bluuebunny/crossref_metadata_2025 huggingface dataset:
Swine RNF5 positively regulates the antiviral activity of IFITM1 by mediating the degradation of ABHD16A
Authors: Shi Xuemeng , Shen Lingyi , Chen Shuaiwu , Liu Mingyang , Wang Jingyi , Wen Xin , Liu Wei , Mao Lin , Ding Yunyun , Yu Li , Xu Jun
Published: November 2024

Interferon-inducible transmembrane (IFITM) proteins are broad-spectrum antiviral factors that confer cellular resistance to virus invasion. α/β-Hydrolase domain-containing 16A (ABHD16A) has recently been identified as a novel depalmitoylase that can inhibit the antiviral activity of IFITM proteins by catalyzing the depalmitoyl reaction; this pattern may be crucial for the host to avoid damage caused by excessive immune response. However, it remains largely elusive about how host cells regulate the activity of ABHD16A. In the present study, we performed the AlphaFold2-based protein-protein interaction prediction and identified swine E3 ubiquitin ligase ring finger protein 5 (sRNF5) as a sABHD16A-interacting protein and negatively regulated the stability of sABHD16A. Using immunofluorescence and co-immunoprecipitation techniques, we uncovered that sRNF5 targeted sABHD16A for ubiquitination and degradation via the proteasomal pathway at residues K3 and K452. Furthermore, sABHD16A catalyzed the depalmitoylation of sIFITM1, which obstructed the antiviral function of sIFITM1, while sRNF5 caused ubiquitination of sABHD16A, which attenuated the depalmitoylation effect on sIFITM1, and consequently restored the antiviral activity of sIFITM1. Collectively, our findings demonstrate for the first time that sRNF5 positively regulates the antiviral function of sIFITM1 by mediating the degradation of sABHD16A, which expands the biological functions of RNF5 and ABHD16A in immune regulation. Moreover, our work highlights the well-designed interplay between RNF5, ABHD16A, and IFITM, which balances antiviral immune responses to avoid the disorders induced by excessive immune response.

IMPORTANCE

Interferon and interferon-stimulated genes play significant and protective roles in the host’s defense against viral infection. IFITM family proteins, which can be strongly induced by interferon, have been identified as the first line of defense to prevent invasion of various viruses. Further analysis reveals the antiviral activity of IFITMs depends on palmitoylation/depalmitoylation. Recently, we reported that ABHD16A, as the first depalmitoylase of IFITMs, negatively regulated the antiviral activity of IFITMs. However, these raise crucial questions: how ABHD16A is regulated and remained in a balanced manner? Here, we show that swine RNF5 attenuates the negative regulation of sIFITM1 against virus invasion by modifying sABHD16A through ubiquitination and guiding sABHD16A for degradation. Thus, sRNF5-sABHD16A interplay plays an indispensable role in regulating immune response and avoiding the disorders induced by elevated interferon levels. Overall, our findings extend the upstream subtle regulatory molecular mechanism of IFITMs and provide potential targets for viral disease therapy.
Canine parvovirus NS1 induces host translation shutoff by reducing mTOR phosphorylation
Authors: Wang Xinrui , Hao Xiangqi , Zhao Yaning , Xiao Xiangyu , Li Shoujun , Zhou Pei
Published: November 2024

Canine parvovirus type 2 (CPV-2) is a member of the Parvoviridae family, characterized by its small, non-enveloped virions containing a linear single-stranded DNA genome of approximately 5 kb. Parvoviruses entirely reliant on the host cell’s division machinery for replication. In this study, we demonstrate that CPV-2 infection triggers the host translation shutoff, a process in which the nonstructural protein 1 (NS1) plays a pivotal role. Our findings indicate that the CPV-2 NS1-induced host translation shutoff is not associated with transcription, protein degradation pathways, or eIFα phosphorylation, but rather involves the reduction of phosphorylation of the mammalian target of rapamycin (mTOR). In conclusion, this research reveals that CPV-2 NS1 induces a host translation shutoff by reducing mTOR phosphorylation, a mechanism that could potentially inform the development of more efficacious control and therapeutic strategies for CPV-2 and other parvoviral infections.

IMPORTANCE

Autonomous parvoviruses, which possess compact genomes, are obligate intracellular parasites that necessitate host cell division for their replication cycle. Consequently, the modulation of host translation and usurpation of cellular machinery are hypothesized to facilitate immune evasion, enhance viral transmission, and perpetuate long-term infection. Despite the biological significance, the precise mechanisms by which autonomous parvoviruses regulate host translation remain understudied. Our study elucidates that CPV-2 infection induces a shutoff of host translation through the attenuation of mTOR phosphorylation. This mechanism may enable the virus to subvert the host immune response and engender pathogenic effects.
Unraveling dual fusion mechanisms in BmNPV GP64: critical roles of CARC motifs and signal peptide retention
Authors: Sun Luping , Xu Ying , Chen Kai , Nan Wenbin , Wang Meixian , Zhang Yiling , Hao Bifang , Huang Jinshan
Published: November 2024

