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Mechanisms of aureobasidin A inhibition and drug resistance in a fungal IPC synthase complex

Lessons learned from the COVID-19 pandemic in Latin America: A Data Science standpoint

In the 21st century, the world has faced the devastating impacts of three acute respiratory diseases: Middle East respiratory Syndrome (MERS), Severe Acute respiratory Syndrome (SARS), and COVID-19, which evolved into a pandemic. These diseases have not only caused a large number of deaths but have also damaged the economies of the affected regions. Particularly, countries in the Latin American and Caribbean (LAC) region have faced additional challenges due to more significant social inequalities, limited access to Healthcare services, and precarious living conditions, and it is not clear how these challenges impacted the effects of the mitigation actions adopted by each country. However, this understanding is crucial to guide measures to mitigate Health and socioeconomic impacts if (or when) new acute respiratory diseases emerge, especially in these countries. A retrospective study was conducted to model the dynamics of variation in COVID-19 mortality in LAC countries and to analyze its association with vaccination strategies, containment measures, mobility restrictions, and socioeconomic factors. The study methodology applied clustering techniques that revealed two distinct clusters based on sociodemographic characteristics, followed by the application of XGBoost to model the dynamics of variation in deaths in the countries of each cluster over time. Finally, the SHAP Values technique was applied to understand the associations between mortality and factors such as vaccination, containment measures, and mobility restrictions. The study provides evidence that economic support and the completion of the vaccination scheme were especially relevant in reducing COVID-19 mortality. Two distinct groups of countries were detected, one characterized by a greater vulnerability. The most important interventions for understanding COVID-19 mortality varied between pre- and post-vaccination periods. In the pre-vaccination period, containment measures were the most important interventions for mortality in the less vulnerable countries, while population mobility was more important in the more vulnerable countries. In the post-vaccination period, vaccination coverage was the most important intervention for mortality in the less vulnerable countries, while containment measures impacted the more vulnerable countries.

CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly

Abstract The SWI/SNF (or BAF) complex is an essential chromatin remodeler, which is frequently mutated in cancer and neurodevelopmental disorders. These are often heterozygous loss-of-function mutations, indicating a dosage-sensitive role for SWI/SNF subunits. However, the molecular mechanisms regulating SWI/SNF subunit dosage to ensure complex assembly remain largely unexplored. We performed a CRISPR KO screen, using epigenome editing in mouse embryonic stem cells, and identified Mlf2 and Rbm15 as regulators of SWI/SNF complex activity. First, we show that MLF2, a poorly characterized chaperone protein, promotes SWI/SNF assembly and binding to chromatin. Rapid degradation of MLF2 reduces chromatin accessibility at sites that depend on high levels of SWI/SNF binding to maintain open chromatin. Next, we find that RBM15, part of the m 6 A writer complex, controls m 6 A modifications on specific SWI/SNF mRNAs to regulate subunit protein levels. Misregulation of m 6 A methylation causes overexpression of core SWI/SNF subunits leading to the assembly of incomplete complexes lacking the catalytic ATPase/ARP subunits. These data indicate that targeting modulators of SWI/SNF complex assembly may offer a potent therapeutic strategy for diseases associated with impaired chromatin remodeling.

Risk factors for, metrics of, and consequences of access to veterinary care for companion animals: A scoping review

Background Barriers to accessing veterinary care can be challenging for companion-animal caregivers and may lead to preventable health conditions or even death of pets. Objectives We conducted a scoping review to: 1) catalog the definitions of access to veterinary care (A2VC) used by researchers, 2) identify risk factors for and consequences of A2VC, and 3) map the risk factors onto dimensions of access to care (affordability, availability, accessibility, accommodation, acceptability). Eligibility criteria Primary research on companion animals not involved in commercial enterprises (e.g., horse racing) examining consequences of and/or risk factors for A2VC for which the full text was available in English. Sources of evidence PubMed (1996–6 July 2023) and CAB Abstracts (1973–13 July 2023, Web of ScienceTM) were searched. Additionally, a topic expert (KM) identified relevant references. Two reviewers independently screened titles/abstracts and full texts of potentially relevant references. Forward and backward citation searches were also conducted on all eligible studies using Citation Chaser. Charting methods Risk factors were categorized and mapped to the five dimensions of access to care. An evidence gap map was created using the risk factor studies. Results Fifty-one references describing fifty-two relevant studies were included. Forty-one studied risk factors associated with A2VC, and twelve studied consequences of A2VC. (One study examined both risk factors and consequences.) The majority of risk factors examined were demographic. The majority of outcomes measured were pet-centric. No relevant studies focused on pet horses, representing a gap in the literature. Conclusions Consensus needs to be reached on how A2VC is defined and measured to help reduce research wastage and strengthen impact of future studies on improving A2VC. Future studies of risk factors for A2VC should focus on creating a risk-mapping framework specific for A2VC, distinguishing factors that are susceptible to change and those which are not.

