bluuebunny/crossref_metadata_2025_split huggingface dataset:
The
Vibrio
type VI secretion system induces intestinal macrophage redistribution and enhanced intestinal motility
Authors: Ngo Julia S. , Amitabh Piyush , Sokoloff Jonah G. , Trinh Calvin , Wiles Travis J. , Guillemin Karen , Parthasarathy Raghuveer 
Published: November 2024

ABSTRACT

Intestinal microbes, whether resident or transient, influence the physiology of their hosts, altering both the chemical and the physical characteristics of the gut. An example of the latter is the human pathogen
Vibrio cholerae’s
ability to induce strong mechanical contractions, discovered in zebrafish. The underlying mechanism has remained unknown, but the phenomenon requires the actin crosslinking domain (ACD) of
Vibrio
’s type VI secretion system (T6SS), a multicomponent protein syringe that pierces adjacent cells and delivers toxins. By using a zebrafish-native
Vibrio
and imaging-based assays of host intestinal mechanics and immune responses, we find evidence that macrophages mediate the connection between the T6SS ACD and intestinal activity. Inoculation with
Vibrio
gives rise to strong, ACD-dependent, gut contractions whose magnitude resembles those resulting from genetic depletion of macrophages.
Vibrio
also induces tissue damage and macrophage activation, both ACD-dependent, recruiting macrophages to the site of tissue damage and away from their unperturbed positions near enteric neurons that line the midgut and regulate intestinal motility. Given known crosstalk between macrophages and enteric neurons, our observations suggest that macrophage redistribution forms a key link between
Vibrio
activity and intestinal motility. In addition to illuminating host-directed actions of the widespread T6SS protein apparatus, our findings highlight how localized bacteria-induced injury can reshape neuro-immune cellular dynamics to impact whole-organ physiology.

IMPORTANCE

Gut microbes, whether beneficial, harmful, or neutral, can have dramatic effects on host activities. The human pathogen
Vibrio cholerae
can induce strong intestinal contractions, though how this is achieved has remained a mystery. Using a zebrafish-native
Vibrio
and live imaging of larval fish, we find evidence that immune cells mediate the connection between bacteria and host mechanics. A piece of
Vibrio
’s type VI secretion system, a syringe-like apparatus that stabs cellular targets, induces localized tissue damage, activating macrophages and drawing them from their normal residence near neurons, whose stimulation of gut contractions they dampen, to the damage site. Our observations reveal a mechanism in which cellular rearrangements, rather than bespoke biochemical signaling, drives a dynamic neuro-immune response to bacterial activity.
Genomic insights into the alphaproteobacterium
Georhizobium
sp. MAB10 revealed a pathway of Mn(II) oxidation-coupled anoxygenic photoautotrophy: a novel understanding of the biotic process in deep-sea ferromanganese nodule formation
Authors: Xu Xiuli , Zhang Litao , Song Fuhang , Zhang Guoliang , Ma Linlin , Yang Na 
Published: November 2024

ABSTRACT

Under light conditions, Mn(II) facilitates the photoautotrophic growth of
Georhizobium
sp. MAB10, a strain derived from deep-sea ferromanganese nodules, along with the generation of dark Mn oxides (β-MnO
2
). This study investigated the genetic basis of Mn(II) oxidation-coupled anoxygenic photoautotrophy using genome sequencing and biochemical assays of strain MAB10. Preliminary results indicated the presence of genes encoding a functional pheophytin-quinone-type photosynthetic reaction center and a putative key enzyme for Mn(II) oxidation, namely FtsP/CotA-like multicopper oxidase GE001273. Under light conditions, Mn(II) significantly reduced the respiration rate and elevated the intracellular NADH/NAD
total
ratio. This suggested that Mn(II)-derived electrons entered the cyclic photophosphorylation, partially replacing the oxidative phosphorylation for ATP production and enhancing the electron flow to complex I for NADH generation.
In vitro
enzymatic studies confirmed that GE001273 was a catalyst for Mn(II) oxidation in the outer membrane. Comprehensive genomic analyses of respiration and carbon and nitrogen metabolism revealed the high ecophysiological flexibility of strain MAB10 during Mn(II) oxidation-coupled anoxygenic photoautotrophy in deep-sea habitats. These analyses provided insights into bacterial Mn(II) oxidation-coupled anoxygenic photoautotrophy during microorganism-mediated deep-sea ferromanganese nodule formation.

