bluuebunny/crossref_metadata_2025 huggingface dataset:
The Scratch-Collapse Test
Authors: Jain Nirbhay S. , Miller Amanda , Barr Meaghan L. , Gajewski Christopher R. , Pflibsen Lacey , Azari Kodi K. , Benhaim Prosper
Published: June 2024

Introduction

Carpal tunnel syndrome is commonly managed by hand and upper extremity surgeons. Though electrodiagnostics are considered the gold standard diagnosis, the scratch collapse test (SCT) was introduced to address uncertainty, despite remains controversial. To address this, we sought to identify if the SCT can correlate with EDS studies if the SCT can identify actual changes in measures of nerves.

Methods

We reviewed patients who underwent electrodiagnostic studies (EDX) and SCT for carpal tunnel syndrome (CTS). Demographic data as well as sensorimotor amplitudes, latencies, and velocities on nerve conduction and electromyography were collected. Analogous values based on SCT findings were analyzed for statistical significance.

Results

Three hundred fifty patients with CTS were included. Sensory and motor velocities and amplitudes were significantly lower in patients with a positive SCT. Motor values were independent of age, though younger patients had larger measured changes. Obese patients did not show any motor EDX changes with the scratch collapse test, though thinner patients did. All changes were seen in nerve conduction only.

Conclusions

Carpal tunnel can be a difficult problem to diagnose as one study does not singularly determine the condition. The SCT was introduced to facilitate easier diagnosis. We demonstrate that the SCT correlates with changes on nerve conduction studies, especially in relation to decreased amplitudes and velocities, suggesting that it does identify changes in nerve with compression, specifically axonal, and myelin damage. These findings support the use of the SCT maneuver to evaluate and diagnose in appropriate patients.
ATP dependence of decision-making capacity in a fine-grained model of gene regulatory networks
Authors: Kumar Rajneesh , Johnston Iain G.
Published: June 2024

Cellular decision-making is fundamental to life, from developmental biology to environmental responses and antimicrobial resistance. Many regulatory processes that drive cellular decisions rely on gene expression, which requires energy in the form of ATP. As even genetically identical cells can have dramatically different ATP levels, bioenergetic status can be an important source of variability in cellular decision-making. Existing studies have investigated this energy dependence but often use coarse-grained modelling approaches (which are not always readily connected to the underlying molecular processes of gene regulation). Here, we use a fine-grained mathematical model of gene expression in a two-gene decision-making regulatory network to explore cellular decision-making capacity as energy availability varies. We simulate both a deterministic model, to explore the emergence of different cell fate attractors as ATP levels vary, and a stochastic case to explore how ATP influences the noisy dynamics of stochastic cell decision-making. Higher energy levels typically support increased decision-making capacity (higher numbers of, and more separated, cell states that can be selected), and the fine-grained modelling reveals some differences in behaviour from previous coarse-grained modelling approaches.
Novel Gammapapillomavirus type in the nasal cavity of a wild red colobus (Piliocolobus tephrosceles)
Authors: Weary Taylor E. , Mehta Kavi P.M. , Goldberg Tony L.
Published: June 2024

Papillomaviruses (PVs) are double-stranded, circular, epitheliotropic DNA viruses causing benign warts (papillomas) or inducing dysplasia that can progress to cancer. Although they have been identified in all vertebrate taxa, most classified types are human PVs (HPVs); relatively little is known about PVs in other species. Here we characterize a novel Gammapapillomavirus type, PtepPV1, from a nasal swab of a wild red colobus (Piliocolobus tephrosceles) in Kibale National Park, Uganda. The virus has a genome of 6,576 bases, encoding the seven canonical early (E) ORFs (E6, E7, E1, E2, E4, E1^E4, and E8^E2) and two late (L) ORFs (L1 and L2) of the gammapapillomaviruses, and is 81.0% similar to HPV-mSK_118, detected in a cutaneous wart from an immunocompromised human patient, in the L1 gene at the amino acid level. Alphapapillomaviruses (genus Alphapapillomavirus) cause anogenital carcinomas such as cervical cancer and have been described previously in several nonhuman primates. However, the first gammapapillomavirus (genus Gammapapillomavirus), which cause transient cutaneous infections, was not described until 2019 in a healthy rhesus macaque (Macaca mulatta) genital swab. The new virus from red colobus, PtepPV1, has many genomic features encoded by high-risk oncogenic PVs, such as the E7 gene LXSXE and CXXC motifs, suggesting potential for pRb and zinc-finger binding, respectively. To our knowledge, PtepPV1 is also the first reported nonhuman primate PV found in the nasal cavity. PtepPV1 expands the known host range, geographic distribution, tissue tropism, and biological characteristics of nonhuman primate PVs.
Comparative Evaluation of Soil DNA Extraction Kits for Long Read Metagenomic Sequencing
Authors: Child Harry T. , Wierzbicki Lucy , Joslin Gabrielle R. , Tennant Richard
Published: June 2024

