bluuebunny/crossref_metadata_2025 huggingface dataset:
Necropolitics Narratives and Disposition of Lives in Sport Spectacle: Negotiating the Death of Mexican Boxer Jeanette Zacarías Zapata in Quebec’s Sport/Media Landscape
Authors: Sirois-Moumni Bachir , Lavoie-Moore Myriam
Published: December 2024

This study critically examines Quebec sports media narratives surrounding the death of Mexican boxer Jeanette Zacarías Zapata to interrogate how mortality is negotiated within the Quebec boxing sport/media landscape. Applying the concepts of necropolitics and necrocapitalism, we analyze how media narratives divide those who can/cannot die, rendering certain lives disposable, particularly precarious boxers within unequal circuits. We contextualize the boxing industry’s organization and analyze media coverage of Zacarías Zapata’s passing, which demonstrates how narratives construct characters and resolution of a story, isolating mortality through a distorted morality in which death would constitute a failure of certain groups of people or even certain individuals rather than a structural problem of the sport spectacle of boxing in Quebec.
Lactose-assimilating yeasts with high fatty acid accumulation uncovered by untargeted bioprospecting
Authors: Persson Karl , Onyema Vanessa O. , Nwafor Ijeoma Princess , Peri Kameshwara V. R. , Otti Chika , Nnaemeka Priscilla , Onyishi Chioma , Okoye Sylvia , Moneke Anene , Amadi Onyetugo , Warringer Jonas , Geijer Cecilia
Published: December 2024

Bioprospecting can uncover new yeast strains and species with interesting ecological characteristics and valuable biotechnological traits, such as the capacity to convert different carbon sources from industrial side and waste streams into bioproducts. In this study, we conducted untargeted yeast bioprospecting in tropical West Africa, collecting 1,996 isolates and determining their growth in 70 different environments. While the collection contains numerous isolates with the potential to assimilate several cost-effective and sustainable carbon and nitrogen sources, we focused on characterizing the 203 strains capable of growing on lactose, the main carbon source in the abundant side stream cheese whey from dairy industries. Through internal transcribed spacer sequencing of the lactose-assimilating strains, we identified 30 different yeast species from both the
Ascomycota
and
Basidiomycota
phyla, of which several have not previously been shown to grow on lactose, and some are candidates for new species. Observed differences in growth and ratios of intra- and extracellular lactase activities suggest that the yeasts use a range of different strategies to metabolize lactose. Notably, several basidiomycetous yeasts, including
Apiotrichum mycotoxinivorans
,
Papiliotrema laurentii
, and
Moesziomyces antarcticus
, accumulated lipids up to 40% of their cell dry weight, proving that they can convert lactose into a bioproduct of significant biotechnology interest.

IMPORTANCE

This study paves the way to a better understanding of the natural yeast biodiversity in the largely under-sampled biodiversity hotspot area of tropical West Africa. Our discovery of several yeasts capable of efficiently converting lactose into lipids underscores the value of bioprospecting to identify yeast strains with significant biotechnological potential, which can aid the transition to a circular bioeconomy. Furthermore, the extensive strain collection gathered will facilitate future screening and the development of new cell factories.
Bacillus safensis
APC 4099 has broad-spectrum antimicrobial activity against both bacteria and fungi and produces several antimicrobial peptides, including the novel circular bacteriocin safencin E
Authors: Kamilari E. , O'Connor P. M. , Farias F. Miceli de , Johnson C. N. , Buttimer C. , Deliephan A. , Hill D. , Fursenko O. , Wiese J. , Stanton C. , Hill C. , Ross R. P.
Published: December 2024

Bacillus safensis
APC 4099, isolated from bees’ gut, has been identified as a promising candidate for food biopreservation. Antimicrobial activity screening revealed a broad-spectrum inhibition potential, ranging from gram-positive pathogenic bacteria to fungi responsible for food spoilage. Genomic analysis identified biosynthetic gene clusters coding for several antimicrobial peptides and secondary metabolites. Specifically, a novel, anionic, 6 kDa circular bacteriocin, named safencin E, was detected, showing 52.5% similarity to butyrivibriocin AR10. Additionally, gene clusters coding for the biosynthesis of bacteriocins such as pumilarin and plantazolicin and biosynthetic pathways for secondary metabolites, including pumilacidin A, bacilysin, and bacillibactin, were identified. Matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis detected molecular masses correlating to safencin E, plantazolicin, pumilarin, and pumilacidin A from the cell-free supernatant, cell extracts, or both. Overall, the broad-spectrum antimicrobial activity of
B. safensis
APC 4099 indicates that this strain is a promising candidate for the biological control of food ecosystems and thus has the potential to enhance food safety.

