bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro
potentiation of tetracyclines in
Pseudomonas aeruginosa
by RW01, a new cyclic peptide
Authors: Roson-Calero Natalia , Gomis Font María A. , Ruiz-Soriano Albert , Just-Baringo Xavier , Pachón-Ibáñez María Eugenia , Salvador J. Pablo , Marco M. Pilar , Giralt Ernest , Oliver Antonio , Ballesté-Delpierre Clara , Vila Jordi 
Published: December 2024

ABSTRACT

The pipeline for new drugs against multidrug-resistant
Pseudomonas aeruginosa
remains limited, highlighting the urgent need for innovative treatments. New strategies, such as membrane-targeting molecules acting as adjuvants, aim to enhance antibiotic effectiveness and combat resistance. RW01, a cyclic peptide with low antimicrobial activity, was selected as an adjuvant to enhance drug efficacy through membrane permeabilization. RW01’s activity was evaluated via antimicrobial susceptibility testing in combination with existing antibiotics on 10
P. aeruginosa
strains and analog synthesis. Synergy was assessed using checkerboard assays, and one-step mutants were generated to identify altered pathways through whole-genome sequencing and variant analysis. Permeabilizing activity was studied using flow cytometry and real-time fluorescence measurement.
In vivo
toxicity was assessed in female C57BL/6J mice, and possible interaction with mouse serum was also evaluated. Susceptibility testing revealed specific synergy with tetracyclines, with up to a 16-fold reduction in minimum inhibitory concentrations. Sequencing revealed that resistance to the RW01-minocycline combination involved mutations in the
pmrB
gene, affecting outer membrane lipopolysaccharide composition. This was further confirmed by the identification of cross-resistance to colistin in these mutants. RW01 reduced the mutant prevention concentration of minocycline from 64 to 8 mg/L. RW01 was demonstrated to enhance membrane permeabilization and therefore minocycline uptake with statistical significance. Synthetic derivatives of RW01 showed a complete loss of activity, highlighting the importance of RW01’s D-proline(NH2) residue. No acute or cumulative
in vivo
toxicity was observed in mice. These findings suggest that RW01 could revitalize obsolete antimicrobials and potentially expand therapeutic options against multidrug-resistant
P. aeruginosa
.
About bacteriophage tail terminator and tail completion proteins: structure of the proximal extremity of siphophage T5 tail
Authors: Linares Romain , Breyton Cécile 
Published: December 2024

ABSTRACT

Bacteriophages are viruses infecting bacteria. The vast majority of them bear a tail, allowing host recognition, cell wall perforation, and DNA injection into the host cytoplasm. Using electron cryo-microscopy (cryo-EM) and single particle analysis, we determined the organization of the tail proximal extremity of siphophage T5 that possesses a long flexible tail and solved the structure of its tail terminator protein p142 (TrP
142
). It allowed us to confirm the common evolutionary origin between T5 TrP
p142
and other known or putative TrPs from siphophages, myophages, and bacterial tail-like machines, despite very poor sequence conservation. By also determining the structure of the T5 tail proximal extremity after interaction with T5 bacterial receptor FhuA, we showed that no conformational changes occur in TrP
p142
and confirmed that the infection signal transduction is not carried by the tube itself. We also investigated the location of T5 Neck1 or tail completion protein p143 (TCP
p143
) and showed, thanks to a combination of cryo-EM and structure prediction using Alphafold2, that it is not located at the capsid-to-tail interface as suggested by its position in the genome, but instead, very unexpectedly, on the side of T5 tail tip, and that it appears to be monomeric. Based on structure comparison with other putative TCPs predicted structures, this feature could not be shared by other TCPs and questions the affiliation of p143 to this family of protein.

IMPORTANCE
Bacteriophages, viruses infecting bacteria, are the most abundant living entities on Earth. They are present in all ecosystems where bacteria develop and are instrumental in the regulation, diversity, evolution, and pathogeny of microbial populations. Moreover, with the increasing number of pathogenic strains resistant to antibiotics, virulent phages are considered a serious alternative or complement to classical treatments. 96% of all phages present a tail that allows host recognition and safe channeling of the DNA to the host cytoplasm. We present the atomic model of the proximal extremity of the siphophage T5 tail, confirming structural similarities with other phages. This structure, combined with results previously published and further explored, also allowed a review and a discussion on the role and localization of a mysterious tail protein, the tail completion protein, which is known to be present in the phage tails, but that was never identified in a phage structure.
The Mla pathway promotes
Vibrio cholerae
re-expansion from stationary phase
Authors: Leitner Deborah R. , Zingl Franz G. , Morano Alexander A. , Zhang Hailong , Waldor Matthew K. 
Published: December 2024