IMPORTANCE

Microorganisms are believed to participate in the biotic process of deep-sea ferromanganese nodule formation [Mn(II) oxidation]. Despite the multitude of studies and reviews focusing on the details of Mn(II) oxidation catalyzed by diverse heterotrophs, the mechanistic roles of manganese chemolithotrophs from ferromanganese nodules remain unclear. We demonstrate that strain
Georhizobium
sp. MAB10 can utilize Mn(II)-derived electrons for photoautotrophic growth, with concomitant generation of dark β-MnO
2
type Mn oxides under near-infrared light condition. This study uses genomic and biochemical assays to explore the genetic basis of Mn(II) oxidation-coupled anoxygenic photoautotrophy. The comprehensive analyses of respiration and carbon and nitrogen metabolism further elucidated the high ecophysiological flexibility of strain MAB10 in deep-sea habits. These findings expand our understanding of the role of chemolithotrophs in deep-sea ferromanganese nodule formation and justify further investigations into the molecular basis for Mn(II) oxidation-coupled anoxygenic photoautotrophy.
Overexpressing the ClpC AAA+ unfoldase accelerates developmental cycle progression in
Chlamydia trachomatis
Authors: Jensen Aaron A. , Firdous Saba , Lei Lei , Fisher Derek J. , Ouellette Scot P. 
Published: November 2024

ABSTRACT

Chlamydia
is an obligate intracellular bacterium that undergoes a complex biphasic developmental cycle, alternating between the smaller, infectious, non-dividing elementary body (EB) and the larger, non-infectious but dividing reticulate body. Due to the differences between these functionally and morphologically distinct forms, we hypothesize protein degradation is essential to chlamydial differentiation. The bacterial Clp system, consisting of an ATPase unfoldase (e.g., ClpX or ClpC) and a proteolytic component (e.g., ClpP), is critical for the physiology of bacteria through its recognition, and usually degradation, of specific substrates. We observed by transmission electron microscopy that overexpression of wild-type ClpC, but not an ATPase mutant isoform, in
Chlamydia
increased glycogen accumulation within the vacuolar niche of the bacteria earlier in the developmental cycle than typically observed. This suggested ClpC activity may increase the expression of EB-associated genes. Consistent with this, targeted RT-qPCR analyses demonstrated a significant increase in several EB-associated gene transcripts earlier in development. These effects were not observed with overexpression of the ATPase mutant of ClpC, providing strong evidence that the activity of ClpC drives secondary differentiation. By analyzing the global transcriptional response to ClpC overexpression using RNA sequencing, we observed a shift to earlier expression of canonical late developmental cycle genes and other EB-associated genes. Finally, we directly linked overexpression of ClpC with earlier production of infectious chlamydiae. Conversely, disrupting normal ClpC function with an ATPase mutant caused a delay in developmental cycle progression. Overall, these findings provide the first mechanistic insight for initiation of secondary differentiation in
Chlamydia
.

IMPORTANCE

Chlamydia
species are obligate intracellular bacteria that require a host cell in which to complete their unique developmental cycle.
Chlamydia
differentiates between an infectious but non-replicating form, the elementary body, and a non-infectious but replicating form, the reticulate body. The signals that drive differentiation events are not characterized. We hypothesize that proteases are essential for mediating differentiation by allowing remodeling of the proteome as the organism transitions from one functional form to another. We previously reported that the
C
aseino
l
ytic
p
rotease (Clp) system is essential for chlamydial growth. Here, we reveal a surprising function for ClpC, an unfoldase, in driving production of infectious chlamydiae during the chlamydial developmental cycle.
Development of a metabolome-based respiratory infection prognostic during COVID-19 arrival
Authors: Robinson John I. , Marks Laura R. , Hinton Andrew L. , O'Halloran Jane A. , Goss Charles W. , Mucha Peter J. , Henderson Jeffrey P. 
Published: November 2024