Author Correction: An optoelectrochemical synapse based on a single-component n-type mixed conductor

A novel experimental design approach to generating orbital angular momentum waves using wearable textile antenna for sub-6 GHz 5G

This paper presents a novel wearable textile array antenna designed to generate Orbital Angular Momentum (OAM) waves with mode + 1 at 3.5 GHz (3.4 to 3.6 GHz) of the sub-6 GHz 5G New Radio (NR) band. The proposed antenna is based on a uniform circular array (UCA) of four microstrip patch antennas on a felt textile substrate. Compared to previous works involving the use of hard substrates for OAM waves generation, this work explored the use of flexible textile substrates to generate OAM waves for the first time to the best of our knowledge. The overall dimension of the array antenna is 170 ×  156 mm2 while the dimension of each element is 35 ×  35.7 mm2. In order to control the phase and generate OAM waves, the proposed antenna was designed using a felt textile substrate and meandering lines of various lengths connecting the radiating patches. 1.48λ was the separation between radiating patches in order to prevent mutual coupling between them. The antenna was fabricated and measured prior to comparison to simulations to validate this feature. It achieved a measured gain of 3.18 dBi with a bandwidth of 430 MHz (3.24 to 3.67 GHz). Additionally, mode purity analysis was carried out to verify the generation of OAM mode + 1, and the purity obtained was 52.12%. This paper also covered the effect of bending on OAM waves characteristics and the use of airgap technique to enhance the antenna gain. The antenna gain increased from 3.762 dBi to 5.327 dBi by using 1 mm airgap without affecting the mode purity. Furthermore, as per the Specific Absorption Rate (SAR) obtained, it is found that the proposed antenna is safe for on-body use. The novel approach in generating OAM using patch array antenna with flexible substrate by replacing conventional hard substrate has opened up new scope of research in wearable textile antenna domain. The proposed antenna has simple structure, easy to design, fabricate and deploy on human body and has important significance in scaling up this design to generate multiple OAM modes for carrying multiple signals simultaneously.

Bronchopulmonary dysplasia with pulmonary hypertension associates with semaphorin signaling loss and functionally decreased FOXF1 expression

Functional trait identity regulates productivity better than tree diversity and structural complexity in subtropical mixed-species forests

Subtropical forests play an important role in global carbon cycle and in mitigating climate change. Understanding the relationship between multiple diversity and ecosystem function is crucial for protecting and managing forests. Here we used forest inventory data from a 6-hectare sample plot in natural evergreen deciduous broad-leaf mixed forest systems for the years 2016 and 2021. We analyzed the effects of multiple aspects of diversity and topographic factors on forest productivity using multiple causal analyses. We found that Fagaceae was the primary contributor to productivity in the forest stand. Elevation, slope, and convexity showed no significant effects on productivity. Structural complexity (stand density, large-diameter trees and tree-size variation) was significantly positively correlated with productivity. Taxonomic and functional diversity indices were weakly correlated with productivity. Specifically, forest productivity was enhanced by traits associated with greater maximum height and lower wood density. Community-weighted mean traits were the most strongest predictor of productivity relative to other variables. Within this forest stand, the mass-ration hypothesis appeared to be more influential on forest productivity compared to the complementarity and selection effects. By integrating multiple drivers of forest ecosystem functioning, our study provides critical system-level insights needed to predict the potential consequences of regional changes in forest diversity, composition, structure and function.

