bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epistasis, core-genome disharmony, and adaptation in recombining bacteria
Authors: Taylor Aidan J. , Yahara Koji , Pascoe Ben , Ko Seungwon , Mageiros Leonardos , Mourkas Evangelos , Calland Jessica K. , Puranen Santeri , Hitchings Matthew D. , Jolley Keith A. , Kobras Carolin M. , Bayliss Sion , Williams Nicola J. , van Vliet Arnoud H. M. , Parkhill Julian , Maiden Martin C. J. , Corander Jukka , Hurst Laurence D. , Falush Daniel , Keim Paul , Didelot Xavier , Kelly David J. , Sheppard Samuel K. 
Published: April 2024

ABSTRACT

Recombination of short DNA fragments via horizontal gene transfer (HGT) can introduce beneficial alleles, create genomic disharmony through negative epistasis, and create adaptive gene combinations through positive epistasis. For non-core (accessory) genes, the negative epistatic cost is likely to be minimal because the incoming genes have not co-evolved with the recipient genome and are frequently observed as tightly linked cassettes with major effects. By contrast, interspecific recombination in the core genome is expected to be rare because disruptive allelic replacement is likely to introduce negative epistasis. Why then is homologous recombination common in the core of bacterial genomes? To understand this enigma, we take advantage of an exceptional model system, the common enteric pathogens
Campylobacter jejuni
and
C. coli
that are known for very high magnitude interspecies gene flow in the core genome. As expected, HGT does indeed disrupt co-adapted allele pairings, indirect evidence of negative epistasis. However, multiple HGT events enable recovery of the genome’s co-adaption between introgressing alleles, even in core metabolism genes (e.g., formate dehydrogenase). These findings demonstrate that, even for complex traits, genetic coalitions can be decoupled, transferred, and independently reinstated in a new genetic background—facilitating transition between fitness peaks. In this example, the two-step recombinational process is associated with
C. coli
that are adapted to the agricultural niche.

IMPORTANCE

Genetic exchange among bacteria shapes the microbial world. From the acquisition of antimicrobial resistance genes to fundamental questions about the nature of bacterial species, this powerful evolutionary force has preoccupied scientists for decades. However, the mixing of genes between species rests on a paradox: 0n one hand, promoting adaptation by conferring novel functionality; on the other, potentially introducing disharmonious gene combinations (negative epistasis) that will be selected against. Taking an interdisciplinary approach to analyze natural populations of the enteric bacteria
Campylobacter
, an ideal example of long-range admixture, we demonstrate that genes can independently transfer across species boundaries and rejoin in functional networks in a recipient genome. The positive impact of two-gene interactions appears to be adaptive by expanding metabolic capacity and facilitating niche shifts through interspecific hybridization. This challenges conventional ideas and highlights the possibility of multiple-step evolution of multi-gene traits by interspecific introgression.
Complete genome sequence of
Pseudomonas canadensis
strain Pcan-CK-23 isolated from
Zophobas morio
larvae
Authors: Kundlacz Cindy , Aldeia Claudia , Eddoubaji Yasmine , Campos-Madueno Edgar I. , Endimiani Andrea 
Published: April 2024

ABSTRACT

We present the complete genome sequence of
Pseudomonas canadensis
. The strain (Pcan-CK-23) was isolated from
Zophobas morio
(superworm) larvae. The genome consisted of a 6,424,469 bp chromosome with a GC content of 60.3% and 5,973 genes. Pcan-CK-23 can be used as a reference genome for further studies with
P. canadensis
.
Whole-genome sequence of the plant-associated bacterium
Pseudomonas granadensis
CT364 isolated in Seville, Spain
Authors: Cea-Torrescassana Eva , Howard Thomas P. , Stach Jem , Montero-Calasanz Maria del Carmen 
Published: April 2024

ABSTRACT

Pseudomonas
sp. CT364 was isolated from olive tree rhizosphere in Seville (Spain). We report its complete genome sequence, acquired by co-assembling Illumina and Nanopore reads. The genome comprises a circular chromosome of 6.2 Mbp and a G + C content of 60.0%. Taxonomic analyses confirmed it to be
Pseudomonas granadensis
.
Draft genome sequence of
Magnusiomyces
sp. LA-1 isolated from a C6-C8 acid-producing bioreactor
Authors: Gemeinhardt Kurt , Park Hyojung , Won Jong In , Lee Jin Hyung , Hwang Ee Taek , Angenent Largus T. , Jeon Byoung Seung 
Published: April 2024