ABSTRACT

Bacteria have evolved diverse strategies to ensure survival under nutrient-limited conditions, where rapid energy generation is not achievable. Here, we performed a transposon insertion site sequencing loss-of-function screen to identify
Vibrio cholerae
genes that promote pathogen fitness in stationary phase. We discovered that the
m
aintenance of
l
ipid
a
symmetry (Mla) pathway, which is crucial for transferring phospholipids from the outer to the inner membrane, is critical for stationary phase fitness. Competition experiments with barcoded and fluorophore labeled wild-type (WT) and
mlaE
mutant
V. cholerae
revealed that the Mla pathway promotes re-expansion from 48 h stationary phase cultures. The mutant defect in transitioning out of stationary phase into active growth (culturability) was also observed in monocultures at 48 h. However, by 96 h the culturability of the WT and mutant strains were equivalent. By monitoring the abundances of genomically barcoded libraries of WT and ∆
mlaE
strains, we observed that a few barcodes dominated the mutant culture at 96 h, suggesting that the similarity of the population sizes at this time was caused by expansion of a subpopulation containing a mutation that suppressed the defect of ∆
mlaE
. Whole genome sequencing revealed that
mlaE
suppressors inactivated flagellar biosynthesis. Additional mechanistic studies support the idea that the Mla pathway is critical for maintaining the culturability of
V. cholerae
because it promotes energy homeostasis, likely due to its role in regulating outer membrane vesicle shedding. Together our findings provide insights into the cellular processes that control re-expansion from stationary phase and demonstrate a previously undiscovered role for the Mla pathway.

IMPORTANCE

Bacteria regularly encounter conditions with nutrient scarcity, where cell growth and division are minimal. Knowledge of the pathways that enable re-growth following nutrient restriction is limited. Here, using the cholera pathogen, we uncovered a role for the Mla pathway, a system that enables phospholipid re-cycling, in promoting
Vibrio cholerae
re-expansion from stationary phase cultures. Cells labeled with DNA barcodes or fluorophores were useful to demonstrate that though the abundances of wild-type and Mla mutant cells were similar in stationary phase cultures, they had marked differences in their capacities to regrow on plates. Of note, Mla mutant cells lose cell envelope components including high-energy phospholipids due to OMV shedding. Our findings suggest that the defects in cellular energy homeostasis that emerge in the absence of the Mla pathway underlie its importance in maintaining
V. cholerae
culturability.
Antimicrobial peptide LL37 is potent against non-growing
Escherichia coli
cells despite a slower action rate
Authors: Mohammadi Salimeh , Saucedo Derek , Taheri-Araghi Sattar 
Published: December 2024

ABSTRACT

Antimicrobial peptides (AMPs) have long been considered as potential agents against non-growing, dormant cells due to their membrane-targeted action, which is largely independent of the cell’s growth state. However, the relationship between the action of AMPs and the physiological state of their target cells has been unclear, with recent reports offering conflicting views on the efficacy of AMPs against bacteria in a stationary phase. In this study, we employ single-cell approaches combined with population-level experiments to examine the action of human LL37 peptides against
Escherichia coli
cells in different growth phases. Time-lapse, single-cell data from our experiments reveal that LL37 peptides act faster on large, dividing cells than on small, newborn cells. We extend this investigation to non-growing
E. coli
cells in a stationary phase, where we observe that the action of LL37 peptides is slower on non-growing cells compared to exponentially growing cells. This slower action rate is, however, not mirrored in the minimum bactericidal concentration (MBC) measurements. Notably, we find that the MBC for non-growing cells is lower than for exponentially growing cells, indicating that, given sufficient time, LL37 peptides exhibit strong potency against non-growing cells. We propose that the enhanced potency of LL37 peptides against non-growing cells, despite their slower action, can be attributed to continuous absorption of AMPs on the cell membrane over time.