IMPORTANCE

The present article highlights the importance of the strain
Bacillus safensis
APC 4099 as a potential biocontrol agent. The strain possesses biosynthetic gene clusters coding for various antimicrobial peptides and secondary metabolites, including a novel circular bacteriocin, safencin E, and the bacteriocins pumilarin and plantazolicin. This diversity in the production of antimicrobial peptides renders the producer with broad-spectrum antimicrobial activity, ranging from gram-positive pathogenic and spoilage bacteria to spoilage molds. Considering that 1.3 billion tons of food appropriate for human consumption is lost or wasted annually, identifying strains or novel antimicrobial peptides capable of biopreservation is highly relevant. This strain and its bioactive compounds offer a solution to this global problem as biocontrol agents for food ecosystems against spoilage and pathogenic microbes.
RecA deletion disrupts protein homeostasis, leading to deamidation, oxidation, and impaired glycolysis in
Cronobacter sakazakii
Authors: Lu Ping , Xue Juan , Ji Xuemeng
Published: December 2024

Cronobacter sakazakii
is a foodborne pathogen linked to severe infections in infants and often associated with contaminated powdered infant formula. The RecA protein, a key player in DNA repair and recombination, also influences bacterial resilience and virulence. This study investigated the impact of
recA
deletion on the pathogenicity and environmental stress tolerance of
C. sakazakii
BAA-894. A
recA
knockout mutant displayed impaired growth, desiccation tolerance, and biofilm formation. In a rat model, the mutant demonstrated significantly reduced virulence evidenced by higher host survival rates and lower bacterial loads in blood and tissues compared to the wild-type strain. Proteomic analysis revealed extensive disruptions in protein expression, particularly downregulation of carbohydrate metabolism and respiration-related proteins, alongside increased protein deamidation and oxidation. Functional assays identified fructose-bisphosphate aldolase as a target of oxidative and deamidative damage, resulting in reduced enzymatic activity and glycolytic disruption. These findings highlight the critical role of RecA in maintaining protein homeostasis, environmental resilience, and pathogenicity in
C. sakazakii
, providing valuable insights for developing targeted interventions against this pathogen.

IMPORTANCE

Cronobacter sakazakii
poses significant risks due to its ability to persist in low-moisture environments and cause severe neonatal infections. This study identifies RecA as a key factor in environmental resilience and virulence, making it a promising target for mitigating infections and contamination. Inhibiting RecA function could sensitize
C. sakazakii
to stress during production and sterilization processes, reducing its persistence in powdered infant formula. Future research on RecA-specific inhibitors may lead to innovative strategies for enhancing food safety and preventing infections caused by this pathogen.
A multicenter performance evaluation of cefiderocol MIC results: ComASP in comparison to CLSI broth microdilution
Authors: Koeth L. M. , DiFranco-Fisher J. M. , Palavecino E. , Kilic A. , Hardy D. , Vicino D. , Stracquadanio S. , Stefani S.
Published: December 2024

The performance of the Liofilchem Compact Antimicrobial Susceptibility Panel (ComASP) Cefiderocol was evaluated in a multicenter study. Enterobacterales,
Acinetobacter baumannii
, and
Pseudomonas aeruginosa
clinical isolates and challenge isolates were tested by three and one sites, respectively. Minimum inhibitory concentration (MIC) testing was performed by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution and ComASP, which included two reading endpoints (CLSI read; MIC is the first well in which reduction of growth is <1 mm or light haze/faint turbidity] and ComASP [ComASP read; MIC is the first well at which 100% inhibition of growth occurs]). Each site performed reproducibility and quality control (QC) by ComASP and broth microdilution (BMD). Reproducibility was excellent (97.4% within ±1 dilution of modal MIC). All QC results were within CLSI QC ranges by BMD and ComASP, except for two
E. coli
ATCC 25922 results from one site. Essential agreement for combined clinical and challenge Enterobacterales was 84.3% (CLSI read) and 95.7% (ComASP read),
P. aeruginosa
was 83.3% (CLSI read) and 93.7% (ComASP read), and
A. baumannii
was 78.3% (CLSI read) and 96.7% (ComASP read). Categorical agreement for Enterobacterales was 92.4% for both CLSI read and ComASP read, for
P. aeruginosa
was 89.7% (CLSI read) and 92.1% (ComASP read), and for
A. baumannii
was 72.8% (CLSI read) and 91.3% (ComASP read). There were no very major errors using the ComASP read. One very major error for
P. aeruginosa
occurred using the CLSI read method. Three very major errors for
A. baumannii
occurred using the CLSI read method. ComASP Cefiderocol was shown to be a reliable method for testing cefiderocol MIC against relevant clinical isolates when ComASP read is used.

IMPORTANCE

There are very limited commercial methods available to clinical laboratories for cefiderocol minimum inhibitory concentration (MIC) testing. The Compact Antimicrobial Susceptibility Panel (ComASP) Cefiderocol method includes iron-depleted cation-adjusted Mueller–Hinton broth, which eliminates variability in cefiderocol MIC results based on iron levels. The lyophilized multi-well format of ComASP also provides for room temperature storage. In comparison to what an individual lab may do for method verification, this multi-site, multi-isolate study provides a robust evaluation and greater assurance to clinical microbiologists of the method's accurate and reproducible performance.
High-sensitivity detection of
Mycobacterium tuberculosis
DNA in tongue swab samples
Authors: Olson Alaina M. , Wood Rachel C. , Weigel Kris M. , Yan Alexander J. , Lochner Katherine A. , Dragovich Rane B. , Luabeya Angelique K. , Yager Paul , Hatherill Mark , Cangelosi Gerard A.
Published: December 2024

