bluuebunny/crossref_metadata_2025 huggingface dataset:
Sutton Hoo and Syria: The Anglo-Saxons Who Served in the Byzantine Army?
Authors: Gittos Helen
Published: January 2025

The Sutton Hoo ship burial is one of the most famous examples of a group of lavishly furnished graves of the late sixth and early seventh centuries in south-east England. The discovery in 2003 of another, at Prittlewell (in Southend, Essex), and its publication in 2019, has brought our knowledge of them into sharper focus. One of the characteristics of these burials is that they tend to contain objects that were made in the eastern Mediterranean which were current, rather than old, when buried, and were of very unusual types. This article argues that they were acquired by men who were recruited into the Byzantine army in 575 to serve on the eastern front against the Sasanians. Those who returned brought back with them metalwork and other items which were current, and distinctive, and not the kinds of things that were part of normal trading networks. This opens up a startlingly new view onto early medieval British history.
Jacalin Attenuates Colitis-Associated Colorectal Carcinogenesis by Inhibiting Tumor Cell Proliferation and Intestinal Inflammation
Authors: Veronez Luciana Chain , Silveira Denise Sayuri Calheiros da , Lopes-Júnior Luis Carlos , dos Santos Jéssica Cristina , Barbisan Luis Fernando , Pereira-da-Silva Gabriela
Published: January 2025

Background

Colorectal cancer (CRC) remains a significant cause of morbidity and mortality worldwide. In patients with inflammatory bowel disease, who have twice the risk of developing CRC, chronic inflammation has been recognized to contribute to colitis-associated cancer (CAC) development. Jacalin, a lectin extracted from jackfruit seeds, has been shown to recognize altered glycosylation and to exert antiproliferative and cytotoxic effects in CRC. However, its activity in CAC remains unknown. Herein, we sought to investigate the effects of jacalin in CAC progression using the dextran sulfate sodium (DSS) and azoxymethane (AOM) mouse model.

Methods

Colitis-associated cancer induction was performed in male C57BL/6 mice by an intraperitoneal injection of AOM, followed by 3 cycles of 2.5% DSS diluted in drinking water for 7 days, intercalated by 2 weeks of normal drinking water. After 1 week of daily pretreatment, mice were orally treated with phosphate-buffered saline (control group), 100 or 500 µg of jacalin three times a week for an additional 11 weeks.

Results

We showed that jacalin-treated mice presented tumors with reduced volumes and mean size compared to the control group. In addition, both doses of jacalin reduced the number of proliferating cells (Ki-67 positive cells) in tumor tissues, while the higher dose (500 µg) showed also a similar effect in “normal-appearing” colonic crypts. Jacalin treatment attenuated the clinical scores of inflammations, which was accompanied by a reduction of intestinal and/or tumoral production of IL-1β, IL-23, and IL-17.

Conclusions

Collectively, our findings demonstrated that jacalin suppresses CAC development, highlighting its anti-inflammatory and antitumoral role in the AOM/DSS-induced model.
Polymerase-usage sequencing identifies initiation zones with less bias across S phase in mouse embryonic stem cells
Authors: Matsumoto Akino , Daigaku Yasukazu , Tsubouchi Tomomi
Published: January 2025

Various methods have been developed to map replication initiation zones (IZs) genome-wide, often finding far fewer IZs than expected. In particular, IZs corresponding to later stages of S phase are under-represented. Here, we reanalysed IZs with respect to replication timing in mouse ES cells. These datasets identified over five times as many early IZs compared to late IZs. In addition, we have set up a polymerase-usage sequencing (Pu-seq) system in mouse ES cells to map IZs genome-wide. Pu-seq showed less bias towards early IZs, potentially indicating better sensitivity for identifying IZs in late S phase.
Complete traumatic urethral cut and vesicovaginal fistula in a 3-year-old girl, managed by Mitrofanoff procedure: a case report
Authors: Bael Peter R , Alqtishat Bayan F , Salahaldeen Riyad , Barbarawi Wadee’
Published: January 2025