Metagenomics has been transformative in our understanding of the diversity and function of soil microbial communities. Applying long read sequencing to whole genome shotgun metagenomics has the potential to revolutionise soil microbial ecology through improved taxonomic classification, functional characterisation and metagenome assembly. However, optimisation of robust methods for long read metagenomics of environmental samples remains undeveloped. In this study, Oxford Nanopore sequencing using samples from five commercially available soil DNA extraction kits was compared across four soil types, in order to optimise read length and reproducibility for comparative long read soil metagenomics. Average extracted DNA lengths varied considerably between kits, but longer DNA fragments did not translate consistently into read lengths. Highly variable decreases in the length of resulting reads from some kits were associated with poor classification rate and low reproducibility in microbial communities identified between technical repeats. Replicate samples from other kits showed more consistent conversion of extracted DNA fragment size into read length and resulted in more congruous microbial community representation. Furthermore, extraction kits showed significant differences in the community representation and structure they identified across all soil types. Overall, the QIAGEN DNeasy PowerSoil Pro Kit displayed the best suitability for reproducible long-read WGS metagenomic sequencing, although further optimisation of DNA purification and library preparation may enable translation of higher molecular weight DNA from other kits into longer read lengths. These findings provide a novel insight into the importance of optimising DNA extraction for achieving replicable results from long read metagenomic sequencing of environmental samples.
Paenalcaligenes faecalis sp. nov., a novel species of the family Alcaligenaceae isolated from chicken faeces
Authors: Zhang Yiran , Quensen John , Chen Bo , Li Hailong , Tiedje James , Sun Wei , Qian Xun
Published: June 2024

A Gram-negative, motile, rod-shaped aerobic and alkalogenic bacterium, designated as strain YLCF04T, was isolated from chicken faeces. Its growth was optimal at 28 °C (range, 10–40 °C), pH 8 (range, pH 6–9) and in 1 % (w/v) NaCl (range, 0–10 %). It was classified to the genus Paenalcaligenes and was most closely related to Paenalcaligenes hominis CCUG 53761AT (97.5 % similarity) based on 16S rRNA gene sequence analysis. Average nucleotide identity and digital DNA–DNA hybridization values between YLCF04T and P. hominis CCUG 53761AT were 76.3 and 18.2 %, respectively. Strain YLCF04T has a genome size of 2.7 Mb with DNA G+C content of 46.3 mol%. Based on its phylogenetic, genomic, phenotypic and biochemical characteristics, strain YLCF04T represents a novel species of the genus Paenalcaligenes, for which the name Paenalcaligenes faecalis sp. nov. is proposed. The type strain is YLCF04T (=CCTCC AB 2022359T= KCTC 92789T).
Cellular and transcriptional profiles of peripheral blood mononuclear cells pre-vaccination predict immune response to preventative MUC1 vaccine
Authors: Yuan Daniel Y , McKeague Michelle L , Raghu Vineet K , Schoen Robert E , Finn Olivera J , Benos Panayiotis V
Published: June 2024

A single arm trial (NCT007773097) and a double-blind, placebo controlled randomized trial (NCT02134925) were conducted in individuals with a history of advanced colonic adenoma to test the safety and immunogenicity of the MUC1 tumor antigen vaccine and its potential to prevent new adenomas. These were the first two trials of a non-viral cancer vaccine administered in the absence of cancer. The vaccine was safe and strongly immunogenic in 43% (NCT007773097) and 25% (NCT02134925) of participants. The lack of response in a significant number of participants suggested, for the first time, that even in a premalignant setting, the immune system may have already been exposed to some level of suppression previously reported only in cancer. Single-cell RNA-sequencing (scRNA-seq) on banked pre-vaccination peripheral blood mononuclear cells (PBMCs) from 16 immune responders and 16 non-responders identified specific cell types, genes, and pathways of a productive vaccine response. Responders had a significantly higher percentage of CD4+ naive T cells pre-vaccination, but a significantly lower percentage of CD8+ T effector memory (TEM) cells and CD16+ monocytes. Differential gene expression (DGE) and transcription factor inference analysis showed a higher level of expression of T cell activation genes, such as Fos and Jun, in CD4+ naive T cells, and pathway analysis showed enriched signaling activity in responders. Furthermore, Bayesian network analysis suggested that these genes were mechanistically connected to response. Our analyses identified several immune mechanisms and candidate biomarkers to be further validated as predictors of immune responses to a preventative cancer vaccine that could facilitate selection of individuals likely to benefit from a vaccine or be used to improve vaccine responses.
Combinatorial engineering reveals shikimate pathway bottlenecks in para-aminobenzoic acid production inPseudomonas putida
Authors: Campos-Magaña Marco A , Moreno-Paz Sara , Martins dos Santos Vitor AP , Garcia-Morales Luis , Suarez-Diez Maria
Published: June 2024

Combinatorial approaches in metabolic engineering enable the optimization of multigene pathways, thereby improving product titers. However, the optimization of complex metabolic pathways is hindered by their multiple interactions. Testing all possible combinations of suitable genetic parts is often prevented by the large number of possible variants. A valuable alternative to this is to use statistical design of experiments and linear modeling to collect important information for optimization without testing every possible combination. The shikimate pathway is an example of a complex metabolic pathway involved in the production of aromatic compounds, which are prevalent in industry. In this study, we explore the impact of the modulation of the expression levels of all the genes in the shikimate and para-aminobenzoic acid (pABA) biosynthesis pathways for pABA production (a widely used industrial intermediate) inPseudomonas putida. We used this approach to select 14 representative strains from a total of 512 possible combinations. We obtained a range of product titers from 2 to 186.2 mg/l. This information was used to guide a second round of strain construction to further increase the production to 232.1 mg/l. Using this strategy, we demonstrate thataroBexpression, encoding 3-dehydroquinate synthase, is a significant limiting factor in the production of pABA.
Transcranial Direct Current Stimulation over the Posterior Parietal Cortex Increases Non-target Retrieval during Visual Working Memory
Authors: Ye Shengfeng , Wu Menglin , Yao Congyun , Xue Gui , Cai Ying
Published: June 2024