Tongue swab (TS) sampling combined with quantitative PCR (qPCR) to detect
Mycobacterium tuberculosis
(MTB) DNA is a promising alternative to sputum testing for tuberculosis (TB) diagnosis. In prior studies, the sensitivity of tongue swabbing has usually been lower than sputum. In this study, we evaluated two strategies to improve sensitivity. In one, centrifugation was used to concentrate tongue dorsum bacteria from 2-mL suspensions eluted from high-capacity foam swab samples. The pellets were resuspended as 500-µL suspensions, and then mechanically lysed prior to dual-target qPCR to detect MTB insertion elements IS
6110
and IS
1081
. Fractionation experiments demonstrated that most of the MTB DNA signal in clinical swab samples (99.22% ± 1.46%) was present in the sedimentable fraction. When applied to archived foam swabs collected from 124 South Africans with presumptive TB, this strategy exhibited 83% sensitivity (71/86) and 100% specificity (38/38) relative to sputum microbiological reference standard (MRS; sputum culture and/or Xpert Ultra). The second strategy used sequence-specific magnetic capture (SSMaC) to concentrate DNA released from MTB cells. This protocol was evaluated on archived Copan FLOQSwabs flocked swab samples collected from 128 South African participants with presumptive TB. Material eluted into 500 µL buffer was mechanically lysed. The suspensions were digested by proteinase K, hybridized to biotinylated dual-target oligonucleotide probes, and then concentrated ~20-fold using magnetic separation. Upon dual-target qPCR testing of concentrates, this strategy exhibited 90% sensitivity (83/92) and 97% specificity (35/36) relative to sputum MRS. These results point the way toward automatable, high-sensitivity methods for detecting MTB DNA in TS.

IMPORTANCE

Improved testing for tuberculosis (TB) is needed. Using a more accessible sample type than sputum may enable the detection of more cases, but it is critical that alternative samples be tested appropriately. Here, we describe two new, highly accurate methods for testing tongue swabs for TB DNA.
Dengue and Zika virus NS4B proteins differ in topology and in determinants of ER membrane protein complex dependency
Authors: Porter Samuel S. , Gilchrist Talon M. , Schrodel Samantha , Tai Andrew W.
Published: December 2024

Flaviviruses utilize the cellular endoplasmic reticulum (ER) for all aspects of their lifecycle. Genome replication and other viral activities take place in structures called replication organelles (ROs), which are invaginations induced in the ER membrane. Among the required elements for RO formation is the biogenesis of viral nonstructural proteins NS4A and NS4B. We have previously shown that NS4A and NS4B from Dengue virus (DENV) and Zika virus (ZIKV) depend on the cellular ER membrane protein complex (EMC) for biogenesis. Here, we find that this dependency extends to the NS4A and NS4B proteins of Yellow Fever virus (YFV) and West Nile virus (WNV), which share similar computationally predicted membrane topologies. However, we demonstrate that ZIKV NS4B has different determinants of its dependency on the EMC than those for DENV NS4B, as well as a different membrane topology. Furthermore, we characterize mutant isolates of DENV and ZIKV that were serially passaged in EMC knockout cells and find that none are completely independent of the EMC for infection, and that mutant NS4B proteins remain sensitive to EMC depletion, suggesting a high genetic barrier to EMC depletion. Collectively, our findings are consistent with a model in which the EMC recognizes multiple determinants in the NS4B protein to support infection in several flaviviruses of critical public health importance.

IMPORTANCE

The NS4A and NS4B proteins of flaviviruses are critically important to replication, but little is known about their function. It has been previously reported that the cellular EMC supports the biogenesis of NS4A and NS4B from Dengue and Zika virus. In this work, we demonstrate that this dependency on the EMC for NS4A and NS4B biogenesis extends to the West Nile and Yellow Fever viruses. Furthermore, we examine the features of ZIKV NS4B and find that its membrane topology of ZIKV NS4B and its determinants of dependency on the EMC are different from those previously described in DENV NS4B. Finally, we present evidence that there is a high genetic barrier for Dengue and Zika viruses to overcome EMC depletion.
Induction of PD-1 and CD44 in CD4
+
T cells by circulatory extracellular vesicles from severe dengue patients drives endothelial damage via the NF-kB signaling pathway
Authors: Kumari Sharda , Biswas Ankit , Maiti Tushar Kanti , Bandyopadhyay Bhaswati , Banerjee Arup
Published: December 2024

Extracellular vesicles (EVs) emerged as critical contributors to the pathogenesis of vascular endothelial barrier dysfunction during the inflammatory response to infection. However, the contribution of circulating EVs to modifying endothelial function during dengue virus infection remains unclear. In this study, we showed that severe dengue patients’ plasma-derived EV (SD-EV) were found to carry elevated levels of different protein cargos, e.g., immunoregulatory proteins (PD-L1, CD44). Further, we demonstrated that SD-EV induces PD-1 and CD44 expression on CD4
+
T cells. SD-EV-modulated CD4
+
T (SD-EV-CD4) cells released secretome delayed endothelial cell (EC) migration, arrested them in the G1 phase, and augmented the expression of PD-L1 and ICAM-1 expression on EC through the Notch signaling pathway. Blocking SD-EV and CD4
+
T-cell interaction through the PD-1/PD-L1 pathway partially rescued the CD4
+
T cell’s effect on EC but did not alter ICAM-1 expression on EC. We observed that the ICAM-1 expression on EC and hyaluronic acid (HA) release from EC was mediated by CD44, which was elevated on SD-EV-modulated CD4
+
T cells (SD-EV-CD4), indicating a permeability defect. Blocking of CD44 on SD-EV-CD4 significantly reduced ICAM-1 expression on EC. Further, depletion of specific cytokines, e.g., TNF-α and not IFN-γ from the SD-EV-CD4 secretome, reduced ICAM-1 expression, decreased transendothelial electrical resistance, and induced apoptosis on EC significantly. Treatment with NF-kB inhibitor before secretome addition to EC reduced ICAM-1 expression on EC. In conclusion, we provided evidence that SD-EV-CD4 carrying PD-1 and CD44, when interacting with EC, significantly affected endothelial cell properties and may be significant in dengue-mediated endothelial dysfunction.