ABSTRACT

In a new respiratory virus pandemic, optimizing allocation of scarce medical resources becomes an urgent challenge. Infection prognosis takes on particular importance when allocating scarce antiviral antibodies and drugs, which are most effective when administered before the onset of severe disease. During arrival of the COVID-19 pandemic to the United States in 2020, we conducted a prognostic biomarker discovery and validation effort based upon metabolomic profiling with a liquid-chromatography-mass spectrometer (LC-MS) type used clinically for rapid toxicology. We obtained urine specimens from 163 patients presenting for evaluation. We obtained LC-MS profiles in the initial cohort and used machine learning methods to define a simplified urine metabolomic signature associated with respiratory failure or death by 90 days. This signature was composed of three metabotypes linked to intestinal microbiome metabolism and anticonvulsant use, with a receiver-operator characteristic area under the curve (ROC AUC) of 89.4%. Blinded application of this signature to the subsequent validation cohort yielded a ROC AUC of 81.2%. A model trained on the two baseline metabotypes present before intubation exhibited similar performance in the validation cohort. This study demonstrates the plausibility and promise of rapid metabolome-based prognostic discovery and validation in the opening wave of a pandemic. The approach used here could be used to inform therapeutic and resource allocation decisions early in a future epidemic.

IMPORTANCE
In a new respiratory virus pandemic, the ability to identify patients at greatest risk for severe disease is essential to direct scarce medical resources to those most likely to benefit from them. Tools to predict disease severity are best developed early in a pandemic, but laboratory-based resources to develop these may be limited by available technology and by infection precautions. Here, we show that an accessible metabolic profiling approach could identify a prognostic signature of severe disease in the initial wave of COVID-19, when patients presenting for care often exceeded the available doses of convalescent plasma and remdesivir. In a future pandemic, this approach, alongside efforts to identify clinical disease severity predictors, could improve patient outcomes and facilitate therapeutic trials by identifying individuals at high risk for severe disease.
Whole-genome sequence of
Psychrobacter
sp. strain AH5, isolated from salted bluespot mullet (
Valamugil seheli
)
Authors: Al-Harbi Ahmed H. 
Published: November 2024

ABSTRACT

Herein is reported the whole-genome sequence of
Psychrobacter
sp. strain AH5 that was isolated from salted bluespot mullet (
Valamugil seheli
). The genome assembly comprises a total of 3,241,797 bp with a GC content of 43.73% and encodes 2,541 protein-coding genes.
Enhancing pathogens detection in suspected geriatric bloodstream infections using Nanopore-targeted sequencing
Authors: Zhao Menghui , Ouyang Yan , Mei Junchi , Liu Hang 
Published: November 2024

ABSTRACT

Bloodstream infections (BSIs) are a critical concern for elderly patients, where prompt and accurate diagnosis is vital for effective treatment. Traditional blood culture methods suffer from delayed results and susceptibility to false-negatives. Nanopore-targeted sequencing (NTS) offers rapid pathogen detection and reporting, presenting a promising alternative. However, the application of NTS for diagnosing suspected BSIs in geriatric patients remains insufficiently studied. We conducted a retrospective cohort study from January 2022 to January 2024, including 198 geriatric patients suspected of BSIs. We utilized NTS to detect pathogen characteristics and compared the effectiveness and consistency of NTS with simultaneous blood culture testing for pathogen detection. NTS demonstrated a pathogen detection rate of 61.1%. The most common bacterial pathogens were
Escherichia coli
and
Staphylococcus aureus
(each 7.7%), while
Candida albicans
was the most prevalent fungal pathogen (30%). Mixed-bacterial infections were detected in 21.7% of NTS-positive cases, and concurrent bacterial–fungal infections were observed in 9.92% of these cases. NTS-positive patients had higher rates of comorbidities, elevated inflammatory markers, and worse prognoses compared to NTS-negative patients. NTS exhibited a significantly higher pathogen detection rate and faster turnaround time than blood culture (78.1% vs 42.2%,
P
< 0.001), with an agreement rate of 65.6%. The elderly BSI patients frequently involve multiple or mixed infections and correlate with poorer prognoses. NTS provides a faster and more sensitive diagnostic alternative to traditional blood culture, potentially improving clinical outcomes and guiding more effective treatment strategies. This study highlights the need for further research to validate the routine clinical integration of NTS for managing BSIs in geriatric populations.

