bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micrococcin cysteine-to-thiazole conversion through transient interactions between the scaffolding protein TclI and the modification enzymes TclJ and TclN
Authors: Calvopina-Chavez Diana G. , Bursey Devan M. , Tseng Yi-Jie , Patil Leena M. , Bewley Kathryn D. , Bennallack Philip R. , McPhie Josh M. , Wagstaff Kimberly B. , Daley Anisha , Miller Susan M. , Moody James D. , Price John C. , Griffitts Joel S. 
Published: May 2024

ABSTRACT

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a broad group of compounds mediating microbial competition in nature. Azole/azoline heterocycle formation in the peptide backbone is a key step in the biosynthesis of many RiPPs. Heterocycle formation in RiPP precursors is often carried out by a scaffold protein, an ATP-dependent cyclodehydratase, and an FMN-dependent dehydrogenase. It has generally been assumed that the orchestration of these modifications is carried out by a stable complex including the scaffold, cyclodehydratase, and dehydrogenase. The antimicrobial RiPP micrococcin begins as a precursor peptide (TclE) with a 35-amino acid N-terminal leader and a 14-amino acid C-terminal core containing six Cys residues that are converted to thiazoles. The putative scaffold protein (TclI) presumably presents the TclE substrate to a cyclodehydratase (TclJ) and a dehydrogenase (TclN) to accomplish the two-step installation of the six thiazoles. In this study, we identify a minimal TclE leader region required for thiazole formation, demonstrate complex formation between TclI, TclJ, and TclN, and further define regions of these proteins required for complex formation. Our results point to a mechanism of thiazole installation in which TclI associates with the two enzymes in a mutually exclusive fashion, such that each enzyme competes for access to the peptide substrate in a dynamic equilibrium, thus ensuring complete modification of each Cys residue in the TclE core.

IMPORTANCE
Thiopeptides are a family of antimicrobial peptides characterized for having sulfur-containing heterocycles and for being highly post-translationally modified. Numerous thiopeptides have been identified; almost all of which inhibit protein synthesis in gram-positive bacteria. These intrinsic antimicrobial properties make thiopeptides promising candidates for the development of new antibiotics. The thiopeptide micrococcin is synthesized by the ribosome and undergoes several post-translational modifications to acquire its bioactivity. In this study, we identify key interactions within the enzymatic complex that carries out cysteine to thiazole conversion in the biosynthesis of micrococcin.
Functional characterization of a novel flavin reductase from a deep-sea sediment metagenomic library and its application for indirubin production
Authors: Du Jikun , Li Yuanhua , Chen Zhengzhuang , Wang Chang , Huang Yali , Li Li 
Published: May 2024

ABSTRACT

Microbial synthesis is a desirable approach to produce indirubin but suffers from low synthetic efficiency. Insufficient supply of reduced flavins is one major factor limiting synthetic efficiency. To address this, a novel flavin reductase, MoxB, was discovered through screening of the metagenomic library. MoxB showed a strong preference for NADH over NADPH as the electron source for FMN/FAD reduction and exhibited the highest activity at pH 8.0 and 30°C. It displayed remarkable thermostability by maintaining 80% of full activity after incubation at 60°C for 1 h. Furthermore, MoxB showed great organic solvent tolerance and its activity could be significantly increased by bivalent metal ions. In addition, heterologous expression of the
moxB
gene in the indirubin-producing
E. coli
significantly improved indirubin production up to 15.12-fold. This discovery expands the understanding of flavin reductases and provides a promising catalytic tool for microbial indirubin production.

IMPORTANCE

Much effort has been exerted to produce indirubin using engineered
Escherichia coli
, but high-level production has not been achieved so far. Insufficient supply of reduced flavins is one key factor limiting the catalytic efficiency. However, the flavin reductases involved in indirubin biosynthesis have not been hitherto reported. Discovery of the novel flavin reductase MoxB provides a useful tool for enhancing indirubin production by
E. coli
. Overexpression of MoxB in indirubin-producing
E. coli
increased indirubin production by 15.12-fold in comparison to the control strain. Our results document the function of flavin reductase that reduces flavins during indirubin biosynthesis and provide an important foundation for using the flavin reductases to improve indirubin production by engineered microorganisms.
Applying lessons of COVID-19 and other emerging infectious diseases to future outbreaks
Authors: Bloch Evan M. , Sullivan David J. , Casadevall Arturo , Shoham Shmuel , Tobian Aaron A. R. , Gebo Kelly 
Published: May 2024