IMPORTANCE

Extracellular vesicles (EVs) are small membrane vesicles secreted into biological fluids, including plasma from living cells, holding insights into pathological processes. Studying EVs under pathological conditions is extremely important as they play a selective role in intercellular communication and modulation of immune response under diverse pathological conditions. However, there is less clarity on how circulatory extracellular vesicles influence immune cells during dengue virus (DV) infection and impact pathogenesis. Our present study highlights the impact of severe dengue patients’ plasma-derived EV (SD-EV) on CD4
+
T cells and together induce endothelial barrier dysfunction. We provided evidence that SD-EV induces PD-1 and CD44 on CD4
+
T cells and, when interacting with endothelial cells (EC), drives endothelial damage through direct interaction or secretome and may be significant in dengue-mediated endothelial dysfunction.
YBX1 is required for assembly of viral replication complexes of chikungunya virus and replication of multiple alphaviruses
Authors: Li Zhen-Qi , Zhao Li-Xin , Wang Su-Yun , Hu Chu-Yu , Wang Yan-Yi , Yang Yan
Published: December 2024

Chikungunya virus (CHIKV), an enveloped positive-sense RNA virus, is a member of the alphaviruses and cause fever and arthralgia in humans. We performed genome-wide CRISPR/Cas9-based screens and identified Y-box binding protein 1 (YBX1) as an essential cellular factor for CHIKV. Deficiency of YBX1 inhibited CHIKV RNA replication and impaired virus production. Upon CHIKV infection, YBX1 showed a striking re-localization to viral replication complexes (vRCs), where it co-localized with CHIKV nsP3 and dsRNA intermediates. YBX1 directly interacted with CHIKV nsP3, and mutation of the YBX1-binding motif in CHIKV nsP3 suppressed viral replication in host cells. Furthermore, YBX1 bound to viral RNA and increased the viral RNA-binding activity of CHIKV nsP3. Consistently, the RNA-binding activity of YBX1, as well as the ability of nsP3 to bind to YBX1, was required for efficient CHIKV replication. In addition to CHIKV, YBX1 was also essential for replication of all examined alphaviruses including the prototypic alphavirus. Our findings suggest that YBX1 acts as a scaffold for assembly of chikungunya vRCs and an important factor for replication of multiple alphaviruses, which may serve as a potential target for the development of anti-alphavirus therapies.

IMPORTANCE

Alphaviruses are a group of mosquito-transmitted, enveloped, positive-strand RNA viruses in the
Togaviridae
family. Most alphaviruses are important pathogens that continue to cause human disease ranging from severe and potentially fatal neurological disease to chronic arthritic disease on a global scale. Here, we found that YBX1 promotes binding of CHIKV genomic RNA to nsP3, which is a key component of the replication complex, and is therefore pivotal for CHIKV replication. Deficiency of YBX1 results in reduced replication of multiple alphaviruses, including arthritogenic and encephalitic alphaviruses. These findings suggest that YBX1 is an important cellular factor for multiple alphaviruses and a potential target for preventing alphavirus infections.
Discovery of small molecules against porcine reproductive and respiratory syndrome virus replication by targeting NendoU activity
Authors: Zhu Jiaqi , Lai Yunqiang , Cheng Mengqi , Dash Radha Charan , Guo Shuangshuang , Guo Jintong , Su Yue , Wolek Andrew , Issacs Brianna , Liu Zhenming , Li Qi , Mishra Neha , Garmendia Antonio , Hadden M. Kyle , Tian X. Cindy , He Xin , Tang Young
Published: December 2024

Porcine reproductive and respiratory syndrome (PRRS) remains a major threat to animal health and causes substantial economic losses worldwide. The nonstructural protein 11 (NSP11) of the causative agent, PRRS virus (PRRSV), contains a highly conserved nidoviral uridylate-specific endoribonuclease (NendoU) domain essential for viral replication and immune evasion. Targeting NSP11 offers a novel approach to antiviral intervention. Through
in silico
virtual screening followed by a fluorescence resonance energy transfer assay , we identified A8-A2 as a promising candidate that effectively inhibits NendoU activity. Molecular docking and mutational analysis revealed that A8-A2 and its analogs target the key catalytic residues His144 and Thr217 of NSP11, located within the NendoU enzyme activity loop and pocket region, respectively. A8-A2 demonstrated dose-dependent inhibition of PRRSV replication in porcine alveolar macrophages. Notably, the NendoU is conserved across PRRSV strains and other Nidoviruses, and A8-A2 exhibited antiviral activity against both type I and type II PRRSV strains, as well as the infectious bronchitis virus, a coronavirus in the order
Nidovirales
. Further investigations revealed that A8-A2 impedes viral replication early in infection and reverses NSP11-mediated suppression of Poly(I:C)-induced interferon production. However, this effect occurs independently of mRNA splicing inhibition. These findings indicate that A8-A2 could act as an effective antiviral agent against infections caused by diverse PRRSV strains and may serve as a broad-spectrum agent for other Nidoviruses.

