bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of glycogen metabolism in
Clostridioides difficile
virulence
Authors: Hasan Md Kamrul , Pizzarro-Guajardo Marjorie , Sanchez Javier , Govind Revathi 
Published: August 2024

ABSTRACT

Glycogen plays a vital role as an energy reserve in various bacterial and fungal species.
Clostridioides difficile
possesses a glycogen metabolism operon that contains genes for both glycogen synthesis and utilization. In our investigation, we focused on understanding the significance of glycogen metabolism in the physiology and pathogenesis of
C. difficile
. To explore this, we engineered a
C. difficile
JIR8094 strain lacking glycogen synthesis capability by introducing a group II intron into the
glgC
gene, the operon’s first component. Quantification of intracellular glycogen levels validated the impact of this modification. Interestingly, the mutant strain exhibited a 1.5-fold increase in toxin production compared with the parental strain, without significant changes in the sporulation rate. Our analysis also revealed that wild-type
C. difficile
spores contained glycogen, whereas spores from the mutant strain lacking stored glycogen showed increased sensitivity to physical and chemical treatments and had a shorter storage life. By suppressing
glgP
expression, the gene coding for glycogen-phosphorylase, via CRISPRi, we demonstrated that glycogen accumulation but not the utilization is needed for spore resilience in
C. difficile
. Transmission electron microscopy analysis revealed a significantly lower core/cortex ratio in
glgC
mutant strain spores. In hamster challenge experiments, both the parental and
glgC
mutant strains colonized hosts similarly; however, the mutant strain failed to induce infection relapse after antibiotic treatment cessation. These findings highlight the importance of glycogen metabolism in
C. difficile
spore resilience and suggest its role in disease relapse.

IMPORTANCE

This study on the role of glycogen metabolism in
Clostridioides difficile
highlights its critical involvement in the pathogen’s energy management, its pathogenicity, and its resilience. Our results also revealed that glycogen presence in spores is pivotal for their structural integrity and resistance to adverse conditions, which is essential for their longevity and infectivity. Importantly, the inability of the mutant strain to cause infection relapse in hamsters post-antibiotic treatment pinpoints a potential target for therapeutic interventions, highlighting the importance of glycogen in disease dynamics. This research thus significantly advances our understanding of
C. difficile
physiology and pathogenesis, offering new avenues for combating its persistence and recurrence.
Overexpression of native carbonic anhydrases increases carbon conversion efficiency in the methanotrophic biocatalyst
Methylococcus capsulatus
Bath
Authors: Lee Spencer A. , Henard Jessica M. , Alba Robyn A. C. , Benedict Chance A. , Mayes Tyler A. , Henard Calvin A. 
Published: August 2024

ABSTRACT

Methanotrophic bacteria play a vital role in the biogeochemical carbon cycle due to their unique ability to use CH
4
as a carbon and energy source. Evidence suggests that some methanotrophs, including
Methylococcus capsulatus
, can also use CO
2
as a carbon source, making these bacteria promising candidates for developing biotechnologies targeting greenhouse gas capture and mitigation. However, a deeper understanding of the dual CH
4
and CO
2
metabolism is needed to guide methanotroph strain improvements and realize their industrial utility. In this study, we show that
M. capsulatus
expresses five carbonic anhydrase (CA) isoforms, one α-CA, one γ-CA, and three β-CAs, that play a role in its inorganic carbon metabolism and CO
2
-dependent growth. The CA isoforms are differentially expressed, and transcription of all isoform genes is induced in response to CO
2
limitation. CA null mutant strains exhibited markedly impaired growth compared to an isogenic wild-type control, suggesting that the CA isoforms have independent, non-redundant roles in
M. capsulatus
metabolism and physiology. Overexpression of some, but not all, CA isoforms improved bacterial growth kinetics and decreased CO
2
evolution from CH
4
-consuming cultures. Notably, we developed an engineered methanotrophic biocatalyst overexpressing the native α-CA and β-CA with a 2.5-fold improvement in the conversion of CH
4
to biomass. Given that product yield is a significant cost driver of methanotroph-based bioprocesses, the engineered strain developed here could improve the economics of CH
4
biocatalysis, including the production of single-cell protein from natural gas or anaerobic digestion-derived biogas.

