bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal binding of cyclophilin A and CPSF6 to capsid regulates HIV-1 nuclear entry and integration
Authors: Ingram Zachary , Kline Christopher , Hughson Alexandra K. , Singh Parmit K. , Fischer Hannah L. , Radhakrishnan Rajalingham , Sowd Gregory A. , Dos Santos Nayara F. B. , Ganser-Pornillos Barbie K. , Watkins Simon C. , Kane Melissa , Engelman Alan N. , Ambrose Zandrea 
Published: February 2025

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) capsid, which is the target of the antiviral lenacapavir, protects the viral genome and binds multiple host proteins to influence intracellular trafficking, nuclear import, and integration. Previously, we showed that capsid binding to cleavage and polyadenylation specificity factor 6 (CPSF6) in the cytoplasm is competitively inhibited by cyclophilin A (CypA) binding and regulates capsid trafficking, nuclear import, and infection. Here, we determined that a capsid mutant with increased CypA binding affinity had significantly reduced nuclear entry and mislocalized integration. However, disruption of CypA binding to the mutant capsid restored nuclear entry, integration, and infection in a CPSF6-dependent manner. Furthermore, relocalization of CypA expression from the cell cytoplasm to the nucleus failed to restore mutant HIV-1 infection. Our results clarify that sequential binding of CypA and CPSF6 to HIV-1 capsid is required for optimal nuclear entry and integration targeting, providing insights for the development of antiretroviral therapies, such as lenacapavir.

IMPORTANCE
Human immunodeficiency virus (HIV) encodes a protein that forms a conical shell, called a capsid, that surrounds its genome. The capsid has been shown to protect the viral genome from innate immune sensors in the cell, to help transport the genome toward and into the nucleus, to keep the components of reverse transcription together for conversion of the RNA genome into DNA, and to target viral DNA integration into specific regions of the host genome. In this study, we show that HIV hijacks two host proteins to bind to capsid sequentially in order to choreograph the precise order and timing of these virus replication steps. Disruption of binding of these proteins to capsid or their location in the cell leads to defective HIV nuclear import, integration, and infection. Mutations that exist in the capsid protein of HIV in infected individuals may reduce the efficacy of antiretroviral drugs that target capsid.
HPSE-mediated proinflammatory signaling contributes to neurobehavioral deficits following intranasal HSV-1 infection
Authors: Borase Hemant , Patil Chandrashekhar D. , Valyi-Nagy Tibor , Shukla Deepak 
Published: February 2025

ABSTRACT

Herpes simplex virus-1 (HSV-1) is a neurotropic virus that can infect the brain, and an uncontrolled infection can lead to a range of diseases, including chronic nerve pain, encephalitis, and neurobehavioral abnormalities. These outcomes are often severe and have lasting consequences, highlighting the need to identify host factors that contribute to disease severity. In this study, we report that intranasal HSV-1 infection in murine model, which promotes viral dissemination into the brain, implicates the host protein heparanase (HPSE) as a key mediator of neuroinflammation. Specifically, we observed that the HPSE activity during HSV-1 infection in naïve animals promotes the upregulation of proinflammatory cytokines, enhances microglial activity in the brain, and contributes to cognitive impairment, anxiety, and motor coordination deficits. Such effects are significantly less detectable in heparanase deficient (
Hpse−/
−) mice. Additionally, we found that moderate activation of toll-like receptors (TLRs), particularly in
Hpse+/+
mice, may contribute to the activation of the inflammasome pathway. This, in turn, leads to the activation of caspase-1 (
Casp1
) and caspase-3 (
Casp3
), which may play a role in nerve function loss. Our findings position HPSE as a potential therapeutic target for mitigating virus-induced neuroinflammation and neurobehavioral defects.