We report a 3-year-old patient with urethral cut injury and iatrogenic vesicovaginal fistula following a pelvic fracture; managed with Mitrofanoff procedure. Our patient presented with straining on urination with continuous colorless discharge on her diaper for the past 4 months. Investigations identified vesicovaginal fistulization making a definitive diagnosis of complete urethral injury. It was managed with the Mitrofanoff procedure to preserve the patient’s urinary continence. Our case is to our knowledge the youngest reported case of a complete traumatic urethral cut in a female; an already rare encounter in this population. This is also the first such case to be managed via the Mitrofanoff procedure. Although the management was delayed, it was successful.
Distressing dreams in trauma survivors: using a sleep diary mobile app to reveal distressing dream characteristics and their relationship to symptoms and suicidal ideation in trauma-exposed adults
Authors: Richards Anne , Santistevan Anthony , Kovnick Miles , Orlova Polina , Yack Leslie , Berg Emily , Pracar Shane , Metzler Thomas , Neylan Thomas , Woodward Steven
Published: January 2025

Study Objectives

Trauma nightmares are a core feature of PTSD, with potentially devastating implications for mental health outcomes. Treatments remain unsatisfactory and nightmares are poorly understood, both biologically and phenomenologically; measurement methods are limited. The aims of the current analyses were to (1) characterize distressing dreams in trauma survivors, (2) examine the relationships of dream features to next-day symptoms and to suicidal ideation, and (3) validate sleep diary mobile app items for the measurement of clinically relevant dream characteristics.

Methods

Adult male and female veterans and nonveterans with a history of PTSD criterion trauma and at least 1 nightmare weekly were enrolled. Participants completed 3 weeks of sleep diary, including bedtime and morning surveys and weekly assessments. They also completed a Clinician-Administered PTSD Scale (CAPS)-5 PTSD assessment. Multivariable mixed models with repeated measures and standard regression were utilized to examine relationships between dream features and next-day symptoms and suicidal ideation.

Results

Dream features and dream distress independently predict clinically relevant outcomes; no single feature was sufficient for predicting all outcomes of interest. In particular, the replicative quality of trauma nightmares stood out in terms of associations with next-day symptoms, CAPS severity, and suicidal ideation. Subjective dream duration, extent of postdream arousal, and subjective distress severity also independently predicted daytime symptoms.

Conclusions

Results underscore the importance of examining dream characteristics to understand nightmare effects and associations with suicidal ideation. These findings also underscore the utility of mobile app technology for obtaining informative data with high temporal resolution in an appealing and user-friendly manner.
Assessing Susceptibility of Grapevine Cultivars to Latent Plasmopara viticola Infections Using Molecular Disease Index
Authors: Yang Lujia , Chu Bingyao , Deng Jie , Shen Zhaomeng , Sun Qiuyu , Lv Xuan , Zhan Jiasui , Ma Zhanhong
Published: January 2025