Viral membrane fusion is a critical process enabling viruses to invade host cells, driven by viral membrane fusion proteins (MFPs). Cholesterol plays a pivotal role in this process, which is essential for the infectivity of many enveloped viruses. The interaction between MFPs and cholesterol is often facilitated by specific amino acid motifs known as cholesterol recognition/interaction amino acid consensus (CRAC) motifs and reverse CARC motifs. In a previous study, we demonstrated that CRAC1 and CRAC2 in GP64 are required for Bombyx mori nucleopolyhedrovirus (BmNPV) infection. This study further investigates the role of CARC in the GP64 protein of BmNPV, revealing their complex interaction with cholesterol and the influence of signal peptide (SP) retention on viral infectivity. We identified six putative CARC motifs in GP64 and generated mutants to assess their function. Our findings show that CARC1, CARC2, CARC3, and CARC4 are indispensable for viral fusion and infection when the SP is retained, whereas only CARC2 and CARC3 remain essential after SP cleavage. In contrast, CARC1 and CARC4 are necessary for viral infection through a cholesterol-independent mechanism resulting from double mutations in the CRAC1 and CRAC2 motifs of GP64. These insights not only deepen our understanding of BmNPV GP64-mediated fusion but also highlight potential antiviral targets, underscoring the adaptability and resilience of viral fusion mechanisms.

IMPORTANCE

Understanding viral membrane fusion mechanisms is crucial for developing antiviral strategies. This study provides novel insights into the intricate roles of CARC and CRAC motifs in the GP64 protein of BmNPV, particularly their interaction with cholesterol and the influence of signal peptide retention. The discovery that certain CARC motifs are essential for cholesterol-dependent fusion, whereas others function in a cholesterol-independent context advances our understanding of viral fusion processes. These findings emphasize the potential of targeting CARC motifs for therapeutic interventions and underline the importance of cholesterol interactions in viral infections. This research not only deepens our understanding of BmNPV fusion mechanisms but also has broader implications for other enveloped viruses.
The antiviral activity of myricetin against pseudorabies virus through regulation of the type I interferon signaling pathway
Authors: Song Yizhen , Zhao Xufan , Chen Yaqin , Yu Xingyue , Su Tianli , Wang Juan , He Tingke , Yin Zhongqiong , Jia Renyong , Zhao Xinhong , Zhou Xun , Li Lixia , Zou Yuanfeng , Li Mingyue , Zhang Dongmei , Zhang Yingying , Song Xu
Published: November 2024

The type I interferon signaling pathway constitutes a pivotal component of the innate immune response, encompassing the cGAS/STING and JAK/STAT pathways. Drugs that affect the body’s innate immune response could potentially be used as broad-spectrum antivirals. In this study, the antiviral activities of 25 flavonoids against pseudorabies virus (PRV) were tested in PK-15 cells. Eight active flavonoids were identified, with IC
50
values ranging from 23.24 to 323.09 µM. Subsequently, the regulatory effects of these flavonoids on the cGAS/STING pathway in PRV-infected cells were investigated. It was found that Myricetin significantly increased the transcriptional levels of
cGAS
,
STING
,
IRF3
, and
IFN-β
, which had been reduced by PRV infection. The regulation of the type I in

terferon signaling pathways by myricetin following PRV infection was further investigated through the production of cGAMP and the assessment of transcriptional and protein levels of pivotal genes and proteins. To confirm the activation of the innate immune response, a dual luciferase gene reporter study found that the expression of the IFN-β promoter in the myricetin-treated group was significantly elevated in a cellular model of type I interferon signaling pathway, and the contents of IFN-β were also significantly higher than those observed in the infected-untreated group in a PRV-infected mice model. Moreover, the transcriptional and protein levels of key genes and proteins in cell and mouse models exhibited analogous outcomes to those observed in PRV-infected cells. These findings suggest that myricetin can effectively activate the type I interferon signaling pathway, thereby enhancing the innate immune response during PRV infection.

IMPORTANCE

PRV, belonging to the
Herpesviridae
family, is an easily overlooked zoonotic pathogen that can threaten human health. The immunoprotective efficacy of conventional vaccines is significantly reduced due to the continuous mutation of the PRV genome, which constantly generates new viral strains. Therefore, there is a need to develop potent therapeutic drugs. PRV is capable of evading the host's natural immunity by suppressing the host's type I interferon signaling pathway, and the search for drugs that activate natural immunity can induce the body to produce type I IFN interferon and exert antiviral effects. Accordingly, the present study sought to identify active compounds from flavonoids that modulate the type I IFN interferon signaling pathway and thus inhibit the proliferation of PRV, which provides a new idea for the development of anti-PRV drugs from flavonoids that modulate the type I IFN interferon signaling pathway to enhance the body's antiviral immunity.
The characterization and structural basis of a human broadly binding antibody to HBV core protein
Authors: Yan Hu , Liu Congcong , Li Yuxiao , Tang Shilong , Guo Huimin , Zhou Bing , Fan Qing , Wang Haiyan , Ge Xiangyang , Wang Xin , Liao Xuejiao , Li Jin , Zhang Zheng , Ju Bin
Published: November 2024