IMPORTANCE

Methanotrophs transform CH
4
into CO
2
and multi-carbon compounds, so they play a critical role in the global carbon cycle and are of interest for biotechnology applications. Some methanotrophs, including
Methylococcus capsulatus
, can also use CO
2
as a carbon source, but this dual one-carbon metabolism is incompletely understood. In this study, we show that
M. capsulatus
carbonic anhydrases are critical for this bacterium to optimally utilize CO
2
. We developed an engineered strain with improved CO
2
utilization capacity that increased the overall carbon conversion to cell biomass. The improvements to methanotroph-based product yields observed here are expected to reduce costs associated with CH
4
conversion bioprocesses.
Honeybee gut bacterial strain improved survival and gut microbiota homeostasis in
Apis mellifera
exposed
in vivo
to clothianidin
Authors: El Khoury Sarah , Gauthier Jeff , Mercier Pierre Luc , Moïse Stéphane , Giovenazzo Pierre , Derome Nicolas 
Published: August 2024

ABSTRACT

Pesticides are causing honeybee mortality worldwide. Research carried out on honeybees indicates that application of pesticides has a significant impact on the core gut community, which ultimately leads to an increase in the growth of harmful pathogens. Disturbances caused by pesticides also affect the way bacterial members interact, which results in gut microbial dysbiosis. Administration of beneficial microbes has been previously demonstrated to be effective in treating or preventing disease in honeybees. The objective of this study was to measure under
in vivo
conditions the ability of two bacterial strains (the
Enterobacter
sp. and
Pantoea
sp.) isolated from honeybee gut to improve survival and mitigate gut microbiota dysbiosis in honeybees exposed to a sublethal clothianidin dose (0.1 ppb). Both gut bacterial strains were selected for their ability to degrade clothianidin
in vitro
regardless of their host–microbe interaction characteristics (e.g., beneficial, neutral, or harmful). To this end, we conducted cage trials on 4- to 6-day-old newly emerging honeybees. During microbial administration, we jointly monitored the taxonomic distribution and activity level of bacterial symbionts quantifying 16S rRNA transcripts. First, curative administration of the
Pantoea
sp. strain significantly improved the survival of clothianidin-exposed honeybees compared to sugar control bees (i.e., supplemented with sugar [1:1]). Second, curative administration of the
Enterobacter
sp. strain significantly mitigated the clothianidin-induced dysbiosis observed in the midgut structural network, but without improving survival.

IMPORTANCE
The present work suggests that administration of bacterial strains isolated from honeybee gut may promote recovery of gut microbiota homeostasis after prolonged clothianidin exposure, while improving survival. This study highlights that gut bacterial strains hold promise for developing efficient microbial formulations to mitigate environmental pesticide exposure in honeybee colonies.
Comparison and evaluation of neutralization of clinically frequently used antimicrobial agents using three different culture media in simulated blood cultures
Authors: Hang Yaping , Xiong Jianqiu , Hu Longhua , Chen Yanhui , Zou Shan , Fang Xueyao , Xiao Yanping , Cao Xingwei , Lou Hong , Li Xiuzhen , Liu Yanhua , Zhong Qiaoshi 
Published: August 2024

ABSTRACT

The performance of BACT/ALERT FA/FN Plus (France) blood culture containing a novel resin, DL (China) blood culture containing common resin, and adsorbent-free REDOX (USA) blood culture relying on dilution for antimicrobial neutralization at %peak serum concentration was evaluated by measuring the recovery of organisms and time to detection (TTD) in nine simulated microorganism-antimicrobial combination blood cultures. Significant differences were observed in the recovery rates among the aerobic media: 87.5% for BACT/ALERT media, 42.9% for DL media, and 12.5% for REDOX media. In contrast, no statistical difference was found in the TTD between FA Plus media and DL aerobic media. For the anaerobic media, the recovery rates were 91.4% for BACT/ALERT media, 2.9% for DL media, and 14.3% for REDOX media, with significant differences only between BACT/ALERT FN Plus media and the others. Among the seven main antimicrobial categories, only BACT/ALERT FA/FN Plus culture media demonstrated high recovery of microorganisms, with the exception of carbapenems. The DL culture media exhibited a relatively high recovery rate of microorganisms in the presence of piperacillin/tazobactam, levofloxacin, and gentamicin, but only in aerobic conditions. Conversely, REDOX media displayed microorganism recovery solely in the presence of gentamicin. BACT/ALERT FA/FN Plus culture media with novel resin showed absolute advantages over DL and REDOX culture media and can, therefore, be selectively applied in clinical settings when antimicrobials are used prior to blood collection. DL culture media, containing common resin, outperformed adsorbent-free dilution-based REDOX culture media, making it a viable backup option. There is a need to focus on improving the neutralization of carbapenems with current inefficiency in all three medias.