Identification of covalent inhibitors of Staphylococcus aureus serine hydrolases important for virulence and biofilm formation

Exploring the impact of nature connectedness on well-being and mental distress among urban youth: Evidence from 25 most populated cities in India

In contemporary urban settings, enhancing the well-being of youth is a challenge. The proliferation of screen time, particularly post-pandemic, has contributed to an alarming disconnection with nature. This study investigates the impact of nature connectedness on the well-being of urban youth residing in the 25 most populated cities in India. 2283 urban youth responded to an online survey questionnaire that aimed to assess participants’ exposure to and interaction with nature. Respondents self-reported their proximity to green and blue spaces near their residences, the frequency of recreational visits to these areas, time spent in indoor environments, nature connectedness, and well-being. Multivariate regression analysis results show that urban youth with access to both green and blue spaces within 1-kilometre or between 1-3 kilometres radius, along with frequent recreational visits to these spaces, reported a significant positive impact on well-being. Additionally, spending less than 8 hours in indoor environments and a high nature connectedness score had a significant positive impact on well-being. Moreover, a logistic regression analysis shows that urban youth with well-being score less than 13, considered mentally distressed, who have access to both green and blue spaces within 1 kilometres or access to green spaces between 1-3 kilometres, along with frequent recreational visits to these spaces, and a high nature connectedness score, increases their log-odds of well-being significantly. This study conducted in the 25 most populated cities, represents a comprehensive exploration of the impact of nature connectedness on well-being in India. The study does, however, have limitations, including uneven sample distribution among cities, the absence of temporal analysis, and a restricted age range of 18-25 years. These limitations will be addressed in future research. The implications of the study extend to policy recommendations, advocating for the development of more parks in close proximity to residential areas. Such initiatives aim to encourage urban youth to actively engage with and experience nature, fostering improved well-being and reduced distress levels.

Heterogeneous III-V/Si micro-ring laser array with multi-state non-volatile memory for ternary content-addressable memories

Integrated pan-cancer analysis revealed therapeutic targets in the ABC transporter protein family

Next-generation sequencing technology enables uniform and impartial assessment of cancer diagnoses and prognosis. However, such studies are mostly type-specific, and capturing shared genomic abnormalities responsible for neoplastic transformation and progression is a challenging task. Pan-cancer analysis offers insights into the shared and unique molecular mechanisms driving cancer. We conducted an integrated gene-expression analysis using 10,629 samples from 30 distinct cancer types characterized by The Cancer Genome Atlas (TCGA). A gene co-expression network was constructed and genes overlapping between the selected modules and Differentially Expressed Genes (DEGs) were designated as genes of interest. Following a comprehensive literature review, ATP binding cassette subfamily A member 10 (ABCA10) and ATP binding cassette subfamily B member 5 (ABCB5) were selected as key candidates for downstream analysis due to the absence of systematic pan-cancer analysis of these genes. This study presents a unique contribution as the first comprehensive pan-cancer analysis of ABCA10 and ABCB5, highlighting their roles in tumor biology and clinical outcomes. We employed a variety of bioinformatics tools to explore the role of these genes across different tumors. Our research demonstrated that ABCA10 shows reduced expression, while ABCB5 displays variable expression patterns across tumors, indicating their opposing roles and flexible functions in pan-cancer. In many cancer patients, these expression patterns are correlated with worse survival outcomes. Furthermore, immunotherapy responses and immune infiltration across a variety of tumor types are associated with the expression levels of both ABCA10 and ABCB5. These results imply that ABCA10 and ABCB5 could serve as valuable predictive markers and potential therapeutic targets across various cancers.