IMPORTANCE
Bloodstream infections (BSIs) in elderly patients pose substantial diagnostic and therapeutic challenges due to the limitations of traditional blood culture methods, which are hampered by slow turnaround times and false-negatives. Nanopore-targeted sequencing (NTS) emerges as a significant advancement, offering rapid and accurate pathogen detection directly from blood samples. This study demonstrates that NTS provides a higher detection rate and faster results than conventional blood cultures, crucial for the timely management of BSIs in geriatric patients, who often present with multiple or mixed infections and have poorer clinical outcomes. The findings underscore the potential of NTS to enhance diagnostic accuracy and speed, informing more effective treatment strategies and improving overall patient outcomes. Further research is essential to establish NTS as a routine diagnostic tool in the clinical management of BSIs in the elderly.
Sedimentary record of oceanic plateau accretion: Revisiting the Eocene to Miocene stratigraphy of the northern Olympic Peninsula, Washington (USA)
Authors: Donaghy Erin E. , Eddy Michael P. , Ridgway Kenneth D. , Ickert Ryan B. 
Published: November 2024

Abstract
Oceanic plateaus are common in modern oceanic basins and will ultimately collide with continental subduction zones. Despite the frequency of these events, complete sedimentary records of oceanic plateau collision and accretion have remained limited to only a few Cenozoic examples with excellent exposure and tectonic context. Our study focuses on building a stratigraphic record of plateau collision using the sedimentary strata deposited on the Siletzia oceanic plateau, which accreted to the Pacific Northwest at ca. 50 Ma. By combining previously published provenance and stratigraphic data with new lithofacies and geologic mapping, measured stratigraphic sections, conglomerate clast counts, and U-Pb zircon geochronology, we were able to divide the strata of the northern Olympic Peninsula in Washington, USA, into precollisional, syn-collisional, and postcollisional stages. Precollisional strata include early Eocene deep-marine hemipelagic to pelagic mudstones of the Aldwell Formation that were deposited directly on Siletzia basalts. These strata were deformed during collision and are separated from the overlying syn-collisional middle Eocene sandstone and conglomerate of the marine (?) Lyre Formation by an angular unconformity. Postcollisional strata were deposited by submarine fans and include interbedded sandstone and siltstone of the Hoko River and Makah formations. These units initially record the filling of isolated trench-slope basins by late Eocene time before eventual integration into an Oligocene regional forearc basin as the accreted Siletzia plateau began to subside. Our chronostratigraphy permits the correlation of basin strata across tectonic domains and provides more general insight into how forearc sedimentary systems evolve following the accretion of a young, buoyant oceanic plateau.
Clinical utility of novel diabetes subgroups in predicting vascular complications and mortality: up to 25 years of follow-up of the HUNT Study
Authors: Bjarkø Vera Vik , Haug Eirin Beate , Langhammer Arnulf , Ruiz Paz Lopez-Doriga , Carlsson Sofia , Birkeland Kare I , Berg Tore Julsrud , Sørgjerd Elin Pettersen , Lyssenko Valeriya , Åsvold Bjørn Olav 
Published: November 2024

IntroductionCluster analysis has previously revealed five reproducible subgroups of diabetes, differing in risks of diabetic complications. We aimed to examine the clusters’ predictive ability for vascular complications as compared with established risk factors in a general adult diabetes population.Research design and methodsParticipants from the second (HUNT2, 1995–1997) and third (HUNT3, 2006–2008) surveys of the Norwegian population-based Trøndelag Health Study (HUNT Study) with adult-onset diabetes were included (n=1899). To identify diabetes subgroups, we used the same variables (age at diagnosis, body mass index, HbA1c, homeostasis model assessment estimates of beta cell function and insulin resistance, and glutamic acid decarboxylase antibodies) and the same data-driven clustering technique as in previous studies. We used Cox proportional hazards models to investigate associations between clusters and risks of vascular complications and mortality. We estimated the C-index and R2to compare predictive abilities of the clusters to those of established risk factors as continuous variables. All models included adjustment for age, sex, diabetes duration and time of inclusion.ResultsWe reproduced five subgroups with similar key characteristics as identified in previous studies. During median follow-up of 9–13 years (differing between outcomes), the clusters were associated with different risks of vascular complications and all-cause mortality. However, in prediction models, individual established risk factors were at least as good predictors as cluster assignment for all outcomes. For example, for retinopathy, the C-index for the model including clusters (0.65 (95% CI 0.63 to 0.68)) was similar to that of HbA1c (0.65 (95% CI 0.63 to 0.68)) or fasting C-peptide (0.66 (95% CI 0.63 to 0.68)) alone. For chronic kidney disease, the C-index for clusters (0.74 (95% CI 0.72 to 0.76)) was similar to that of triglyceride/high-density lipoprotein ratio (0.74 (95% CI 0.71 to 0.76)) or fasting C-peptide (0.74 (95% CI 0.72 to 0.76)), and baseline estimated glomerular filtration rate yielded a C-index of 0.76 (95% CI 0.74 to 0.78).ConclusionsCluster assignment did not provide better prediction of vascular complications or all-cause mortality compared with established risk factors.
Malnutrition and associated risk factors in orphanages in Punjab, Pakistan: an analytical study
Authors: Farid Muhammad Farhan , Rehman Alfur , Khaliq Ahmad Mujtaba , Ali Naveed , Tareq Ahmad Hussen 
Published: November 2024