Hepatitis B virus (HBV) core protein (HBc) plays a crucial role in the virus life cycle, making it an important detection marker for HBV infection and a potential target for treatment. However, several commercially available monoclonal antibodies (mAbs) or polyclonal antibodies (pAbs) targeting HBc have certain limitations in detecting HBV across different genotypes in various biochemical assays, such as enzyme-linked immunosorbent assay, western blot, immunofluorescence assay, flow cytometry, and immune spot assay. In this study, we identified 12 human anti-HBc mAbs and evaluated their potential application in multiple biochemical assays. These mAbs mainly recognized the epitopes near residues 20–22 amino acids (a.a.) and 77–78 a.a. of HBc, demonstrating a broadly cross-genotypic activity. Notably, three Group II mAbs, named cAbA1, cAbD4, and cAbF9, displayed excellent capacities for the detection of HBV infection in all tested biochemical assays. Furthermore, we determined a 3.22 Å of cryo-electron microscopy (cryo-EM) structure of the fragment of antigen binding (Fab) of cAbD4 complexed with HBc dimer, which was the highest resolution of the structural model for Fab-HBc to date. Collectively, our findings provided excellent and reliable antibody candidates for live HBV detection and revealed the recognition mechanism and the detailed interaction information of a potent human anti-HBc mAb binding to the spike tips of HBc dimer.

IMPORTANCE

The lack of excellent detection Abs for live hepatitis B virus (HBV) infection and high-resolution structures of the Ab-HBV core protein (HBc) complex largely limited the development of HBV-related research. This study reports a panel of anti-HBc monoclonal antibodies (mAbs) with excellent capacities for detecting HBV infection in multiple biochemical assays and determines a 3.22 Å of cryo-EM structure of HBc with a potent binding mAb. These findings provide excellent and reliable detecting tools for HBV-related research and promote the understanding of the recognition mechanism of anti-HBc mAbs to HBc particles.
CDK12 antagonizes a viral suppressor of RNAi to modulate antiviral RNAi in
Drosophila
Authors: Zhang Liqin , Liang Yu , Qin Jiayu , Liu Chen , Shang Mengwei , Sun Xiaoming
Published: November 2024

The primary antiviral immunity in insects is mediated by the RNA interference (RNAi) pathway. To counteract this antiviral RNAi response, viruses employ virulence factors known as viral suppressors of RNAi (VSR). The question of whether host factors can activate a counter-counter-defense mechanism to cope with VSR-mediated RNA silencing suppression remains unanswered. In this study, cyclin-dependent kinase 12 (CDK12) was identified to interact with B2, a VSR of Flock House virus (FHV), and the critical amino acids responsible for dsRNA binding and dimerization in B2 were essential for this interaction. Silencing of CDK12 facilitated FHV RNA accumulation only in the context of B2, not for FHVΔB2. Notably, CDK12 abrogated the RNAi suppression exerted by B2. Furthermore, the knockdown of CDK12 inhibited the production of vsiRNAs in FHV-infected
Drosophila
cells. This study revealed that CDK12 mediated a counter-counter-defense strategy against VSR, thereby enhancing antiviral RNAi immunity in
Drosophila
.

IMPORTANCE

The arms race between virus and host immunity is never-ending. This study enhances our understanding of antiviral defenses in insects by uncovering a novel counter-counter-defense mechanism against viral suppressors of RNA interference (VSRs). The RNA interference (RNAi) pathway serves as a primary antiviral response in insects, but viruses, such as Flock House virus (FHV), have evolved VSRs like B2 to disrupt this defense. Our research identifies cyclin-dependent kinase 12 (CDK12) as a critical host factor that interacts with the VSR B2. The discovery that CDK12 can counteract B2-mediated RNAi suppression and stimulate the production of viral small interfering RNAs (vsiRNAs) in FHV-infected
Drosophila
cells highlights its pivotal role in enhancing antiviral RNAi immunity. This study not only reveals a new dimension of host-virus interactions but also opens avenues for developing strategies to strengthen RNAi-based antiviral defenses.
Transcriptomic and genetic analysis reveals a Zn2Cys6 transcription factor specifically required for conidiation in submerged cultures of
Thermothelomyces thermophilus
Authors: Drescher Florian , Li Yang , Villalobos-Escobedo Jose Manuel , Haefner Stefan , Huberman Lori B. , Glass N. Louise
Published: November 2024

Filamentous fungi are important producers of enzymes and secondary metabolites. The industrial thermophilic species,
Thermothelomyces thermophilus,
is closely related to the model fungus,
Neurospora crassa
. A critical aspect of the filamentous fungal life cycle is the production of asexual spores (conidia), which are regulated by various stimuli, including nutrient availability. Several species of fungi, including
T. thermophilus
, produce conidia under submerged fermentation conditions, which can be detrimental to product yields. In this study, transcriptional profiling of
T. thermophilus
was used to map changes during asexual development in submerged cultures, which revealed commonalities of regulation between
T. thermophilus
and
N. crassa
. We further identified a transcription factor,
res1
, whose deletion resulted in a complete loss of conidia production under fermentation conditions, but which did not affect conidiation on plates. Under fermentation conditions, the ∆
res1
deletion strain showed increased biomass production relative to the wild-type strain, indicating that the manipulation of
res1
in
T. thermophilus
has the potential to increase productivity in industrial settings. Overexpression of
res1
caused a severe growth defect and early conidia production on both plates and in submerged cultures, indicating
res1
overexpression can bypass regulatory aspects associated with conidiation on plates. Using chromatin-immunoprecipitation sequencing, we identified 35 target genes of Res1, including known conidiation regulators identified in
N. crassa
, revealing common and divergent aspects of asexual reproduction in these two species.

