms, of which the most commonly reported indicators wereE. coliand fecal coliforms. Hand contamination with 12 unique enteric pathogens was reported, with adenovirus and norovirus as the most frequent. MeanE. coliprevalence on hands was 62% [95% CI 40%-82%] and mean fecal coliform prevalence was 66% [95% CI 22%-100%]. Hands were more likely to be contaminated withE. coliin low/lower-middle-income countries (prevalence: 69% [95% CI 48% - 88%]) than in upper-middle/high-income countries (6% [95% CI 2% - 12%]). The review also highlighted the importance of standardizing hand sampling methods, as hand rinsing was associated with greater fecal contamination compared to other sampling methods.
Effect of Stay-at-Home Orders and Other COVID-Related Policies on Trauma Hospitalization Rates and Disparities in the United States: A Statewide Time-Series Analysis
Authors: Strassle Paula D , Kinlaw Alan C , Ko Jamie S , Quintero Stephanie M , Bonilla Jackie , Ponder Madison , María Nápoles Anna , Schiro Sharon E
Published: July 2022

Background

To combat the coronavirus pandemic, states implemented several public health policies to reduce infection and transmission. Increasing evidence suggests that these prevention strategies also have had a profound impact on non-COVID healthcare utilization. The goal of this study was to determine the impact of a statewide Stay-at-Home and other COVID-related policies on trauma hospitalizations, stratified by race/ethnicity, age, and sex.

Methods

We used the North Carolina Trauma Registry, a statewide registry of trauma hospitalizations to 18 hospitals across North Carolina, including all North Carolina trauma centers, to calculate weekly assault, self-inflicted, unintentional motor vehicle collision (MVC), and other unintentional injury hospitalization rates between January 1, 2019 and December 31, 2020. Interrupted time-series design and segmented linear regression were used to estimate changes in hospitalizations rates after several COVID-related executive orders, overall and stratified by race/ethnicity, age, and gender. Hospitalization rates were compared after 1) U.S. declaration of a public health emergency; 2) North Carolina statewide Stay-at-Home order; 3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and 4) further lifting of restrictions (Phase 2.5: Safer-at-Home).

Results

There were 70,478 trauma hospitalizations in North Carolina from 2019-2020. In 2020, median age was 53 years old and 59% were male. Assault hospitalization rates (per 1,000,000 NC residents) increased after the Stay-at-Home order, but only among Black/African American residents (incidence rate difference [IRD]=7.9; other racial/ethnic groups’ IRDs ranged 0.9 to 1.7) and 18-44 year-old males (IRD=11.9; other sex/age groups’ IRDs ranged -0.5 to 3.6). After major restrictions were lifted, assault rates returned to pre-COVID levels. Unintentional injury hospitalizations decreased after the public health emergency, especially among older adults, but returned to 2019 levels within several months.

Conclusions

Statewide Stay-at-Home orders put Black/African American residents at higher risk for assault hospitalizations, exacerbating pre-existing disparities. Fear of COVID-19 may have also led to decreases in unintentional non-MVC hospitalization rates, particularly among older adults. Policy makers must anticipate possible negative effects and develop approaches for mitigating harms that may disproportionately affect already disadvantaged communities.
Cryo-electron tomography reveals the multiplex anatomy of condensed native chromatin and its unfolding by histone citrullination
Authors: Jentink Nathan , Purnell Carson , Kable Brianna , Swulius Matthew , Grigoryev Sergei A.
Published: July 2022

Nucleosome chains fold and self-associate to form higher order structures whose internal organization is unknown. Here, cryo-electron tomography (cryo-ET) of native human chromatin reveals novel folding motifs such as 1) non-uniform nucleosome stacking, 2) intermittent parallel and perpendicular orientations of adjacent nucleosome planes, and 3) an inverse zigzag nucleosome chain path, which deviates from the direct zigzag topology seen in reconstituted nucleosomal arrays. By examining these self-associated structures, we observed prominent nucleosome stacking in-cis and anti-parallel nucleosome interactions in-trans, which are consistent with partial nucleosome interdigitation. Histone citrullination strongly inhibits nucleosome stacking and self-association with a modest effect on chromatin folding, while the reconstituted arrays showed a zigzag topology which undergoes a dramatic unfolding induced by histone citrullination. This study sheds light on the internal structure of compact chromatin nanoparticles and suggests a novel mechanism for how epigenetic changes in chromatin are retained across both open and condensed forms of chromatin.
Re-emergence of Severe Acute Diarrhea Syndrome Coronavirus (SADS-CoV) in Guangxi, China, 2021
Authors: Sun Yan-kuo , Xing Jia-bao , Xu Zhi-ying , Gao Han , Xu Si-jia , Liu Jing , Zhu Di-hua , Guo Yi-fan , Yang Bin-shuo , Chen Xiong-nan , Zheng Ze-zhong , Wang Heng , Gong Lang , Holmes Edward C. , Zhang Gui-hong
Published: July 2022