IMPORTANCE

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the pig industry, and vaccination is the principal method to prevent this viral infection currently. However, vaccination often fails to provide protection against heterologous strains, highlighting the need for alternative strategies for broad protection. The nidoviral uridylate-specific endoribonuclease (NendoU) domain plays a crucial role in viral replication and evasion of host immune responses. In this study, we identified a group of new compounds with similar chemical structures that could interfere with NendoU enzyme activity. Among these compounds, A8-A2 significantly inhibited PRRSV replication in host cells with minimal cytotoxicity. Our findings provide a new direction for developing potent antiviral compounds that can offer broad protection against different PRRSV strains, thereby mitigating their impact on pig health and benefiting the husbandry industry.
Draft whole-genome sequence of
Enterococcus faecium
isolate from a clinical sample from Dhaka, Bangladesh
Authors: Towhid Syeda Tasneem , Shihab Md Maksudur Rahman , Jubair Mohammad , Faisal Naimul Islam , Rahman Md. Mustafizur
Published: December 2024

We collected a urine specimen from a 20-year-old male, cultured it on Chrom-agar
Enterococcus
, identified it with VITEK2, and whole-genome sequenced it using the PacBio RSII. The genome was 3,111,621 nucleotides long with a GC% of 37.6%. It was identified as a human pathogen with a 92.3% probability and is available on NCBI with an accession ID of
JBFBPS000000000.1
.
A novel robust network construction and analysis workflow for mining infant microbiota relationships
Authors: Jiang Wei , Zhai Yue , Chen Dongbo , Yu Qinghua
Published: December 2024

The gut microbiota plays a crucial role in infant health, with its development during the first 1,000 days influencing health outcomes. Understanding the relationships within the microbiota is essential to linking its maturation process to these outcomes. Several network-based methods have been developed to analyze the developing patterns of infant microbiota, but evaluating the reliability and effectiveness of these approaches remains a challenge. In this study, we created a test data pool using public infant microbiome data sets to assess the performance of four different network-based methods, employing repeated sampling strategies. We found that our proposed Probability-Based Co-Detection Model (PBCDM) demonstrated the best stability and robustness, particularly in network attributes such as node counts, average links per node, and the positive-to-negative link (P/N) ratios. Using the PBCDM, we constructed microbial co-existence networks for infants at various ages, identifying core genera networks through a novel network shearing method. Analysis revealed that core genera were more similar between adjacent age ranges, with increasing competitive relationships among microbiota as the infant microbiome matured. In conclusion, the PBCDM-based networks reflect known features of infant microbiota and offer a promising approach for investigating microbial relationships. This methodology could also be applied to future studies of genomic, metabolic, and proteomic data.

IMPORTANCE

As a research method and strategy, network analysis holds great potential for mining the relationships of bacteria. However, consistency and solid workflows to construct and evaluate the process of network analysis are lacking. Here, we provide a solid workflow to evaluate the performance of different microbial networks, and a novel probability-based co-existence network construction method used to decipher infant microbiota relationships. Besides, a network shearing strategy based on percolation theory is applied to find the core genera and connections in microbial networks at different age ranges. And the PBCDM method and the network shearing workflow hold potential for mining microbiota relationships, even possibly for the future deciphering of genome, metabolite, and protein data.
RamA upregulates the ATP-binding cassette transporter
mlaFEDCB
to mediate resistance to tetracycline-class antibiotics and the stability of membranes in
Klebsiella pneumoniae
Authors: Zhao Xiaoyu , Zhang Yixin , Ju Mohan , Yang Yang , Liu Haoqi , Qin Xiaohua , Xu Qingqing , Hao Min
Published: December 2024

RamA is an intrinsic regulator in
Klebsiella pneumoniae
, belonging to the AraC family of transcription factors and conferring a multidrug resistance phenotype, especially for tetracycline-class antibiotics. The ATP-binding cassette transporters MlaFEDCB in bacteria play essential roles in functions essential for cell survival and intrinsic resistance to many antibiotics. We found deletion of
ramA
resulted in a fivefold decrease in the transcriptional levels of the
mlaFEDCB
operon. After complementation with ramA, the transcriptional levels were comparable to those of wild-type strain. Furthermore, an electrophoretic mobility shift assay showed that RamA could bind to the promoter region of
mlaEFDCB
operon, which confirmed RamA is an activator of
mlaEFDCB
operon. The
mlaEFDCB
operon could mildly mediate resistance to the tetracycline family of antibiotics under RamA regulation. The MIC (minimum inhibitory concentration) of tigecycline decreased fourfold, and the MIC of doxycycline, minocycline, and eravacycline decreased twofold after
mlaE
-knockout. The
ramA
- and
mlaE
-knockout strains exhibited greater sensitivity to sodium dodecyl sulfate (SDS)-EDTA than the wild-type. Growth of Δ
ramA
cells was severely compromised in 0.25/0.5% SDS and 0.55 mM EDTA, and this sensitivity was restored by complementation with
ramA
and
mlaE
. This study demonstrates that RamA can directly regulate the
malEFEDCB
operon, thereby mediating resistance to tetracycline-class antibiotics, contributing to the stability of bacterial membranes in
K. pneumoniae
. We identified a novel signal pathway in which RamA mediates multidrug resistance of
K. pneumoniae
, leading to new ideas for the development of novel antimicrobial therapeutics, therefore deserving further comprehensive study.