IMPORTANCE
We present a study on performance comparison of three different commercial culture media for neutralization of antibiotic effects in simulated blood cultures. BACT/ALERT (FA Plus and FN Plus) culture media with novel resin showed absolute advantages over DL and REDOX culture media at %PSL concentration of antimicrobials.
Somatic cell count as an indicator of subclinical mastitis and increased inflammatory response in asymptomatic lactating women
Authors: Angelopoulou Angeliki , Harris Hugh M. B. , Warda Alicja K. , O'Shea Carol-Anne , Lavelle Aonghus , Ryan C. Anthony , Dempsey Eugene , Stanton Catherine , Hill Colin , Ross R. Paul 
Published: August 2024

ABSTRACT

Subclinical mastitis is an asymptomatic inflammatory condition that can be difficult to define and diagnose. In the dairy industry, subclinical mastitis is diagnosed by milk somatic cell counts (SCCs) of ≥250,000 cells mL
−1
. In this pilot study, we assessed the efficacy of this index to identify human subclinical mastitis by comparing SCC levels with the inflammatory response [interleukin-8 (IL-8) levels] in 37 samples from asymptomatic and 10 clinical mastitis (CM) lactating women. The milk microbiota was determined by 16S rRNA gene sequencing. The SCC of CM samples ranged from 310,000 to 6,600,000 cells mL
−1
. However, 14 of 37 (37.8%) asymptomatic samples had high SCC (250,000–460,000 cells mL
−1
), indicating subclinical mastitis. SCC levels significantly (
P
< 0.001) and positively correlated with milk IL-8 levels reflecting the escalating inflammatory response across subclinical and clinical mastitis samples. Samples with an SCC of ≥250,000 cells mL
−1
showed significant increases in IL-8 responses when compared with milk samples from healthy women. The milk microbiome of CM samples was dominated by streptococcal and staphylococcal species (89.9% combined median relative abundance). In contrast, the combined median streptococcal/staphylococcal relative levels were 75.4% and 66.3% in milks from asymptomatic (subclinical mastitis) and healthy groups, respectively. The
Streptococcus
genus was increased in samples with an SCC of ≥250,000, although this should be interpreted with caution. Thus, the index of ≥250,000 somatic cells mL
−1
could be a reliable indicator of subclinical mastitis in humans and should aid future studies investigating the impact of subclinical mastitis on maternal health, breastfeeding behaviors, infant health, and development.

IMPORTANCE

This pilot study suggests that SCC at a level of (greater than or equal to) 250,000 cells mL
−1
, as used in the dairy industry, is a suitable index to identify asymptomatic subclinical mastitis in lactating women since it reflects a significant increase in the inflammatory response compared to milk samples from healthy women. Using this index should aid studies into the short- and long-term consequences of subclinical mastitis for mother and infant.
Don’t mind the “charcoal gap”: A reassessment of Devonian wildfire
Authors: Glasspool Ian J. , Gastaldo Robert A. 
Published: August 2024