ABSTRACT

Here, we report the draft genome of
Magnusiomyces
sp. LA-1, which was isolated from a C6-C8 carboxylic acid-producing bioreactor. The draft genome of
Magnusiomyces
sp. LA-1 is 19,829,165 bp in length, is divided into six contigs that comprise 6,557 CDS regions, and has a GC content of 34.5%.
The EH domain-containing protein, EdeA, is involved in endocytosis, cell wall integrity, and pathogenicity in
Aspergillus fumigatus
Authors: Dai Mengyao , Liu Xintian , Goldman Gustavo H. , Lu Ling , Zhang Shizhu 
Published: April 2024

ABSTRACT

Endocytosis has been extensively studied in yeasts, where it plays crucial roles in growth, signaling regulation, and cell-surface receptor internalization. However, the biological functions of endocytosis in pathogenic filamentous fungi remain largely unexplored. In this study, we aimed to functionally characterize the roles of EdeA, an ortholog of the
Saccharomyces cerevisiae
endocytic protein Ede1, in
Aspergillus fumigatus
. EdeA was observed to be distributed as patches on the plasma membrane and concentrated in the subapical collar of hyphae, a localization characteristic of endocytic proteins. Loss of
edeA
caused defective hyphal polarity, reduced conidial production, and fewer sites of endocytosis initiations than that of the parental wild type. Notably, the
edeA
null mutant exhibited increased sensitivity to cell wall-disrupting agents, indicating a role for EdeA in maintaining cell wall integrity in
A. fumigatus
. This observation was further supported by the evidence showing that the thickness of the cell wall in the Δ
edeA
mutant increased, accompanied by abnormal activation of MpkA, a key component in the cell wall integrity pathway. Additionally, the Δ
edeA
mutant displayed increased pathogenicity in the
Galleria mellonella
wax moth infection model, possibly due to alterations in cell wall morphology. Site-directed mutagenesis identified the conserved residue E348 within the third EH (
E
ps15
h
omology) domain of EdeA as crucial for its subcellular localization and functions. In conclusion, our results highlight the involvement of EdeA in endocytosis, hyphal polarity, cell wall integrity, and pathogenicity in
A. fumigatus
.

IMPORTANCE

Aspergillus fumigatus
is a significant human pathogenic fungus known to cause invasive aspergillosis, a disease with a high mortality rate. Understanding the basic principles of
A. fumigatus
pathogenicity is crucial for developing effective strategies against this pathogen. Previous research has underscored the importance of endocytosis in the infection capacity of pathogenic yeasts; however, its biological function in pathogenic mold remains largely unexplored. Our characterization of EdeA in
A. fumigatus
sheds light on the role of endocytosis in the development, stress response, and pathogenicity of pathogenic molds. These findings suggest that the components of the endocytosis process may serve as potential targets for antifungal therapy.
Effects of short-term nitrogen and phosphorus addition on soil bacterial community of different halophytes
Authors: Zhang Zehao , Wang Lijie , Li Tian , Fu Zhanyong , Sun Jingkuan , Hu Rui , Zhang Yao 
Published: April 2024

ABSTRACT

Soil microbial community composition and diversity are often affected by nutrient enrichment, which may influence soil microbes to affect nutrient cycling and plant community structure. However, the response of soil bacteria to nitrogen (N) and phosphorus (P) addition and whether it is influenced by plants remains unclear. By 16S rRNA sequencing, we investigated the response of the rhizosphere and bulk soil bacterial communities of different halophytes (salt-rejecting, salt-absorbing, and salt-secreting plant) in the Yellow River Delta to short-term N and P addition. The response of rhizosphere bacterial diversity to N and P addition was opposite in
Phragmites communis
and
Suaeda salsa
. N addition increased the rhizosphere soil bacterial α-diversity of
S. salsa
and
Aeluropus sinensis
, while P addition decreased the rhizosphere bacterial α-diversity bacteria of
S. salsa
. The N and P addition had a weak effect on the rhizosphere bacterial community composition and a significant effect on the bulk soil bacterial community composition of halophytes. The
S. salsa
and
P. communis
bulk soil bacterial community were mainly influenced by P addition, while it was influenced by N addition in
A. sinensis
. N and P addition reduced the difference in bacterial community composition between the two types of soil. N and P addition increased the eutrophic taxa (
Proteobacteria
and
Bacteroidetes
) and decreased the oligotrophic taxa (
Acidobacteria
). Redundancy analysis showed that soil organic matter, salt, and total N content had significant effects on the bacterial community composition. The results clarify that the response of soil bacterial communities to N and P additions is inconsistent across the three halophyte soils, and the effect of plant species on the bacterial community was stronger than short-term N and P addition.

