bluuebunny/crossref_metadata_2025 huggingface dataset:
Venous thromboembolism in pediatric inflammatory bowel disease: an 11-year population-based nested case–control study in Canada
Authors: Ding Zhaolu , Sherlock Mary , Chan Anthony K.C. , Zachos Mary
Published: November 2022

To investigate the occurrence of venous thromboembolism (VTE), clinical characteristics, risk factors, treatment outcomes, and anticoagulation safety in pediatric inflammatory bowel disease (IBD) over an 11-year period. A nested case–control study within an identified cohort was performed amongst children with IBD from 2009 to 2020 in Canada. There were 890 hospitalizations during the study period, and 15 venous thromboembolic events (1.69%) among 12 patients occurred, including 12 with ulcerative colitis and three with Crohn's disease. VTE proportions were significantly different between female (2.7%) and male (0.8%) patients (P = 0.03). VTE in the ulcerative colitis group (4.2%) was significantly higher than in the Crohn's disease group (0.6%) (P = 0.001). Central venous catheter and length of hospital stay were correlated to VTE development. Twelve of 15 (80%) with VTEs presented symptoms related to extremity thrombosis and pulmonary embolism. Nine of the 15 (60%) had a deep vein thrombosis, and 2 (13.3%) developed a severe pulmonary embolism. Seven of 15 (47%) received anticoagulation therapy for 1–6 months. VTE-related symptoms and repeat imaging tests improved with no bleeding complication in those treated with anticoagulation therapy. No patients received long-term thromboprophylaxis after antithrombotic treatment was discontinued. The VTE proportion in pediatric IBD patients was relatively low. Children with VTE were disproportionately females with ulcerative colitis compared with children without VTE. Patients with VTE had a good prognosis after anticoagulation therapy without mortality or increased bleeding events. The role of VTE screening and efficacy of thromboprophylaxis need to be further evaluated.
Phenotypic variation in severe hemophilia A is related to endogenous thrombin potential and plasma levels of factor VII
Authors: Chaves Daniel Gonçalves , Fonseca Fernanda Martins Lott , Araújo Hayama Cristina Braga , de Oliveira Larissa Maira Moura , Amorim Marcos Vinicius de Almeida , Assis Neto Carolina Correia , Carvalho Maria das Graças
Published: November 2022

Hemophilia A is a bleeding disorder caused by deficiency or low activity of circulating factor VIII characterized by prolonged blood coagulation time and often spontaneous bleeding. Patients with the severe form of the disease may present considerable heterogeneity in the occurrence of bleeding episodes and some of them have a mild hemophilia A phenotype. This study aimed to evaluate the association of biomarkers and coagulation parameters to the differential hemorrhagic profile of severe hemophilia A patients. Polymorphisms in the genes of proteins C and S, factors V and VII and prothrombin were evaluated in a group of severe hemophilia A patients with a broad spectrum of bleeding profile. Plasma levels of coagulation factors and thrombin generation were also analyzed. This study included 59 Brazilian hemophilia A patients who were allocated into low bleeding profile (LBP; n = 33) and high bleeding profile (HBP; n = 26) groups based on their joint and muscle bleeding episodes requiring treatment in the 5 years before inclusion in the study. Results evidenced that endogenous thrombin potential (ETP) and plasma factor VII levels were significantly higher in the LBP group. Results indicate a prominent importance of FVII plasma activity and endogenous thrombin potential on the differential bleeding phenotype of hemophilia A patients.
Readiness Tests
Authors: Getselman Tracy , Ma Holly
Published: November 2022

Certification of nursing staff has been associated with improved patient outcomes; however, time, cost, and test anxiety are barriers to achieving it. Readiness tests can reduce test anxiety related to certification examinations. A readiness test helps nurses prepare by providing a simulated experience that matches the actual testing environment and identifying knowledge gaps. These tests can be added to other steps nurse leaders can take to encourage certification and support staff professional development.
Exploring Hybrid Leadership
Authors: Ameel Maria , Myllynen Mika , Kallakorpi Susanna
Published: November 2022

OBJECTIVE

The aim of this study was to describe leaders' experiences of remote leadership during the 1st year of the COVID-19 pandemic.

BACKGROUND

The COVID-19 pandemic accelerated remote work. However, there is little research on the experience of remote leadership in the healthcare setting.

METHODS

Data were collected using focus group interviews and analyzed by thematic analysis.

RESULTS

A total of 8 leaders from a psychiatric care setting participated. The following themes were identified: increased work efficiency, work well-being, lack of organizational support, the need to be present, and the desire for a hybrid leadership model for the future.