Traditional assessments of grapevine susceptibility to grapevine downy mildew (GDM) caused by Plasmopara viticola rely on the visual evaluation of leaf symptoms. In this study, we used a well-established quantitative real-time PCR TaqMan assay (real-time PCR) to quantify the number of P. viticola infecting 12 grapevine cultivars under controlled conditions. The molecular disease index (MDI), derived from molecular detection methods, reflects the relative abundance of pathogens in plant tissues during the latent infection phase. Our application of MDI revealed a progressive increase in latent P. viticola levels over time, indicating dynamic levels of latent P. viticola infection across the inoculation processes. We calculated the area under the disease progression curve in terms of MDI (AUDPCMDI) to evaluate the susceptibility of each cultivar to GDM. Cultivars with lower AUDPCMDI values consistently exhibited reduced pathogen establishment, suggesting higher levels of innate resistance. Correlation analysis revealed a significant correlation between the visual disease index (DI) and the AUDPCMDI values (r = 0.790, P = 0.002), indicating that higher levels of latent P. viticola infections were associated with higher disease severity. Grapevine cultivars were clustered into distinct groupings, indicating variability in their susceptibility to the pathogen. Cultivars with similar levels of susceptibility were grouped, highlighting that the real-time PCR assay used in this study represents a robust, rapid, and standardized method for quantifying pathogens, which significantly improves the efficiency of evaluating the susceptibility of grapevine cultivars to GDM This quantitative protocol provides practical guidelines for selecting resistant cultivars and implementing effective disease management strategies.
Prevalence of Words and Phrases Associated With Large Language Model–Generated Text in the Nursing Literature
Authors: Bailey Hannah E. , Carter-Templeton Heather , Peterson Gabriel M. , Oermann Marilyn H. , Owens Jacqueline K.
Published: January 2025

All disciplines, including nursing, may be experiencing significant changes with the advent of free, publicly available generative artificial intelligence tools. Recent research has shown the difficulty in distinguishing artificial intelligence–generated text from content that is written by humans, thereby increasing the probability for unverified information shared in scholarly works. The purpose of this study was to determine the extent of generative artificial intelligence usage in published nursing articles. The Dimensions database was used to collect articles with at least one appearance of words and phrases associated with generative artificial intelligence. These articles were then searched for words or phrases known to be disproportionately associated with large language model–based generative artificial intelligence. Several nouns, verbs, adverbs, and phrases had remarkable increases in appearance starting in 2023, suggesting use of generative artificial intelligence. Nurses, authors, reviewers, and editors will likely encounter generative artificial intelligence in their work. Although these sophisticated and emerging tools are promising, we must continue to work toward developing ways to verify accuracy of their content, develop policies that insist on transparent use, and safeguard consumers of the evidence they generate.
Prevention of gynecological cancers: cervical cancer screening in Turkey: a role model for the world
Authors: Akgör Utku , Temiz Bilal Esat , Gultekin Murat
Published: January 2025

Purpose of review

This review examines Turkey's cervical cancer screening programme, highlighting its evolution from a cytology-based approach to a more effective HPV-based strategy. The review is timely given the global push to reduce cervical cancer incidence through improved screening practices, and it positions Turkey's programme as a potential model for other countries facing similar public health challenges.

Recent findings

Recent advances in cervical cancer screening in Turkey include the nationwide introduction of HPV DNA testing, centralized laboratory systems and innovative management software. The programme has significantly improved screening coverage and early detection rates, particularly in underserved communities. However, challenges remain in areas such as training healthcare workers, raising awareness of HPV vaccination, and integrating self-sampling methods into the screening process.

The Turkish experience demonstrates that a well organized HPV-based cervical cancer screening programme can overcome significant cultural and logistical barriers and lead to improved public health outcomes. Future efforts should focus on refining triage strategies, exploring new molecular tests, and expanding the use of self-sampling to further improve the effectiveness of cervical cancer prevention efforts worldwide.
Contemporary nonsurgical management of Peyronie's disease
Authors: Pinkhasov Alexandr M. , Yang David Y. , Tentis Elise , Ziegelmann Matthew
Published: January 2025

Purpose of review

Peyronie's disease characterizes a condition in which there is angular curvature of the penis. We know that the most patients with Peyronie's disease will not have spontaneous resolution of their penile curvature. As such, patients who desire treatment can elect for either surgical or nonsurgical therapy. Herein, we discuss the contemporary nonsurgical management options for Peyronie's disease.

