bluuebunny/crossref_metadata_2025_split huggingface dataset:
Requirement of GrgA for
Chlamydia
infectious progeny production, optimal growth, and efficient plasmid maintenance
Authors: Lu Bin , Wang Yuxuan , Wurihan Wurihan , Cheng Andrew , Yeung Sydney , Fondell Joseph D. , Lai Zhao , Wan Danny , Wu Xiang , Li Wei Vivian , Fan Huizhou 
Published: December 2023

ABSTRACT

Chlamydia
, an obligate intracellular bacterial pathogen, has a unique developmental cycle involving the differentiation of invading elementary bodies (EBs) to noninfectious reticulate bodies (RBs), replication of RBs, and redifferentiation of RBs into progeny EBs. Progression of this cycle is regulated by three sigma factors, which direct the RNA polymerase to their respective target gene promoters. We hypothesized that the
Chlamydia-
specific transcriptional regulator GrgA, previously shown to activate σ66 and σ28, plays an essential role in chlamydial development and growth. To test this hypothesis, we applied a novel genetic tool known as dependence on plasmid-mediated expression to create
Chlamydia trachomatis
with conditional GrgA deficiency. We show that GrgA-deficient
C. trachomatis
RBs have a growth rate that is approximately half of the normal rate and fail to transition into progeny EBs. In addition, GrgA-deficient
C. trachomatis
fails to maintain its virulence plasmid. Results of RNA-Seq analysis indicate that GrgA promotes RB growth by optimizing tRNA synthesis and expression of nutrient-acquisition genes, while it enables RB-to-EB conversion by facilitating the expression of a histone and outer membrane proteins required for EB morphogenesis. GrgA also regulates numerous other late genes required for host cell exit and subsequent EB invasion into host cells. Importantly, GrgA stimulates the expression of σ54, the third and last sigma factor, and its activator, AtoC, and thereby indirectly upregulating the expression of σ54-dependent genes. In conclusion, our work demonstrates that GrgA is a master transcriptional regulator in
Chlamydia
and plays multiple essential roles in chlamydial pathogenicity.

IMPORTANCE

Hallmarks of the developmental cycle of the obligate intracellular pathogenic bacterium
Chlamydia
are the primary differentiation of the infectious elementary body (EB) into the proliferative reticulate body (RB) and the secondary differentiation of RBs back into EBs. The mechanisms regulating these transitions remain unclear. In this report, we developed an effective novel strategy termed dependence on plasmid-mediated expression (DOPE) that allows for the knockdown of essential genes in
Chlamydia
. We demonstrate that GrgA, a
Chlamydia
-specific transcription factor, is essential for the secondary differentiation and optimal growth of RBs. We also show that GrgA, a chromosome-encoded regulatory protein, controls the maintenance of the chlamydial virulence plasmid. Transcriptomic analysis further indicates that GrgA functions as a critical regulator of all three sigma factors that recognize different promoter sets at developmental stages. The DOPE strategy outlined here should provide a valuable tool for future studies examining chlamydial growth, development, and pathogenicity.
The post-COVID-19 population has a high prevalence of cross-reactive antibodies to spikes from all
Orthocoronavirinae
genera
Authors: Singh Gagandeep , Abbad Anass , Kleiner Giulio , Srivastava Komal , Gleason Charles ,   PARIS Study Group, Carreño Juan Manuel , Simon Viviana , Krammer Florian , Andre Dalles , Bermúdez-González Maria C , Bielak Dominika , Cai Gianna , Cognigni Christian , Chen Yuexing , Fried Miriam , Kang Hyun Min , Lyttle Neko , Mauldin Jacob , Monahan Brian , Morris Sara , Nardulli Jessica , Oostenink Annika , Salimbangon Ashley-Beathrese , Sullivan Leeba , Van Kesteren Morgan , Yellin Temima 
Published: December 2023

ABSTRACT
The Orthocoronavirinae subfamily is large comprising four highly divergent genera. Four seasonal coronaviruses were circulating in humans prior to the coronavirus disease 2019 pandemic. Infection with these viruses induced antibody responses that are relatively narrow with little cross-reactivity to spike proteins of other coronaviruses. Here, we report that infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces broadly cross-reactive binding antibodies to spikes from a wide range of coronaviruses including members of the sarbecovirus subgenus, other betacoronaviruses including Middle Eastern respiratory syndrome coronavirus, and extending to alpha-, gamma-, and delta-coronavirus spikes. These data show that the coronavirus spike antibody landscape in humans has profoundly been changed and broadened as a result of the SARS-CoV-2 pandemic. While we do not understand the functionality of these cross-reactive antibodies and their impact, there is the possibility that they may lead to enhanced resistance of the population to infection with newly emerging coronaviruses with pandemic potential.