IMPORTANCE

Antibiotic treatments can fail because of the regrowth of a bacterial subpopulation that resumes proliferation once the treatment ceases. This resurgence is primarily driven by non-growing, dormant bacterial cells that withstand the action of antibiotics without developing resistance. In this study, we explore the potency of the human antimicrobial peptide LL37 against non-growing
Escherichia coli
cells. Our findings reveal that despite a slower initial action, LL37 peptides, given sufficient time, demonstrate strong efficacy against non-growing cells. These insights suggest a potential role of antimicrobial peptides in combating persistent bacterial infections by targeting the non-growing cells.
SCovid v2.0: a comprehensive resource to decipher the molecular characteristics across tissues in COVID-19 and other human coronaviruses
Authors: Zhu Zijun , Chen Xinyu , He Guoyou , Yu Rui , Wang Chao , Qi Changlu , Cheng Liang 
Published: December 2024

ABSTRACT

SCovid v2.0 (
http://bio-annotation.cn/scovid
or
http://bio-computing.hrbmu.edu.cn/scovid/
) is an updated database designed to assist researchers in uncovering the molecular characteristics of coronavirus disease 2019 (COVID-19) across various tissues through transcriptome sequencing. Compared with its predecessor, SCovid v2.0 is enhanced with comprehensive data, practical functionalities, and a reconstructed pipeline. The current release includes (i) 3,544,360 cells from 45 single-cell RNA-seq (scRNA-seq) data sets encompassing 789 samples from 15 tissues; (ii) the addition of 62 COVID-19 bulk RNA-seq data comprising 1,688 samples from 12 tissues; (iii) incorporation of seven bulk RNA-seq data sets related to other human coronaviruses, such as HCoV-229E, HCoV-OC43, and MERS-CoV for a thorough comparative analysis of pan-coronavirus mechanisms in COVID-19; and (iv) systematic comparisons between the data sets conducted using standardized procedures. Furthermore, we have developed an advanced search engine and upgraded web interface to browse, search, visualize, and download detailed information. Overall, SCovid v2.0 is a valuable resource for exploring molecular characteristics of COVID-19 across different tissues.

IMPORTANCE
This manuscript provides a comprehensive analysis of the molecular characteristics of COVID-19 through cross-tissue transcriptome analysis, contributing to the understanding of COVID-19 by clinicians and scientists. Considering the cyclical nature of coronavirus outbreaks, this updated database adds transcriptome data on other human coronaviruses, contributing to potential and existing mechanisms of other human coronaviruses.
Listeria monocytogenes
use multiple mechanisms to disseminate from the intestinal lamina propria to the mesenteric lymph nodes
Authors: Nowacki Joshua S. , Jones Grant S. , D'Orazio Sarah E. F. 
Published: December 2024

ABSTRACT

Listeria monocytogenes
are facultative intracellular bacterial pathogens that cause foodborne disease in humans. The bacteria can use the surface protein InlA to invade intestinal epithelial cells or transcytose across M cells in the gut, but it is not well understood how the bacteria traffic from the underlying lamina propria to the draining mesenteric lymph nodes (MLN). Previous studies indicated that
L. monocytogenes
associated with both monocytes and dendritic cells in the intestinal lamina propria. We show here that CCR2
−/−
mice had a significant reduction in Ly6C
hi
monocytes in the MLN but no change in bacterial burden following foodborne infection; thus, dissemination of
L. monocytogenes
associated with monocytes is not required for colonization of the MLN. To block CCR7-mediated trafficking of dendritic cells from the lamina propria, we treated mice with anti-VEGFR3 antibody (clone AFL4) prior to and during infection but did not see a change in dendritic numbers in the MLN as had been previously reported with other anti-VEGFR3-specific antibodies. However, increasing the number of circulating dendritic cells by treating mice with rFlt3L resulted in a significant increase in
L. monocytogenes
in the lymph nodes that drain the small intestine and the spleen. Whole-mount fluorescent microscopy of lymphatic vessels following ligated loop infection revealed both free-floating
L. monocytogenes
and cell-associated bacteria within lymphatic vessels. Together, these results suggest that
L. monocytogenes
can use multiple, redundant mechanisms to disseminate from the gut tissue to the MLN.

IMPORTANCE

Consumption of the foodborne bacterial pathogen
Listeria monocytogenes
results in a wide spectrum of human disease from mild self-limiting gastroenteritis to life-threatening infections of the bloodstream, brain, and placenta. It is not well understood how the bacteria migrate from the intestines to the draining mesenteric lymph nodes, which are thought to serve as the last barrier to prevent systemic infections. Results presented here reveal multiple redundant mechanisms
L. monocytogenes
can use to disseminate from the ileum or colon to the mesenteric lymph nodes.
Tri-vector deformations with external fluxes
Authors: Barakin Sergei , Gubarev Kirill , Musaev Edvard T. 
Published: December 2024