Recent findings

Nonsurgical management options for Peyronie's disease include oral therapy, intra-lesional injections, and penile traction therapy. At the time of this review, there is essentially no high-level evidence demonstrating any benefit for oral therapy. Penile traction therapy has evolved over the past decade with second-generation devices demonstrating strong efficacy and more convenient treatment regimens. Intra-lesional options include collagenase Clostridium histolyticum (CCH), verapamil, and interferon alpha-2b. The IMPRESS trial garnered the strongest level of evidence (two randomized, double-blind, placebo-controlled trials) to support the safety and efficacy of CCH. Verapamil is an option supported by several urological societies; however, the evidence supporting its efficacy is inconsistent between several notable series and randomized studies. IFN alpha 2b can produce modest improvement in curvature, however, is not available for use in North America.

Herein, we will discuss notable advances in nonsurgical management of Peyronie's disease.
A Meta-analysis of Breast Implant Irrigation Solutions' Effect on Infection and Capsular Contracture Frequencies
Authors: Engels Ella , Sweitzer Keith , Kumar Shivram , Jones Courtney , Leach Candice
Published: January 2025

Background

In implant-based breast surgery, use of implant irrigation to reduce biofilm, thus reducing infection and capsular contracture, is standard practice. However, it is unclear which irrigation is superior.

Objective

The aim of this systematic review was to evaluate the most commonly cultured bacteria from infected implants and the efficacy of different irrigation solutions in reducing the risk of implant infection and capsular contracture.

Methods

Using Covidence, 808 studies published in the last 30 years in relation to implant irrigation use during implant-based breast augmentation and reconstruction surgery were identified. These studies were screened based on the eligibility criteria, and 27 studies were included as a part of the systematic review. The primary outcome measures of interest were implant infection and capsular contracture frequencies. Saline, povidone-iodine, chlorhexidine, triple antibiotic solution (TAS), and other antibiotics (eg, biodegradable antibiotic beads, bacitracin, and continuous vancomycin), were the different types of irrigation solutions identified in these studies. Descriptive analysis of the different species of bacteria cultured from all infected implants was conducted. A meta-analysis was performed to generate a summary proportion of the primary outcomes for implant irrigations.

Results

Staphylococcus aureus (25.5%), coagulase-negative Staphylococcus (19.8%), and Pseudomonas aeruginosa (9.1%) were the most frequently cultured bacteria from infected implants. Gram-positive bacteria (62.6%) were more commonly cultured from infected implants than gram-negative (16.1%) bacteria. Povidone-iodine showed the lowest infection frequency, while saline and TAS showed the highest infection frequencies. Additionally, TAS showed the lowest capsular contracture frequency, while saline and povidone-iodine showed higher capsular contracture frequency.

Conclusions

Povidone-iodine was the most effective in reducing infection frequency while TAS was the most effective in reducing capsular contracture frequency. As the TAS in these studies include cefazolin, gentamycin, and bacitracin (which is no longer available as a solution), further research to determine efficacy of antibiotic solution without bacitracin is required. To potentially reduce the risk of implant infection and capsular contracture, plastic surgeons should consider which implant irrigation solutions are most effective against common bacterial pathogens.
Tracing the stepwise Darwinian evolution of a plant halogenase
Authors: Kim Colin Y. , Kastner David W. , Mitchell Andrew J. , Gutierrez Michael A. , Yao Jocelyn S. , Neumann Edwin N. , Kulik Heather J. , Weng Jing-Ke
Published: January 2025