IMPORTANCE
Herpes simplex virus-1 (HSV-1) infection in the brain can lead to severe and often permanent neurological consequences. Host factors influence disease outcomes in response to infection, and understanding these factors is crucial for developing effective therapies. This study identifies the host protein HPSE as a key mediator of neuroinflammation in response to HSV-1 infection. We demonstrate that the HPSE activity drives proinflammatory cytokine expression and microglial activation and promotes a signaling cascade involving toll-like receptors and caspase activation, potentially intensifying neuroinflammatory responses. These findings implicate HPSE as an important player in HSV-1 pathogenesis in the central nervous system and suggest that targeting HPSE could provide a novel therapeutic strategy to mitigate virus-induced neuroinflammation and neurobehavioral disturbance.
Draft genome sequences of 58 isolates of
Campylobacter jejuni
and
Campylobacter coli
from domestic ducks
Authors: Meinersmann Richard J. , Robinson-McKenzie Tanisha S. , McMillan Elizabeth 
Published: February 2025

ABSTRACT

We present the draft genomic sequences of 58 isolates of
Campylobacter
spp. (32
Campylobacter coli
and 26
Campylobacter jejuni
) isolated from domestic ducks (
Anas platyrhynchos domesticus
). This provides a substantial increase in the number of publicly available genomic sequences of
Campylobacter
isolated from farm-raised ducks in the United States.
Long-read transcriptomics of caviid gammaherpesvirus 1: compiling a comprehensive RNA atlas
Authors: Torma Gábor , Dörmő Ákos , Fülöp Ádám , Tombácz Dóra , Mizik Máté , Pretory Amanda M. , Lee See-Chi , Toth Zsolt , Boldogkői Zsolt 
Published: February 2025

ABSTRACT

Caviid gammaherpesvirus 1 (CaGHV-1), formerly known as the guinea pig herpes-like virus, is an oncogenic gammaherpesvirus with a sequenced genome but an as-yet uncharacterized transcriptome. Using nanopore long-read RNA sequencing, we annotated the CaGHV-1 genome and constructed a detailed transcriptomic atlas. Our findings reveal diverse viral mRNAs and non-coding RNAs, along with mapped promoter elements for each viral gene. We demonstrated that the CaGHV-1 RTA lytic cycle transcription factor activates its own promoter, similar to Kaposi’s sarcoma-associated herpesvirus (KSHV), and that the CaGHV-1 ORF50 promoter responds to RTA proteins from other gammaherpesviruses, highlighting the evolutionary conservation of RTA-mediated transcriptional mechanisms. Additionally, our analysis uncovered extensive transcriptional overlap within the viral genome, suggesting a role in regulating global gene expression. Given its tumorigenic properties, broad host range, and non-human pathogenicity, this work establishes CaGHV-1 as a promising small animal model for investigating human gammaherpesvirus pathogenesis.

IMPORTANCE
The molecular underpinnings of gammaherpesvirus pathogenesis remain poorly understood, partly due to limited animal models. This study provides the first comprehensive transcriptomic atlas of CaGHV-1, highlighting both coding and non-coding RNAs and revealing regulatory elements that drive viral gene expression. Functional studies of the CaGHV-1 RTA transcription factor demonstrated its ability to self-activate and cross-activate promoters from homologous gammaherpesviruses, reflecting conserved mechanisms of transcriptional control. These findings solidify CaGHV-1 as a unique and versatile small animal model, offering new opportunities to investigate gammaherpesvirus replication, transcriptional regulation, and tumorigenesis in a controlled experimental system.
Evolutionary trajectory of bacterial resistance to antibiotics and antimicrobial peptides in
Escherichia coli
Authors: Yu Feiyu , Wang Dejuan , Zhang Haijie , Wang Zhiqiang , Liu Yuan 
Published: February 2025

ABSTRACT

The global crisis of antimicrobial resistance poses a major threat to human health, underscoring the urgency of developing new antibacterial strategies. Antimicrobial peptides (AMPs) are promising alternatives to antibiotic therapy, yet potential microbial resistance is of great concern. Resistance is often accompanied by fitness costs, which may in turn influence the spread of drug-resistant bacteria and their susceptibility to other antimicrobial agents. Herein, we investigate the evolutionary trajectory of bacterial resistance to antibiotics and AMPs in
Escherichia coli
, and evaluate the fitness costs and collateral sensitivity of drug-resistant strains. We reveal that
E. coli
develops resistance to antibiotics, particularly ciprofloxacin and kanamycin, at a notably faster rate than to AMPs. Moreover, antibiotic-evolved strains exhibit slightly higher fitness costs than AMP-evolved bacteria, primarily manifested in reduced bacterial growth and swimming motility. Notably, we demonstrate that trimethoprim-resistant
E. coli,
with mutations in
thyA
gene, displays enhanced susceptibility to pexiganan, as evidenced by both
in vitro
and
in vivo
studies. Overall, our findings shed new insights for the clinical deployment of AMPs and propose innovative therapeutic strategies for combating antibiotic-resistant bacterial infections.