CONCLUSIONS

Remote leadership includes both benefits and challenges for healthcare leaders and organizations. Leaders in this study emphasized the need to be present for the clinical personnel and proposed a hybrid leadership model. To succeed in combining remote and face-to-face work and leadership in a new model, organizations need to provide clear guidelines and training for remote work and leadership.
First Year Outcomes
Authors: Cadmus Edna , Roberts Michele Livich
Published: November 2022

In New Jersey, a statewide nurse residency program was implemented using an apprenticeship model. The pandemic created disruption to registered nurse residency programs. This included rapid restructuring of program delivery to online methods and a need to adapt curricula to reflect changing practice and guidelines. As a result of the pandemic, new graduates had educational gaps and nurse leaders experienced staffing shortages. First year program outcomes demonstrated a 90% retention of new graduates and financial benefits for organizations participating in the statewide nurse residency program.
Beyond Adaptive Alloreactivity: Contribution of Innate B Cells to Allograft Inflammation and Rejection
Authors: Sayin Ismail , Chong Anita S.
Published: November 2022

Innate B cells are a heterogeneous group of cells that function in maintaining homeostatic levels of circulating natural antibodies and being the first line of defense against infections. Innate B-1 cells and marginal zone B cells may relocate to lymphoid follicles and differentiate into cytokine and antibody-secreting cells in T-independent and T-dependent manners. Although marginal zone B cells are widely described in humans, the presence of B-1 cells is more controversial. Here, we review the basic features of the innate B-cell subsets identified in mice and their equivalent in humans, as well as their potential roles in transplantation. We summarize the findings of Cascalho and colleagues on the unexpected protective role of tumor necrosis factor receptor superfamily member 13B in regulating circulating levels of protective natural immunoglobulin M, and the studies by Zorn and colleagues on the potential pathogenic role for polyreactive innate B cells infiltrating allograft explants. Finally, we discuss our studies that took a transcriptomic approach to identify innate B cells infiltrating kidney allografts with antibody-mediated rejection and to demonstrate that local antigens within the allograft together with inflammation may induce a loss of B-cell tolerance.
Chloroquine Supplementation for the Treatment of Glioblastoma: A Meta-analysis of Randomized Controlled Studies
Authors: Deng Qiang , Tao Sihong , Huang Hui , Lv Qikun , Wang Wei
Published: November 2022

Introduction

Chloroquine supplementation may show some potential in improving the efficacy for glioblastoma, and this meta-analysis aimed to identify the efficacy of chloroquine supplementation for patients with glioblastoma.

Methods

Several databases including PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases have been systematically searched through August 2022, and we included randomized controlled trials assessing the efficacy of chloroquine supplementation for glioblastoma. This meta-analysis was performed using the random-effect model or fixed-effect model based on the heterogeneity.

Results

Four randomized controlled trials were finally included in this meta-analysis. In comparison with control group for glioblastoma, chloroquine supplementation was associated with substantially decreased mortality (odd ratio [OR], 0.17; 95% confidence interval [CI], 0.06–0.53; P = 0.002), improved survival time (mean difference, 15.63; 95% CI, 2.27–28.99; P = 0.02), and remission (OR, 15.63; 95% CI, 2.27–28.99; P = 0.02), but unraveled no obvious impact on the incidence of adverse events (OR, 3.27; 95% CI, 0.29–36.44; P = 0.34) or seizure (OR, 2.57; 95% CI, 0.05–127.68; P = 0.64).

Conclusions

Chloroquine supplementation may be effective to improve the treatment efficacy for glioblastoma.
Hemophagocytic lymphohistiocytosis due to Burkholderia pseudomallei in a primigravida.
Authors: al Waseem Shaikh Mohammed Haroon , Antony Tessa , Suresh Suchitra , Gopalan Sowmya
Published: November 2022

Introduction

Introduction: Melioidosis is an infection caused by, Burkholderia pseudomallei (B.pseudomallei), a facultative intracellular gram-negative, saprophytic bacilli, commonly found in soil or contaminated water.The organism is aptly called the “great mimicker” as it produces a wide variety of clinical manifestations.
Case report: A 24-year-old primigravida was referred to the medicine outpatient department with complaints of fever and myalgia of 45 days duration. Laboratory investigations revealed anaemia, elevated serum ferritin and hepatosplenomegaly. Bone marrow study showed the presence of hemophagocytes and a diagnosis of hemophagocytic lymphohistiocytosis(HLH) was made. Blood and bone marrow culture sent to the microbiology laboratory grew non fermenting gram negative bacilli which was misidentified as Burkholderia cepacia by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (VITEK 2 system bioMérieux ). It was further identified as B.pseudomallei by 16S ribosomal RNA sequencing. Patient was treated with steroids and ceftazidime. She had to undergo medical termination of pregnancy as there was severe intrauterine growth restriction(IUGR) of the foetus. She responded well to the treatment and was discharged with maintenance therapy of  sulfamethoxazole and  trimethoprim.
Conclusion: It is important to find out if the suspected pathogen is listed in the database of the automated identification system. Prognosis of melioidosis  is excellent if early diagnosis and appropriate antibiotic treatment is provided.
Solving the remaining problems with names of classes. Request for an Opinion
Authors: Göker Markus
Published: November 2022

The legitimacy, spelling and grammatical gender of names of classes validly published under the International Code of Nomenclature of Prokaryotes (ICNP) is reviewed in the aftermath of the decision to make Rule 8 of the ICNP non-retroactive regarding the formation of such names. This ruling removed most of the nomenclatural uncertainty that affected names of classes but some issues remain to be solved. Some previously legitimate names of classes became illegitimate by this decision while others retained their illegitimacy. The Judicial Commission is asked to conduct according clarifications. It is proposed to place the names at the rank of class