Severe acute diarrhea syndrome coronavirus (SADS-CoV) has had a major impact on the swine industry in China, but has not been detected since 2019. Using real-time qPCR and metagenomic surveillance we identified SADS-CoV in a pig farm experiencing diarrheal disease. Genomic analysis supported the undetected circulation of SADS-CoV since 2019.
Spatial and temporal muscle synergies provide a dual characterization of low-dimensional and intermittent control of upper-limb movements
Authors: Brambilla Cristina , Atzori Manfredo , Müller Henning , d’Avella Andrea , Scano Alessandro
Published: July 2022

Muscle synergy analysis is commonly used for investigating the neurophysiological mechanisms that the central nervous system employs to control muscle activations. In the last two decades, several models have been developed to decompose EMG signals into spatial, temporal or spatiotemporal synergies. However, the presence of different approaches complicates the comparison and interpretation of results. Spatial synergies represent invariant activation weights in muscle groups modulated with variant temporal coefficients, while temporal synergies are based on invariant temporal profiles that coordinate variant muscle weights. While non-negative matrix factorization (NMF) allows to extract both spatial and temporal synergies, temporal synergies and the comparison between the two approaches have been barely investigated and so far no study targeted a large set of multi-joint upper limb movements. Here we present several analyses that highlight the duality of spatial and temporal synergies as a characterization of low-dimensional and intermittent motor coordination in the upper limb, allowing high flexibility and dexterity. First, spatial and temporal synergies were extracted from two datasets representing a comprehensive mapping of proximal (REACH PLUS) and distal (NINAPRO) upper limb movements, focusing on their differences in reconstruction accuracy and inter-individual variability. For both models, we extracted synergies achieving a given level of the goodness of reconstruction (R2), and we compared the similarity of the invariant components across participants. The two models provide a compact characterization of motor coordination at spatial or temporal level, respectively. However, a lower number of temporal synergies are needed to achieve the same R2 with a higher inter-subject similarity. Spatial and temporal synergies may thus capture different levels of motor control. Second, we showed the existence of both spatial and temporal structure in the EMG data, extracting spatial and temporal synergies from a surrogate dataset in which the phases were shuffled preserving the same frequency content of the original data. Last, a detailed characterization of the structure of the temporal synergies suggested that they can be related to an intermittent control of the movement. These results may be useful to improve muscle synergy analysis in several fields such as rehabilitation, prosthesis control and motor control studies.
Kynurenic acid promotes A1 to A2 astrocyte conversion against HIV-associated neurocognitive disorder
Authors: Lun Jingxian , Li Yubin , Gao Xuefeng , Gong Zelong , Chen Xiaoliang , Zou Jinhu , Zhou Chengxing , Huang Yuanyuan , Zhou Bingliang , Huang Pengwei , Cao Hong
Published: July 2022

Although extensive astrocyte activation is present in the CNS of patients suffering from HIV-associated neurocognitive disorder (HAND), little is known about the contribution of reactive astrocytes to HAND neuropathology. Here, we report that the imbalance between neurotoxic (A1 astrocytes) and protective astrocytes (A2 astrocytes) occurring in HIV-1 gp120 transgenic mice impedes the resolution of inflammation in the CNS, perpetuating neuron damage and cognitive deficits. Kynurenic acid (KYNA), a tryptophan metabolite with α7 nicotinic acetylcholine receptors (α7nAChR) inhibitory property, blunts gp120-induced A1 astrocyte activation while promoting A2 astrocyte formation through blockade of α7nAChR/JAK2/STAT3 signaling activation. Meanwhile, we provide evidence that α7nAChR deletion and tryptophan administration convert astrocyte phenotypes, ultimately facilitating neuronal and cognitive improvement in the gp120tg mice. These initial and determinant findings mark a turning point in our understanding of the role of α7nAChR in gp120-mediated astrocyte activation, which opens new opportunities to control reactive astrocyte generation through KYNA and tryptophan administration as a pharmacological approach for treating HAND.
Tetraspanin 4 mediates migrasome formation via a two-stage mechanism
Authors: Dharan Raviv , Huang Yuwei , Cheppali Sudheer Kumar , Goren Shahar , Shendrik Petr , Kozlov Michael M. , Yu Li , Sorkin Raya
Published: July 2022