Abstract
We extend the formalism of tri-vector deformations to the full SL(5) exceptional field theory with no truncation assumed thus covering 11D backgrounds of any form. We derive explicit transformation rules for 11D supergravity component fields and prove that these generate solutions given the same algebraic conditions hold: generalized Yang–Baxter equation and the unimodularity condition.
Testing the molecular nature of the $$\Omega (2012)$$ with the $$\psi (3770) \rightarrow \bar{\Omega } \bar{K} \Xi $$ and $$\psi (3770) \rightarrow \bar{\Omega } \bar{K} \Xi ^*(1530) (\bar{\Omega } \bar{K} \pi \Xi )$$ reactions
Authors: Song Jing , Liang Wei-Hong , Xiao Chu-Wen , Dias Jorgivan Morais , Oset Eulogio 
Published: December 2024

Abstract
We report on the reactions

$$\psi (3770)\rightarrow \bar{\Omega }^+ \bar{K} \Xi $$

ψ

(
3770
)

→

Ω

¯

+

K

¯

Ξ

and

$$\psi (3770)\rightarrow \bar{\Omega }^+ \bar{K}\Xi ^*(1530) \;(\Xi ^*(1530)\rightarrow \pi \Xi $$

ψ

(
3770
)

→

Ω

¯

+

K

¯

Ξ
∗

(
1530
)

(

Ξ
∗

(
1530
)

→
π
Ξ

), and calculate the mass distributions

$$\frac{\textrm{d}\Gamma }{\textrm{d}M_\text {inv}(\bar{K}\Xi )}$$

d
Γ

d

M
inv

(

K

¯

Ξ
)

and

$$\frac{\textrm{d}\Gamma }{\textrm{d}M_\text {inv}(\bar{K}\Xi ^*)}$$

d
Γ

d

M
inv

(

K

¯

Ξ
∗

)

, respectively. We obtain clear peaks corresponding to the

$$\Omega (2012)$$

Ω
(
2012
)

. From the decay of

$$\psi (3770)\rightarrow \bar{\Omega }^+ \bar{K}\Xi ^*$$

ψ

(
3770
)

→

Ω

¯

+

K

¯

Ξ
∗

, we also get a second, broader, peak around

$$2035\,\mathrm MeV$$

2035

M
e
V

, which comes from the

$$\Omega (2012)$$

Ω
(
2012
)

decay to

$$\bar{K}\Xi ^*$$

K

¯

Ξ
∗

. This second peak is closely tied to the molecular picture of the

$$\Omega (2012)$$

Ω
(
2012
)

with the

$$\bar{K}\Xi ^*(1530)$$

K

¯

Ξ
∗

(
1530
)

and

$$\eta \Omega $$

η
Ω

components. Its observation would provide a boost to the molecular picture of the

$$\Omega (2012)$$

Ω
(
2012
)

.
The Efficacy and Tolerability of Prostaglandin Analogues in Treating Systemic Sclerosis‐Associated Raynaud Phenomenon: A Systematic Review and Meta‐Analysis
Authors: Alahmari Hana , Jazayeri Hila , Johnson Sindhu R. 
Published: December 2024

Background: Systemic sclerosis‐associated Raynaud phenomenon (SSc‐RP) confers poor outcomes, including ulceration, gangrene, autoamputation, and hand disability. Prostaglandin analogues (PG) are a group of prostacyclin‐derived drugs with properties that may address underlying complex mechanisms of SSc‐RP. This systematic review and meta‐analysis evaluated the efficacy and tolerability of PGs in SSc‐RP.Methods: We systematically reviewed randomized control trials (RCTs) evaluating PG use in SSc‐RP. The primary outcome was the severity of RP attacks. The secondary outcomes were the frequency and duration of RP attacks, healing of digital ulcers, development of new digital ulcers, change of capillary blood flow, patient health‐reported outcome measure (PROM‐VAS), and tolerability.Results: Eleven RCTs were included, reporting a total of n = 1081 individuals with SSc. PG confers a beneficial effect on RP severity in the short‐term, weighted Mean difference (WMD) −0.63 (95% CI −0.99, −0.27, I2 0%), with no difference in tolerability compared to placebo OR 1.88 (95% CI 1.00, 3.55, I2 = 1%). PG has nonsignificant trends towards improvement in RP frequency WMD of −0.32 (95% CI −0.76, 0.13, I2 = 0%), RP duration WMD −4.78 (95% CI −14.69, 5.14, I2 = 1%), PROM‐VAS WMD −4.81 (95% CI −11.31, 1.69, I2 = 67%), and new or recurrent digital ulcers OR 0.92 (95% CI 0.48, 1.76, I2 = 34%).Conclusion: PGs are beneficial in the short term to reduce the RP severity and are tolerable. Larger, adequately powered trials are needed for higher certainty evidence across SSc‐RP outcomes.
Sex Differences in Participation and Performance Trends in Time‐Limited Ultramarathon Events
Authors: Thuany Mabliny , Gomes Thayse Natacha , Villiger Elias , Nikolaidis Pantelis T. , Scheer Volker , Weiss Katja , Rosemann Thomas , Knechtle Beat 
Published: December 2024