Anoxyphotobacteria

(Gibbons and Murray 1978) Murray 1988,

Archaeobacteria

Murray 1988, Bacteria Haeckel 1894 (Approved Lists 1980),

Firmibacteria

Murray 1988,

Microtatobiotes

Philip 1956 (Approved Lists 1980),

Oxyphotobacteria

(ex Gibbons and Murray 1978) Murray 1988,

Photobacteria

Gibbons and Murray 1978 (Approved Lists 1980),

Proteobacteria

Stackebrandt et al. 1988,

Schizomycetes

Nägeli 1857 (Approved Lists 1980) and

Scotobacteria

Gibbons and Murray 1978 (Approved Lists 1980) on the list of rejected names. It is also requested to orthographically correct the names

Aquificae

Reysenbach 2002,

Chrysiogenetes

Garrity and Holt 2002,

Gemmatimonadetes

Zhang et al. 2003,

Opitutae

Choo et al. 2007 and

Verrucomicrobiae

Hedlund et al. 1998.
Unravelling microbial efflux through mathematical modelling
Authors: Jabbari Sara
Published: November 2022

Abstract

Mathematical modelling is a useful tool that is increasingly used in the life sciences to understand and predict the behaviour of biological systems. This review looks at how this interdisciplinary approach has advanced our understanding of microbial efflux, the process by which microbes expel harmful substances. The discussion is largely in the context of antimicrobial resistance, but applications in synthetic biology are also touched upon. The goal of this paper is to spark further fruitful collaborations between modellers and experimentalists in the efflux community and beyond.
Improved high-dimensional multivariate autoregressive model estimation of human electrophysiological data using fMRI priors
Authors: Nagle Alliot , Gerrelts Josh P. , Krause Bryan M. , Boes Aaron D. , Bruss Joel E. , Nourski Kirill V. , Banks Matthew I. , Van Veen Barry
Published: November 2022

Multivariate autoregressive (MVAR) model estimation enables assessment of causal interactions in brain networks. However, accurately estimating MVAR models for high-dimensional electrophysiological recordings is challenging due to the extensive data requirements. Hence, the applicability of MVAR models for study of brain behavior over hundreds of recording sites has been very limited. Prior work has focused on different strategies for selecting a subset of important MVAR coefficients in the model and is motivated by the potential of MVAR models and the data requirements of conventional least-squares estimation algorithms. Here we propose incorporating prior information, such as fMRI, into MVAR model estimation using a weighted group LASSO regularization strategy. The proposed approach is shown to reduce data requirements by a factor of two relative to the recently proposed group LASSO method of Endemann et al. (2022) while resulting in models that are both more parsimonious and have higher fidelity to the ground truth. The effectiveness of the method is demonstrated using simulation studies of physiologically realistic MVAR models derived from iEEG data. The robustness of the approach to deviations between the conditions under which the prior information and iEEG data is obtained is illustrated using models from data collected in different sleep stages. This approach will allow accurate effective connectivity analyses over short time scales, facilitating investigations of causal interactions in the brain underlying perception and cognition during rapid transitions in behavioral state.
Interactive Effects of Venlafaxine and Thermal Stress on Zebrafish (Danio rerio) Inflammatory and Heat Shock Responses
Authors: Weber A.V. , Firth B.F. , Cadonic I. G. , Craig P.M.
Published: November 2022

Venlafaxine (VFX), a commonly prescribed antidepressant often detected in wastewater effluent, and acute temperature elevations from climate change and increased urbanization, are two environmental stressors currently placing freshwater ecosystems at risk. This study focused on understanding if exposure to VFX impacts the agitation temperature (Tag) and critical thermal maximum (CTmax) of zebrafish (Danio rerio). Additionally, we examined the interactive effects of VFX and acute thermal stress on zebrafish heat shock and inflammatory immune responses. A 96 hour 1.0 μg/L VFX exposure experiment was conducted, followed by assessment of thermal tolerance via CTmaxchallenge. Heat shock proteins and pro-inflammatory immune cytokines were quantified through gene expression analysis by quantitative PCR (qPCR) onhsp 70, hsp 90, hsp 47, il-8, tnfα, andil-1βwithin gill and liver tissue. No significant changes in agitation temperature between control and exposed fish were observed, nor were there any differences in CTmaxbased on treatment. Unsurprisingly,hsp 47, 70, and 90were all upregulated in groups exposed solely to CTmax, while onlyhsp 47within gill tissue showed signs of interactive effects, which was significantly decreased in fish exposed to both VFX and CTmax. No induction of an inflammatory response occurred. This study demonstrated that environmentally relevant concentrations of VFX have no impact on thermal tolerance performance in zebrafish. However, VFX is capable of causing diminished function of protective heat shock mechanisms, which could be detrimental to freshwater fish populations and aquatic ecosystems as temperature spikes become more frequent from climate change and urbanization near watersheds.