Abstract
Little evidence of macrofossil charcoal, a wildfire proxy, is recorded from upper Lower to lowermost Upper Devonian rocks. Coals of this age are few, and petrographic data indicate low volumes (&lt;10% mineral-matter free) of charcoal. This paucity of data forms the basis of the “charcoal gap,” which is used to suggest an extended interval of abnormally low atmospheric oxygen (pO2). We reassess the current evidence for this hiatus using Emsian–Eifelian charcoal from the Trout Valley and St. Froid Lake Formations, Maine (northeastern United States), and integrate the microscopic charcoal record of dispersed organic matter. We conclude there is ample evidence of fire in the Middle Devonian. This interval is not innately of low pO2. Rather, it is one in which under-interpretation of available data has led to a perceived paucity of charcoal. This reconciliation indicates the Phanerozoic record of wildfire was substantially uninterrupted. Hence, we propose that pO2 achieved levels &gt;16% and remained at such levels from the Silurian through the floral and faunal colonization of land and, from our current estimates, stayed as such until the present.
At-home specimen self-collection as an additional testing strategy for chlamydia and gonorrhoea: a systematic literature review and meta-analysis
Authors: Smith Amanda C , Thorpe Phoebe G , Learner Emily R , Galloway Eboni T , Kersh Ellen N 
Published: August 2024

IntroductionChlamydia trachomatis(Ct) andNeisseria gonorrhoeae(Ng) infections are often asymptomatic; screening increases early detection and prevents disease, sequelae and further spread. To increase Ct and Ng testing, several countries have implemented specimen self-collection outside a clinical setting. While specimen self-collection at home is highly acceptable to patients and as accurate as specimens collected by healthcare providers, this strategy is new or not being used in some countries. To understand how offering at home specimen self-collection will affect testing uptake, test results, diagnosis and linkage to care, when compared with collection in clinical settings, we conducted a systematic literature review and meta-analysis of peer-reviewed studies.MethodsWe searched Medline, Embase, Global Health, Cochrane Library, CINAHL (EBSCOHost), Scopus and Clinical Trials. Studies were included if they directly compared specimens self-collected at home or in other non-clinical settings to specimen collection at a healthcare facility (self or clinician) for Ct and/or Ng testing and evaluated the following outcomes: uptake in testing, linkage to care, and concordance (agreement) between the two settings for the same individuals. Risk of bias (RoB) was assessed using Cochrane Risk of Bias (RoB2) tool for randomised control trials (RCTs).Results19 studies, from 1998 to 2024, comprising 15 RCTs with a total of 62 369 participants and four concordance studies with 906 participants were included. Uptake of Ct or Ng testing was 2.61 times higher at home compared with clinical settings. There was a high concordance between specimens collected at home and in clinical settings, and linkage to care was not significantly different between the two settings (prevalence ratio 0.96 (95% CI 0.91–1.01)).ConclusionOur meta-analysis and systematic literature review show that offering self-collection of specimens at home or in other non-clinical settings could be used as an additional strategy to increase sexually transmitted infection testing in countries that have not yet widely adopted this collection method.
Far-from-equilibrium attractors with full relativistic Boltzmann approach in boost-invariant and non-boost-invariant systems
Authors: Nugara Vincenzo , Plumari Salvatore , Oliva Lucia , Greco Vincenzo 
Published: August 2024

AbstractWe study the universal behavior associated with a Relativistic Boltzmann Transport (RBT) approach with the full collision integral in 0+1D conformal systems. We show that all momentum moments of the distribution function exhibit universal behavior. Furthermore, the RBT approach allows to calculate the full distribution function, showing that an attractor behavior is present in both the longitudinal and transverse momentum dependence. We compare our results to the far-from-equilibrium attractors determined with other approaches, such as kinetic theory in Relaxation Time Approximation (RTA) and relativistic hydrodynamic theories, both in their viscous (DNMR) an anisotropic (aHydro) formulations, finding a very similar evolution, but an even faster thermalization in RBT for higher order moments. For the first time, we extended this analysis also to study the attractor behavior under a temperature-dependent viscosity $$\eta /s(T)$$

η
/
s
(
T
)

, accounting also for the rapid increase toward the hadronic phase. We find that a partial breaking of the scaling behavior with respect to $$\tau /\tau _{eq}$$

τ
/

τ

eq

emerges only at $$T \approx T_c$$

T
≈

T
c

generating a transient deviation from attractors; interestingly this in realistic finite systems may occur around the freeze-out dynamics. Finally, we investigate for the first time results beyond the boost-invariant picture, finding that also in such a case the system evolves toward the universal attractor. In particular, we present the forward and pull-back attractors at different space-time rapidities including rapidity regions where initially the distribution function is even vanishing.
Derived Time in Range and Other Metrics of Poor Glycemic Control Associated With Adverse Hospital Outcomes in Patients With Diabetes Mellitus Admitted to Non‐ICU Wards at a Tertiary‐Level Hospital in Colombia: A Cross‐Sectional Study
Authors: Mora Garzón Edwin , González Montoya Alexandra , Hernández Herrera Gilma 
Published: August 2024