IMPORTANCE
The bulk soil bacterial community was more affected by nutrient addition. Nitrogen (N) and phosphorus (P) have different effects on bacterial community. Soil organic matter is a key factor influencing the response of bacterial community to nutrient addition. N and P influence on bacterial community changes with plants.
A library of reporters of the global regulators of gene expression in
Escherichia coli
Authors: Dash Suchintak , Jagadeesan Rahul , Baptista Ines S. C. , Chauhan Vatsala , Kandavalli Vinodh , Oliveira Samuel M. D. , Ribeiro Andre S. 
Published: April 2024

ABSTRACT

The topology of the transcription factor network (TFN) of
Escherichia coli
is far from uniform, with 22 global regulator (GR) proteins controlling one-third of all genes. So far, their production rates cannot be tracked by comparable fluorescent proteins. We developed a library of fluorescent reporters for 16 GRs for this purpose. Each consists of a single-copy plasmid coding for green fluorescent protein (GFP) fused to the full-length copy of the native promoter. We tracked their activity in exponential and stationary growth, as well as under weak and strong stresses. We show that the reporters have high sensitivity and specificity to all stresses tested and detect single-cell variability in transcription rates. Given the influence of GRs on the TFN, we expect that the new library will contribute to dissecting global transcriptional stress-response programs of
E. coli
. Moreover, the library can be invaluable in bioindustrial applications that tune those programs to, instead of cell growth, favor productivity while reducing energy consumption.

IMPORTANCE

Cells contain thousands of genes. Many genes are involved in the control of cellular activities. Some activities require a few hundred genes to run largely synchronous transcriptional programs. To achieve this, cells have evolved global regulator (GR) proteins that can influence hundreds of genes simultaneously. We have engineered a library of
Escherichia coli
strains to track the levels over time of these, phenotypically critical, GRs. Each strain has a single-copy plasmid coding for a fast-maturing green fluorescent protein whose transcription is controlled by a copy of the natural GR promoter. By allowing the tracking of GR levels, with sensitivity and specificity, this library should become of wide use in scientific research on bacterial gene expression (from molecular to synthetic biology) and, later, be used in applications in therapeutics and bioindustries.
Comparison of rectal swabs and fecal samples for the detection of
Clostridioides difficile
infections with a new in-house PCR assay
Authors: Huletsky Ann , Loo Vivian G. , Longtin Yves , Longtin Jean , Trottier Sylvie , Tremblay Cécile L. , Gilca Rodica , Lavallée Christian , Brochu Éliel , Bérubé Ève , Bastien Martine , Bernier Marthe , Gagnon Martin , Frenette Johanne , Bestman-Smith Julie , Deschênes Louise , Bergeron Michel G. 
Published: April 2024

ABSTRACT

The detection of
Clostridioides difficile
infections (CDI) relies on testing the stool of patients by toxin antigen detection or PCR methods. Although PCR and antigenic methods have significantly reduced the time to results, delays in stool collection can significantly add to the turnaround time. The use of rectal swabs to detect
C. difficile
could considerably reduce the time to diagnosis of CDI. We developed a new rapid PCR assay for the detection of
C. difficile
and evaluated this PCR assay on both stool and rectal swab specimens. We recruited a total of 623 patients suspected of
C. difficile
infection. Stool samples and rectal swabs were collected from each patient and tested by our PCR assay. Stool samples were also tested by the cell cytotoxicity neutralization assay (CCNA) as a reference. The PCR assay detected
C. difficile
in 60 stool specimens and 61 rectal swabs for the 64 patients whose stool samples were positive for
C. difficile
by CCNA. The PCR assay detected an additional 35 and 36 stool and rectal swab specimens positive for
C. difficile
, respectively, for sensitivity with stools and rectal swabs of 93.8% and 95.3%, specificity of 93.7% and 93.6%, positive predictive values of 63.2% and 62.9%, and negative predictive values of 99.2% and 99.4%. Detection of
C. difficile
using PCR on stools or rectal swabs yielded reliable and similar results. The use of PCR tests on rectal swabs could reduce turnaround time for CDI detection, thus improving CDI management and control of
C. difficile
transmission.