Summary Statement

This study predicts the effects that climate change and anthropogenic pollutants may have on fish ability to tolerate elevated temperatures, and examines the physiologic challenges these stressors may introduce.
Human Monkeypox Virus outbreak among Men who have Sex with Men in Amsterdam and Rotterdam, the Netherlands: no evidence for undetected transmission prior to May 2022 in a retrospective study
Authors: de Vries Henry J. , Götz Hannelore M. , Bruisten Sylvia , van der Eijk Annemiek A. , Prins Maria , Oude Munnink Bas B. , Welkers Matthijs R.A. , Jonges Marcel , Molenkamp Richard , Westerhuis Brenda M. , Schuele Leonard , Stam Arjen , Boter Marjan , Hoornenborg Elske , Mulders Daphne , van den Lubben Mariken , Koopmans Marion
Published: November 2022

Since May 2022 over 20.000 human monkeypox virus (hMPXV) cases have been reported from 29 EU/EEA countries, predominantly among men who have sex with men. With over 1200 cases, and a crude notification rate of 70.7 per million population, the Netherlands was in the top 5 European countries most affected. The first national case was reported from May 10th, yet potential prior transmission remains unknown. Insight into prolonged undetected transmission can help to understand the current outbreak dynamics and aid future public health interventions. We therefor performed a retrospective study to elucidate whether undetected transmission of hMPXV occurred prior to the first reported cases in Amsterdam and Rotterdam. In 401 anorectal- and ulcer samples from visitors of the Centers for Sexual Health of Amsterdam and Rotterdam dating back to February 14th, we identified 2 new cases, the earliest from the first week of May (week 18), 2022. This coincides with the first cases reported in the United Kingdom, Spain and Portugal. We found no evidence of widespread hMPXV transmission in Dutch sexual networks of MSM prior to May 2022. Likely, the hMPXV outbreak expanded across Europe within a short period in the spring of 2022 in an international highly intertwined network of sexually active MSM.

Ethical statement

The Amsterdam University Medical Centre Ethical committee approved the study and deemed a full review not necessary according to the Medical Research Involving Human Subjects Act (reference letter: W22_257 # 22.313, dd July 14, 2022). Samples included from Rotterdam were required to be collected more than 3 weeks prior to the analysis (i.e. the duration of quarantine in case of a positive result) as they were deemed to be of no consequence for the index or his/her contacts. All samples and collected data were fully de-identified before sample analysis assuring anonymity.
Aerobic exercise training selectively improves cortical inhibitory function after stroke
Authors: Palmer Jacqueline A , Whitaker Alicen A , Payne Aiden M , Bartsch Bria L , Reisman Darcy S , Boyne Pierce E , Billinger Sandra A
Published: November 2022

Background

Aerobic exercise elicits striking effects on neuroplasticity and cognitive executive function but is poorly understood after stroke.

Objective

We tested the effect of 4 weeks of aerobic exercise training on inhibitory and facilitatory elements of cognitive executive function and electroencephalography (EEG) markers of cortical inhibition and facilitation. We investigated relationships between stimulus-evoked cortical responses, blood lactate levels during training, and aerobic fitness post-intervention.

Methods

Twelve individuals with chronic (>6mo) stroke completed an intensive aerobic exercise intervention (40-mins, 3x/week). Electroencephalography and motor response times were assessed during congruent (response facilitation) and incongruent (response inhibition) stimuli of a Flanker task. Aerobic fitness capacity was assessed as VO2-peak during a treadmill test pre- and post-intervention. Blood lactate was assessed acutely (<1 min) after exercise each week. Cortical inhibition (N2) and facilitation (frontal P3) were quantified as peak amplitudes and latencies of stimulus evoked EEG activity over the frontal cortical region.

Results

Following exercise training, the response inhibition speed increased while response facilitation remained unchanged. A relationship between earlier cortical N2 response and faster response inhibition emerged post-intervention. Individuals who produced higher lactate during exercise training achieved faster response inhibition and tended to show earlier cortical N2 responses post-intervention. There were no associations between VO2-peak and metrics of behavioral or neurophysiologic function.

Conclusions

These findings provide novel evidence for selective benefits of aerobic exercise on inhibitory control during the initial 4-week period after initiation of exercise training, and implicate a potential therapeutic effect of lactate on post-stroke cortical inhibitory function.

Trial Registration

ClinicalTrials.govIdentifier:NCT03760016. First posted: November 30, 2018.https://clinicaltrials.gov/ct2/show/NCT03760016
The Molecular Endotypes of Type 1 and Type 2 SLE
Authors: Robl Robert D. , Eudy Amanda M. , Bachali Prathyusha S. , Rogers Jennifer L. , Clowse Megan E.B. , Pisetsky David S. , Lipsky Peter E.
Published: November 2022

Objective

To characterize the molecular landscape of patients with Type 1 and Type 2 systemic SLE erythematosus (SLE) by analyzing gene expression profiles from peripheral blood.

Methods

Full transcriptomic RNA sequencing was carried out on whole blood samples from 18 subjects with SLE selected by the presence of manifestations typical of Type 1 and Type 2 SLE. The top 5,000 row variance genes were analyzed by Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) to generate gene co-expression modules, that were functionally annotated and correlated to various demographic traits, clinical features and laboratory measures.