IMPORTANCE

Multidrug-resistant and extensively drug-resistant
Klebsiella pneumoniae
have emerged as significant global health concerns resulting in high mortality rates. Although previous research has investigated the maintenance of lipid asymmetry (Mla) pathway, the extent to which it mediates antimicrobial resistance in
K. pneumoniae
and the underlying upstream regulatory mechanisms remain unclear. In this study, we sought to determine at the molecular level how the AraC-type global regulator RamA directly regulates mlaFEDCB, which mediates resistance to tetracycline-class antibiotics and the stability of bacterial membranes in
K. pneumoniae
.
Regional differences in millennial-scale climate variability in northeastern Tibet loess deposits spanning 34 ka to 8 ka
Authors: Gao Zihan , Wang Zhixiang , Wang Yixuan , Zhang Ze , Cao Mengmeng , Kemp David B.
Published: December 2024

Paleoclimate reconstructions from East Asian loess records are often inconsistent, especially at the junction between the relatively humid East Asia and more arid Central Asia regions. We present two high-resolution paleoclimatic records spanning 34−8 ka from northeastern Tibet (based on grain size, element abundance, and magnetic susceptibility), which have been temporally constrained using optically stimulated luminescence dating. Both records, from sites <200 km apart, demonstrate a significant climate shift at ca. 15 ka. In the section located farthest south, this shift manifests as an increase in humidity. By contrast, the northernmost section shows a decreasing trend in effective humidity at ca. 15 ka. The differences between these records demonstrates how regional factors can lead to marked differences in reconstructed paleoclimate in loess records. Our work additionally reveals millennial-scale signals recorded in northeastern Tibet loess deposits, and that these signals reflect a nonlinear response of the East Asian summer monsoon to insolation and other climatic components (e.g., the North Atlantic system).
Mathematical modelling and analysis for the co-infection of viral and bacterial diseases: a systematic review protocol
Authors: Yano Timothy Kiprono , Afrifa-Yamoah Ebenezer , Collins Julia , Mueller Ute , Richardson Steven
Published: December 2024

Introduction

Breaking the chain of transmission of an infectious disease pathogen is a major public health priority. The challenges of understanding, describing and predicting the transmission dynamics of infections have led to a wide range of mathematical, statistical and biological research problems. Advances in diagnostic laboratory procedures with the ability to test multiple pathogens simultaneously mean that co-infections are increasingly being detected, yet little is known about the impact of co-infections in shaping the course of an infection, infectivity, and pathogen replication rate. This is particularly true of the apparent synergistic effects of viral and bacterial co-infections, which present the greatest threats to public health because of their lethal nature and complex dynamics. This systematic review protocol is the foundation of a critical review of co-infection modelling and an assessment of the key features of the models.

Methods and analysis

MEDLINE through PubMed, Web of Science, medRxiv and Scopus will be systematically searched between 1 December 2024 and 31 January 2025 for studies published between January 1980 and December 2024. Three reviewers will screen articles independently for eligibility, and quality assessment will be performed using the TRACE (TRAnsparent and Comprehensive Ecological) standard modelling guide. Data will be extracted using an Excel template in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis standard reporting guidelines. This systematic review will apply the SWiM (Synthesis Without Meta-analysis) approach in its narrative synthesis coupled with tables and figures to present data. The synthesis will highlight key dynamical co-infection model features such as assumptions, data fitting and estimation methods, validation and sensitivity analyses, optimal control analyses, and the impact of co-infections.

Ethics and dissemination

Ethics approval is not required for a systematic review since it will be based on published work. The output of this study will be submitted for publication in a peer-reviewed journal.

PROSPERO registration number

CRD42023481247.
Factors associated with foot self-care behaviour and foot screening attendance in people with type 2 diabetes: a cross-sectional study in primary care
Authors: Zhu Xiaoli , Tjhin Silvana , Goh Ling Jia , De Roza Jacqueline Giovanna , Chan Frederick H F , Yin Ruoyu , Lee Eng Sing , Griva Konstadina
Published: December 2024

Objectives

To assess the factors associated with foot self-care behaviour and non-adherence to foot screening among patients with type 2 diabetes mellitus (T2DM).

Design and setting

A multicentre cross-sectional study was undertaken in seven primary care polyclinics in Singapore between October 2020 and December 2021.

Participants and outcomes

275 adults (male 55.3%) with T2DM were included and assessed with the foot self-care behaviour questionnaire, including two aspects of foot care behaviour-preventative behaviour and potential damaging behaviour, and foot care confidence scale. Non-adherence to diabetic foot screening (DFS) attendance was also collected and assessed.

Results

The average preventive behaviour score was 0.65 (SD 0.13, range 0–1) and potential damaging behaviour score was 0.43 (SD 0.09, range 0–1). Patients with greater foot care confidence (β=0.272) and being married (β=0.141) were more likely to adopt preventive behaviours, while patients aged between 21 and 45 years (β=0.136), having shorter DM duration (<5 years) (β=0.142) and moderate foot risk category (β=0.138) were more likely to adopt potential damaging behaviours. Non-adherence to DFS attendance was prevalent up to 43.3%. Non-adherence was higher in patients with higher HbA1c ≥7% (adjusted OR (AOR) 1.878, 95% CI 1.090 to 3.235) and moderate foot risk category (AOR 2.935, 95% CI 1.426 to 7.744).