IMPORTANCE

Filamentous fungi, such as
Thermothelomyces thermophilus,
are important industrial species and have been harnessed in the Biotechnology industry for the production of industrially relevant chemicals and proteins. However, under fermentation conditions, some filamentous fungi will undergo a switch from mycelial growth to asexual development. In this study, we use transcriptional profiling of asexual development in
T. thermophilus
and identify a transcription factor that specifically regulates the developmental switch to the production of unwanted asexual propagules under fermentation conditions, thus altering secreted protein production. Mutations in this transcription factor Res1 result in the loss of asexual development in submerged cultures but do not affect asexual sporulation when exposed to air. The identification of stage-specific developmental regulation of asexual spore production and comparative analyses of conidiation in filamentous ascomycete species have the potential to further manipulate these species for industrial advantage.
Complete genome of
Nanosynbacter
sp. strain BB002, isolated and cultivated from a site of periodontal disease
Authors: Atkinson Celine Grace F. , Kerns Kristopher A. , Hendrickson Erik L. , He Xuesong , Bor Batbileg , McLean Jeffrey S.
Published: November 2024

Nanosynbacter sp.
strain BB002, was isolated from the human oral cavity on its basibiont bacterial host
Actinomyces
sp. oral taxon 171 strain F0337, related to
Actinomyces oris
. As a member of the
Saccharibacteria
within the candidate phylum radiation group (CPR), its reduced genome facilitates the survival as an ultrasmall (<0.2 μm) epibiont.
Draft genome sequence of
Zygosaccharomyces siamensis
kiy1 isolated from unpasteurized honey
Authors: Iwata Kan , Minegishi Daisuke , Maeda Mayumi , Maehashi Kenji , Yoshikawa Jun
Published: November 2024

In this study, a draft genome sequence of
Zygosaccharomyces siamensis
kiy1 isolated from unpasteurized honey in Japan was analyzed. This strain was reported to be a promising arabitol-producing strain, and this report contributes to a better understanding of arabitol production in yeasts.
Draft genomes of two
Roseibium
spp. isolated from the coral
Pachyseris speciosa
from a Singaporean reef
Authors: Tang Pei Yi Peggy , Loh Aaron An Rong , Hu Dalong , Deignan Lindsey Kane , Summers Stephen , Pereyra Joao Paulo Andre , Case Rebecca J.
Published: November 2024

Two
Roseibium
spp. strains were isolated from skeletal macerates of the Singaporean coral
Pachyseris speciosa
at an ambient high temperature. We sequenced the genomes of SCP14 (
JBDZYH000000000
) and SCP15 (
JBDZYI000000000
), which revealed genomes containing genetic elements that play a role in coral health during thermal stress.
Genome sequences of three
Streptomyces
isolated from the soil of soybean field in Tsuruoka, Japan
Authors: Sato Ryuki , Saito Rena , Takeda Tomoki , Sasaki Nobuhiro , Yuzawa Satoshi , Saito Natsumi , Arakawa Kazuharu
Published: November 2024

Streptomyces
are Gram-positive bacteria typically found in the soil, with very large genomes and high GC content, and are known to produce a wide range of secondary metabolites. We isolated and sequenced the genomes of three
Streptomyces
bacteria from the soil of soybean field in Tsuruoka, Japan.
The buoyancy of cryptococcal cells and its implications for transport and persistence of
Cryptococcus
in aqueous environments
Authors: Jimenez Isabel A. , Stempinski Piotr R. , Dragotakes Quigly , Greengo Seth D. , Sanchez Ramirez Lia , Casadevall Arturo
Published: November 2024

Cryptococcus
is a genus of saprophytic fungi with global distribution. Two species complexes,
Cryptococcus neoformans
and
Cryptococcus gattii
, pose health risks to humans and animals. Cryptococcal infections result from inhalation of aerosolized spores and/or desiccated yeasts from terrestrial reservoirs such as soil and trees. More recently,
C. gattii
has been implicated in infections in marine mammals, suggesting that inhalation of cells from the air-water interface is also an important, yet understudied, mode of respiratory exposure. Based on historical records and epidemiological factors, water transport has been hypothesized to play a role in the spread of
C. gattii
from tropical to temperate environments. However, the dynamics of fungal persistence and transport in water have not been fully studied. The size of the cryptococcal capsule was previously shown to reduce cell density and increase buoyancy. Here, we demonstrate that cell buoyancy is also impacted by the salinity of the solution in which cells are suspended, with the formation of a halocline significantly slowing the rate of settling and resulting in persistence of
C. neoformans
within 1 cm of the water surface for over 60 min and
C. gattii
for 4–6 h. During the culture of three strains of
C. gattii
in yeast peptone dextrose media, we also identified aggregates of extracellular polysaccharide with complex structures, which we hypothesize from rafts that entrap cells and augment buoyancy. These findings illustrate new mechanisms by which cryptococcal cells may persist in aquatic environments, with important implications for aqueous transport and pathogen exposure.