Accurate visual working memory (VWM) requires precise content-context binding. Previous studies have revealed a close relationship between the posterior parietal cortex (PPC) and feature binding during VWM, this study further examined their causal relationship through three transcranial direct current stimulation (tDCS) experiments. In Experiment 1 (N= 57), participants underwent three sessions of tDCS separately, including PPC stimulation, occipital cortex stimulation, and sham stimulation, and completed a series of delayed estimation tasks for orientations before and after stimulation. Results showed that tDCS over PPC selectively prolonged recall response time (RT) and increased the probability of non-target responses (a.k.a. failure of feature binding). In Experiment 2 (N= 29), combining metacognition estimation during the task, we further investigated whether the effects of PPC stimulation on RT and increased probability of non-target responses were attributed to more mis-binding (i.e., participants self-reported "remembered" in non-target responses) or informed guessing (participants self-reported "forgotten" in non-target responses). We replicated the main findings in Experiment 1, and we also observed greater tDCS effects of PPC on RT in informed guessing trials than mis-binding trials while comparable effects on non-target response rates in these two types of trials. In Experiment 3 (N= 28), we then examined whether the effects of tDCS over PPC specifically influenced the memory retrieval process by using a change detection task. We found that PPC stimulation did not influence the recognition RT or accuracy. Together, this study provides causal evidence supporting the involvement of PPC in feature binding during VWM retrieval.

Significance Statement

Visual working memory (VWM) enables humans to temporarily store and process visual information, which requires accurate binding of items to their unique context. Accumulating studies posited that the posterior parietal cortex (PPC) is closely related to this binding process, the current study further examined their causal relationship. Through three strictly within-subject well-designed non-invasive neural stimulation experiments, we found that PPC stimulation selectively increased response time (RT) and binding error during VWM. Moreover, we found these changes were modulated by individual metacognition and only occurred during memory recall instead of recognition. Together, our results provided strong evidence that PPC is causally involved in the binding process during visual working memory retrieval.
Navigated ultrasound bronchoscopy with integrated positron emission tomography - A human feasibility study
Authors: Kildahl-Andersen Arne , Hofstad Erlend Fagertun , Solberg Ole-Vegard , Sorger Hanne , Amundsen Tore , Langø Thomas , Leira Håkon Olav
Published: June 2024

Background and objective

Patients suspected to have lung cancer, undergo endobronchial ultrasound bronchoscopy (EBUS) for the purpose of diagnosis and staging. For presumptive curable patients, the EBUS bronchoscopy is planned based on images and data from computed tomography (CT) images and positron emission tomography (PET). Our study aimed to evaluate the feasibility of a multimodal electromagnetic navigation platform for EBUS bronchoscopy, integrating ultrasound and segmented CT, and PET scan imaging data.

Methods

The proof-of-concept study included patients with suspected lung cancer and pathological mediastinal/hilar lymph nodes identified on both CT and PET scans. Images obtained from these two modalities were segmented to delineate target lymph nodes and then incorporated into the CustusX navigation platform. The EBUS bronchoscope was equipped with a sensor, calibrated, and affixed to a 3D printed click-on device positioned at the bronchoscope’s tip. Navigation accuracy was measured postoperatively using ultrasound recordings.

Results

The study enrolled three patients, all presenting with suspected mediastinal lymph node metastasis (N1-3). All PET-positive lymph nodes were displayed in the navigation platform during the EBUS procedures. In total, five distinct lymph nodes were sampled, yielding malignant cells from three nodes and lymphocytes from the remaining two. The median accuracy of the navigation system was 7.7 mm.

Conclusion

Our study introduces a feasible multimodal electromagnetic navigation platform that combines intraoperative ultrasound with preoperative segmented CT and PET imaging data for EBUS lymph node staging examinations. This innovative approach holds promise for enhancing the accuracy and effectiveness of EBUS procedures.
Depressive, anxiety and stress symptoms among university students from Bogotá, Colombia and electronic nicotine delivery systems (ENDS) use: Findings from a prevalence survey 2021
Authors: García Durán María Camila , Botero Ruge María Catalina , Perdomo Patiño Gustavo , Pulido Álvarez Adriana , Lüchau Manuela , Borrero Elizabeth , Moreno Sergio
Published: June 2024