Results

Expression of specific gene coexpression modules correlated with individual features of Type 1 and 2 SLE and also effectively segregated samples from Type 1 from Type 2 SLE patients. Unique Type 1 SLE enrichments included IFN, monocytes, T cells, cell cycle, and neurotransmitter pathways, whereas unique Type 2 SLE enrichments included B cells and metabolic and neuromuscular pathways. Gene co-expression modules of Type 2 SLE patients were identified in subsets of previously reported patients with inactive SLE and idiopathic fibromyalgia (FM) and also identified subsets of patients with active SLE with a greater frequency of severe fatigue.

Conclusion

Gene co-expression analysis successfully identified unique transcriptional patterns that segregate Type 1 SLE from Type 2 SLE and further identified Type 2 molecular features in patients with inactive SLE or FM and with active SLE with severe fatigue.
Multi-centric evaluation of Biomeme Franklin Mobile qPCR for rapid detection ofMycobacterium ulceransin clinical specimens
Authors: Frimpong Michael , Frimpong Venus Nana Boakyewaa , Numfor Hycenth , Donkeng Valerie , Amedior Jennifer Seyram , Deegbe Daniella Emefa , Dadson Baaba , Ablordey Anthony , Eyangoh Sara , Phillips Richard , Vedithi Sundeep Chaitanya
Published: November 2022

The gold standard forMycobacterium ulceransdetection is PCR due to its high accuracy in confirmation of suspected cases. But the available PCR assays are design for standard size thermocyclers which are immobile and suited for reference laboratories far away from endemic communities. This makes it a challenge to obtain immediate results for patient management. We have validated and evaluated a dried reagent-based PCR assay adapted for a handheld, battery-operated, portable thermocycler with the potential of extending diagnostics to endemic communities with limited infrastructure. The diagnostic accuracy of the assay following a multi-centre evaluation by three Buruli ulcer reference laboratories with over 300 clinical samples showed sensitivity and specificity of 100% - 97% and 100% - 94%. This assay coupled with a field-friendly extraction method fulfill almost all the target product profile of Buruli ulcer for decentralized testing at districts, health centres and community level. A key critical action for achieving the NTD Road Map 2030 target for Buruli ulcer.
Antagonistic antimalarial properties of a methoxyamino chalcone derivative and 3-hydroxypyridinones in combination with dihydroartemisinin againstPlasmodium falciparum
Authors: Kampoun Tanyaluck , Koonyosying Pimpisid , Ruangsuriya Jetsada , Prommana Parichat , Shaw Philip J. , Kamchonwongpaisan Sumalee , Suwito Hery , Puspaningsih Ni Nyoman Tri , Uthaipibull Chairat , Srichairatanakool Somdet
Published: November 2022

The spread of artemisinin (ART)-resistantPlasmodium falciparumthreatens the control of malaria and mutations in the propeller domains ofP. falciparumKelch13 (k13) are strongly associated with the resistance. Ferredoxin (Fd) in the ferredoxin/NADP+reductase (Fd/FNR) redox system is essential for isoprenoid precursor synthesis in the plasmodial apicoplast; nonetheless, mutations of Fd gene (fd) may modulate ART resistance and Fd would be an important target for antimalarial drugs. We investigated the inhibitory effects of dihydroartemisinin (DHA), methoxyamino chalcone (C3), and iron chelators including deferiprone (DFP), 1-(N-acety1-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and deferiprone-resveratrol hybrid (DFP-RVT) against the growth of wild-type (WT)P. falciparumparasites and those withk13andfdmutations. C3 showed antimalarial potency similar to the iron chelators. Surprisingly, combined treatments of DHA with the C3 or iron chelators showed moderately antagonistic effects against P. falciparum growth. No differences were observed among the mutant parasites with respect to their sensitivity to C3 and the chelators, or the interactions of these compounds with DHA. The data suggest that inhibitors of the Fd/FNR redox system should be avoided as ART partner drugs in ART combination therapy for treating malaria.
Identifying Strong Modulators of Cellular Quiescence Depth Across Different Quiescent Cells and Conditions
Authors: Lu Eric , Yao Guang
Published: November 2022

The proper balance and transition between cellular quiescence and proliferation are critical to tissue homeostasis, repair, and regeneration. The likelihood of quiescence-to-proliferation transition is inversely correlated with quiescence depth, and deep quiescent cells are less likely to exit quiescence and reenter the cell cycle than shallow quiescent cells. The regulatory mechanisms of quiescence depth are poorly understood but essential for developing strategies against hypo- or hyper-proliferation diseases such as aging and cancer. Our earlier studies have demonstrated that the activation threshold of the bistable Rb-E2F gene network switch (ThE2F) controls quiescence depth. We have also identified coarse- and fine-tuning ThE2Fmodulators in rat embryonic fibroblasts. To examine whether other quiescent cells (including most adult stem and progenitor cells) under different environmental conditions use the same or different modulators of quiescence depth, here we studied the behaviors of 30,000 theoretical quiescent cell models that each support a functional Rb-E2F bistable switch with a unique parameter set. We found that although the vastly heterogeneous quiescent cell models exhibited no apparent parameter patterns, they converged at two alternative groups of strong quiescence-depth modulators (G1 cyclin/cdk-related and Rb/E2F complex-related). Our further machine learning (decision tree) analysis suggested that the Rb protein level and dephosphorylation rate in quiescent cells determine which modulator group to use to regulate quiescence depth.
Homeotic compartment curvature and tension control spatiotemporal folding dynamics
Authors: Villedieu Aurélien , Alpar Lale , Gaugue Isabelle , Joudat Amina , Graner François , Bosveld Floris , Bellaïche Yohanns
Published: November 2022