Migrasomes are recently discovered signalling organelles, enriched with tetraspanin proteins (TSPAN)1. They form by local swelling of retraction fibers, the cylindrical protrusions of cell membranes that form as a result of cell migration along external substrates. Migrasomes can grow up to several micrometers in diameter2, and allow cells to release contents such as chemokines at specific locations, hence, transmitting signals to surrounding cells through the relevant chemokine receptors. Recently, evidence emerged showing that migrasomes play essential roles in fundamental cellular processes such transfer of mRNA and proteins3, organ morphogenesis4, and mitochondria quality control5. Thus, understanding the mechanism of migrasome biogenesis is of outstanding importance. Previously, it was established that the molecules crucial for migrasome formation are tetraspanin proteins and cholesterol forming macrodomains in the migrasome membrane, while the physical forces driving local swelling of the retraction fibers originate from membrane tension and bending rigidity1. Yet, it remained unknown how and in which time sequence these factors are involved in migrasome nucleation, growth, and stabilization, and what are the possible intermediate stages of migrasome biogenesis.
The global distribution and environmental drivers of the soil antibiotic resistome
Authors: Delgado-Baquerizo Manuel , Hu Hang-Wei , Maestre Fernando T. , Guerra Carlos A. , Eisenhauer Nico , Eldridge David J. , Zhu Yong-Guan , Chen Qing-Lin , Trivedi Pankaj , Du Shuai , Makhalanyane Thulani P. , Verma Jay P. , Gozalo Beatriz , Ochoa Victoria , Asensio Sergio , Wang Ling , Zaady Eli , Illán Javier G. , Siebe Christina , Grebenc Tine , Zhou Xiaobing , Liu Yu-Rong , Bamigboye Adebola R. , Blanco-Pastor José L. , Duran Jorge , Rodríguez Alexandra , Mamet Steven , Alfaro Fernando , Abades Sebastian , Teixido Alberto L. , Peñaloza-Bojacá Gabriel F. , Molina-Montenegro Marco , Torres-Díaz Cristian , Perez Cecilia , Gallardo Antonio , García-Velázquez Laura , Hayes Patrick E. , Neuhauser Sigrid , He Ji-Zheng
Published: July 2022

Background

Little is known about the global distribution and environmental drivers of key microbial functional traits such as antibiotic resistance genes (ARGs). Soils are one of Earth’s largest reservoirs of ARGs, which are integral for soil microbial competition, and have potential implications for plant and human health. Yet, their diversity and global patterns remain poorly described. Here, we analyzed 285 ARGs in soils from 1012 sites across all continents, and created the first global atlas with the distributions of topsoil ARGs.

Results

We show that ARGs peaked in high latitude cold and boreal forests. Climatic seasonality and mobile genetic elements, associated with the transmission of antibiotic resistance, were also key drivers of their global distribution. Dominant ARGs were mainly related to multidrug resistance genes and efflux pump machineries. We further pinpointed the global hotspots of the diversity and proportions of soil ARGs.

Conclusions

Together, our work provides the foundation for a better understanding of the ecology and global distribution of the environmental soil antibiotic resistome.
Separating the effects of sex hormones and sex chromosomes on behavior in the African pygmy mouse Mus minutoides, a species with XY female sex reversal
Authors: Veyrunes Frederic , Perez Julie , Heitzmann Louise , Saunders Paul A , Givalois Laurent
Published: July 2022