The use of electronic nicotine delivery systems (ENDS) has increased in recent years, particularly among young people. The association between mental health disorders and conventional cigarettes is well established. However, information on ENDS use and mental health is still emerging. This study i) determines the frequency of depression, anxiety and stress symptoms among university students in Bogotá, Colombia, ii) examines the association between sociodemographic variables and mental health symptoms, and iii) analyses whether there is an association between tobacco and/or ENDS use and depression, anxiety and/or stress. The study is cross-sectional, analytical, retrospective and based on a multistage random sample. 3850 students from 21 universities completed an online survey and were included as participants. We assessed demographic variables, tobacco use, ENDS use and symptoms of depression, anxiety and stress. 667 participants from our sample had a previous diagnosis of a mental disorder, and the most common diagnoses were any type of anxiety disorder (7.27%) or depressive disorder (6.70%). Ever use of conventional cigarettes was 63.71% and ever use of ENDS was 31%. More than 65% of the participants had mild symptoms of depression, anxiety and stress. However, between 16.4% and 19.5% of participants reported severe or very severe symptoms of these three diagnoses. Severe or very severe symptoms were more likely to be reported by women, public university students and those from higher socio-economic backgrounds. Those who reported having tried conventional cigarettes or ENDS had more severe or extremely severe symptoms than those who had never tried them. Multivariate analysis using ordinal logistic regression showed that depression, anxiety and stress levels were more severe in participants who had tried ENDS. In addition, having nuclear family members, family members or close friends with a history of nicotine use was positively associated with higher levels of depression, anxiety and stress.
Exploring the factors associated with prelacteal feeding in Papua New Guinea: a population-based cross-sectional study
Authors: Maviso McKenzie , Namosha Elias , Guldan Georgia
Published: June 2024

ObjectivePrelacteal feeds disrupt early breastfeeding initiation and exclusive breastfeeding and increase the risk of childhood illnesses and under-five mortality. Despite its negative health outcomes, prelacteal feeding prevails in Papua New Guinea (PNG). This study aimed to investigate the factors associated with prelacteal feeding among women in PNG.Design and settingA population-based cross-sectional study based on Demographic and Health Survey dataSettingPapua New GuineaParticipantsA total weighted sample of 4399 women was included in the study.Main outcome measuresPrelacteal feeding, modeled using multivariable logistic regression.ResultsAbout 10% (95% CI: 9 to 11) of women provided prelacteal feeds to their infants in PNG. The most frequently reported prelacteal feed was plain water (71.7%), followed by grains (eg, noodles) (47.1%), dark green leafy vegetables (42.1%), and soup (39.7%). Women with no formal (AOR 1.4, 95% CI: 1.0 to 3.0) or primary education (AOR 1.5, 95% CI: 1.0 to 2.9), from the Islands region (AOR 2.3, 95% CI: 1.5 to 3.5), who had a cesarean section (AOR 4.1, 95% CI: 2.4 to 7.2), and who had given birth at home or in the village (AOR 3.7, 95% CI: 2.1 to 6.8) had higher odds of providing prelacteal feeds. No statistically significant association was found between immediate newborn skin-to-skin contact after birth and prelacteal feeding.ConclusionOur study underscores the role of sociodemographic and healthcare system factors in prelacteal feeding. Strengthening healthcare providers' capacity to increase mothers' awareness of optimal breastfeeding and promote more health facility births is warranted. Comprehensive breastfeeding education should also be promoted at antenatal clinics and during outreach healthcare activities.
Leptin augmented model to include the role of obesity in insulin-glucose regulatory system for T2DM subjects
Authors: Aravindakshan Manoja Rajalakshmi , Ghosh Devleena , Mandal Chittaranjan , Sarkar Jit , Maity Sujay K , Chakrabarti Partha
Published: June 2024

Leptin is a fat cell-derived hormone involved in satiety and body weight regulation. It also plays a critical regulatory role in the insulin-glucose regulatory system by modulating glucose metabolism and energy homeostasis. However, existing insulin-glucose models often fail to consider the impact of body weight indicators mainly body mass index (BMI) and plasma leptin. To address this limitation, we propose augmenting the ordinary differential equations (ODE) of the Oral Minimal Model (OMM) with an additional equation, incorporating leptin as well as supplementary terms and parameters. By estimating the model parameters, the model behaviour is aligned with the observed data of glucose, insulin and leptin for individuals with type 2 diabetes mellitus (T2DM). Based on model behaviour, revised indices formulated from Oral Glucose Tolerance Test (OGTT) data by including BMI and fasting leptin values are found to have a better correlation with existing indices. Additionally, parameter sensitivity analysis is performed to investigate the influence of the model parameters on the observed variables. Validation of the augmented model with clinical data (without leptin) demonstrates a superior fit to glucose and insulin data compared to the base model. This model emphasizes the intricate associations between leptin, glucose, and insulin concentrations with a potential for developing targeted interventions and therapies for T2DM. Notably, this manuscript introduces the first ODE-based model that incorporates leptin and BMI in the insulin-glucose pathway.
Performance and validation of a digital memory test across the Alzheimer’s Disease continuum
Authors: Toniolo Sofia , Attaallah Bahaaeddin , Maio Maria Raquel , Tabi Younes Adam , Slavkova Elitsa , Klar Verena Svenja , Saleh Youssuf , Idris Mohamad Imran , Turner Vicky , Preul Christoph , Srowig Annie , Butler Christopher , Thompson Sian , Manohar Sanjay G. , Finke Kathrin , Husain Masud
Published: June 2024