Shape is a conspicuous and fundamental property of biological systems entailing the function of organs and tissues. While much emphasis has been put on how tissue tension and mechanical properties drive shape changes, whether and how a given tissue geometry influences subsequent morphogenesis remains poorly characterized. Here, we explored how curvature, a key descriptor of tissue geometry, impinges on the dynamics of epithelial tissue invagination. We found that the morphogenesis of the fold separating the adultDrosophilahead and thorax segments is driven by the invagination of the Deformed (Dfd) homeotic compartment. Dfd controls invagination by modulating actomyosin organization and in-plane epithelial tension via the Tollo and Dystroglycan receptors. By experimentally introducing curvature heterogeneity within the homeotic compartment, we established that a curved tissue geometry converts the Dfd-dependent in-plane tension into an inward force driving folding. Accordingly, the interplay between in-plane tension and tissue curvature quantitatively explains the spatiotemporal folding dynamics. Collectively, our work highlights how genetic patterning and tissue geometry provide a simple design principle driving folding morphogenesis during development.
Long-read genomes reveal pangenomic variation underlying yeast phenotypic diversity
Authors: Weller Cory A. , Andreev Ilya , Chambers Michael J. , Park Morgan ,   NISC Comparative Sequencing Program, Bloom Joshua S. , Sadhu Meru J.
Published: November 2022

Understanding the genetic causes of trait variation is a primary goal of genetic research. One way that individuals can vary genetically is through the existence of variable pangenomic genes – genes that are only present in some individuals in a population. The presence or absence of entire genes could have large effects on trait variation. However, variable pangenomic genes can be missed in standard genotyping workflows, due to reliance on aligning short-read sequencing to reference genomes. A popular method for studying the genetic basis of trait variation is linkage mapping, which identifies quantitative trait loci (QTLs), regions of the genome that harbor causative genetic variants. Large-scale linkage mapping in the budding yeastSaccharomyces cerevisiaehas found thousands of QTLs affecting myriad yeast phenotypes. To enable the resolution of QTLs caused by variable pangenomic genes, we used long-read sequencing to generate highly complete de novo assemblies of 16 diverse yeast isolates. With these assemblies we resolved growth QTLs to specific genes that are absent from the reference genome but present in the broader yeast population at appreciable frequency. Copies of genes also recombine onto chromosomes where they are absent in the reference genome, and we found that these copies generate additional QTLs whose resolution requires pangenome characterization. Our findings demonstrate the power of long-read sequencing to identify the genetic basis of trait variation.
Short heat shock has a long-term effect on mesenchymal stem cells’ transcriptome
Authors: Ribarski-Chorev Ivana , Schudy Gisele , Strauss Carmit , Schlesinger Sharon
Published: November 2022

The harmful consequences of heat stress (HS) on physiology are well documented, but the molecular aspects of changing thermal conditions are poorly understood. Therefore, a better understanding of the effects of this stress on the morphology, phenotype, proliferative capacity, and fate decision of MSCs is required. Our thorough characterization of MSCs’ transcriptome showed a major effect of HS on the transcriptional landscape. Specifically, examining the effect after three days of moderate HS shows changes in many cell processes, such as immune response, cell cycle, and differentiation. Surprisingly, we detected a long-term effect on cell identity even after short stress, possibly through the activation of bivalent genes related to cell lineage decisions. Finally, comparing the differentially expressed genes following short HS with their transcriptional state after three days of recovery, we find transient upregulation of many members of the MLL family and other histone modifiers; a finding which offers a potential mechanistic account for the stable bivalent genes activation. This could be used to predict and modify the long-term effect of HS on cell identity.

Summary blurb

Heat shock alters mesenchymal stem cells’ transcriptional programs, resulting in stable activation of lineage commitment genes, thus explaining the shift in the identity and fate of the cells.

Graphical abstract
Global connectivity and networks of marine reserves
Authors: McDowell Julia , Andrello Marco , Velez Laure , Barrier Nicolas , Manel Stephanie , Pollock Laura J. , Mouillot David
Published: November 2022

Cooperation between countries in managing and protecting shared marine resources is beneficial both ecologically and economically, but how best to establish the cooperation needed at a global scale is largely unknown. Here, we used hydrodynamic modelling to identify ecologically connected networks of marine reserves (MRs) and evaluated these networks with socio-economic indicators. Most of the networks are homogenous with similar levels of development, shared languages, and other cultural values. However, we found that 17% (11/66) of the largest networks (>20 MRs) span multiple countries. These heterogenous networks are composed of countries with different economic, political, and cultural views. Countries that control more, larger marine reserves also have a more even ratio of source reserves to sinks. We discuss that, while such economic and cultural homogeneity might lead to more efficient ecological management in the short term, heterogeneous networks may prove to be more resilient in the longer term, when climate change will modify marine connectivity.
Architecture of chloroplast TOC-TIC translocon supercomplex
Authors: Liu Hao , Li Anjie , Rochaix Jean-David , Liu Zhenfeng
Published: November 2022