In vivo structure profiling reveals human cytosolic and mitochondrial tRNA structurome and interactome in response to stress

Lessons from a systematic tracing process aimed to reduce initial loss to follow-up (ILTFU) among people diagnosed with tuberculosis (TB) in Cape Town, South Africa

Background South Africa is a high tuberculosis (TB) burdened country. People who are newly diagnosed with TB must link to a TB treatment facility and be registered in the electronic TB notification system for ongoing care. Delayed linkage to care increases the risk of disease progression, mortality, and ongoing TB transmission. We describe lessons from a systematic tracing process aimed to support linkage to care for people diagnosed with TB. Methods The study used the Western Cape Provincial Health Data Centre (PHDC) to identify persons newly diagnosed with TB (January-December 2020) who were not recorded as linked to care after routine linking efforts, in one peri-urban health sub-district in Cape Town, South Africa. A systematic tracing process was followed, including visits to primary health care (PHC) facilities, and home visits for those with no evidence of linkage at PHC level. Descriptive statistics were used to analyse quantitative data. Lessons learned during the process were documented. Results Within the PHDC, 406 persons diagnosed with TB had no evidence of being linked to TB care. Verification at PHC facilities found that 153/406 (38%) had linked to care. We traced 219 persons; of which107 (49%) could not be found. Overall, the PHDC showed 76% linkage among those traced and found and 72% among those not found. Lessons learned include the need for improved; (i) record keeping enabling the allocation of resources to patients who are truly lost to follow up, (ii) communication to improve patient understanding of timely treatment initiation and (iii) interpersonal relationships to encourage trust. Conclusion The systematic tracing process was useful to understand the complexities around delayed linkage to care. To reduce ILTFU, we recommend, improving accuracy and timely recording of TB data, updating patient contact details regularly and strengthening interpersonal relations and communication between patients and healthcare workers.

Author Correction: Resistance to anti-LAG-3 plus anti-PD-1 therapy in head and neck cancer is mediated by Sox9+ tumor cells interaction with Fpr1+ neutrophils

Integrated nutritional care in long-term care: From theory to evidence-based practice

Against the background of ageing societies and worldwide growing populations with complex care needs, the reorganization of health and social care provision from fragmented towards integrated healthcare is becoming essential. Nutritional challenges, such as malnutrition, are one of the key areas of interest, when redesigning care systems for ageing societies, especially when older people are residing in long-term care. In response to that, this study describes the development of an evidence-based inter-professional nutritional care pathway in long-term care settings. A qualitative multi-method approach of four consecutive sub-processes was performed guided by principles derived from implementation science: 1) Regional maturity assessment, 2) Matching process with existing care pathways, 3) Step-based co-creation with stakeholders, 4) Local implementation, accompanied by a planned multi-level evaluation procedure. The research process resulted in a final nutritional care pathway, structured into seven care episodes leveraging capacity around nutritional care needs of long-term care residents in an inter-professional and person-centered manner. Early evaluation results indicate that the care pathway serves as evidence-based guideline and facilitates resource-efficient practice routines in long-term care. This paper describes an iterative approach to transform nutritional care provision in long-term care. Although the concept was contextualized and developed around local needs and circumstances, it may serve as case example for subsequent integrated care efforts. Further evaluation results are needed to disclose long-term outcomes and effectiveness.

Mapping grey and white matter activity in the human brain with isotropic ADC-fMRI

Effects of whole-body vibration training on muscle performance in healthy women: A systematic review and meta-analysis of randomized controlled trials

