bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-assembling a 1,4-dioxane-degrading consortium and identifying the key role of
Shinella
sp. through dilution-to-extinction and reculturing
Authors: Tian Kun , Zhang Yue , Chen Ruihuan , Tan Ding , Zhong Ming , Yao Dandan , Dong Yuanhua , Liu Yun 
Published: October 2023

ABSTRACT

Assembling a functional consortium and identifying novel degraders from contaminated environments are still challenging due to the large diversity of microorganisms and the difficulty in isolating pure cultures. Here, we constructed a relatively simple functional consortium by enriching 1,4-dioxane-degrading-consortia using a culture-dependent dilution-to-extinction (DTE) method and reported a new key dioxane-degrader
Shinella
sp. Our results showed that serial dilution and reculture led to a divergence in the degradation ability of each consortium. Next-generation sequencing data revealed that the divergence in degradation performance was due to the reassembly of microbiota in the DTE process, which occurred most notably in 10
−8
and 10
−9
dilutions. The shift in community structure at 10
−9
prevented the recovery of 1,4-dioxane degradation capacity, and the newly dominant taxa,
Xanthobacter
and
Acinetobacter
, struggled to replace the original dominant genus
Shinella
for 1,4-dioxane biodegradation. Combining differential analysis of community structure and metabolic function, we confirmed that
Shinella
species have a stronger 1,4-dioxane degradation ability than
Xanthobacter
species in the enriched consortium. In addition, we verified our findings using our isolated dioxane-degrading bacteria,
Shinella yambaruensis
, resulting in the rapid recovery of degradation performance of a 10
−9
dilution consortium with
Xanthobacter
and
Acinetobacter
as the dominant microbiota. Taken together, this study provides a strategy for self-assembling functional consortiums and identifying the key degraders to explore the underlying biological mechanisms of enriched contaminant-degrading consortia.

IMPORTANCE

Assembling a functional microbial consortium and identifying key degraders involved in the degradation of 1,4-dioxane are crucial for the design of synergistic consortia used in enhancing the bioremediation of 1,4-dioxane-contaminated sites. However, due to the vast diversity of microbes, assembling a functional consortium and identifying novel degraders through a simple method remain a challenge. In this study, we reassembled 1,4-dioxane-degrading microbial consortia using a simple and easy-to-operate method by combining dilution-to-extinction and reculture techniques. We combined differential analysis of community structure and metabolic function and confirmed that Shinella species have a stronger 1,4-dioxane degradation ability than Xanthobacter species in the enriched consortium. In addition, a new dioxane-degrading bacterium was isolated,
Shinella yambaruensis
, which verified our findings. These results demonstrate that DTE and reculture techniques can be used beyond diversity reduction to assemble functional microbial communities, particularly to identify key degraders in contaminant-degrading consortia.
A novel
TRIM22
gene polymorphism promotes the response to PegIFNα therapy through cytokine-cytokine receptor interaction signaling pathway in chronic hepatitis B
Authors: Wang Long , Lin Ni , Zhang Yanfang , Guo Shaoying , Liu Can , Lin Caorui , Zeng Yongbin , Wu Wennan , Guo Jianhui , Zhu Chenggong , Zhan Fuguo , Ou Qishui , Xun Zhen 
Published: October 2023

ABSTRACT

Objectives: Pegylated interferon alfa (PegIFNα) has limited efficacy in patients with chronic hepatitis B (CHB). Because single-nucleotide polymorphisms (SNPs) are known to confer disease susceptibility and influence treatment response, we aimed to identify novel tripartite motif-containing 22 (TRIM22) SNPs that were associated with therapeutic efficacy in patients with CHB after PegIFNα treatment. Samples from 107 patients with CHB were genotyped using Asian Screening Array gene chips. The related mechanisms of SNPs screened were explored through both cell experiments and RNA sequence methods.
TRIM22
was the most upregulated upon stimulation with PegIFNα. Specifically, the SNP rs10838543 CC genotype in
TRIM22
was found to be associated with the positive response to PegIFNα treatment. The SNP rs10838543 CC genotype in
TRIM22
was more stable and more robustly inhibited hepatitis B virus (HBV) replication in HepAD38 cells compared to the TT genotype. Mechanistically, we showed that the cytokine-cytokine receptor interaction signaling pathway was significantly upregulated in HepAD38 cells stably expressing the SNP rs10838543 CC genotype of
TRIM22
compared to the TT genotype after PegIFNα treatment and that the SNP rs10838543 CC genotype in
TRIM22
enhanced PegIFNα-induced anti-HBV activity by inducing the secretion of IFNL1, CCL3, and CCL5. The SNP rs10838543 CC genotype in
TRIM22
increased the secretion of the cytokines IFNL1, CCL3, and CCL5 from hepatocytes by regulating the cytokine-cytokine receptor interaction signaling pathway and was positively correlated with the PegIFNα-induced treatment response in patients with CHB. Our findings suggest that genotyping patients with CHB for the SNP rs10838543 in
TRIM22
may be a useful biomarker to help physicians identify patients who are most likely to benefit from PegIFNα treatment.