Conclusion

Self-efficacy and being married are associated with preventive behaviours, while clinical parameters (eg, HbA1c, duration of DM and foot risk category) and age were associated with potential damaging behaviours and non-adherence to DFS appointments. Longitudinal studies are needed to confirm the findings for developing foot behavioural education to support foot care behaviours for primary care patients with T2DM.
Developing the allied health professionals workforce within mental health, learning disability and autism inpatient services: rapid review of learning from quality and safety incidents
Authors: Wilson Ceri , Wakefield Rachel , Prothero Louise , Janes Gillian , Nolan Fiona , Fowler-Davis Sally
Published: December 2024

Background

Allied health professionals (AHPs) in inpatient mental health, learning disability and autism services work in cultures dominated by other professions who often poorly understand their roles. Furthermore, identified learning from safety incidents often lacks focus on AHPs and research is needed to understand how AHPs contribute to safe care in these services.

Methods

A rapid literature review was conducted on material published from February 2014 to February 2024, reporting safety incidents within adult inpatient mental health, learning disability and autism services in England, with identifiable learning for AHPs. 115 reports/publications were included, predominantly consisting of independent investigations by NHS England, prevent future deaths reports and Care Quality Commission reports.

Findings

Misunderstanding of AHP roles, from senior leadership to frontline staff, led to AHPs being disempowered and excluded from conversations/decisions, and patients not getting sufficient access to AHPs, contributing to safety incidents. A central thread ‘organisational culture’ ran through five subthemes: (1) (lack of) effective multidisciplinary team (MDT) working, evidenced by poor communication, siloed working, marginalisation of AHPs and a lack of psychological safety; (2) (lack of) AHP involvement in patient care including care and discharge planning, and risk assessment/management. Some MDTs had no AHPs, some recommendations by AHPs were not actioned and referrals to AHPs were not always made when indicated; (3) training needs were identified for AHPs and other professions; (4) staffing issues included understaffing of AHPs and (5) senior management and leadership were found to not value/understand AHP roles, and instil a blame culture. A need for cohesive, well-led and nurturing MDTs was emphasised.

Conclusion

Understanding and recognition of AHP roles is lacking at all levels of healthcare organisations. AHPs can be marginalised in MDTs, presenting risks to patients and missed opportunities for quality improvement. Raising awareness of the essential roles of AHPs is critical for improving quality and safety in inpatient mental health, learning disability and autism services.
Cystic fibrosis carrier screening in Australia: comparing sequencing and targeted panels across diverse ancestries
Authors: Lee Eric , Orton Kaylee
Published: December 2024

Background

Targeted cystic fibrosis (CF) carrier screening panels may lack sensitivity in non-European ancestry groups. This study aims to evaluate the sensitivity of various panels in Australian CF carriers identified through sequencing.

Methods

The following panels were evaluated in 869 CF carriers: Asuragen, Elucigene, Devyser, American College of Medical Genetics and Genomics and Victorian Clinical Genetics Services. Ancestry-specific CF carrier frequencies from population databases and Bayesian analysis were used to estimate post-test residual carrier risks.

Results

When variants with varying clinical consequences (VCC) were not considered, mean test sensitivity was highest in the Northern Europe group (95.6%) and lowest in the Southern Asia group (64.0%). The post-test residual carrier risk in the Northern Europe group was approximately 1 in 546, with only the Southern Asia group having a higher residual carrier risk of 1 in 179.

Conclusion

The Southern Asia group exhibited the lowest test sensitivity and the highest post-test residual carrier risk, surpassing that of the Northern Europe group. The inclusion or exclusion of VCC significantly impacted the calculated test sensitivities. Further research is suggested to better characteriseCFTRvariants in non-European ancestry groups and to determine which VCC, if any, should be included in carrier screening reports.
Using Multi-objective Optimization Algorithms to Balance Landscape Design of Historic and Cultural Districts with Urban Development Needs
Authors: Gao Yun , Zheng Zeling
Published: December 2024

Urban land-use planning, particularly in historical and cultural districts, requires an impressive balance among various competing social, economic, and environmental considerations. In cities across China, the challenge lies in reconciling the demands of modern urban growth with the preservation of rich historical legacies. The preservation of historic landmarks meets the demands of an expanding urban area and infrastructure that the city faces. To improve land-use planning efforts in these contexts, this research proposes an approach that leverages multi-objective evolutionary algorithms combined with remote sensing techniques, specifically the Strength Pareto Evolutionary Algorithm 2 (SPEA2). The research analyses government plans and expert interviews to identify major objectives of urban growth and cultural preservation. To maximize land-use planning, two multi-objective functions are established, one to reduce impacts on historical and cultural areas and the other to optimize the efficiency of urban growth. The findings indicate that this multi-objective optimization technique can significantly support sustainable land-use planning in Chinese cities, ensuring that development requirements are satisfied without sacrificing the integrity of cultural assets using the parameter multi-objective optimization result and Pareto front visualization which considers cultural significance, economic validity, environmental impact, and also using fitness evaluation over generations. These are recommended for Chinese cities that aim to balance growth with historical preservation and use similar approaches.
Quantum chromodynamics Lagrangian density and SU(3) gauge symmetry: A fractional approach
Authors: Likéné A. A. Atangana , Ongodo D. Nga , Tsila P. Mah , Atangana A. , Ben-Bolie G. H.
Published: December 2024