ABSTRACT

Infectious diseases are emerging and re-emerging far more frequently than many appreciate. In the past two decades alone, there have been numerous outbreaks (e.g., Ebola, chikungunya, Zika, and Mpox) and pandemics (i.e., swine flu and coronavirus disease 2019) with profound effects to public health, the economy, and society at large. Rather than view these in isolation, there are important lessons pertaining to how best to contend with future outbreaks of emerging infectious diseases. Those lessons span definition (i.e., what constitutes a pandemic), through deficiencies in surveillance, data collection and reporting, the execution of research in a rapidly changing environment, the nuances of study design and hierarchy of clinical evidence, triage according to clinical need as supply chains become overwhelmed, and the challenges surrounding forecasting of outbreaks. Understanding those lessons and drawing on both the successes and failures of the past are imperative if we are to overcome the challenges of outbreak/pandemic responsiveness.
A novel clinical metaproteomics workflow enables bioinformatic analysis of host-microbe dynamics in disease
Authors: Do Katherine , Mehta Subina , Wagner Reid , Bhuming Dechen , Rajczewski Andrew T. , Skubitz Amy P. N. , Johnson James E. , Griffin Timothy J. , Jagtap Pratik D. 
Published: May 2024

ABSTRACT

Clinical metaproteomics has the potential to offer insights into the host-microbiome interactions underlying diseases. However, the field faces challenges in characterizing microbial proteins found in clinical samples, usually present at low abundance relative to the host proteins. As a solution, we have developed an integrated workflow coupling mass spectrometry-based analysis with customized bioinformatic identification, quantification, and prioritization of microbial proteins, enabling targeted assay development to investigate host-microbe dynamics in disease. The bioinformatics tools are implemented in the Galaxy ecosystem, offering the development and dissemination of complex bioinformatic workflows. The modular workflow integrates MetaNovo (to generate a reduced protein database), SearchGUI/PeptideShaker and MaxQuant [to generate peptide-spectral matches (PSMs) and quantification], PepQuery2 (to verify the quality of PSMs), Unipept (for taxonomic and functional annotation), and MSstatsTMT (for statistical analysis). We have utilized this workflow in diverse clinical samples, from the characterization of nasopharyngeal swab samples to bronchoalveolar lavage fluid. Here, we demonstrate its effectiveness via analysis of residual fluid from cervical swabs. The complete workflow, including training data and documentation, is available via the Galaxy Training Network, empowering non-expert researchers to utilize these powerful tools in their clinical studies.

IMPORTANCE
Clinical metaproteomics has immense potential to offer functional insights into the microbiome and its contributions to human disease. However, there are numerous challenges in the metaproteomic analysis of clinical samples, including handling of very large protein sequence databases for sensitive and accurate peptide and protein identification from mass spectrometry data, as well as taxonomic and functional annotation of quantified peptides and proteins to enable interpretation of results. To address these challenges, we have developed a novel clinical metaproteomics workflow that provides customized bioinformatic identification, verification, quantification, and taxonomic and functional annotation. This bioinformatic workflow is implemented in the Galaxy ecosystem and has been used to characterize diverse clinical sample types, such as nasopharyngeal swabs and bronchoalveolar lavage fluid. Here, we demonstrate its effectiveness and availability for use by the research community via analysis of residual fluid from cervical swabs.
Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B
6
metabolism
Authors: Zheng Lifeng , Jiao Yinming , Zhong Haolin , Tan Yan , Yin Yiming , Liu Yanhong , Liu Ding , Wu Manli , Wang Guoyun , Huang Jinqun , Wang Ping , Qin Meirong , Wang Mingbang , Xiao Yang , Lv Tiying , Luo Yangzi , Hu Han , Hou Sheng-Tao , Kui Ling 
Published: May 2024

ABSTRACT

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific
Bacteroides
species and vitamin B
6
metabolism. Indeed, vitamin B
6
supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B
6
metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.

IMPORTANCE

Accumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B
6
metabolism. Bacterial species and compounds with beneficial roles in vitamin B
6
metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.
Activation Analysis of the Temperature Dependence of the Dielectric Constant of Ferroelectrics
Authors: Kuzenko D. V. 
Published: May 2024

Abstract
For ferroelectrics lead zirconate titanate and barium titanate, an exponential dependence of the dielectric constant on temperature is shown, provided that the Curie–Weiss law is satisfied. The temperature of equality of ferroelectric dielectric constants for activation processes caused by the interaction of domain walls with point defects, as well as the corresponding activation energies, have been determined.
Uterovaginal prolapse complicated by urogenital myiasis
Authors: Bahadur Anupama , Mundhra Rajlaxmi , Gill Poonam , Mathuria Yogendra 
Published: May 2024