Halogenation chemistry is rare in plant metabolism, with the chloroalkaloid
acutumine produced by Menispermaceae species being the only well characterized
example, involving a specialized dechloroacutumine halogenase (DAH) from the
iron(II)- and 2-oxoglutarate-dependent dioxygenase (2ODD) superfamily. While DAH
is presumed to have evolved from an ancestral 2ODD enzyme, the broader question
of how new enzymes arise through Darwinian processes, such as the birth of DAH
in Menispermaceae, remains a fundamental challenge in understanding metabolic
evolution. Here, we investigate DAH’s evolutionary trajectory using the
chromosomal-level genome assembly ofMenispermum
canadense. By analyzing the genomic context
ofDAHinM. canadenseand
syntenic regions in related plants, we show
thatDAHevolved through tandem duplication of an
ancestralflavonol
synthase(FLS) gene, followed by a
series of neofunctionalization and gene loss events. Through structural
modeling, molecular dynamics simulations, and site-directed mutagenesis, we
identify residue changes enabling the transition from FLS to DAH. This
functional switch required traversing a complex evolutionary landscape where
adaptive peaks were separated by deep fitness valleys. Our work illustrates how
new enzymatic functions can arise through lineage-specific evolutionary pathways
that gradually reshape the active site architecture through permissive
mutations, ultimately enabling mechanism-switching mutations that establish
novel catalytic activities.
Genomic Insights into Hybridization and Speciation of Mitten Crabs in
theEriocheirGenus
Authors: Wang Jun , Hou Xin , Chen Xiaowen , Mandal Roland Nathan , Kanika Nusrat Hasan , Yuan Chunhong , Luo Yongju , Wang Chenghui
Published: January 2025

Hybridization is a prominent and influential phenomenon with significant
implications for adaptive evolution, species distribution and biodiversity.
However, the intricacies of how hybridization influences genomic structure and
facilitates adaptive evolution still elude our full understanding. Analyzing
whole genome data from seven populations
withinEriocheirgenus across diverse geographic
regions, we have validated a complex hybridization history between Chinese and
Japanese mitten crabs. This hybridization gave rise to two distinct ecological
species: Hepu and Russian mitten crabs with unique genomic architectures and
adaptations. Genes related to reproduction, development, and temperature
adaptation exhibit divergent selection signals, potentially contributing to
their phenotypic diversity and ecological niches. Meanwhile, genes associated
with reproduction,
namelyBirc6,Bap31,
andPoxn, displayed robust evidence of selective
sweeps in Hepu mitten crab. Notably, the favored alleles for these genes
originated from the parental lineages during the hybridization process.
Furthermore, Hepu mitten crab is a homoploid hybrid species that originated from
an ancient hybridization event, resolving its longstanding taxonomic
controversy. Our study sheds light on the evolutionary history of mitten crabs
and highlights the crucial role of hybridization in driving adaptation, range
expansion, and diversification within
theEriochiergenus.
Microbial functional guilds and genes are key to explaining soil nutrient
cycling alongside soil and plant variables
Authors: Vietorisz Corinne , Policelli Nahuel , Li Abigail , Adams Lindsey A. , Bhatnagar Jennifer M.
Published: January 2025

Microbes play central roles in soil nutrient cycling, yet a limited range of
microbial community characteristics have been used to explain ecosystem nutrient
cycling rates and their importance relative to plant and abiotic factors remains
unclear. In this study, we assessed which of 126 commonly measured soil fungal
and bacterial community characteristics best explained soil nitrogen (N) and
phosphorus (P) cycling rates in temperate forests in the Northeastern U.S., as
well as the relative contributions of microbial, plant, and abiotic factors.
Using boosted regression tree modeling, we identified the microbial variables
with the highest contributions to models explaining nutrient cycling rates: the
relative abundances of ectomycorrhizal fungi and N-decomposition genes from
oligotrophic bacteria were the most important for net ammonification, the
relative abundances of indicator taxa in bacterial networks, nitrifying
bacteria, and copiotrophic bacteria were the most important for net
nitrification, and the relative abundance of fungal P-cycling oxidoreductase
genes was the most important for net soil phosphate change. Microbial variables
explained more variation than plant and abiotic variables in multivariate linear
models of net nitrification and net phosphate release rates, but not net
ammonification rates, which were largely explained by soil edaphic factors. Leaf
litter traits were also important in explaining variation in net nitrification
rates, and soil temperature was important in explaining rates of net phosphate
release in soil. Collectively, our findings suggest that the N-cycling capacity
of microbial functional guilds and fungal community P-cycling capacity should be
incorporated into ecosystem biogeochemical models to improve our predictions and
understanding of nutrient cycling and related ecological processes.
An unsupervised framework for comparing SARS-CoV-2 protein sequences using
LLMs
Authors: Littlefield Sayantani B. , Campbell Roy H.
Published: January 2025