Digital cognitive testing using online platforms has emerged as a potentially transformative tool in clinical neuroscience. In theory, it could provide a powerful means of screening for and tracking cognitive performance in people at risk of developing conditions such as Alzheimer’s Disease (AD). Here we investigate whether digital metrics derived from a tablet-based short-term memory task – “What was where?” Oxford Memory Task – were able to clinically stratify patients at different points within the AD continuum and to track disease progression over time. Performance of these metrics to traditional neuropsychological pen-and-paper screening tests of cognition was also analyzed. A total of 325 people participated in this study: 49 patients with subjective cognitive impairment (SCI), 57 with mild cognitive impairment (MCI), 63 with AD dementia and 156 elderly healthy controls (EHC). Most digital metrics were able to discriminate between healthy controls and patients with MCI and between MCI and AD patients. Some, including Absolute Localization Error, also differed significantly between patients with SCI and MCI. Identification accuracy was the best predictor of hippocampal atrophy, performing as well as standard screening neuropsychological tests. A linear support vector model combining digital metrics achieved high accuracy and performed at par with standard testing in discriminating between EHC and SCI (AUC 0.82) and between SCI and MCI (AUC 0.92). Memory imprecision was able to predict cognitive decline on standard cognitive tests over one year. Overall, these findings show how it might be possible to use a digital memory test in clinics and clinical trial contexts to stratify and track performance across the Alzheimer’s disease continuum.
Differences in neuromusculoskeletal injury and disability rates between US Navy aircraft carrier and amphibious assault ships
Authors: Fraser John J. , Halfpap Joshua , Rosenthal Michael
Published: June 2024

Structured Summary

Introduction

Musculoskeletal injuries (MSKI) are the most common clinical condition in the military that affect medical readiness. Evaluation of MSKI burden and the effects of these injuries on readiness in large deck Navy ships is warranted.

Materials and Methods

A retrospective cohort study assessing population-level MSKI rates, limited duty (LIMDU), and long-term disability episode counts of all Sailors assigned to US Navy Aircraft Carriers (CVNs) and Amphibious Assault Ships (LHA/LHD) from November 2016 to February 2023 were extracted from the Musculoskeletal Naval Epidemiological Surveillance Tool. A negative binomial regression and general additive (gaussian) models evaluated the association of ship platform, deployment status, days underway, and sex on MSKI rates and the proportion of cases that resulted in LIMDU, returned-to-duty following LIMDU, or progressed to long-term disability.

Results

Sailors attached to CVNs contributed a mean 17893.8±23280.6 person-months, with those attached to LHA/LHDs contributing an average 5981.8±8432.7 person-months. Aboard CVNs, MSKI occurred at a rate of 0.30±0.16/1000 person-months while deployed and 0.64±0.31/1000 person-months in homeport. Aboard LHA/LHDs, Sailors incurred MSKI at a rate of 0.59±0.58/1000 person-months while on deployment and 1.24±0.68/1000 person-months in homeport. Among Sailors aboard CVNs, LIMDU occurred in 7.95±7.75% of MSKI cases while deployed and 5.13±5.26% while in homeport. Aboard LHA/LHDs, 8.57±13.42% of MSKI cases were placed on LIMDU while deployed and 4.95±5.27% while in homeport. In the multivariable assessment of LIMDU, being deployed underway was a significant factor (B=3.62 p=.03, variance explained=3.86%). Sailors that were female and served aboard LHA/LHDs returned to full duty at a significantly greater frequency compared to their male counterparts and Sailors serving aboard CVNs. None of the independent variables evaluated were associated with long-term disability.

Conclusion

The findings in the current study demonstrate the substantial burden of MSKI aboard large deck ships, both in homeport and while deployed. Inclusion of a PT aboard LHA/LHDs, like the CVN, may help to prevent and mitigate the effects of MSKI through early access to specialized care and integral injury prevention and performance optimization methods.
Knock-down of genes essential for homoacetogenic growth using sugar inducible promoters in the thermophileThermoanaerobacter kivui
Authors: Zeldes Benjamin , Mittelstedt Sabina , Baum Christoph , Shakirova Adilia , Poehlein Anja , Daniel Rolf , Müller Volker , Basen Mirko
Published: June 2024

Given recent interest in hydrogen (H2) as a medium for storing and transporting renewable energy, the ability of acetogenic bacteria to use H2to directly fix carbon dioxide (CO2) shows great promise. Thermophilic bacteria have long been of interest as industrial strains due to their resistance to contamination.Thermoanaerobacter kivuiis among the most thermophilic acetogens. It can be genetically manipulated, but as yet only in an all-or-nothing manner, either complete gene knockouts or very strong constitutive promoters leading to protein overexpression. The sugar inducible promoters characterized here provide the finer control necessary to close remaining gaps in understanding ofT. kivui’s energy metabolism and for controlled expression of recombinant genes of industrial relevance.

Acetogenic bacteria are capable of growing on mixtures of the gasses H2, CO2, and CO using the Wood-Ljungdahl pathway, the most energy efficient CO2fixation pathway.T. kivuiis a thermophilic (Topt= 66°C) acetogen also capable of growth on sugars including glucose, mannitol, and fructose. RNA-sequencing indicated an operon of phosphotransferase import genes up-regulated on mannitol, and growth on a mixture of glucose and mannitol was diauxic. Given this evidence for sugar responsive transcriptional regulation, the promoter region from the mannitol operon, and a similar operon involved in fructose uptake were used to control expression of a thermostable β-galactosidase reporter gene. Both promoters resulted in higher reporter gene activity when grown on their inducing sugar relative to glucose. The inducible promoters were used to create “knock-down” mutants of the proton-pumping Ech1 hydrogenase. Ech1 is believed to be essential because repeated attempts to knock-out the gene operon have failed. The resulting sugar-inducible Ech1 expression strains grew better on their inducing sugar than on glucose. The mannitol inducible promoter was also used to control expression of an essential gene of the Wood-Ljungdahl pathway, formyl-THF synthetase (fhs), involved in consuming the metabolic intermediate formate. Whenfhsrepressed by growth on glucose significantly more formate accumulated in the culture medium than during growth on mannitol, clear evidence of a metabolic bottleneck under the knock-down condition. The promoters characterized here provide finer control of recombinant or native gene expression inT. kivui, while the thermostable reporter gene allows for rapid characterization of new promoters.
TENT-5 regulates the expression of male-specific genes inCaenorhabditis elegans
Authors: Mackiewicz Zuzanna , Liudkovska Vladyslava , Dziembowski Andrzej
Published: June 2024