IMPORTANCE

Cryptococcosis is a major fungal disease leading to morbidity and mortality worldwide.
Cryptococcus neoformans
is a major fungal species of public health concern, causing opportunistic systemic infections in immunocompromised patients.
Cryptococcus gattii
was traditionally a pathogenic fungus confined primarily to tropical regions, but in the 1990s, it emerged in the temperate climates of British Columbia, Canada and the Pacific Northwest of the United States. Outbreaks in these areas also led to the first host record of cryptococcosis in free-ranging cetaceans.
C. gattii
is particularly concerning as an emerging fungal pathogen due to its capacity to cause clinical disease in immunocompetent patients, its recent spread to a new ecological niche, and its higher resistance to antifungal therapies. Our research defines fungal characteristics that influence the transport of cryptococci through water and persistence of fungal cells near the water surface, improving our understanding of potential mechanisms for cryptococcal environmental transport.
Distinct transcriptome and traits of freshly dispersed
Pseudomonas aeruginosa
cells
Authors: Kalia Manmohit , Sauer Karin
Published: November 2024

Bacteria assume two distinct lifestyles: the planktonic and biofilm modes of growth. Additionally, dispersion has emerged as a third phenotype, accompanied by the distinct phenotypes and the unique expression of >600 genes. Here, we asked whether the distinct phenotype of dispersed cells is already apparent within minutes of egressing from the biofilm. We used RNA-seq to show that the physiology of freshly dispersed cells from
Pseudomonas aeruginosa
biofilms is highly different from those of planktonic and biofilm cells, apparent by dispersed cells uniquely expressing 194 genes. Unique and differentially expressed genes relative to planktonic or biofilm cells include genes associated with type IV pili, pyoverdine, type III and type VI secretion systems, and antibiotic resistance that are downregulated in dispersed cells, whereas the transcript abundance of genes involved in swimming motility, Hxc type II secretion system and various other virulence factors, and metabolic and energy-generating pathways are increased, indicative of dispersion coinciding with an awakening and re-energizing of dispersed cells, and a switch in virulence, further apparent by freshly dispersed cells significantly subverting engulfment by macrophages. The findings suggest that dispersed cells display a distinct phenotype within minutes of egressing from the biofilm, with freshly dispersed cells already capable of efficiently evading phagocytosis.

IMPORTANCE

Dispersion is considered a transitionary phenotype, enabling bacteria to switch between the communal, biofilm lifestyle, where cells share resources and are protected from harmful conditions to the planktonic state. Here, we demonstrate that within minutes of leaving the biofilm, dispersed cells express genes and display phenotypic traits that are distinct from biofilms and planktonic cells. Our findings suggest that dispersed cells quickly adapt to a less structured and protected but more nutrient-rich environment, with this trade-off in environment coinciding with an awakening and a switch in virulence, specifically a switch from directly intoxicating host cells and potential competitors toward more broadly active virulence factors and strategies of evasion. To our knowledge, this is the first report of dispersed cells’ distinct (trade-off) phenotype and their enhanced resilience so soon after egressing from the biofilm.
Different artificial feeding strategies shape the diverse gut microbial communities and functions with the potential risk of pathogen transmission to captive Asian small-clawed otters (
Aonyx cinereus
)
Authors: Gao Yuanda , Zhang Hangyu , Zhu Dapeng , Guo Long
Published: November 2024

Captive otters raised in zoos are fed different artificial diets, which may shape gut microbiota. The objective is to evaluate the impacts of two different artificial diets on microbial communities and function capabilities and short-chain fatty acid (SCFA) profiles in healthy otters’ feces. A total of 16 Asian small-clawed otters in two groups (
n
= 8) were selected. Group A otters were fed raw loaches supplemented with commercial cat food (LSCF) diet, and group B otters were fed raw crucian diet. The communities and functional capabilities of microbiota in feces were assessed with metagenomic sequencing. Captive otters fed two kinds of diets possessed different gut microbial communities and functional capabilities. Various pathogenic bacteria, like
Escherichia coli
and
Clostridium perfringens
, were enriched in the samples from the two groups, respectively. Most of the differential pathways of nutrient metabolism were significantly enriched in group A, and the distributions of carbohydrate enzymes in the two groups significantly differed from each other. Multiple resistance genes markedly accumulated in fecal samples of the group A otters with LSCF diet. Higher concentrations of SCFAs were also observed in group A otters. Two feeding strategies were both likely to facilitate the colonization and expansion of various pathogenic bacteria and the accumulation of resistance genes in the intestines of captive otters, suggesting that risk of pathogen transmission existed in the current feeding process. Commercial cat food could supplement various nutrients and provide a substrate for the production of SCFAs, which might be beneficial for the otters’ intestinal fermentation and metabolism.

IMPORTANCE

Captive otters fed with different diets possessed distinct gut microbial communities and functions, with the enrichment of several pathogens and multiple resistance genes in their gut microbiota. The current artificial feeding strategies had the possibility to accelerate the colonization and proliferation of various pathogenic bacteria in the intestines of otters and the spread of resistance genes, increasing the risk of diseases. In addition, supplementation with commercial cat food had benefits for otters’ intestinal fermentation and the metabolism of gut microbiota.
Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in Israel
Authors: Koch Rachelle E. , Barth Jackson , Clark Andrew E. , Desai Dhara , Kim Jiwoong , Pybus Christine A. , Zhan Xiaowei , Leibovici Leonard , Yahav Dafna , Greenberg David E.
Published: November 2024