IMPORTANCE

Clostridioides difficile
infection (CDI) is the leading cause of healthcare-associated diarrhea, resulting in high morbidity, mortality, and economic burden. In clinical laboratories, CDI testing is currently performed on stool samples collected from patients with diarrhea. However, the diagnosis of CDI can be delayed by the time required to collect stool samples. Barriers to sample collection could be overcome by using a rectal swab instead of a stool sample. Our study showed that CDI can be identified rapidly and reliably by a new PCR assay developed in our laboratory on both stool and rectal swab specimens. The use of PCR tests on rectal swabs could reduce the time for the detection of CDI and improve the management of this infection. It should also provide a useful alternative for infection-control practitioners to better control the spread of
C. difficile
.
What is the role of out of programme clinical fellowships in the era of Shape of Training? A single-centre cohort study
Authors: Raju Suneil A , Bowker-Howell Freya J , Aziz Imran , Thoufeeq Mo , Lobo Alan J , Gleeson Dermot C , Al-Joudeh Amer , McAlindon Mark E , Hopper Andrew D , Kumar Sampath , Sidhu Reena , Sanders David S 
Published: April 2024

BackgroundThe updated Shape of Training curriculum has shortened the duration of specialty training. We present the potential role of out of programme clinical fellowships.MethodAn electronic online survey was sent to all current fellows to understand their experiences, training opportunities and motivations.Data were collected on fellows’ endoscopic experiences and publications using PubMed for all previous doctors who have completed the Sheffield Fellowship Programme.ResultsSince 2004, 39 doctors have completed the Sheffield Fellowship.Endoscopic experience: current fellows completed a median average of 350 (IQR 150–500) gastroscopies and 150 (IQR 106–251) colonoscopies per year. Fellows with special interests completed either 428 hepato-pancreato-biliary procedures or 70 endoscopic mucosal resections per year.Medline publications: Median average 9 publications(IQR 4–17). They have also received multiple national or international awards and 91% achieved a doctoral degree.The seven current fellows in the new Shape of Training era (57% male, 29% Caucasian, aged 31–40 years) report high levels of enjoyment due to their research projects, supervisory teams and social aspects. The most cited reasons for undertaking the fellowship were to develop a subspecialty interest, take time off the on-call rota and develop endoscopic skills. The most reported drawback was a reduced income.All current fellows feel that the fellowship has enhanced their clinical confidence and prepared them to become consultants.ConclusionOut of programme clinical fellowships offer the opportunity to develop the required training competencies, subspecialty expertise and research skills in a supportive environment.
Rapid diagnostic test: a critical need for outbreak preparedness and response for high priority pathogens
Authors: Yimer Solomon Abebe , Booij Birgitte Boonstra , Tobert Gwen , Hebbeler Andrew , Oloo Paul , Brangel Polina , L'Azou Jackson Maïna , Jarman Richard , Craig Danielle , Avumegah Michael Selorm , Mandi Henshaw , Endy Timothy , Wooden Stacey , Clark Carolyn , Bernasconi Valentina , Shurtleff Amy , Kristiansen Paul A 
Published: April 2024

Rapid diagnostic tests (RDTs) are critical for preparedness and response against an outbreak or pandemic and have been highlighted in the 100 Days Mission, a global initiative that aims to prepare the world for the next epidemic/pandemic by driving the development of diagnostics, vaccines and therapeutics within 100 days of recognition of a novel Disease X threat.RDTs play a pivotal role in early case identification, surveillance and case management, and are critical for initiating deployment of vaccine and monoclonal antibodies. Currently available RDTs, however, have limited clinical sensitivity and specificity and inadequate validation. The development, validation and implementation of RDTs require adequate and sustained financing from both public and private sources. While the World Health Assembly recently passed a resolution on diagnostic capacity strengthening that urges individual Member States to commit resources towards this, the resolution is not binding and implementation will likely be impeded by limited financial resources and other competing priorities, particularly in low-income countries. Meanwhile, the diagnostic industry has not sufficiently invested in RDT development for high priority pathogens.Currently, vaccine development projects are getting the largest funding support among medical countermeasures. Yet vaccines are insufficient tools in isolation, and pandemic preparedness will be incomplete without parallel investment in diagnostics and therapeutics.The Pandemic Fund, a global financing mechanism recently established for strengthening pandemic prevention, preparedness and response, may be a future avenue for supporting diagnostic development.In this paper, we discuss why RDTs are critical for preparedness and response. We also discuss RDT investment challenges and reflect on the way forward.
Association between daily step counts and healthy life years: a national cross-sectional study in Japan
Authors: Nishi Masahiro , Nagamitsu Reo , Matoba Satoaki 
Published: April 2024