Polyadenylation is an important post-transcriptional process that governs mRNA stability and expression. Advancements in direct RNA sequencing in recent years have clarified many aspects of this intricate regulation, revealing the influence of various factors. Here, we used Nanopore Direct RNA Sequencing to investigate the association between genome-wide mRNA poly(A) tail profiles and sexual dimorphism inCaenorhabditis elegans. Our results demonstrate sex-dependent differences in both gene expression and poly(A) tail metabolism. Notably, we discovered that cytoplasmic poly(A) polymerase TENT-5 regulates multiple male-specific transcripts, predominantly encoding putative seminal fluid components with predicted extracellular localization. TENT-5 expression in male-specific tissues, such as seminal vesicle and vas deference, corroborates its functional significance. Intriguingly, despite extensive TENT-5-mediated polyadenylation of male-specific transcripts, males devoid of TENT-5 show no abnormalities in mating behavior, sperm morphology, or fertility. Our findings suggest that TENT-5 plays a role in regulating sex-related processes in males, although the physiological consequences remain to be fully elucidated.
Increase of permissive secondary antiviral mutations in the evolution of A(H1N1)pdm09 influenza virus neuraminidases
Authors: Duwe Susanne , Milde Jeanette , Heider Alla , Wedde Marianne , Schweiger Brunhilde , Dürrwald Ralf
Published: June 2024

Background

The unexpected emergence of oseltamivir-resistant A(H1N1) viruses in 2008 was facilitated in part by the establishment of permissive secondary neuraminidase (NA) substitutions that compensated for the fitness loss due to the NA-H275Y resistance substitution. These viruses were replaced in 2009 by oseltamivir-susceptible A(H1N1)pdm09 influenza viruses.

Methods

Genetic analysis and screening A(H1N1)pdm09 viruses circulating in Germany between 2009 and 2024 were conducted to identify any potentially permissive or resistance-associated NA substitutions. Selected viruses were then subjected to further characterization in vitro.

Results

In the NA gene of circulating A(H1N1)pdm09 viruses, two secondary permissive substitutions, NA-V241I and NA-N369K, were identified. These substitutions demonstrated a stable lineage in phylogenetic analysis since the 2010-2011 influenza season. The data indicates a slight increase in viral NA bearing two additional potentially permissive substitutions, NA-I223V and NA-S247N, in the 2023-2024 season, that both result in a slight reduction in susceptibility to NA inhibitors.

Conclusions

The accumulation of secondary permissive substitutions in the NA of A(H1N1)pdm09 viruses increases the probability of the emergence of antiviral-resistant viruses. Therefore, it is crucial to closely monitor the evolution of circulating influenza viruses and to develop additional antiviral drugs against different target proteins.
Changes in urinary proteome in healthy individuals taking multi-vitamin/mineral supplements
Authors: Shen Ziyun , Yang Minhui , Wang Haitong , Liu Yuqing , Gao Youhe
Published: June 2024

Multivitamin/mineral supplements are widely used in many populations. Urine proteome has not been used to investigate its overall effects on healthy individuals. In this study, the urine proteome changed after taking compound nutrient supplements for 2 weeks and 4 weeks, and the differential proteins and their enriched pathways may be associated with nutrient supplementation. We noted that after taking the supplements for 2 weeks, the amount of erythropoietin receptor in urine was average 449 times higher than before, with four out of nine people experiencing changes from 0 to 14635, 11851, 11181, and 5930. The results of this study revealed that the urine proteome can provide new clues about the relatively short-term health effects of the supplements. It may help optimize guidelines and recommendations for the use of supplements.
Telomeric lncRNA TERRA localizes to stress granules in human ALT cells
Authors: Larini Luca , Goretti Elena , Zulian Eleonora , Busarello Emma , Marino Stefano Maria , Hajikazemi Mona , Paeschke Katrin , Tebaldi Toma , Cusanelli Emilio , Jurikova Katarina
Published: June 2024

TERRA, the lncRNA derived from the ends of chromosomes, has a number of well-described nuclear roles including telomere maintenance and homeostasis. A growing body of evidence now points at its role in human cells outside of nucleus—it has been found to be a component of extracellular vesicles, a player in inflammation signalling and its capacity for translation has been shown. In this work, using a combination of sensitive microscopy methods, cellular fractionation, proteomics and transcriptome analysis, we demonstrate directly for the first time that TERRA is present in the cytoplasm of human telomerase-negative cells, especially upon various stress stimuli, and that it associates with stress granules. Confirming the presence of TERRA in the cytoplasm, our work fills an important gap in the field, and contributes to the discussion about the role of TERRA as a transcript involved in nucleo-cytoplasmic stress communication.
Functional segregation of conversational production and comprehension when using word predictability
Authors: Arvidsson Caroline , Sundström Johanna , Uddén Julia
Published: June 2024