Antibiotic resistance is a major cause of morbidity and mortality. However, a better understanding of the relationship between bacterial genetic markers, phenotypic resistance, and clinical outcomes is needed. We performed whole-genome sequencing on five medically important pathogens (
Acinetobacter baumannii
,
Enterobacter cloacae
,
Escherichia coli
,
Klebsiella pneumoniae
, and
Pseudomonas aeruginosa
) to investigate how resistance genes impact patient outcomes. A total of 168 isolates from 162 patients with Gram-negative infections admitted to Beilinson Hospital at Rabin Medical Center in Israel were included for final analysis. Genomes were analyzed for resistance determinants and correlated with microbiologic and clinical data. Thirty-day mortality from time of culture was 26.5% (43/162). Twenty-nine patients had carbapenem-resistant isolates (29/168, 17.2%), while 63 patients had multidrug-resistant isolates (63/168, 37.5%). Albumin levels were inversely associated with mortality and length of stay, while arrival from a healthcare facility and cancer chemotherapy predicted having a multidrug-resistant isolate. Sequencing revealed possible patient-to-patient transmission events.
bla
CTX-M-15
was associated with multidrug-resistance in
E. coli
(OR = 3.888,
P
= 0.023) on multivariate analysis. Increased
bla
OXA-72
copy number was associated with carbapenem-resistance in
A. baumannii
(
P
= 0.003) and meropenem minimum inhibitory concentration (
P
= 0.005), yet carbapenem-resistant isolates retained sensitivity to cefiderocol and sulbactam–durlobactam. RJX84154 was associated with multidrug-resistance across all pathogens (
P
= 0.0018) and in
E. coli
(
P
= 0.0024). Low albumin levels were associated with mortality and length of stay in this sample population.
bla
CTX-M-15
was correlated with multidrug-resistance in
E. coli
, and
bla
OXA-72
depth predicted meropenem minimum inhibitory concentration in
A. baumannii
. RJX84154 may play a role in multidrug-resistance.

IMPORTANCE

While there have been several studies that attempt to find clinical predictors of outcomes in patients hospitalized with bacterial infections, less has been done to combine clinical data with genomic mechanisms of antibiotic resistance. This study focused on a hospitalized patient population in Israel with infections due to medically important bacterial pathogens as a way to build a framework that would unite clinical data with both bacterial antibiotic susceptibility and genomic data. Merging both clinical and genomic data allowed us to find both bacterial and clinical factors that impact certain clinical outcomes. As genome sequencing of bacteria becomes both rapid and commonplace, near real-time monitoring of resistance determinants could help to optimize clinical care and potentially improve outcomes in these patients.
Deposition, deformation, and flexure in a transpressional trough, Queen Charlotte fault, offshore Haida Gwaii (British Columbia, Canada)
Authors: Rohr Kristin M.M. , Riedel Michael , Furlong Kevin P.
Published: November 2024

Transpressional deformation along the Pacific–North American plate boundary off British Columbia (Canada) generates interactions between tectonic and depositional processes; first-order deformation is creation of a bathymetric trough by flexure of the Pacific plate. Interpretation of a suite of single-channel seismic reflection data in the central and southern trough shows second-order internal structure and depositional systems within the trough. Much of these sediments originated from Quaternary slope fans, although the age of the underlying oceanic crust is 8–13 Ma. These turbidite deposits overlie hemipelagic deposits. Two distinct layers of turbidite deposits in the trough can be explained by sediment deposition systems rather than tectonic events. We infer that the most recent flat-lying deposits, which have been previously interpreted in the northern trough as indicating a lack of compressive deformation, consist, in fact, of along-axis flows based on the general geomorphology of the margin. Second-order deformation consists of small-offset extensional and compressive structures common within 15 km of the foot of the continental slope. A few normal faults are observed tens of kilometers further out on the flexural bulge. Recent faults that cut the seafloor are observed offshore from the rupture plane of the 2012 M7.8 earthquake and match an area of extensional aftershocks. These faults may not be from bending of the entire bulge, which is 30–40 km wide, but from the plate being pulled into the underthrust zone. Maximum depression of the Pacific plate is also offshore from the region of recent rupture, indicating that this rupture is representative of long-term geologic processes.
Pulmonary hypertension in preterm neonates with bronchopulmonary dysplasia: a meta-analysis
Authors: Mascarenhas Dwayne , Al-Balushi Marwa , Al-Sabahi Aida , Weisz Dany E , Jain Amish , Jasani Bonny
Published: November 2024

Context

Knowledge gaps exist on the incidence and risk factors for developing pulmonary hypertension (PH) in preterm infants with bronchopulmonary dysplasia (BPD) and its impact on outcomes.

Objective

To systematically review and meta-analyse the incidence, risk factors and short- and long-term outcomes of BPD-PH in preterm infants.

Design

PubMed, Embase, Cochrane CENTRAL and CINAHL were searched for studies including infants<37 weeks gestational age (GA) or birth weight<2500 g with BPD-PH versus BPD-no PH from inception until 5 April 2023.

Main outcome measures

Incidence, risk factors and short- and long-term outcomes.