IMPORTANCE
Pegylated interferon alfa (PegIFNα) has limited efficacy in the treatment of chronic hepatitis B (CHB). Although many biomarkers related to hepatitis B virus (HBV) have been proposed to stratify patients, the response rate to PegIFNα is still unsatisfactory. Herein, our data suggest that the single-nucleotide polymorphism (SNP) rs10838543 in TRIM22 potentiates a positive clinical response to PegIFNα treatment in patients with hepatitis B e antigen-positive CHB by increasing the levels of IFNL1, CCL3, and CCL5. These observations can help guide treatment decisions for patients with CHB to improve the response rate to PegIFNα.
Resistance mechanisms for Gram-negative bacteria-specific lipopeptides, turnercyclamycins, differ from that of colistin
Authors: Lim Albebson L. , Miller Bailey W. , Lin Zhenjian , Fisher Mark A. , Barrows Louis R. , Haygood Margo G. , Schmidt Eric W. 
Published: October 2023

ABSTRACT

Turnercyclamycin A and B lipopeptides exhibit Gram-negative bacteria-specific toxicity. This includes CDC urgent threat organisms such as multidrug-resistant
Acinetobacter baumannii
. Like the last-line agent colistin, turnercyclamycins interact with the lipopolysaccharide (LPS) pathway, but they remain active against clinical isolates that are colistin resistant. Here, we aimed to determine why turnercyclamycins A and B show little cross-resistance with colistin despite some potential mechanistic and structural similarities. The outer membrane was important in the actions of all three agents, since the deletion of
lpxC
that synthesizes LPS and the addition of exogenous LPS led to resistance to turnercyclamycins and colistin. Even so, it was much more difficult to generate resistance to turnercyclamycin A than turnercyclamycin B. In
Escherichia coli
, disruption of the
mlaA
gene, which is involved in outer membrane homeostasis, resulted in resistance to turnercyclamycin B. However,
mlaA
disruption blocked neither turnercyclamycin A nor colistin activity. This activity was recapitulated in
A. baumannii
, where transposon mutants were more resistant to turnercyclamycin B. Moreover, the common
A. baumannii
colistin resistance gene
mcr-1
blocked colistin activity in
E. coli
but did not affect turnercyclamycins. These results demonstrate a unique resistance profile for turnercyclamycins A and B, in addition to suggesting differences in the mechanism of action. Further, turnercyclamycin A was effective in a mouse model of
A. baumannii
infection, indicating that this compound class may have potential promise in treating drug-resistant infections.

IMPORTANCE

Bacterial resistance to antibiotics is a crisis.
Acinetobacter baumannii
is among the CDC urgent threat pathogens in part for this reason. Lipopeptides known as turnercyclamycins are produced by symbiotic bacteria that normally live in marine mollusks, where they may be involved in shaping their symbiotic niche. Turnercyclamycins killed Gram-negative pathogens including drug-resistant
Acinetobacter
, but how do the mechanisms of resistance compare to other lipopeptide drugs? Here, we define resistance from a truncation of MlaA, a protein involved in regulating bacterial membrane phospholipids. Intriguingly, this resistance mechanism only affected one turnercyclamycin variant, which differed only in two atoms in the lipid tail of the compounds. We could not obtain significant resistance to the second turnercyclamycin variant, which was also effective in an infection model. This study reveals an unexpected subtlety in resistance to lipopeptide antibiotics, which may be useful in the design and development of antibiotics to combat drug resistance.
Broad-range capsule-dependent lytic
Sugarlandvirus
against
Klebsiella
sp.
Authors: Concha-Eloko Robby , Barberán-Martínez Pilar , Sanjuán Rafael , Domingo-Calap Pilar 
Published: October 2023