IMPORTANCE

The global spread of antimicrobial resistance necessitates the development of innovative anti-infective strategies. Antimicrobial peptides (AMPs) represent promising alternatives in the post-antibiotic era. By monitoring the evolutionary trajectory of bacterial resistance to eight antibiotics and ten AMPs in
Escherichia coli
, we demonstrate that
E. coli
exhibits slower emergence of resistance against AMPs compared with antibiotics. Additionally, these antibiotic-resistant strains incur significant fitness costs, particularly in bacterial growth and motility. Most importantly, we find that some antibiotic-resistant strains show collateral sensitivity to specific AMPs in both
in vitro
and animal infection models, which is conducive to accelerating the development of AMP-based antibacterial treatment.
In vitro
activities of lipopeptides against fluconazole-resistant
Candida auris
Authors: Fioriti Simona , Pallotta Francesco , D'Achille Gloria , Cirioni Oscar , Simonetti Oriana , Neubauer Damian , Kamysz Elzbieta , Kamysz Wojciech , Brescini Lucia , Caucci Sara , Caggiano Giuseppina , Giacometti Andrea , Morroni Gianluca , Barchiesi Francesco 
Published: February 2025

ABSTRACT

Candida auris
has increasingly become a global threat due to its wide range of antifungal resistances as well as its ability to sustain outbreaks in clinical settings. Two lipopeptides, C14-NleRR-NH
2
(Nel) and C14-WRR-NH
2
(WR), were evaluated against six fluconazole-resistant
C. auris
isolates. Both molecules showed good antimicrobial activity as demonstrated by MIC determination, time-kill, and microscopy experiments. The peptides were able to inhibit fungal growth, while sub-MIC concentrations of the molecules delayed the growth. Moreover, the combinations of the two peptides with fluconazole demonstrated a reciprocal potentiation by checkerboard and time-kill experiments. Our results showed that antimicrobial peptides could be a promising option for the treatment of antifungal-resistant
C. auris
.

IMPORTANCE

As well as antibiotics, also in fungal infections, antimicrobial resistance increased over the years. Moreover, in the last years, a new species emerged,
Candida auris
, as a nosocomial pathogen.
C. auris
possesses intrinsic resistance to common antifungals, such as azoles, that complicate therapeutic options. The combination of these two elements poses a risk for the treatment of fungal infections in the next years. The search for novel compounds with antimicrobial properties is crucial for the treatment of infections to overcome the increasing resistance of these etiological agents.
Comparative phenotypic and genotypic antimicrobial susceptibility surveillance in
Achromobacter
spp. through whole genome sequencing
Authors: Ray Sreejana , Flemming Laurie K. , Scudder Chelsea J. , Ly Melissa A. , Porterfield Harry S. , Smith Richard D. , Clark Andrew E. , Johnson J. Kristie , Das Sanchita 
Published: February 2025

ABSTRACT

Treatment of
Achromobacter
infections remains challenging due to intrinsic and acquired resistance to commonly used antimicrobial agents and no established clinical breakpoints. We attempted accurate species-level identification and compared the presence of genotypic resistance markers to phenotypic susceptibility patterns in retrospectively collected clinical isolates of
Achromobacter
spp. Our study concludes that
Achromobacter xylosoxidans
is the most prevalent species. Commercial matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) systems cannot accurately identify all
Achromobacter
species due to the limited inclusion of spectra in the databases. Phenotypic antimicrobial susceptibility testing (AST) confirms resistance to the majority of antibiotics tested. Newer agents like delafloxacin, plazomicin, and omadacycline showed little or no activity, while minimum inhibitory concentrations were low for eravacycline. In general, the species other than
A. xylosoxidans
showed lower MIC
50
and MIC
90
, especially to carbapenems and β-lactamase inhibitor combinations like piperacillin-tazobactam, meropenem-vaborbactam, and imipenem-relebactam. Genotypic analysis confirmed that
A. xylosoxidans
carries a high number of resistance genes, including multidrug efflux pump AxyXY-OprZ, several class D (OXA-type), and the Class A ß-lactamase