Results

44 observational studies evaluating 7677 preterm infants were included. The incidence of PH in mild, moderate and severe BPD was 5%, 18% and 41%, respectively. Small for GA (25 studies; N=5814; OR 1.8; 95% CI 1.3, 2.5), necrotising enterocolitis (22 studies; N=3387; OR 1.6; 95% CI 1.3, 2.2), early PH (four studies; N=820 OR 2.2; 95% CI 1.5, 3.3) and severe BPD (20 studies; N=2587; OR 5.4; 95% CI 3.2, 9.1) were significant risk factors for BPD-PH. Compared with BPD-no PH, the BPD-PH group had significantly higher mortality (22 studies; N=4882; OR 6.4; 95% CI 4.7, 8.6), longer duration of mechanical ventilation, oxygen supplementation, length of hospital stay, need for home oxygen and tracheostomy requirement. The BPD-PH infants also had a significantly higher risk of neurodevelopmental impairment in the motor domain.

Conclusions

PH increases across the severity of BPD and is associated with higher odds of mortality and adverse short-term and neurodevelopmental outcomes.

PROSPERO registration number

CRD42023413119.
Why exercise may never be effective medicine: an evolutionary perspective on the efficacy versus effectiveness of exercise in treating type 2 diabetes
Authors: MacDonald Christopher , Bennekou Mia , Midtgaard Julie , Langberg Hennig , Lieberman Daniel
Published: November 2024

Most cases of type 2 diabetes (T2D) can be prevented by adopting a healthy lifestyle, highlighting that lifestyle modifications should be the primary defence against developing T2D. Although accumulating evidence suggests that exercise can be an efficacious therapy for T2D, especially in conjunction with pharmacological interventions, its long-term effectiveness remains controversial owing to significant adherence challenges. In this narrative review, we combine an evolutionary perspective with epidemiological and prospective interventional studies to examine the efficacy versus effectiveness of varying volumes of exercise prescriptions for treating T2D. Commonly prescribed and recommended volumes of moderate-intensity physical activity (150 min/week) have demonstrated low-to-moderate efficacy in improving glycaemic control, reflected by improvements in glycated haemoglobin levels. Higher exercise volumes have been shown to enhance efficacy. While exercise can be moderately efficacious under the optimal circumstances of short-term exercise interventions (≤1 year), there is little evidence of its long-term effectiveness, primarily due to poor adherence. To date, no study has demonstrated long-term adherence to exercise programmes in individuals with T2D (>1 year). From an evolutionary perspective, the finding that exercise interventions are often ineffective over time is unsurprising. Although often overlooked, humans never evolved to exercise. Exercise is a counter-instinctive behaviour that can be difficult to maintain, even in healthy populations and can be especially challenging for individuals who are unfit or have T2D morbidities. We conclude by presenting several considerations informed by evolutionary logic that may be useful for practitioners, policymakers and advocates of exercise as medicine to improve exercise adherence.
Kinematics of post-wildfire debris flow initiation mechanism: impact of hydrophobic layer spatial variability and particle size
Authors: Movasat Mahta , Tomac Ingrid
Published: November 2024

Post-wildfire debris flow events have been more frequent due to climate change and increased wildfire adversity. Changes in noncohesive soil hydrophobicity, burn, and vegetation removal during wildfires dramatically enhance slopes’ vulnerability to rainfall-induced failure in the arid Southwest USA and similar areas worldwide. This paper contributes to a better understanding the hydrophobic sand slope failure mechanism using experiments and theory. In total, 36 indoor raining experiments use different configurations of fine, medium, and coarse hydrophobic sands subjected to various rain intensities on different slope inclinations. Specific findings contribute to understanding how the spatial variability of the post-wildfire hydrophobic layer, concerning depth and the sand grain size variations, affects the slope failure mechanisms. Clarifying slope failure mechanisms in different layouts is crucial for understanding the initiation and further spatiotemporal debris flow evolution. Results indicate that the surficial hydrophobic layer fails because erosion develops simultaneously from many small failure patches. Erosion pattern, time to failure, water, and sediment overflow temporal dynamics correlate to the dominant sand grain size. Furthermore, seepage-induced shallow infinite slope occurs when the hydrophobic sand layer develops below the surface. Finally, this study identifies the fine sand as the most vulnerable to failure in both configurations.
Exploring dielectric relaxation in 1,2-propanediol and 1,4-dioxane binary mixtures: time-domain reflectometry analysis
Authors: Garad Nitin P. , Kumbharkhane Neha A. , Kumbharkhane Ashok C.
Published: November 2024

This study investigates dielectric relaxation in binary mixtures of 1,2-propanediol and 1,4-dioxane using time-domain reflectometry. The dielectric parameters, including the static dielectric constant, relaxation time, the Kirkwood correlation factor, excess properties, thermodynamic parameters, and Bruggeman factor, are analyzed to study molecular dynamics, dipole orientation, and intermolecular interactions within the mixture. The experimental results provide insights into the dielectric behavior of the binary system, with implications for various applications in material science, chemistry, and chemical engineering. The Luzar theory is applied to study the hydrogen bonding interaction in alcohols mixture. The results have been compared with our previously published work N.P. Garad et al. to study the effect of number of carbon atoms on dielectric properties.
Ab initio description of monopole resonances in light- and medium-mass nuclei
Authors: Porro A. , Duguet T. , Ebran J.-P. , Frosini M. , Roth R. , Somà V.
Published: November 2024