ABSTRACT

The emergence of antibiotic-resistant bacteria has become a serious global health threat requiring the development of novel treatments.
Klebsiella pneumoniae
is an encapsulated bacterium considered a major concern due to its high resistance, prevalence, and mortality rates. Phage therapy has been proposed as a very promising alternative to combat infections by
Klebsiella
sp. infections. However, most of the
Klebsiella
phages described so far present a high specificity, infecting one or a few capsular types due to the presence of depolymerases in their genomes, which limits their therapeutic potential. Here, we present three new
Klebsiella
phages isolated from the environment, vB_Kpn_K7PH164C4, vB_Kpn_K30λ2.2, and vB_Kpl_K32PH164C1, belonging to the family
Demerecviridae
and the genus
Sugarlandvirus
. The most important feature of these new
Klebsiella
phages is their broad host range, especially vB_Kpn_K7PH164C4 and vB_Kpn_K30λ2.2, which infects strains of more than 20 different capsular types, representing the broadest infection range observed for
Klebsiella
phages. Genomic analysis revealed the presence of three receptor-binding proteins lacking depolymerase domains. Nevertheless, capsule expression is suggested to be a determining factor in phage infectivity, despite the absence of depolymerase activity against capsular components. Our findings hold potential for the development of promising phage-based therapeutics directed against
K. pneumoniae
.

IMPORTANCE

The emergence of multi-drug resistant bacteria is a global health problem. Among them,
Klebsiella pneumoniae
is considered a high-priority pathogen, making it necessary to develop new therapeutic tools to reduce the bacterial burden in an effective and sustainable manner. Phages, bacterial viruses, are very promising tools. However, phages are highy specific, rendering large-scale therapeutics costly to implement. This is especially certain in
Klebsiella
, a capsular bacterium in which phages have been shown to be capsular type dependent, infecting one or a few capsular types through specific enzymes called depolymerases. In this study, we have isolated and characterized novel phages with lytic ability against bacteria from a wide variety of capsular types, representing the
Klebsiella
phages with the widest range of infection described. Remarkably, these broad-range phages showed capsule dependency, despite the absence of depolymerases in their genomes, implying that infectivity could be governed by alternative mechanisms yet to be uncovered.
No evidence for a volcanic trigger for late Cambrian carbon-cycle perturbations
Authors: Frieling J. , Mather T.A. , Fendley I.M. , Jenkyns H.C. , Zhao Z. , Dahl T.W. , Bergquist B.A. , Cheng K. , Nielsen A.T. , Dickson A.J. 
Published: October 2023

Abstract
The early Paleozoic was marked by several carbon-cycle perturbations and associated carbon-isotope excursions (CIEs). Whether these CIEs are connected to significant (external) triggers, as is commonly considered to be the case for CIEs in the Mesozoic and Cenozoic, or result from small carbon-cycle imbalances that became amplified through lack of efficient silicate weathering or other feedbacks remains unclear. We present concentration and isotope data for sedimentary mercury (Hg) and osmium (Os) to assess the impact of subaerial and submarine volcanism and weathering during the late Cambrian and early Ordovician. Data from the Alum Shale Formation (Sweden) cover the Steptoean positive carbon-isotope excursion (SPICE; ca. 497–494 Ma), a period marked by marine anoxia and biotic overturning, and several smaller CIEs extending into the early Ordovician. Our Hg and Os data offer no strong evidence that the CIEs present in our record were driven by (globally) elevated volcanism or continental weathering. Organic-carbon and Hg concentrations covary cyclically, providing further evidence of an unperturbed Hg cycle. Mesozoic and Cenozoic CIEs are commonly linked to enhanced volcanic activity and weathering, but similar late Cambrian–early Ordovician events cannot easily be connected to such external triggers. Our results are more consistent with reduced early Paleozoic carbon-cycle resilience that allowed small imbalances to develop into large CIEs.
Clumped isotope evidence for microbial alteration of thermogenic methane in terrestrial mud volcanoes
Authors: Liu Jiarui , Treude Tina , Abbasov Orhan R. , Baloglanov Elnur E. , Aliyev Adil A. , Harris Carolynn M. , Leavitt William D. , Young Edward D. 
Published: October 2023