Objective This study aimed to perform a comprehensive meta-analysis of randomized controlled trials examining the effectiveness of whole-body vibration training (WBVT) on muscle performance in healthy women. Methods A systematic search of studies available up to 30 May 2024 was conducted using seven databases, including PubMed, EMBASE, Web of Science, Scopus, CINAHL, PEDro, and the Cochrane Library. Studies with a randomized and controlled protocol in which the effect of WBVT on muscle performance variables was compared to that of a) a non-exercise intervention or b) exercise intervention in healthy women were assessed for eligibility. The methodological quality of the included studies was assessed using the PEDro scale. Meta-analyses were performed using random effects models, and the results were expressed as standardized mean differences (SMDs) with corresponding 95% confidence intervals (95% CIs). Results A total of 21 randomized controlled trials, encompassing 748 healthy women, was included in the meta-analysis. WBVT demonstrated significantly greater effects on muscle strength and power when compared with the non-exercise control groups with regard to knee extension (SMD = 0.534, 95% CI: 0.303 to 0.766, p < 0.001), leg press (SMD = 0.794, 95% CI = 0.424 to 1.163, p < 0.001), ankle plantar flexion (SMD = 0.462, 95% CI: 0.019 to 0.904, p = 0.041), and the countermovement jump performance (SMD = 0.470, 95% CI: 0.211 to 0.729, p < 0.001). However, WBVT significantly improved only the countermovement jump performance (SMD = 0.338, 95% CI: 0.037 to 0.640, p = 0.028) when compared with the exercise control groups. Subgroup analyses revealed that longer periods (≥ 12 weeks) of WBVT resulted in greater benefits for both muscle strength and power compared to the non-exercise control group. Additionally, higher frequencies (> 30 Hz, SMD = 0.736, p < 0.001; ≤ 30 Hz, SMD = 0.284, p = 0.109) provided greater benefits for improving muscle strength. Last, post-menopausal women (post-menopausal, SMD = 0.561, p = 0.001; pre-menopausal, SMD = 0.354, p = 0.076) obtained greater benefits in muscle power with WBVT than pre-menopausal women. Conclusions WBVT is efficacious in improving lower-body muscle strength and power in healthy women. However, the potential benefits of WBVT compared to other exercise interventions were only associated with an enhancement in countermovement jump performance. Longer periods (≥ 12 weeks) of WBVT resulted in greater benefits for both muscle strength and power compared to the non-exercise control group. Additionally, higher vibration frequencies (> 30 Hz) provided greater improvements in muscle strength, while post-menopausal women reaped greater benefits in muscle power than pre-menopausal women.

Antarctic glaciers export carbon-stabilised iron(II)-rich particles to the surface Southern Ocean

Abstract Iron is an essential micronutrient for phytoplankton and plays an integral role in the marine carbon cycle. The supply and bioavailability of iron are therefore important modulators of climate over glacial-interglacial cycles. Inputs of iron from the Antarctic continental shelf alleviate iron limitation in the Southern Ocean, driving hotspots of productivity. Glacial meltwater fluxes can deliver high volumes of particulate iron. Here, we show that glacier meltwater provides particles rich in iron(II) to the Antarctic shelf surface ocean. Particulate iron(II) is understood to be more bioavailable to phytoplankton, but less stable in oxic seawater, than iron(III). Using x-ray microscopy, we demonstrate co-occurrence of iron and organic carbon-rich phases, suggesting that organic carbon retards the oxidation of potentially-bioavailable iron(II) in oxic seawater. Accelerating meltwater fluxes may provide an increasingly important source of bioavailable iron(II)-rich particles to the Antarctic surface ocean, with implications for the Southern Ocean carbon pump and ecosystem productivity.

Beyond the ORF: Paralog-specific regulation of RPS7/eS7 mRNAs via 3’-UTRs and promoter sequences

In a classical view, each paralogous ribosomal protein (RP) is equally synthesized and integrated into the ribosome. Therefore, RP-paralog mRNAs are generally believed to be similarly regulated on their transcription and/or stability. In this paper, we report that two Rps7p/eS7 paralogs of Saccharomyces cerevisiae are differently regulated; deletion of RPS7A upregulates RPS7B paralogous mRNA expression but not vice versa. Their 3’-UTR sequences critically regulated the stabilities of both RPS7A and RPS7B mRNAs. Alterations in these sequences led to a diminished expression of RPS7A and RPS7B mRNAs in a transcript-dependent manner, suggesting that RPS7-paralog mRNAs have different properties for their expression and/or stability. The C-terminal tagging of the ORF and mutation analyses in the 3’-UTR indicate that both RPS7-paralog mRNAs critically rely on their 3’-UTRs for mRNA expressions and/or stabilities. We also found that activities of both RPS7A and RPS7B promoters are regulated by abundance of Rps7Ap and that Fhl1p, a key transcriptional regulator of RP genes, is essential for transcription of RPS7B but not RPS7A while simultaneous deletion of a consensus sequence for Fhl1p in the RPS7A promoter region and the FHL1 gene completely abolishes the promoter activity. These results indicate that yeast has a distinct buffering system for Rps7p production between the two RPS7-paralogs, which is sensitive to variation on their 3’-UTRs and is partially mediated in a transcription-dependent manner.