Giant Resonances are, with nuclear rotations, the most evident expression of collectivity in finite nuclei. These two categories of excitations, however, are traditionally described within different formal schemes, such that vibrational and rotational degrees of freedom are separately treated and coupling effects between those are often neglected. The present work puts forward an approach aiming at a consistent treatment of vibrations and rotations. Specifically, this paper is the last in a series of four dedicated to the investigation of the giant monopole resonance in doubly open-shell nuclei via the ab initio Projected Generator Coordinate Method (PGCM). The present focus is on the treatment and impact of angular momentum restoration within such calculations. The PGCM being based on the use of deformed mean-field states, the angular-momentum restoration is performed when solving the secular equation to extract vibrational excitations. In this context, it is shown that performing the angular momentum restoration only after solving the secular equation contaminates the monopole response with an unphysical coupling to the rotational motion, as was also shown recently for (quasi-particle) random phase approximation calculations based on a deformed reference state. Eventually, the present work based on the PGCM confirms that an a priori angular momentum restoration is necessary to handle consistently both collective motions at the same time. This further pleads in favor of implementing the full-fledged projected (quasi-particle) random phase approximation in the future.
Genuine N-partite entanglement in Schwarzschild-de Sitter black hole spacetime
Authors: Wu Shu-Min , Teng Xiao-Wei , Huang Xiao-Li , Lu Jianbo
Published: November 2024

Complex quantum information tasks in a gravitational background require multipartite entanglement for effective processing. Therefore, it is necessary to investigate the properties of multipartite entanglement in a relativistic setting. In this paper, we study genuine N-partite entanglement of massless Dirac fields in the Schwarzschild-de Sitter (SdS) spacetime, characterized by the presence of a black hole event horizon (BEH) and a cosmological event horizon (CEH). We obtain the general analytical expression of genuine N-partite entanglement shared by n observers near BEH and m ($$n+m=N$$

n
+
m
=
N

) observers near CEH. It is shown that genuine N-partite entanglement monotonically decreases with the decrease of the mass of the black hole, suggesting that the Hawking effect of the black hole destroys quantum entanglement. It is interesting to note that genuine N-partite entanglement is a non-monotonic function of the cosmological constant, meaning that the Hawking effect of the expanding universe can enhance quantum entanglement. This result contrasts with multipartite entanglement in single-event horizon spacetime, offering a new perspective on the Hawking effect in multi-event horizon spacetime.
Trends and Characteristics of the Whole-Grain Diet
Authors: Pei Qingyan , Chen Chuan , Bai Hao , Xi Yirong , Zhang Leilei , Li Haiming , Liu Houfu , Hao Yibin
Published: November 2024

Whole-grain foods are good choices for a nutritious diet and play an important role in lowering the risk of chronic diseases. China is a large cereal-consuming country that is experiencing rapid economic growth and an increased burden of noncommunicable diseases. Studies have shown that insufficient intake of whole grains has increased the burden on public health to some extent. Therefore, we aimed to analyze the characteristics and trends of whole-grain consumption in China to contribute to the development of a healthy Chinese population. We searched for important policies, standards, and dietary recommendations related to whole grains through the official websites of the China State Council and its affiliated ministries. Official and public databases, such as the National Bureau of Statistics and the China Health and Nutrition Survey (CHNS), were utilized to obtain data on whole grains and different foods. This approach was employed to gain insight into changes in whole-grain intake levels and dietary structure. Since 2010, the development of whole grains in China has received significant attention. Supportive policies have been continuously introduced on both the supply and demand sides. Numerous whole-grain standards have been developed, and terms and definitions related to whole grains have been preliminarily defined. The consumption of whole grains has fluctuated among Chinese residents since 2000, with a downward trend from 2000 to 2009, followed by an upward trend from 2009 to 2018. However, despite this increasing trend, the whole-grain intake of 80% of the adult residents was still lower than the minimum recommended dietary intake (50[Formula: see text]g/day). Furthermore, the dietary structure of Chinese residents has undergone a significant transformation, characterized by high consumption of high-fat foods, excessive consumption of meat, low intake of dietary fiber, and insufficient consumption of whole grains. These findings highlight the need for further monitoring of whole-grain intake in China. In addition, a sound whole-grain standardization system should be established, and the availability and consumer awareness of whole grains should be improved, with the goal of increasing the intake of whole grains.
A thermal insulation microactuator for Braille display using paraffin wax/carbon nanotube composite with induction heating
Authors: Liu Bendong , Ma Yongchang , Qin Hongye , Yang Jiahui , Kang Cunfeng
Published: November 2024

A new thermal insulation microactuator for Braille display using a phase change material (PCM) composite with induction heating is proposed. The PCM composite is prepared by fully mixing paraffin with multi-walled carbon nanotubes (MWCNTs), which is mainly used as both electrically and thermally conductive enhancer. As a result of that, the PCM composite is conductive and a wireless induction heating can be realized with the paraffin composite, which avoids the connection of wires from the inner chamber with a relatively simple fabrication process. In order to prevent the penetration of the paraffin from the elastic film, a solvent-resistant TPU diaphragm is adopted to seal the PCM chamber. In addition, thermal insulation between the higher temperature of PCM and the finger contact is designed by adding the PDMS diaphragm with PDMS pins. When the input power is 1.29[Formula: see text]W at AC frequency of 1[Formula: see text]kHz, the actuation height of the Braille dot reaches 259[Formula: see text][Formula: see text]m within 7[Formula: see text]s. The microactuator for Braille display presented in this paper has the advantages of short response time, thermal isolation, simple fabrication, small size and low cost.