BackgroundDespite accumulating evidence concerning the association between daily step counts and mortality or disease risks, it is unclear whether daily step counts are associated with healthy life years.MethodsWe used the combined dataset of the Comprehensive Survey of Living Conditions and the National Health and Nutrition Survey conducted for a randomly sampled general population in Japan, 2019. Daily step counts were measured for 4957 adult participants. The associations of daily step counts with activity limitations in daily living and self-assessed health were evaluated using a multivariable logistic regression model. The bootstrap method was employed to mitigate uncertainties in estimating the threshold of daily step counts.ResultsThe median age was 60 (44–71) years, and 2592 (52.3%) were female. The median daily step counts were 5650 (3332–8452). The adjusted OR of activity limitations in daily living for the adjacent daily step counts was 0.27 (95% CI 0.26 to 0.27) for all ages and 0.25 (95% CI 0.25 to 0.26) for older adults at the lowest, with the thresholds of significant association at 9000 step counts. The OR of self-assessed unhealthy status was 0.45 (95% CI 0.44 to 0.46) for all ages and 0.42 (95% CI 0.41 to 0.43) for older adults at the lowest, with the thresholds at 11 000 step counts.ConclusionDaily step counts were significantly associated with activity limitations in daily living and self-assessed health as determinants of healthy life years, up to 9000 and 11 000 step counts, respectively. These results suggest a target of daily step counts to prolong healthy life years within health initiatives.
Rationale and design of OPtimising thERapy to prevent Avoidable hospital
admissions in Multimorbid older people (OPERAM): a cluster randomised
controlled trial
Authors: Adam Luise , Moutzouri Elisavet , Baumgartner Christine , Loewe Axel Lennart , Feller Martin , M’Rabet-Bensalah Khadija , Schwab Nathalie , Hossmann Stefanie , Schneider Claudio , Jegerlehner Sabrina , Floriani Carmen , Limacher Andreas , Jungo Katharina Tabea , Huibers Corlina Johanna Alida , Streit Sven , Schwenkglenks Matthias , Spruit Marco , Van Dorland Anette , Donzé Jacques , Kearney Patricia M , Jüni Peter , Aujesky Drahomir , Jansen Paul , Boland Benoit , Dalleur Olivia , Byrne Stephen , Knol Wilma , Spinewine Anne , O’Mahony Denis , Trelle Sven , Rodondi Nicolas 
Published: April 2024

Introduction
Multimorbidity and polypharmacy are important risk factors for
drug-related hospital admissions (DRAs). DRAs are often linked to
prescribing problems (overprescribing and underprescribing), as well as
non-adherence with drug regimens for different reasons. In this trial,
we aim to assess whether a structured medication review compared with
standard care can reduce DRAs in multimorbid older patients with
polypharmacy.

Methods and analysis
OPtimising thERapy to prevent Avoidable hospital admissions in
Multimorbid older people is a European multicentre, cluster randomised,
controlled trial. Hospitalised patients ≥70 years with ≥3 chronic
medical conditions and concurrent use of ≥5 chronic medications are
included in the four participating study centres of Bern (Switzerland),
Utrecht (The Netherlands), Brussels (Belgium) and Cork (Ireland).
Patients treated by the same prescribing physician constitute a cluster,
and clusters are randomised 1:1 to either standard care or Systematic
Tool to Reduce Inappropriate Prescribing (STRIP) intervention with the
help of a clinical decision support system, the STRIP Assistant. STRIP
is a structured method performing customised medication reviews, based
on Screening Tool of Older People’s Prescriptions/Screening  Tool to
Alert to Right Treatment criteria to detect potentially inappropriate
prescribing. The primary endpoint is any DRA where the main reason or a
contributory reason for the patient’s admission is caused by
overtreatment or undertreatment, and/or inappropriate treatment.
Secondary endpoints include number of any hospitalisations, all-cause
mortality, number of falls, quality of life, degree of polypharmacy,
activities of daily living, patient’s drug compliance, the number of
significant drug–drug interactions, drug overuse and underuse and
potentially inappropriate medication.

Ethics and dissemination
The local Ethics Committees in Switzerland, Ireland, The Netherlands
and Belgium approved this trial protocol. We will publish the results of
this trial in a peer-reviewed journal.

Main funding
European Union’s Horizon 2020 programme.

Trial registration number
NCT02986425,
NCT000002183,NCT6012,
U1111-1181-9400.