BackgroundChildren living in orphanages face an increased susceptibility to malnutrition due to inadequate nutrition and psychological factors, in comparison to children who stay with their parents. A considerable proportion of institutionalised children remain unreported, and there is a dearth of information regarding the nutritional status of these children in Pakistan. This study set out to evaluate the status of malnutrition in the orphanages of Social Welfare Department Punjab.MethodologyA multicentre analytical cross-sectional study was conducted from 12 December 2021 to 30 June 2022, with 255 study participants (aged 6–18 years) in seven orphanages (4 girls, 3 boys) out of 12 orphanages of government of Punjab. Anthropometric measurements were taken using standardised measuring instruments, and data were collected using structured questionnaire. Subjects were classed as malnourished based on body mass index for age and height for age reference growth charts of WHO 2007. Binary logistic regression was used to identify potential risk factors of malnutrition in orphanages.ResultsThe study identified 36.1% malnourished children, of whom, 65.2% were orphans and 34% destitute children. The study reported 9.4% moderately underweight, 2.4% severely underweight, 4.3% overweight and 1.2% obese children and adolescents. The study established 17.6% moderately stunted, and 7.1% severely stunted children. Age at admission to orphanages (9–13 years) and lack of milk and meat consumption were identified as significant predictors of malnutrition in institutionalised children of Punjab.ConclusionCentral Punjab had the highest malnutrition rate compared to North and South Punjab. Micronutrient deficiencies were more pronounced in South Punjab orphanages. Effective prevention of malnutrition requires early assessment of malnutritional risk in Pakistani orphanages.
Cancer incidence and competing mortality risk following 15 presenting symptoms in primary care: a population-based cohort study using electronic healthcare records
Authors: Barclay Matthew E , Renzi Cristina , Harrison Hannah , Torralbo Ana , White Becky , Ip Samantha Hiu Yan , Usher-Smith Juliet , Lange Jane , Pashayan Nora , Denaxas Spiros , Wood Angela M , Antoniou Antonis , Lyratzopoulos Georgios 
Published: November 2024

·ObjectivesAssessment of age, sex and smoking-specific risk of cancer diagnosis and non-cancer mortality following primary care consultation for 15 new-onset symptoms.Methods and analysisData on patients aged 30–99 in 2007–2017 were extracted from a UK primary care database (CPRD Gold), comprising a randomly selected reference group and a symptomatic cohort of patients presenting with one of 15 new onset symptoms (abdominal pain, abdominal bloating, rectal bleed, change in bowel habit, dyspepsia, dysphagia, dyspnoea, haemoptysis, haematuria, fatigue, night sweats, weight loss, jaundice, breast lump and post-menopausal bleed).Time-to-event models were used to estimate outcome-specific hazards for site-specific cancer diagnosis and non-cancer mortality and to estimate cumulative incidence up to 12 months following index consultation.ResultsData included 1 622 419 patients, of whom 36 802 had a cancer diagnosis and 28 857 died without a cancer diagnosis within 12 months of the index.The risk of specific cancers exceeded the UK urgent referral risk threshold of 3% from a relatively young age for patients with red flag symptoms. For non-organ-specific symptoms, the risk of cancer at individual sites either did not reach the threshold at any age or reached it only in older patients.ConclusionPatients with new-onset symptoms in primary care often have comparable risks of cancer diagnosis and non-cancer mortality. Non-organ-specific symptoms, in particular, are associated with elevated risk of cancer at multiple different sites. Management of symptomatic patients in primary care should be informed by the risk of different cancer types alongside mortality risk.