Chloroplasts rely on the translocon complexes in the outer and inner envelope membranes (termed TOC and TIC, respectively) to import thousands of different nuclear-encoded proteins from the cytosol1–4. While previous studies indicated that the TOC and TIC complexes may assemble into larger supercomplexes5–7, the overall architectures of the TOC-TIC supercomplexes and the mechanism of preprotein translocation are elusive. Here we report the cryo-electron microscopy (cryo-EM) structure of the TOC-TIC supercomplex fromChlamydomonas reinhardtiiat an overall resolution of 2.8 Å. The major subunits of the TOC complex (Toc75, Toc90 and Toc34) and TIC complex (Tic214, Tic20, Tic100 and Tic56), three chloroplast translocon-associated proteins (Ctap3, Ctap4 and Ctap5) and three newly-identified small inner-membrane proteins (Simp1-3) have been located in the supercomplex. As the largest protein, Tic214 traverses the inner membrane, the intermembrane space and the outer membrane, connecting the TOC complex with the TIC proteins. An inositol hexaphosphate (InsP6 or I6P) molecule is located at the Tic214-Toc90 interface and stabilizes their assembly. Moreover, four lipid molecules are located within or above an inner-membrane funnel formed by Tic214, Tic20, Simp1 and Ctap5. Furthermore, multiple potential pathways found in the TOC-TIC supercomplex may support translocation of different substrate preproteins into chloroplasts.
Polymorphic regions in BA.2.12.1, BA.4 and BA.5 likely implicated in immunological evasion of Omicron subvariant BQ.1.1
Authors: Felix Pierre Teodosio
Published: November 2022

In this work, 45 Spike glycoprotein Chain B polypeptides were used in the subvariants BA.2.12.1, BA.4 and BA.5 were recovered from GENBANK. All sequences were publicly available on the National Biotechnology Information Center (NCBI) platform. The results indicate the existence of informative polymorphic and parsimony sites that may be implicated in the level of diversity of the studied strains, as well as reflect the immunological evasion potential of the subvariant BQ1.1. of the variant Ômicron d and SARS-CoV-2. The results also suggest the formation of ancestral polymorphism with slight retention, and the probable is responsible the diversity of the whole studied set.
Decoding protein binding landscape on circular RNAs with base-resolution Transformer models
Authors: Wu Hehe , Fang Yi , Yang Yang , Pan Xiaoyong , Shen Hong-Bin
Published: November 2022

Circular RNAs (circRNAs) interact with RNA-binding proteins (RBPs) to modulate gene expression. To date, most computational methods for predicting RBP binding sites on circRNAs focus on circRNA fragments instead of circRNAs. These methods detect whether a circRNA fragment contains binding sites, but cannot determine where are the binding sites and how many binding sites are on the circRNA transcript. We report a hybrid deep learning-based tool, CircSite, to predict RBP binding sites at single-nucleotide resolution and detect key contributed nucleotides on circRNA transcripts. CircSite takes advantage of convolutional neural networks (CNNs) and Transformer for learning local and global representations of circRNAs binding to RBPs, respectively. We construct 37 datasets of RBP-binding circRNAs for benchmarking and the experimental results show that CircSite offers accurate predictions of RBP binding nucleotides and detects key subsequences aligning well with known binding motifs.
The mutational signatures of poor treatment outcomes on the drug-susceptibleMycobacterium tuberculosisgenome
Authors: Chen Yiwang , Jiang Qi , Peierdun Mijiti , Takiff Howard E. , Gao Qian
Published: November 2022

Drug resistance is a known risk factor for poor tuberculosis (TB) treatment outcomes, but the contribution of other bacterial factors to poor outcomes in drug susceptible TB is less understood. Here, we generate a population-based dataset of drug-susceptibleMycobacterium tuberculosis(MTB) isolates from China to identify factors associated with poor treatment outcomes. We sequenced the whole genome of 3496 MTB strains and linked genomes to patient epidemiological data. A genome-wide association study (GWAS) was performed to identify bacterial genomic variants associated with poor outcomes. Risk factors identified by logistic regression analysis were used in clinical models to predict treatment outcomes and their associations were assessed with structural equation models (SEM). GWAS identified fourteen MTB variants (24.2% vs 7.5%, P<0.001) and ade novoreactive oxygen species (ROS) mutational signature (26.3%±18.2% vs 22.9%±13.8%, P=0.027) that were more frequent in patients with poor treatment outcomes. Patient age, sex, and duration of diagnostic delay were also independently associated with poor outcomes. The best clinical prediction model, with an AUC of 0.74, incorporates both host and bacterial risk factors, and host factors are more important. Together, our results reveal that although host factors are the most important determinants for poor treatment outcomes, the genomic characteristics of the infecting MTB strain may also contribute significantly to poor treatment outcomes. Fourteen genetic variants were statistically associated with poor TB treatment outcomes, but the optimal model for predicting treatment outcomes includes both patient characteristics and bacterial genomic determinants.
Open-source versatile 3D-print animal conditioning platform design for in-vivo preclinical brain imaging in awake mice and anesthetized mice and rats
Authors: Gironda Zakia Ben Youss , Arefin Tanzil Mahmud , Qayyum Sawwal , Zhang Jiangyang , Wadghiri Youssef Zaim , Alon Leeor , Yaghmazadeh Omid
Published: November 2022