IMPORTANCE
As demonstrated by severe acute respiratory syndrome coronavirus 2, coronaviruses pose a significant pandemic threat. Here, we show that coronavirus disease 2019 mRNA vaccination can induce significant levels of cross-reactive antibodies against diverse coronavirus spike proteins. While these antibodies are binding antibodies that likely have little neutralization capacity and while their contribution to cross-protection is unclear, it is possible that they may play a role in protection from progression to severe disease with novel coronaviruses.
Inoviridae
prophage and bacterial host dynamics during diversification, succession, and Atlantic invasion of Pacific-native
Vibrio parahaemolyticus
Authors: Foxall Randi L. , Means Jillian , Marcinkiewicz Ashely L. , Schillaci Christopher , DeRosia-Banick Kristin , Xu Feng , Hall Jeffrey A. , Jones Stephen H. , Cooper Vaughn S. , Whistler Cheryl A. 
Published: December 2023

ABSTRACT

The epidemiology of
Vibrio parahaemolyticus
, the leading cause of seafood-borne bacterial gastroenteritis of humans worldwide, dramatically changed in the United States following the establishment of a Pacific-native lineage called sequence type (ST) 36 in the Atlantic. In this study, we used phylogeography based on traceback to environmental source locations and comparative genomics to identify features that promoted evolution, dispersal, and competitive dominance of ST36. The major genomic differentiation and competitive success of ST36 were associated with a striking succession of filamentous prophage in the family
Inoviridae
(inoviruses), including loss of an inovirus prophage that had been maintained for decades in the endemic north Pacific population. Subsequently, at least five distinct progenitors arising from this diversification translocated from the Pacific into the Atlantic and established four geographically defined clonal subpopulations with remarkably low migration or mixing. Founders of two prevailing Atlantic subpopulations each acquired new stable and diagnostic inoviruses while other subpopulations that apparently declined did not. Broader surveys indicate inoviruses are common and active among the global population of
V. parahaemolyticus
, and though inovirus replacements, such as in ST36, appear to be infrequent, they are notable in pathogenic lineages that dispersed.

IMPORTANCE

An understanding of the processes that contribute to the emergence of pathogens from environmental reservoirs is critical as changing climate precipitates pathogen evolution and population expansion. Phylogeographic analysis of
Vibrio parahaemolyticus
hosts combined with the analysis of their
Inoviridae
phage resolved ambiguities of diversification dynamics which preceded successful Atlantic invasion by the epidemiologically predominant ST36 lineage. It has been established experimentally that filamentous phage can limit host recombination, but here, we show that phage loss is linked to rapid bacterial host diversification during epidemic spread in natural ecosystems alluding to a potential role for ubiquitous inoviruses in the adaptability of pathogens. This work paves the way for functional analyses to define the contribution of inoviruses in the evolutionary dynamics of environmentally transmitted pathogens.
Understanding Fc function for rational vaccine design against pathogens
Authors: Bowman Kathryn A. , Kaplonek Paulina , McNamara Ryan P. 
Published: December 2023

ABSTRACT
Antibodies represent the primary correlate of immunity following most clinically approved vaccines. However, their mechanisms of action vary from pathogen to pathogen, ranging from neutralization, to opsonophagocytosis, to cytotoxicity. Antibody functions are regulated both by antigen specificity (Fab domain) and by the interaction of their Fc domain with distinct types of Fc receptors (FcRs) present in immune cells. Increasing evidence highlights the critical nature of Fc:FcR interactions in controlling pathogen spread and limiting the disease state. Moreover, variation in Fc-receptor engagement during the course of infection has been demonstrated across a range of pathogens, and this can be further influenced by prior exposure(s)/immunizations, age, pregnancy, and underlying health conditions. Fc:FcR functional variation occurs at the level of antibody isotype and subclass selection as well as post-translational modification of antibodies that shape Fc:FcR-interactions. These factors collectively support a model whereby the immune system actively harnesses and directs Fc:FcR interactions to fight disease. By defining the precise humoral mechanisms that control infections, as well as understanding how these functions can be actively tuned, it may be possible to open new paths for improving existing or novel vaccines.
Variations in the oral microbiome and metabolome of methamphetamine users
Authors: Wang Dawei , Feng Yu , Yang Min , Sun Haihui , Zhang Qingchen , Wang Rongrong , Tong Shuqing , Su Rui , Jin Yan , Wang Yunshan , Lu Zhiming , Han Lihui , Sun Yundong 
Published: December 2023