The extent to which the language production and comprehension systems overlap remains debated. We address this debate using a dataset where participants engaged in unscripted conversations, while scanned with fMRI. Word predictability was hypothesized to rely on different processes, depending on whether the word was uttered or heard. We employed the information-theoretic measure of surprisal (the negative log probability of a word occurring, given the preceding context) as a parametric modulator, controlling for the word’s overall frequency. The results for production surprisal revealed activation in the left superior and inferior frontal gyri and motor areas. A large bilateral cluster in the posterior part of the medial prefrontal cortex extended from the supplementary motor area to the anterior cingulate cortex. The results for comprehension surprisal replicated findings from non-conversational contexts, showing involvement of the bilateral superior temporal gyrus/sulcus, presumably supporting bottom-up processes for prediction error detection. Importantly, no overlap in the neural infrastructure of production and comprehension was observed, suggesting that word predictability processes in production and comprehension differ. We suggest that while the comprehension system handles prediction errors, the production system minimizes these errors through adaptation, all to achieve successful communication.
The HUSH epigenetic repressor complex silences PML nuclear bodies-associated HSV-1 quiescent genomes
Authors: Roubille Simon , Escure Tristan , Juillard Franceline , Corpet Armelle , Néplaz Rémi , Binda Olivier , Seurre Coline , Gonin Mathilde , Bloor Stuart , Cohen Camille , Texier Pascale , Haigh Oscar , Pascual Olivier , Ganor Yonatan , Magdinier Frédérique , Labetoulle Marc , Lehner Paul J. , Lomonte Patrick
Published: June 2024

Herpes simplex virus 1 (HSV-1) latently infected neurons show multiple patterns in the distribution of the viral genomes within the nucleus, at least in mouse models. One of the major patterns is characterized by the presence of quiescent HSV-1 genomes trapped in promyelocytic leukemia nuclear bodies (PML NBs) to form viral DNA-containing PML-NBs (vDCP NBs). Using a cellular model reproducing the formation of vDCP NBs we previously showed that viral genomes are chromatinized with the H3.3 histone variant modified on its lysine 9 by tri-methylation (H3.3K9me3) a chromatin mark associated with transcriptional repression. Here we identify an essential role for the HUSH complex and its SETDB1 and MORC2 effectors in the acquisition of the H3K9me3 mark on the PML NBs-associated HSV-1 and in the maintenance of HSV-1 transcriptional repression. ChiP-seq analyses highlight the association of the H3K9me3 mark with the entire viral genome. Inactivating the HUSH-SETDB1-MORC2 repressor complex prior to viral infection results in a significant reduction of H3K9me3 on the viral genome, while the overall impact on the cellular genome is minimal, except for expected changes in families of LINE1 retroelements. Depletion of HUSH, SETDB1, or MORC2, relieves the repressive state of HSV-1 in infected primary human fibroblasts as well as human induced pluripotent stem cell-derived sensory neurons (hiPSDN). We discovered that the viral protein ICP0 induces MORC2 degradation via the proteasome machinery. This process is concurrent with ICP0 and MORC2 depletion capability to reactivate silenced HSV-1 in hiPSDN. Overall, our findings underscore the robust antiviral function of the HUSH-SETDB1-MORC2 repressor complex against a herpesvirus by modulating chromatin marks linked to repression, thus presenting promising avenues for novel anti-herpesvirus therapeutic strategies.

Significance statement

Herpes simplex virus 1 (HSV-1) is a major human pathogen, which remains latent in the trigeminal ganglia (TG) neurons of the infected individuals. Its reactivation is characterized by a variety of clinical symptoms the most severe ones being keratitis and herpesvirus encephalitis. The colonization of the CNS by the virus during the individual life is a well-known fact but the pathophysiological effects on neurons homeostasis are still underestimated. It is thus paramount to understand the molecular mechanisms that control HSV-1 latency and maintain the virus in a pseudo silent state.
Comparative Analysis of Commercial Single-Cell RNA Sequencing Technologies
Authors: De Simone Marco , Hoover Jonathan , Lau Julia , Bennet Hayley , Wu Bing , Chen Cynthia , Menon Hari , Au-Yeung Amelia , Lear Sean , Vaidya Samir , Shi Minyi , Lund Jessica M. , Xavier-Magalhaes Ana , Liang Yuxin , Kurdoglu Ahmet , O’Gorman William E. , Modrusan Zora , Le Daniel , Darmanis Spyros
Published: June 2024

This study evaluates ten commercially available single-cell RNA sequencing (scRNA-seq) approaches across four technology groups: Emulsion-based kits from 10x Genomics and Fluent Biosciences; Microwell-based kits from Becton Dickinson, Honeycomb Technologies and Singerlon Technologies; Combinatorial-indexing kits from Parse Biosciences and Scale Biosciences; and a Matrigel-based kit from Scipio Biosciences. Peripheral blood mononuclear cells (PBMCs) from a single donor were used to assess analytical performance. Key features such as sample compatibility, cost, and experimental duration were also compared. Notably, superior analytical performance was demonstrated by the Chromium Fixed RNA Profiling kit from 10x Genomics, which uniquely features probe hybridization for transcript detection. Additionally, the Rhapsody WTA kit from Becton Dickinson provided a cost-effective balance of performance and expense per cell. With a rich dataset of 218,154 cells, this work provides a basis for differentiating commercial scRNA-seq technologies, which is intended to facilitate the effective application and further methodological development of single cell transcriptomics.
Anti-Nucleocapsid and Anti-Spike Antibody Trajectories in People with Post-Covid Condition versus Acute-Only Infections: Results from the Virus Watch Prospective Cohort Study
Authors: Beale Sarah , Yavlinsky Alexei , Moncunill Gemma , Fong Wing Lam Erica , Nguyen Vincent Grigori , Kovar Jana , Hayward Andrew C , Abubakar Ibrahim , W Aldridge Robert
Published: June 2024