Urogenital myiasis is a rare entity that is usually manifested in women belonging to lower socioeconomic status residing in tropical or subtropical nations with poor hygiene or intellectual disability. It is caused by fly larvae capable of penetrating body orifices and healthy or necrotic tissue. The larvae penetrate the skin, forming painful, inflammatory nodules that can form fistula to the internal organs or the skin’s surface. Serous and haemorrhagic exudation, along with crawling larvae, are encountered. Some complications, such as secondary infection and tetanus, have been documented. The prognosis is generally good, and treatment consists of removing the parasitic larvae and thoroughly cleansing the affected area.We present a case of a postmenopausal woman with parity 3 and live issue 1 in her early 50s from lower socioeconomic status diagnosed with uterovaginal prolapse complicated by myiasis. The patient was managed successfully with systemic antibiotics, manual removal of myiasis and hysterectomy.
Clinician and health service interventions to reduce the greenhouse gas emissions generated by healthcare: a systematic review
Authors: Pickles Kristen , Haas Romi , Guppy Michelle , O'Connor Denise A , Pathirana Thanya , Barratt Alexandra , Buchbinder Rachelle 
Published: May 2024

Objective
To synthesise the available evidence on the effects of interventions designed to improve the delivery of healthcare that reduces the greenhouse gas (GHG) emissions of healthcare.

Design
Systematic review and structured synthesis.

Search sources
Cochrane Central Register of Controlled Trials, PubMed, Web of Science and Embase from inception to 3 May 2023.

Selection criteria
Randomised, quasi-randomised and non-randomised controlled trials, interrupted time series and controlled or uncontrolled before�after studies that assessed interventions primarily designed to improve the delivery of healthcare that reduces the GHG emissions of healthcare initiated by clinicians or healthcare services within any setting.

Main outcome measures
Primary outcome was GHG emissions. Secondary outcomes were financial costs, effectiveness, harms, patient-relevant outcomes, engagement and acceptability.

Data collection and analysis
Paired authors independently selected studies for inclusion, extracted data, and assessed risk of bias using a modified checklist for observational studies and the certainty of the evidence using Grades of Recommendation, Assessment, Development and Evaluation. Data could not be pooled because of clinical and methodological heterogeneity, so we synthesised results in a structured summary of intervention effects with vote counting based on direction of effect.

Results
21 observational studies were included. Interventions targeted delivery of anaesthesia (12 of 21), waste/recycling (5 of 21), unnecessary test requests (3 of 21) and energy (1 of 21). The primary intervention type was clinician education. Most (20 of 21) studies were judged at unclear or high risk of bias for at least one criterion. Most studies reported effect estimates favouring the intervention (GHG emissions 17 of 18, costs 13 of 15, effectiveness 18 of 20, harms 1 of 1 and staff acceptability 1 of 1 studies), but the evidence is very uncertain for all outcomes (downgraded predominantly for observational study design and risk of bias). No studies reported patient-relevant outcomes other than death or engagement with the intervention.

Conclusions
Interventions designed to improve the delivery of healthcare that reduces GHG emissions may reduce GHG emissions and costs, reduce anaesthesia use, waste and unnecessary testing, be acceptable to staff and have little to no effect on energy use or unintended harms, but the evidence is very uncertain. Rigorous studies that measure GHG emissions using gold-standard life cycle assessment are needed as well as studies in more diverse areas of healthcare. It is also important that future interventions to reduce GHG emissions evaluate the effect on beneficial and harmful patient outcomes.

PROSPERO registration number
CRD42022309428.
Assessment of the methodological, recommendation and reporting quality of global guidelines for neck pain and synthesis of evidence and recommendations: a systematic review protocol
Authors: Li Jiayu , Ou Jiayin , Liu Yang , Shen Chenwei , Chen Xiaoli , Li Ying , Zhao Jiayi , Xu Jing , Zhang Yu , Wang Lin 
Published: May 2024

IntroductionNeck pain is a global health problem that can cause severe disability and a huge medical burden. Clinical practice guideline (CPG) is an important basis for clinical diagnosis and treatment. A high-quality CPG plays a significant role in clinical practice. However, the quality of the CPGs for neck pain lacks comprehensive assessment. This protocol aims to evaluate the methodological, recommendation, reporting quality of global CPGs for neck pain and identify key recommendations and gaps that limit evidence-based practice.MethodCPGs from January 2013 to November 2023 will be identified through a systematic search on 13 scientific databases (PubMed, Cochrane Library, Embase, etc) and 7 online guideline repositories. Six reviewers will independently evaluate the quality of CPGs for neck pain by using the Appraisal of Guidelines for Research and Evaluation, the Appraisal of Guidelines Research and Evaluation-Recommendations Excellence and the Reporting Items for Practice Guidelines in Healthcare tools. Intraclass correlation coefficient will be used to test the consistency of the assessment. We will identify the distribution of evidence and recommendations in each evidence-based CPGs for neck pain and regrade the level of evidence and strength of recommendations by adopting the commonly used Grading of Recommendations, Assessment, Development and Evaluations system. The key recommendations based on high-quality evidence will be summarised. In addition, we will categorise CPGs by different characteristics and conduct a subgroup analysis of the results of assessment.Ethics and disseminationNo subjects will be involved in this systematic review, so there is no need for ethical approval. The finding of this review will be summarised as a paper for publication in a peer-reviewed journal.PROSPERO registration numberCRD42023417717.
Prevalence and correlates of paediatric guideline non-adherence for initial empirical care in six low and middle-income settings: a hospital-based cross-sectional study
Authors: Shawon Riffat Ara , Denno Donna , Tickell Kirkby D , Atuhairwe Michael , Bandsma Robert , Mupere Ezekiel , Voskuijl Wieger , Mbale Emmie , Ahmed Tahmeed , Chisti Md Jobayer , Saleem Ali Faisal , Ngari Moses , Diallo Abdoulaye Hama , Berkley James , Walson Judd , Means Arianna Rubin 
Published: May 2024