Abstract
Methane in oil reservoirs originates mostly from thermogenic sources, yet secondary microbial methane production from petroleum biodegradation is known to be pervasive. The conventional approach for identifying this secondary microbial methane commonly relies on geochemical characteristics of other gas molecules such as the carbon isotopic composition of carbon dioxide and propane. This information is sometimes obscured by isotopic variations in source material and may not be available in certain geological reservoirs. To better constrain the presence of secondary microbial methane, we studied the clumped isotopologue compositions of methane in terrestrial Azerbaijanian mud volcanoes, which support the occurrence of secondary microbial gas. Here, a deficit in Δ12CH2D2 of thermogenic methane occurs due to different δD of hydrogen sources that contribute to the formation of methane molecules (i.e., combinatorial effect). The Δ12CH2D2 is expected to move toward equilibrium as thermal maturity increases. More importantly, both Δ13CH3D and Δ12CH2D2 values of methane approach low-temperature thermodynamic equilibrium in most gases, suggesting that the original thermogenic methane has been altered by newly formed microbial methane in addition to isotope exchange among methane molecules catalyzed by the methyl-coenzyme M reductase enzyme. We conclude that methane clumped isotopes provide a unique proxy for identifying secondary microbial methane and understanding the exact evolution stages for natural gases.
Healthcare professionals’ perspectives of the provision of, and challenges for, eating, drinking and psychological support post stroke: findings from semistructured interviews across India
Authors: Jones Stephanie P , Injety Ranjit J , Pandian Jeyaraj D , Ratra Sanjali , Sylaja PN , Babu Veena , Srivastava MV Padma , Sharma Sakshi , Sharma Sudhir , Webster Jemin , Koirala Amrit , Kaushal Pawna , Kulkarni Girish Baburao , Dixit Anand , Sharma Arvind , Prajapati Jagruti , Weldon Jo Catherine , Kuroski Jennifer A , Watkins Caroline Leigh , Lightbody Catherine Elizabeth 
Published: October 2023

AimThis qualitative study explores with health professionals the provision of, and challenges for, postdischarge stroke care, focussing on eating, drinking and psychological support across India.DesignQualitative semistructured interviews.SettingSeven geographically diverse hospitals taking part in a Global Health Research Programme on Improving Stroke Care in India.ParticipantsA purposive sample of healthcare professionals with current experience of working with patients who had a stroke.ResultsInterviews with 66 healthcare professionals (23 nurses (14 staff nurses; 7 senior nurse officers; 1 intensive care unit nurse; 1 palliative care nurse)); 16 doctors (10 neurologists; 6 physicians); 10 physiotherapists; 5 speech and language therapists; 4 occupational therapists; 4 dieticians; 2 psychiatrists; and 2 social workers resulted in three main themes: integrated inpatient discharge care planning processes; postdischarge patient and caregiver role and challenges; patient and caregiver engagement post discharge.ConclusionsDischarge planning was integrated and customised, although resources were limited in some sites. Task shifting compensated for a lack of specialists but was limited by staff education and training. Caregivers faced challenges in accessing and providing postdischarge care. Postdischarge care was mainly hospital based, supported by teleservices, especially for rural populations. Further research is needed to understand postdischarge care provision and the needs of stroke survivors and their caregivers.
MCT4 blockade increases the efficacy of immune checkpoint blockade
Authors: Babl Nathalie , Decking Sonja-Maria , Voll Florian , Althammer Michael , Sala-Hojman Ada , Ferretti Roberta , Korf Clarissa , Schmidl Christian , Schmidleithner Lisa , Nerb Benedikt , Matos Carina , Koehl Gudrun E , Siska Peter , Bruss Christina , Kellermeier Fabian , Dettmer Katja , Oefner Peter J , Wichland Marvin , Ugele Ines , Bohr Christopher , Herr Wolfgang , Ramaswamy Shivapriya , Heinrich Timo , Herhaus Christian , Kreutz Marina , Renner Kathrin 
Published: October 2023