Quantum ChromoDrynamics (QCD) is a quantum field theory, which describes the strong interaction. It explains how quarks and gluons combine to form hadrons. QCD is part of the standard model of particle physics, along with ElectroWeak (EW) theory. The aim of this study is to explore fractional orders in the QCD Lagrangian density using the Atangana–Baleanu fractional derivative. Starting from the fractional Euler–Lagrange equation, we were able to derive the equation of motion of the quark and gluon fields. Then, based on fractional QCD Lagrangian density, the fractional Hamilton equations were obtained. We demonstrate that the principle of local gauge invariance, a fundamental symmetry in QCD, is preserved under a fractional extension of the theory. Our findings indicate that the fractional equations of QCD encompass the classical equations as a specific case, offering a broader perspective on quark-gluon dynamics. The fractional QCD Lagrangian density provides new insights that are not accessible through classical derivatives, potentially enhancing our understanding of quark-gluon plasmas and contributing to advancements in collider phenomenology and precision measurements. This study opens new avenues for exploring the fundamental nature of the strong interaction and its implications for particle physics beyond the Standard Model.
Quantum coherence, degree of mixedness and entropy squeezing of a two-level atom with the presence of the phase-noisy laser
Authors: Berrada K. , Algarni M. , Abdel-Khalek S.
Published: December 2024

In this paper, we quantitatively examine the dynamics of quantum resources, such as quantum coherence, degree of mixedness, fidelity, and the atomic entropy squeezing, in a quantum system of a two-level atom (TLA) driven by a phase noise laser (PNL) within the context of non-Markovian dynamics. The [Formula: see text] norm is used to quantify coherence, linear entropy to measure the degree of TLA mixedness, and entropy to detect the atomic squeezing. We demonstrate how these quantum resources can be controlled through a suitable selection of model parameters. Furthermore, we provide the optimal conditions required to manipulate these quantum resources based on changes in the damping coupling. Finally, we discuss the relationships among the quantum resources in the present quantum model.
Dual Attention-Based Dense Capsule Bidirectional Gated Recurrent Unit for Classifying Tremor Types in Parkinson’s Disease-Affected Patients
Authors: Wasim Akram Sk. , Siva Kumar A. P.
Published: December 2024

Parkinson’s disease is a genetic disorder which affects the nervous system, including the body’s nerve-controlled organs. Improvements are still required because it is difficult to reduce tremors without impairing voluntary movement. So, in this study, a novel proposed method is used to classify the types of tremors. First, pre-processing is used to remove undesirable noise from the input signals using digital band pass filter (DBPF), Savitzky Golay digital FIR filter (SGDFF), and adaptive wavelet transform (AWT) approaches. Then, the pre-processed signals are fed into the dual attention-based dense capsule bidirectional gated recurrent unit (DA_DCBiGRU) model. A dense capsule is used to extract features, dual attention is utilized to reduce dimensionality, and BiGRU is used to identify tremor kinds such as resting, postural, and action. Finally, the suggested classifier’s efficiency is increased by fine-tuning the parameters with the improved fire hawk optimizer (IFHO). When compared to other existing approaches, the Python tool’s performance measurements indicate the greatest accuracy rate of 98.2%.
Video Library Construction for International Chinese Education
Authors: Chen Jian , Yang Zhaoyong , Rao Gaoqi , Xun Endong
Published: December 2024

This paper proposes four principles for digital resource construction for language education and carries out practical video resource construction. We believe that extraction and generation will be the main methods for machine resource construction. For resource extraction, this paper first introduces subtitle-based video resource extraction and example sentence extraction. For resource generation, this paper discusses the present limitations and future ideal working framework of large video generation models. The video extraction process proposed in this paper can be applied for other resource construction purposes, and the Large Language Model (LLM) resource generation framework proposed in this paper can be applied to the generation of other resources. We believe that with the digital transformation of education, a large number of machine-constructed resources will emerge.
The role of mechanosignaling in the control of myocardial mass
Authors: Landim-Vieira Maicon , Nieto Morales Paula F. , ElSafty Summer , Kahmini Aida Rahimi , Ranek Mark J. , Solís Christopher
Published: December 2024

Regulation of myocardial mass is key for maintaining cardiovascular health. This review highlights the complex and regulatory relationship between mechanosignaling and myocardial mass, influenced by many internal and external factors including hemodynamic and microgravity, respectively. The heart is a dynamic organ constantly adapting to changes in workload (preload and afterload) and mechanical stress exerted on the myocardium, influencing both physiological adaptations and pathological remodeling. Mechanosignaling pathways, such as the mitogen-activated protein kinases (MAPKs) and the phosphoinositide 3-kinases and serine/threonine kinase (PI3K/Akt) pathways, mediate downstream effects on gene expression and play key roles in transducing mechanical cues into biochemical signals, thereby modulating cellular processes, including control of myocardial mass. Dysregulation of these processes can lead to pathological cardiac remodeling, such as hypertrophic cardiomyopathy. Furthermore, recent studies have highlighted the importance of protein quality control mechanisms, such as the ubiquitin-proteasome system, in settings of extreme physiological conditions that alter the heart workload such as pregnancy and microgravity. Overall, this review provides a thorough insight into how mechanical signals are converted into chemical signals to regulate myocardial mass in both healthy and diseased conditions.