Aim: We aimed to analyze sex differences in time‐limited ultramarathon participation, while also identifying trends in participation, age, and performance across different formats of events, from 1990 to 2020.Method: This is an exploratory study, using data obtained from the official event web pages. We downloaded information regarding the year of the event, athletes’ year of birth, sex, race event, ranking, and mean running speed (km/h). The sex gap in participation was presented through equiplots. Regression models were fitted to analyze trends in participation, age, and performance, considering a 95% confidence interval.Results: A similar pattern of increase in participation and age was shown for athletes of both sexes until 2019. The sex gap remained, displaying different patterns across race events. A general trend of slower mean running speeds was shown. The random‐effects analysis showed that sex and age played significant roles in the performance trajectory across the years, in each race event.Conclusions: Apart from the 8‐day race among females, there was a decline in the performance across all race durations. Despite the trend of performance decline, future studies need to address the relevance of this decline in both theoretical and practical terms.
Robust Pronoun Fidelity with English LLMs: Are they Reasoning, Repeating, or Just Biased?
Authors: Gautam Vagrant , Bingert Eileen , Zhu Dawei , Lauscher Anne , Klakow Dietrich 
Published: December 2024

Abstract
Robust, faithful, and harm-free pronoun use for individuals is an important goal for language model development as their use increases, but prior work tends to study only one or two of these characteristics at a time. To measure progress towards the combined goal, we introduce the task of pronoun fidelity: Given a context introducing a co-referring entity and pronoun, the task is to reuse the correct pronoun later. We present RUFF, a carefully designed dataset of over 5 million instances to measure robust pronoun fidelity in English, and we evaluate 37 model variants from nine popular families, across architectures (encoder-only, decoder-only, and encoder-decoder) and scales (11M-70B parameters). When an individual is introduced with a pronoun, models can mostly faithfully reuse this pronoun in the next sentence, but they are significantly worse with she/her/her, singular they, and neopronouns. Moreover, models are easily distracted by non-adversarial sentences discussing other people; even one sentence with a distractor pronoun causes accuracy to drop on average by 34 percentage points. Our results show that pronoun fidelity is not robust, in a simple, naturalistic setting where humans achieve nearly 100% accuracy. We encourage researchers to bridge the gaps we find and to carefully evaluate reasoning in settings where superficial repetition might inflate perceptions of model performance.
Loneliness in older persons with schizophrenia
Authors: Patterson Tess , Sajjadi Fatemeh , Hobbs Linda , Barak Yoram 
Published: December 2024

Background: In tandem with the rise in numbers of older adults in the general population, more people with schizophrenia (PwS) are also living longer. This vulnerable population has several trajectories of ageing driven by a number of social determinants of health, including the experience of loneliness and they may be more at risk of experiencing loneliness. Aim: This study aimed to examine demographic, psychosocial and clinical variables and their relative contribution to the loneliness of older PwS (OPwS) in a large New Zealand community sample. Method: New Zealanders 65 years and older who completed their first interRAI assessment during the study period were included. Data from 1,883 OPwS participants was analysed [mean age, 75.1 + 7.7 years; 1,132 (60.3%) females]. The majority were of European ethnicity (64.8%; Māori 15.7%, Pacifica 5.7%) and only a minority were married (20.6%). Chi-square analysis was used to examine relationships between loneliness and demographic and psychosocial variables. Logistic regression was used to measure the relative contribution of these variables to loneliness. Results: Being lonely was reported for 25.9% of OPwS, a significantly higher rate than that reported in the general population of people over 65 years-of-age. A relationship with loneliness was found for marital status, depression and living arrangements but not gender, ethnicity or social engagement. Co-morbid depression and not being in a marital-type partnership were identified as significant predictors of being lonely. Conversely, living with someone predicted being not lonely. Conclusions: Older community dwelling PwS experience higher rates of loneliness than older adults in a general population. Addressing loneliness, as well as its correlates, co-morbid depressive symptoms and living arrangements, is crucial to supporting the wellbeing of OPwS.