Background

Early evidence suggests that people with Post-Covid Condition (PCC) may demonstrate aberrant immune responses post-infection; however, serological follow-up studies are currently limited. We aimed to compare SARS-CoV-2 serological responses to primary infection and vaccination in people who developed PCC versus those with an acute infection only.

Methods

Participants (n=2,010) were a sub-cohort of the Virus Watch community cohort study in England who experienced mild-moderate SARS-CoV-2 infections, completed surveys on persistent symptoms, and provided monthly finger-prick blood samples for serology. We compared the likelihood of post-infection seroconversion using logistic mixed models and the trajectories of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies using linear mixed models.

Results

Participants who developed PCC (n=394) had 1.8x the odds of post-infection seroconversion for anti-N antibodies compared to those with an acute infection only (n=1616) (adjusted odds ratio= 1.81 (95% confidence interval (CI) 1.16-2.90). Post-infection anti-N levels were persistently elevated in people with PCC (final log anti-N titres at 365 days 0.97, 95% CI 0.76-1.18) compared to those without (0.47, 95% CI 0.31-0.62). No differences were found in post-vaccination anti-S levels or trajectories before or after primary infection between participants with and without PCC; pre-vaccination anti-S responses could not be evaluated.

Conclusion

People with PCC demonstrated greater and more persistent anti-N antibody responses following primary infection compared to those with an acute infection only. Vaccination response pre- or post-infection did not systematically differ between groups. These findings extend emerging evidence around inflammatory and immune activation following infection in people with PCC.
Retaining young employees in the hospitality and tourism sector: the role of workplace context and management practices
Authors: Serhan Carole , Nasr Nour , Cheikh Georges , Nachar Gerard
Published: June 2024

Purpose

This research study investigates the relationship between management practices and young employee retention in the hospitality and tourism industry in Lebanon. Besides, it examines the moderating role of the workplace context in the relationship between management practices and employment retention in the industry.

Design/methodology/approach

Non-probability purposive sampling method was used to collect 421 questionnaires through a survey of young employees. Exploratory factor analysis (EFA) and Cronbach's alpha test are conducted to test the construct validity, reliability, and internal consistency of collected data. Descriptive statistics are used to interpret the data. Zero-order correlations, multiple regression analysis and Fisher's Z-test are applied to assess the interrelations of the various groups of variables and the determinants of young employee retention.

Findings

The findings show that management practices tested in this study have significant relationships with young employee retention in the hospitality and tourism industry in Lebanon. Further, the findings reveal that the workplace context moderates the relationship between three management practices (participation in decision-making, training, and performance recognition) and young employee retention.

Practical implications

The findings suggest that managers in hospitality and tourism businesses must improve their management practices and promote a positive workplace context to retain young employees.

Originality/value

Finally, this study is the only one that tests the moderating role of the workplace context in the relationship between five selected management practices (participation in decision-making, training, performance recognition, remuneration and job continuity) and young employee retention. Previous studies used fewer variables.
Evaluation of competency dimensions for employee performance assessment: evidence from micro, small, and medium enterprises
Authors: Kharub Manjeet , Mondal Sourav , Singh Saumya , Gupta Himanshu
Published: June 2024

Purpose

In recent years, there has been a growing emphasis on competency-based systems as a means of assessing employee performance. These systems assess the degree to which the competencies of employees align with the requirements of their employment positions. This study aims to identify, prioritize, and make contextual interrelationships of the competency dimensions that are relevant for evaluating employees in the context of Indian manufacturing MSMEs.

Design/methodology/approach

These dimensions were identified through an extensive literature review and interviews with industry experts. Further, a mixed-methods approach, including the “Bayesian Best-Worst Method” (BBWM), is applied for prioritizing important dimensions, whereas for making mutual relationships, the “Interpretive Structural Modeling” (ISM) method is utilized. “Matrice d'impacts croisés multiplication appliquée á un classment” (MICMAC) is also known as “cross-impact matrix multiplication applied to classification” is used for clustering competency dimensions based on their “driving power” and “dependence power”.

Findings

The findings reveal that among the primary dimensions, “creative performance,” and among the sub-dimensions, “innovative behaviors,” are the most critical competency dimensions for an employee assessment. The study also found that “smart working”, “factual and theoretical knowledge”, “empathy at work”, “understanding of specific knowledge”, and “engagement ideas and activities” are the main dimensions driving employees' competency.

Originality/value

This paper provides contribution to the competence literature by identifying and evaluating competency dimensions for assessing employees' performance within manufacturing MSMEs in an emerging economy such as India. The study also assesses the rank and contextual relationship between the identified dimensions as no past research focused on the same by using BBWM and ISM in the Indian manufacturing MSMEs context.