Background & AimsIntratumoral lactate accumulation and acidosis impair T-cell function and antitumor immunity. Interestingly, expression of the lactate transporter monocarboxylate transporter (MCT) 4, but not MCT1, turned out to be prognostic for the survival of patients with rectal cancer, indicating that single MCT4 blockade might be a promising strategy to overcome glycolysis-related therapy resistance.MethodsTo determine whether blockade of MCT4 alone is sufficient to improve the efficacy of immune checkpoint blockade (ICB) therapy, we examined the effects of the selective MCT1 inhibitor AZD3965 and a novel MCT4 inhibitor in a colorectal carcinoma (CRC) tumor spheroid model co-cultured with blood leukocytes in vitro and the MC38 murine CRC model in vivo in combination with an antibody against programmed cell death ligand-1(PD-L1).ResultsInhibition of MCT4 was sufficient to reduce lactate efflux in three-dimensional (3D) CRC spheroids but not in two-dimensional cell-cultures. Co-administration of the MCT4 inhibitor and ICB augmented immune cell infiltration, T-cell function and decreased CRC spheroid viability in a 3D co-culture model of human CRC spheroids with blood leukocytes. Accordingly, combination of MCT4 and ICB increased intratumoral pH, improved leukocyte infiltration and T-cell activation, delayed tumor growth, and prolonged survival in vivo. MCT1 inhibition exerted no further beneficial impact.ConclusionsThese findings demonstrate that single MCT4 inhibition represents a novel therapeutic approach to reverse lactic-acid driven immunosuppression and might be suitable to improve ICB efficacy.
Using qualitative free-text data to investigate the lived experience of the COVID-19 pandemic for a large cohort of Australians with different multiple sclerosis related disability levels
Authors: Campbell Julie A , van der Mei Ingrid , Taylor Bruce V , Palmer Andrew J , Henson Glen J , Laslett Laura Louise , Simpson-Yap Steve , Claflin Suzi B 
Published: October 2023

BackgroundNo large-scale qualitative studies have investigated the lived experience of people living with multiple sclerosis (PwMS) during the pandemic according to their disability level. We used qualitative research methods to investigate the lived experience of a large cohort of Australians living with differing multiple sclerosis (MS)-related disability levels during the COVID-19 pandemic. We also provided useful contextualisation to existing quantitative work.MethodsThis was a retrospective survey-based mixed-methods cohort study. A quality-of-life study was conducted within the Australian MS Longitudinal Study during the pandemic. Disability severity was calculated using the Patient Determined Disease Steps. Qualitative free-text data regarding COVID-19 impacts was collected/analysed for word frequency and also thematically (inductively/deductively using sophisticated grounded theory) using NVivo software. We also triangulated word frequency with emerging themes.ResultsN=509 PwMS participated providing n=22 530 words of COVID-19-specific data. Disability severity could be calculated for n=501 PwMS. The word ‘working’ was important for PwMS with no disability, and ‘support’ and ‘isolation’ for higher disability levels. For PwMS with milder disability, thematic analysis established that multitasking increased stress levels, particularly if working from home (WFH) and home-schooling children. If not multitasking, WFH was beneficial for managing fatigue. PwMS with severe disability raised increased social isolation as a concern including prepandemic isolation.ConclusionsWe found negative impacts of multitasking and social isolation for PwMS during the pandemic. WFH was identified as beneficial for some. We recommend targeted resourcing decisions for PwMS in future pandemics including child-care relief and interventions to reduce social isolation and suggest that these could be incorporated into some form of advanced care planning. As the nature of work changes postpandemic, we also recommend a detailed investigation of WFH for PwMS including providing tailored employment assistance.
Boosting new physics searches in $$t{\bar{t}}Z$$ and tZj production with angular moments
Authors: Abraham Roshan Mammen , Gonçalves Dorival 
Published: October 2023

AbstractThe angular moments of the Z boson can be used as analyzers for the underlying production dynamics for the $$t{{\bar{t}}} Z$$

t

t

¯

Z

and tZj processes. In this manuscript, we derive these angular moments at leading and next-to-leading order in QCD at the LHC. We show that these observables work as efficient probes to beyond the Standard Model effects, considering the Standard Model Effective Field theory framework. Remarkably, we observe that these probes unveil blind directions to CP-odd operators, providing sizable new physics sensitivity at the 14 TeV LHC with 3 ab$$^{-1}$$

-
1

of data.