ABSTRACT

Drug addiction can seriously damage human physical and mental health, while detoxification is a long and difficult process. Although studies have reported changes in the oral microbiome of methamphetamine (METH) users, the role that the microbiome plays in the process of drug addiction is still unknown. This study aims to explore the function of the microbiome based on analysis of the variations in the oral microbiome and metabolome of METH users. We performed the 16S rRNA sequencing analysis based on the oral saliva samples collected from 278 METH users and 105 healthy controls (CTL). In addition, the untargeted metabolomic profiling was conducted based on 220 samples. Compared to the CTL group, alpha diversity was reduced in the group of METH users and the relative abundances of
Peptostreptococcus
and
Gemella
were significantly increased, while the relative abundances of
Campylobacter
and
Aggregatibacter
were significantly decreased. Variations were also detected in oral metabolic pathways, including enhanced tryptophan metabolism, lysine biosynthesis, purine metabolism, and steroid biosynthesis. Conversely, the metabolic pathways of porphyrin metabolism, glutathione metabolism, and pentose phosphate were significantly reduced. It was speculated that four key microbial taxa, i.e.,
Peptostreptococcus
,
Gemella
,
Campylobacter
, and
Aggregatibacter
, could be involved in the toxicity and addiction mechanisms of METH by affecting the above metabolic pathways. It was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders was gradually increased. Our study provides novel insights into exploring the toxic damage and addiction mechanisms underlying the METH addiction.

IMPORTANCE
It was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders gradually increased. The prediction models based on oral microbiome and metabolome could effectively predict the methamphetamine (METH) smoking. Our study provides novel insights into the exploration of the molecular mechanisms regulating the toxic damage and addiction of METH as well as new ideas for early prevention and treatment strategies of METH addiction.
Content of Pigments in the Bottom Sediments in a Small Valley Channel Reservoir
Authors: Sigareva L. E. , Timofeeva N. A. , Zakonnov V. V. 
Published: December 2023

Abstract
This paper presents the first data on the content of plant pigments in the bottom sediments of the Uvod Reservoir (Volga basin, Russia), unique in its hydrological regime, which support the hypothesis of more intensive carbon accumulation in small water bodies. It is established that the average concentration of chlorophyll a and its transformation products at the stations is 62.6 ± 10.0 μg/g of dry sediment, 35.2 ± 4.5 mg/(m2 mm) of wet sediment, and 0.73 ± 0.09 mg/g of organic matter of sediments. The ratio of organic carbon to the pigment concentration varies within 400–6000, depending on the type of bottom sediments, which significantly exceeds the values known for macrophytes and phytoplankton. Despite the features of hydrodynamics and geomorphology of the reservoir, the spatial distribution of sedimentary pigments is consistent with the structure of the bottom sediment complex, which is typical for water bodies of different types. A decrease in differences between the pigment concentrations in the sandy and silty biotopes of the Uvod Reservoir compared to the Upper Volga is noted. The average concentration of chlorophyll a with pheopigments (58.5 ± 6.7 μg/g of dry sediment), calculated considering the areas of bottom sediments of different types, in the Uvod Reservoir is 2.3 times higher than in the Gorky Reservoir (25.3 ± 1.5 μg/g), from which water inflows through the Volga–Uvod Canal. According to the content of sedimentary pigments, the trophic state of the reservoir is mesotrophic. Features of eutrophication in the Uvod Reservoir are more distinctly expressed than in the Gorky Reservoir.
Discharge to Assess: an evaluation of three case studies in the southeast of England to inform service improvement
Authors: Jeffery Stuart , Monkhouse Jenny , Bertini Lavinia , Walker Susie , Sharp Rebecca 
Published: December 2023