Proper animal conditioning is a key factor in the quality and success of preclinical neuroimaging applications. We introduce an open-source easy-to-modify multi-modal 3D printable design for rodent conditioning for magnetic resonance imaging (MRI) or other imaging modalities. Our design can be used for brain imaging in anesthetized or awake mice and anesthetized rats. We show ease-of-use and reproducibility of subject conditioning with anatomical T2-weighted imaging for both mice and rats. We also demonstrate application of our design for awake fMRI in mice using both visual evoked potential and olfactory stimulation paradigms. In addition, we demonstrate that our proposed cradle design can be extended to multiple imaging modalities combining MRI, Positron emission tomography and X-ray computed tomography.
Updates inSASfitfor fitting analytical expressions and numerical models to small-angle scattering patterns
Authors: Kohlbrecher Joachim , Breßler Ingo
Published: November 2022

Small-angle scattering is an increasingly common method for characterizing particle ensembles in a wide variety of sample types and for diverse areas of application.SASfithas been one of the most comprehensive and flexible curve-fitting programs for decades, with many specialized tools for various fields. Here, a selection of enhancements and additions to theSASfitprogram are presented that may be of great benefit to interested and advanced users alike: (a) further development of the technical basis of the program, such as new numerical algorithms currently in use, a continuous integration practice for automated building and packaging of the software, and upgrades on the plug-in system for easier adoption by third-party developers; (b) a selection of new form factors for anisotropic scattering patterns and updates to existing form factors to account for multiple scattering effects; (c) a new type of a very flexible distribution called metalog [Keelin (2016).Decis. Anal.13, 243–277], and regularization techniques such as the expectation-maximization method [Dempsteret al.(1977).J. R. Stat. Soc. Ser. B (Methodological),39, 1–22; Richardson (1972)J. Opt. Soc. Am.62, 55; Lucy (1974).Astron. J.79, 745; Lucy (1994).Astron. Astrophys.289, 983–994], which is compared with fits of analytical size distributions via the non-linear least-squares method; and (d) new structure factors, especially for ordered nano- and meso-scaled material systems, as well as the Ornstein–Zernike solver for numerical determination of particle interactions and the resulting structure factor when no analytical solution is available, with the aim of incorporating its effects into the small-angle scattering intensity model used for fitting withSASfit.
The structure of His-tagged Geobacillus stearothermophilus purine nucleoside phosphorylase reveals a `spanner in the works'
Authors: Given Fiona M. , Moran Fuchsia , Johns Ashleigh S. , Titterington James A. , Allison Timothy M. , Crittenden Deborah L. , Johnston Jodie M.
Published: November 2022

The 1.72 Å resolution structure of purine nucleoside phosphorylase from Geobacillus stearothermophilus, a thermostable protein of potential interest for the biocatalytic synthesis of antiviral nucleoside compounds, is reported. The structure of the N-terminally His-tagged enzyme is a hexamer, as is typical of bacterial homologues, with a trimer-of-dimers arrangement. Unexpectedly, several residues of the recombinant tobacco etch virus protease (rTEV) cleavage site from the N-terminal tag are located in the active site of the neighbouring subunit in the dimer. Key to this interaction is a tyrosine residue, which sits where the nucleoside ring of the substrate would normally be located. Tag binding appears to be driven by a combination of enthalpic, entropic and proximity effects, which convey a particularly high affinity in the crystallized form. Attempts to cleave the tag in solution yielded only a small fraction of untagged protein, suggesting that the enzyme predominantly exists in the tag-bound form in solution, preventing rTEV from accessing the cleavage site. However, the tagged protein retained some activity in solution, suggesting that the tag does not completely block the active site, but may act as a competitive inhibitor. This serves as a warning that it is prudent to establish how affinity tags may affect protein structure and function, especially for industrial biocatalytic applications that rely on the efficiency and convenience of one-pot purifications and in cases where tag removal is difficult.
Management-control-system configurations in medium-sized mechanical-engineering firms: an exploratory analysis
Authors: Santini Fabio , Elisei Luca , Malmi Teemu , Scrucca Luca
Published: November 2022

Purpose

Interest has grown in how management controls operate together as a package of interrelated mechanisms. This study aims to contribute to the topic by focusing on a single industry in one country, addressing controls in medium-sized enterprises (MEs). It explores how accounting and other forms of control commonly combine and the associations these combinations have with firm characteristics and context.

Design/methodology/approach

This study used a cross-sectional sample of 242 firms. Data were collected in 2015 from a survey of the Italian mechanical-engineering industry.

Findings

The MEs studied used two different control configurations. One group relatively strongly emphasized most studied controls, except for centralizing decision-making and strong hierarchy; the other relied on centralization and emphasized other controls less. Size, task programmability, outcome measurability, complexity in terms of the extensiveness of the product range and environmental unpredictability can predict the configuration in use.

Originality/value

No broad-based empirical evidence on control configurations in MEs currently exists. Previous research has focused on to what extent control systems affect business effectiveness or efficiency, without assessing how, and in which contexts, they combine.