In mammals, most sex differences in phenotype are controlled by gonadal hormones, but recent work on transgenic mice have shown that sex chromosomes can have a direct influence on sex-specific behaviors. In this study, we take advantage of the naturally occurring sex reversal in a mouse species, Mus minutoides, to investigate for the first time the relationship between sex chromosomes, hormones and behaviors in a wild species. In this model, a feminizing variant of the X chromosome, named X*, produces three types of females with different sex chromosome complements (XX, XX*, and X*Y), associated with alternative behavioral phenotypes, while all males are XY. We thus compared the levels of three major circulating steroid hormones (testosterone, corticosterone and estradiol) in the four sex genotypes to disentangle the influence of sex chromosomes and sex hormones on behavior. First, we did not find any difference in testosterone levels in the three female genotypes, although X*Y females are notoriously more aggressive. Second, in agreement with their lower anxiety-related behaviors, X*Y females and XY males display lower baseline corticosterone concentration than XX and XX* females. Instead of a direct hormonal influence, this result rather suggests that sex chromosomes may have an impact on the baseline corticosterone level, which in turn may influence behaviors. Third, estradiol concentrations do not explain the enhanced reproductive performance and maternal care behavior of the X*Y females compared to the XX and XX* females. Overall, this study highlights that most of the behaviors varying along with sex chromosome complement of this species are driven by genetic factors rather than steroid hormone concentrations.
Whole mitochondrial genome sequencing- a novel approach for studying Phylogenomics for Anas platyrynchos
Authors: Pal Aruna , Chakraborty Argha , Debnath Manti
Published: July 2022

The evolution of duck and its distribution across the globe has been an interesting aspect. Domestication of duck and its evolution was also important to analyze if domesticated duck has migrated to other region of the globe or separate domestication process has occurred in particular region of the world. Mitochondrial genes as D-loop or cytochrome B had been used for studying evolution or molecular phylogeny. In current study, we aim to study phylogenomics for Anas platyrynchos across the globe. Whole mitochondrial genome sequencing for Bengal duck (indigenous duck from West Bengal, India) was performed on illumina platform and gene sequences were analyzed for all 37 mitochondrial genes. Variabilities were observed at nucleotide sequence, but absent in amino acid sequence and corresponding 3D structure of polypeptides coded by mitochondrial genes. We observed Anas platyrynchos from Eurasia (europe and Asia) were clustered together indicating common origin. Extensive variabilities were observed among the chinese duck population. The duck population from US was outgrouped. These ducks might have migrated from China and later bred with wild ducks to evolve as new breed or strain in US.
Antiviral function and viral antagonism of the rapidly evolving dynein activating adapter NINL
Authors: Stevens Donté Alexander , Beierschmitt Christopher , Mahesula Swetha , Corley Miles R. , Salogiannis John , Tsu Brian V. , Cao Bryant , Ryan Andrew P. , Reck-Peterson Samara L. , Daugherty Matthew D.
Published: July 2022

Viruses interact with the intracellular transport machinery to promote viral replication. Such host-virus interactions can drive host gene adaptation, leaving signatures of pathogen-driven evolution in host genomes. Here we leverage these genetic signatures to identify the dynein activating adaptor, ninein-like (NINL), as a critical component in the antiviral innate immune response and as a target of viral antagonism. Unique among genes encoding components of active dynein complexes, NINL has evolved under recurrent positive (diversifying) selection, particularly in its carboxy-terminal cargo binding region. Consistent with a role for NINL in host immunity, we demonstrate that NINL knockout cells exhibit an impaired response to interferon, resulting in increased permissiveness to viral replication. Moreover, we show that proteases encoded by diverse picornaviruses and coronaviruses cleave and disrupt NINL function in a host- and virus-specific manner. Our work reveals the importance of NINL in the antiviral response and the utility of using signatures of host-virus conflicts to uncover new components of antiviral immunity and targets of viral antagonism.
DNA-Stimulated Liquid-Liquid Phase Separation by Eukaryotic Topoisomerase II Modulates Catalytic Function
Authors: Jeong Joshua , Lee Joyce H. , Carcamo Claudia C. , Parker Matthew W. , Berger James M.
Published: July 2022

Type II topoisomerases modulate chromosome supercoiling, condensation, and catenation by moving one double-stranded DNA segment through a transient break in a second duplex. How DNA strands are chosen and selectively passed to yield appropriate topological outcomes – e.g., decatenation vs. catenation – is poorly understood. Here we show that at physiological enzyme concentrations, eukaryotic type IIA topoisomerases (topo IIs) readily coalesce into condensed bodies. DNA stimulates condensation and fluidizes these assemblies to impart liquid-like behavior. Condensation induces both budding yeast and human topo IIs to switch from DNA unlinking to active DNA catenation, and depends on an unstructured C-terminal region, the loss of which leads to high levels of knotting and reduced catenation. Our findings establish that local protein concentration and phase separation can regulate how topo II creates or dissolves DNA links, behaviors that can account for the varied roles of the enzyme in supporting transcription, replication, and chromosome compaction.