BackgroundDischarge to Assess (D2A) emerged as a critical process during the COVID-19 pandemic facilitating patient flow within hospitals, however research on the post-discharge community services of this pathway remains limited. We conducted an evaluation to examine the impacts, capacity, processes and barriers associated with D2A and to identify best practice across three sites in the southeast of England.MethodsWe interviewed 29 commissioners, providers and staff members involved in the delivery of D2A pathways within three Health and Care Partnerships. Framework analysis of the collected data revealed three prominent themes: the commissioning of services encompassing funding, structure, culture, and expected outcomes; multidisciplinary collaboration including staff skills, team connections, and coordination; and information and knowledge exchange such as assessment methods, record management, and availability of operational insights.Results62 specific enablers and blockers to effective D2A practice emerged.DiscussionThese findings supported the development of a comprehensive service improvement toolkit.ConclusionFive recommendations are proposed: 1. Examination of pathways against the 62 enablers and blockers to identify and resolve pathway obstacles; 2. Establish a local operational policy accessible to all providers; 3. Enhance coordination and communication among service providers, patients and carers; 4. Strengthen oversight of service user flow; 5. Develop a consistent Patient Reported Outcomes Measure to facilitate feedback and service enhancements for individuals discharged from urgent care pathways.
Incidental asymptomatic spinal cerebrospinal fluid leaks: single-center experience, and a presentation of seven cases
Authors: Zayat Roaa , Huynh Thien J , Fermo Olga 
Published: December 2023

BackgroundThe majority of patients with spontaneous intracranial hypotension (SIH) are symptomatic. Some patients are discovered incidentally. The proportion of asymptomatic SIH has never been defined. This article reports our institution’s rate of asymptomatic cases among all of our patients with high/intermediate Bern scores on brain MRI, etiology of leak in asymptomatic cases, complications of asymptomatic leaks, and evolution of imaging before and after treatment.MethodsWe retrospectively analyzed data from the Cerebrospinal Fluid (CSF) Dynamics clinic spanning September 2020 to July 2023. Bern score was calculated from all available brain MRIs in patients with confirmed leaks. Patients with iatrogenic leaks or no brain MRI were excluded. The charts of asymptomatic patients were reviewed to obtain MRI indications, SIH progression, complications, leak type, and treatment outcomes.ResultsSome 8.6% (7/81) patients with high/intermediate Bern scores were asymptomatic at the time of imaging. Two patients declined myelography. Four of seven asymptomatic patients were found to have CSF-venous fistulas and underwent embolization with radiographic improvement. Complications of asymptomatic leaks in this population included subdural hematoma and superficial siderosis.ConclusionsAsymptomatic but clearly present spinal CSF leaks were not uncommon in our group. These results highlight the possibility of a presymptomatic phase in patients with CSF leaks. In our sample, myelography was readily positive for etiology of the leak, and leaks promptly responded to targeted treatment.
Are military fitness tests safe for members with a total hip arthroplasty?
Authors: Talbot Max , Pullman L , Sokolov M , Reilly T , Russell R , Dion C-A , Théoret D , Slobogean G 
Published: December 2023

IntroductionCanadian Armed Forces (CAF) members must complete an annual fitness evaluation. Members with a total hip arthroplasty (THA) may be at risk of injury during these strenuous tests. To inform CAF policy, we sought expert consensus on the safety of fitness testing for members with a THA.MethodsWe conducted a three-round Delphi study with a panel of hip arthroplasty experts to determine the safety of CAF operational fitness evaluations for members with a THA. The experts evaluated videos of the 10 individual tasks included in the evaluations.ResultsAll individual tasks were judged to be safe by consensus. One task, which involves digging with a shovel, was considered safe provided that participants avoid deep hip flexion. The nine other tasks were judged to be safe without modifications or interventions. The experts also supported a policy recommendation that would allow members to perform military fitness evaluations if they (1) have a primary THA, (2) had no episodes of instability, (3) are at least 12 months postoperatively and (4) have been cleared by an orthopaedic surgeon and a physiatrist/physiotherapist.ConclusionA panel of arthroplasty experts concluded, based on video analysis, that CAF fitness evaluations are generally safe for members with a THA.
Treatment practice of vasospasm during endovascular thrombectomy: an international survey
Authors: Jesser Jessica , Nguyen Thanh , Dmytriw Adam A , Yamagami Hiroshi , Miao Zhongrong , Sommer Louisa Johanna , Stockero Andrea , Pfaff Johannes Alex Rolf , Ospel Johanna , Goyal Mayank , Patel Aman B , Pereira Vitor Mendes , Hanning Uta , Meyer Lukas , van Zwam Wim H , Bendszus Martin , Wiesmann Martin , Möhlenbruch Markus , Weyland Charlotte Sabine 
Published: December 2023

Background and aim
The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate current expert opinions in neurointervention and therapeutic strategies of iatrogenic vasospasm during EVT.