bla
AXC

, while
Achromobacter mucicolens
has the lowest number of resistance genes and no efflux pumps. This study concludes that there is significant genotypic and phenotypic diversity within the different species of
Achromobacter,
which are important for the identification of the species and for appropriate antimicrobial therapy.

IMPORTANCE

Identification and susceptibility testing of Gram-negative non-fermenting bacteria belonging to the genus
Achromobacter
is difficult due to the lack of robust databases in commercial identification systems such as matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) and clinical breakpoints for antimicrobial agents. Most clinical laboratories interpret minimum inhibitory concentration data using the “non-
Enterobacterales
” breakpoints included in the Clinical and Laboratory Standards Institute (CLSI) M100. These are breakpoints used for a group of organisms for which data is insufficient to provide species-specific interpretation. Our study provides phenotypic data regarding identification and susceptibility testing and correlates this with the genotypic characterization of 109 clinical isolates belonging to
Achromobacter
spp. This comprehensive study sheds light on the phenotypic and genotypic character of this bacteria, that is of increasing clinical relevance in hospital-acquired infections.
Fifteen-minute consultation: Approach to recurrent cutaneous and ophthalmic herpes simplex virus infection
Authors: Moore Tomas , Nourse Clare , Dai Shuan , Zappala Tania , Berkhout Angela 
Published: February 2025

Herpes simplex virus (HSV) infection in children is a common and challenging disease characterised by frequent misdiagnosis, a variety of treatment protocols and frequent recurrences from latent infection. With potential consequences such as pain, disfigurement, self-esteem issues, school exclusion and vision loss in eye disease, early diagnosis, informed management and appropriate interventions to prevent recurrences are essential.Management of HSV disease typically involves the use of oral antivirals for cutaneous disease and a combination of oral and topical treatment for eye disease. For children with recurrent disease, management options include episodic or chronic suppressive treatment for cutaneous disease, while longer-term suppressive therapy is often recommended for eye disease.
Retinal detachment incidence in refractive lens exchange versus cataract surgery: uncommon versus rare – systematic review and meta-analysis
Authors: Passaro Maria Laura , Kilic Deniz , Virgili Gianni , Romano Vito , Lucenteforte Ersilia , Dick Burkhard , Taneri Suphi 
Published: February 2025

AimsRefractive lens exchange (RLE) is becoming a popular refractive solution for patients ineligible for corneal surgeries or phakic intraocular lenses. However, concerns regarding retinal detachment (RD) risk persist.MethodsA systematic literature review and meta-analysis was performed in Medline and Scopus.The final search was updated on 30 March 2024.ResultsOf 2415 full-text screening reports, 40 studies met inclusion criteria, encompassing 8 592 380 eyes. This included 20 264 eyes that underwent RLE and 8 572 116 eyes that underwent cataract surgery. In the RLE surgery subgroup, the RD incidence for follow-up <12 months was 0.00016% (0.00000%; 0.00034%), for follow-up between 12 and 24 months was 0.0000% (0.0000%; 0.03102%), and for follow-up >24 months was 0.02312% (0.00984%; 0.03640%) (p<0.01). In the cataract surgery subgroup, the incidence for follow-up >24 months was 0.01244% (0.00655%; 0.01832%), and for missing follow-up was 0.00429% (0.00221%; 0.00637%).ConclusionsWe found that the incidence of RD after RLE was approximately double that observed after cataract surgery with at least 24 months (median 4 years) follow-up. Thus, RD may be classified as rare complication after cataract surgery (1/1000) and an uncommon complication after RLE (1/500). It must be noted that the heterogeneity of the subgroups after RLE was low. While some limitations, such as the lack of long-term follow-up in certain studies and incomplete reporting of factors like axial length or PVD status, may slightly influence the interpretation, these findings provide valuable insights. Acknowledging the inherent uncertainty in interpreting these results, additional studies are recommended.PROSPERO registration numberCRD42023431420.
Implementation strategies of financial navigation and its effects on alleviating financial toxicity among cancer survivors: a systematic review
Authors: Feng Yujia , Su Mingzhu , Sun Xiaojie , Zhang Jinxin , Yao Nengliang Aaron 
Published: February 2025