ObjectivesThis study evaluated the prevalence and correlates of guideline non-adherence for common childhood illnesses in low-resource settings.Design and settingWe used secondary cross-sectional data from eight healthcare facilities in six Asian and African countries.ParticipantsA total of 2796 children aged 2–23 months hospitalised between November 2016 and January 2019 with pneumonia, diarrhoea or severe malnutrition (SM) and without HIV infection were included in this study.Primary outcome measuresWe identified children treated with full, partial or non-adherent initial inpatient care according to site-specific standard-of-care guidelines for pneumonia, diarrhoea and SM within the first 24 hours of admission. Correlates of guideline non-adherence were identified using generalised estimating equations.ResultsFully adherent care was delivered to 32% of children admitted with diarrhoea, 34% of children with pneumonia and 28% of children with SM when a strict definition of adherence was applied. Non-adherence to recommendations was most common for oxygen and antibiotics for pneumonia; fluid, zinc and antibiotics for diarrhoea; and vitamin A and zinc for SM. Non-adherence varied by site. Pneumonia guideline non-adherence was more likely among patients with severe disease (OR 1.82; 95% CI 1.38, 2.34) compared with non-severe disease. Diarrhoea guideline non-adherence was more likely among lower asset quintile groups (OR 1.16; 95% CI 1.01, 1.35), older children (OR 1.10; 95% CI 1.06, 1.13) and children presenting with wasting (OR 6.44; 95% CI 4.33, 9.57) compared with those with higher assets, younger age and not wasted.ConclusionsNon-adherence to paediatric guidelines was common and associated with older age, disease severity, and comorbidities, and lower household economic status. These findings highlight opportunities to improve guidelines by adding clarity to specific recommendations.
UPDATE trial: investigating the effects of ultra-processed versus minimally processed diets following UK dietary guidance on health outcomes: a protocol for an 8-week community-based cross-over randomised controlled trial in people with overweight or obesity, followed by a 6-month behavioural intervention
Authors: Dicken Samuel , Makaronidis Janine , van Tulleken Chris , Jassil Friedrich C , Hall Kevin , Brown Adrian Carl , Gandini Wheeler-Kingshott Claudia A.M , Fisher Abigail , Batterham Rachel 
Published: May 2024

IntroductionObesity increases the risk of morbidity and mortality. A major driver has been the increased availability of ultra-processed food (UPF), now the main UK dietary energy source. The UK Eatwell Guide (EWG) provides public guidance for a healthy balanced diet but offers no UPF guidance. Whether a healthy diet can largely consist of UPFs is unclear. No study has assessed whether the health impact of adhering to dietary guidelines depends on food processing. Furthermore, our study will assess the impact of a 6-month behavioural support programme aimed at reducing UPF intake in people with overweight/obesity and high UPF intakes.Methods and analysisUPDATE is a 2×2 cross-over randomised controlled trial with a 6-month behavioural intervention. Fifty-five adults aged ≥18, with overweight/obesity (≥25 to <40 kg/m2), and ≥50% of habitual energy intake from UPFs will receive an 8-week UPF diet and an 8-week minimally processed food (MPF) diet delivered to their home, both following EWG recommendations, in a random order, with a 4-week washout period. All food/drink will be provided. Participants will then receive 6 months of behavioural support to reduce UPF intake. The primary outcome is the difference in weight change between UPF and MPF diets from baseline to week 8. Secondary outcomes include changes in diet, waist circumference, body composition, heart rate, blood pressure, cardiometabolic risk factors, appetite regulation, sleep quality, physical activity levels, physical function/strength, well-being and aspects of behaviour change/eating behaviour at 8 weeks between UPF/MPF diets, and at 6-month follow-up. Quantitative assessment of changes in brain MRI functional resting-state connectivity between UPF/MPF diets, and qualitative analysis of the behavioural intervention for feasibility and acceptability will be undertaken.Ethics and disseminationSheffield Research Ethics Committee approved the trial (22/YH/0281). Peer-reviewed journals, conferences, PhD thesis and lay media will report results.Trial registration numberNCT05627570