Methods
We conducted an anonymous international online survey (4 April 2023 to 15 May 2023) addressing treatment standards of neurointerventionalists (NIs) practising EVT. Several illustrative cases of patients with vasospasm during EVT were shown. Two study groups were compared according to the NI’s opinion regarding the potential influence of vasospasm on patient outcome after EVT using descriptive analysis.

Results
In total, 534 NI from 56 countries responded, of whom 51.5% had performed >200 EVT. Vasospasm was considered a complication potentially influencing the patient’s outcome by 52.6% (group 1) whereas 47.4% did not (group 2). Physicians in group 1 more often added vasodilators to their catheter flushes during EVT routinely (43.7% vs 33.9%, p=0.033) and more often treated severe large-vessel vasospasm with vasodilators (75.3% vs 55.9%; p<0.001), as well as extracranial vasospasm (61.4% vs 36.5%, p<0.001) and intracranial medium-vessel vasospasm (27.1% vs 11.2%, p<0.001), compared with group 2. In case of a large-vessel vasospasm and residual and amenable medium-vessel occlusion during EVT, the study groups showed different treatment strategies. Group 2 continued the EVT immediately more often, without initiating therapy to treat the vasospasm first (9.6% vs 21.1%, p<0.001).

Conclusion
There is disagreement among NIs about the clinical relevance of vasospasm during EVT and its management. There was a higher likelihood of use of preventive and active vasodilator treatment in the group that perceived vasospasm as a relevant complication as well as differing interventional strategies for continuing an EVT in the presence of a large-vessel vasospasm.
AMPK and PGC-α following maximal and supramaximal exercise in men and women: a randomized cross-over study
Authors: Arhen Benjamin B. , Renwick J.R.M. , Zedic A.K. , Menezes E.S. , Preobrazenski N. , Simpson C.A. , Stokes T. , McGlory C. , Gurd Brendon J. 
Published: December 2023

We tested the hypothesis that AMPK activation and peroxisome proliferator gamma coactivator 1 alpha (PGC-1 α) expression are not augmented as exercise intensity (power output) increases from maximal to supramaximal intensities and conducted an exploratory analysis comparing AMPK activation and PGC-1α expression in males and females. Seventeen ( n = 9 males; n = 8 females) recreationally active, healthy, young individuals volunteered to participate in the current study. Participants completed work matched interval exercise at 100% (Max) and 133% (Supra) of peak work rate (WRpeak). Intervals were 1 min in duration and participants were prescribed 6 and 8 intervals of Max and Supra, respectively, to equate external work across protocols. PGC-1 α mRNA expression and activation of AMPK (p-ACC) were examined in muscle biopsy samples. Interval WR (watts; W), intensity (%WRpeak) and average HR (bpm), blood lactate (mmol/L) and rating of perceived exertion were all higher (all p < 0.05) in Supra. Fatigue was greater ( p < 0.05) in Supra. PGC-1α mRNA expression significantly increased after exercise in Max ( p < 0.01) and Supra ( p < 0.01), but was not significantly different ( p = 0.71) between intensities. A main effect of time (Pre – 0 h) ( p < 0.01) was observed for p-ACC; however, no effect of intensity ( p = 0.08) or interaction ( p = 0.97) was observed. No significant effects of time ( p = 0.05) intensity ( p = 0.42), or interaction ( p = 0.97) were observed for p-AMPK (Thr172). Exploratory sex analysis demonstrated a main effect of sex for p-ACC (greater p-ACC in males; p < 0.05) but not for p-AMPK or PGC-1 α expression. Our results confirm that AMPK-PGC-1 α signalling is not augmented following supramaximal exercise and provide novel data demonstrating a decrease in AMPK activation (p-ACC) in females compared to men. Trial registration: https://doi.org/10.17605/OSF.IO/U7PX9 .