Aim: This study is aimed at assessing the prevalence of poor glycemic control using different metrics and its association with in‐hospital adverse outcomes.Methods: This cross‐sectional study was conducted in diabetic patients admitted to a third‐level hospital in Colombia between January and July 2022. Poor glycemic control was determined using capillary glucose metrics, including mean glucose values outside the target range, derived time in range (dTIR) (100–180 mg/dL) < 70%, coefficient of variation (CV > 36%), and hypoglycemia (<70 mg/dL). Multiple regression models were adjusted for hospital outcomes based on glycemic control, as well as other sociodemographic and clinical covariates.Results: A total of 330 Hispanic patients were included. A total of 27.6% had mean glucose measurements outside the target range, 33% had a high CV, 64.8% had low dTIR, and 28.8% experienced hypoglycemia. The in‐hospital mortality rate was 8.8%. An admission HbA1c level greater than 7% was linked to an increased mortality risk (p = 0.016), as well as a higher average of glucometer readings (186 mg/dL vs. 143 mg/dL; p < 0.001). A lower average of dTIR (41.0% vs. 60.0%; p < 0.001) was also associated with a higher mortality risk. Glycemic variability was correlated with an increased risk of mortality, hypoglycemia, delirium, and length of hospital stay (LOS).Conclusion: A significant number of hospitalized diabetic patients exhibit poor glycemic control, which has been found to be associated with adverse outcomes, including increased mortality. Metrics like dTIR and glycemic variability should be considered as targets for glycemic control, highlighting the need for enhanced management strategies.
RNA Shielding of p65 Is Required to Potentiate Oncogenic Inflammation in TET2-Mutated Clonal Hematopoiesis
Authors: Ben-Crentsil Nana Adjoa , Mohammed Ismail Wazim , Balasis Maria E. , Newman Hannah , Quintana Ariel , Binder Moritz , Kruer Traci , Neupane Surendra , Ferrall-Fairbanks Meghan C. , Fernandez Jenna , Lasho Terra L. , Finke Christy M. , Ibrahim Mohammed L. , McGraw Kathy L. , Wysota Michael , Aldrich Amy L. , Ryder Christopher B. , Letson Christopher T. , Traina Joshua , McLemore Amy F. , Droin Nathalie , Shastri Aditi , Yun Seongseok , Solary Eric , Sallman David A. , Beg Amer A. , Ma Li , Gaspar-Maia Alexandre , Patnaik Mrinal M. , Padron Eric 
Published: August 2024

Abstract
TET2 mutations (mTET2) are common genetic events in myeloid malignancies and clonal hematopoiesis. These mutations arise in the founding clone and are implicated in many clinical sequelae associated with oncogenic feedforward inflammatory circuits. However, the direct downstream effector of mTET2 responsible for the potentiation of these inflammatory circuits is unknown. To address this, we performed scRNA-seq and scATAC-seq in patients with COVID-19 with and without TET2-mutated clonal hematopoiesis reasoning that inflammation from COVID-19 may highlight critical downstream transcriptional targets of mTET2. Using this approach, we identified metastasis-associated lung adenoma transcript 1 (MALAT1), a therapeutically tractable lncRNA, as a central downstream effector of mTET2 that is both necessary and sufficient to induce the oncogenic proinflammatory features of mTET2 in vivo. We also elucidate the mechanism by which mTET2 upregulate MALAT1 and describe an interaction between MALAT1 and p65, which leads to RNA “shielding” from protein phosphatase 2A dephosphorylation, thus preventing resolution of inflammatory signaling.

Significance:
This work identifies MALAT1 as a requisite downstream effector of oncogenic feedforward inflammatory circuits necessary for the development of TET2-mutated CH and fulminant myeloid malignancy. We elucidate a novel mechanism by which MALAT1 “shields” p65 from dephosphorylation to potentiate this circuit and nominate MALAT1 inhibition as a future therapeutic strategy.