PurposeThis systematic review aims to identify the implementation strategies of financial navigation and systematically synthesise its effects on mitigating financial toxicity among cancer survivors, based on the theoretical framework of implementation science.MethodsMedline, Web of Science Core Collection, ScienceDirect and ProQuest Health & Medical Collection databases were searched for studies published before 22 August 2023. We sought original research on financial navigation interventions among adult cancer survivors with financial toxicity in healthcare settings. The Revised Cochrane risk-of-bias tool for randomised trials, 2.0 and the Risk Of Bias In Non-randomised Studies of Interventions-I were used to assess the risk of bias in included studies. In addition, the implementation strategies of the included studies were categorised and collated based on Expert Recommendations for Implementing Change, and the Consolidated Framework for Implementation Research was adopted to explain barriers and facilities for implementation.ResultsIn total, 6855 records were screened, yielding 14 full-text articles, which were included (3 randomised clinical trials and 11 non-randomised studies). ‘Train and educate stakeholders’ (n=13 (92.9%)) and ‘use evaluative and iterative strategies’ (n=12 (85.7%)) were the most common implementation strategies in financial navigation. The feasibility of financial navigation is relatively high, but generally hindered by the health condition of cancer survivors, low willingness to participate and insufficient number of navigators to cover all participants. After the intervention, three of seven studies reported statistically significant mitigations in patient-reported financial toxicity. In studies reporting statistically significant outcomes, ‘adapt and tailor to the context’ and ‘change infrastructure’ were proposed as key corresponding recommendations.ConclusionsFinancial navigation is a potentially beneficial intervention for lessening the financial toxicity of cancer survivors, but more high-level evidence is needed for further validation. Financial navigation combined with the theoretical framework of implementation science provides a foundation for the future realisation of the leap from knowledge to practice.PROSPERO registration numberCRD42023469114.
Genetic contributions to the educational inequalities in coronary heart disease incidence: a population-based study of 32 000 middle-aged men and women
Authors: Silventoinen Karri , Lahtinen Hannu , Korhonen Kaarina , Morris Tim T , Martikainen Pekka 
Published: February 2025

BackgroundThe background of educational disparities in coronary heart disease (CHD) risk is still not well understood. We used a polygenic score for education (PGSEDU), socioeconomic indicators and indicators of CHD risk to investigate whether these disparities result from causality or are influenced by shared factors.MethodsPopulation-based health surveys including baseline measures on cardiometabolic risk factors at 25–70 years of age (N=32 610) and PGSEDUwere conducted in Finland between 1992 and 2011. Longitudinal information on education, social class, income and CHD incidence (1716 CHD cases up to 2019) was based on national registers. Linear regression, Poisson regression, Cox regression and linear structural equation models were used.ResultsEducation and PGSEDUwere inversely associated with body mass index, systolic and diastolic blood pressure, total cholesterol and CHD incidence and positively associated with high-density lipoprotein cholesterol in men and women. Part of the associations of PGSEDUwith CHD incidence (57% in men and 28% in women) and cardiometabolic factors (30%–55% and 31%–92%, respectively) were mediated by education, social class and income, but a substantial part of them was independent of socioeconomic factors. These associations were consistent across different levels of education.ConclusionsPGSEDUcaptures CHD risk that is not solely attributable to education and other socioeconomic indicators. This suggests that not only causality affects the educational disparities of CHD risk but also factors reflected by PGSEDUcan contribute to them. Identifying these factors can help to understand and reduce socioeconomic health disparities.