The severe acute respiratory system coronavirus 2 (SARS-CoV-2) pandemic led
to more than a 100 million infections and 1.2 million deaths worldwide. While
studying these viruses, scientists developed a large amount of sequencing data
that was made available to researchers. Large language models (LLMs) are
pre-trained on large databases of proteins and prior work has shown its use in
studying the structure and function of proteins. This paper proposes an
unsupervised framework for characterizing SARS-CoV-2 sequences using large
language models. First, we perform a comparison of several protein language
models previously proposed by other authors. This step is used to determine how
clustering and classification approaches perform on SARS-CoV-2 and influenza
sequence embeddings. In this paper, we focus on surface glycoprotein sequences,
also known as spike proteins in SARS-CoV-2 because scientists have previously
studied their involvements in being recognized by the human immune system. Our
contrastive learning framework is trained in an unsupervised manner, leveraging
the Hamming distance from pairwise alignment of sequences when the contrastive
loss is computed by the Siamese Neural Network. Finally, to test our framework,
we perform experiments on two sets of sequences: one group belonging to a
variant the model has not encountered in the training and validation phase
(XEC), and the other group which the model has previously encountered (BA.2). We
show that our model can acknowledge the sequences come from different groups
(variants) as confirmed by a statistical Kolmogorov-Smirnov test. This shows
that our proposed framework has properties suitable for identifying
relationships among different SARS-CoV-2 sequences even in the absence of
variant or lineage labels.
Centralized brain networks underlie body part coordination during
grooming
Authors: Özdil Pembe Gizem , Arreguit Jonathan , Scherrer Clara , Ijspeert Auke , Ramdya Pavan
Published: January 2025

Animals must coordinate multiple body parts to perform important tasks such
as grooming, or locomotion. How this movement synchronization is achieved by the
nervous system remains largely unknown. Here, we uncover the neural basis of
body part coordination during goal-directed antennal grooming in the
fly,Drosophila melanogaster. We find that
unilateral or bilateral grooming of one or both antenna, respectively, arises
from synchronized movements of the head, antennae, and forelegs. Simulated
replay of these body part kinematics in a biomechanical model shows that this
coordination makes grooming more efficient by permitting unobstructed, forceful
collisions between the foreleg tibiae and antennae. Movements of one body part
do not require proprioceptive sensory feedback from the others: neither
amputation of the forelegs or antennae, nor immobilization of the head prevented
movements of the other unperturbed body parts. By constructing a comprehensive
antennal grooming network from the fly brain connectome, we find that
centralized interneurons and shared premotor neurons interconnect and thus
likely synchronize neck, antennal, and foreleg motor networks. A simulated
activation screen of neurons in this network reveals cell classes required for
the coordination of antennal movements during unilateral grooming. These cells
form two coupled circuit motifs that enable robust body part synchronization: a
recurrent excitatory subnetwork that promotes contralateral antennal pitch and
broadcast inhibition that suppresses ipsilateral antennal pitch. Similarly
centralized controllers may enable the flexible co-recruitment of multiple body
parts to subserve a variety of behaviors.
Resolving the Dynamic Interplay of the Conformational States in the TPR
Domain of Human AMPylase FicD
Authors: Runge Svenja , Bilgen Ecenaz , Itzen Aymelt , Lamb Don C.
Published: January 2025

The human Fic-enzyme FicD plays an important role in regulating the Hsp70
homolog BiP in the endoplasmic reticulum (ER): FicD reversibly modulates BiP’s
activity through attaching an adenosine monophosphate (AMP) to the substrate
binding domain. This reduces BIP’s chaperone activity by shifting it into a
conformation with reduced substrate affinity. Crystal structures of FicD in the
apo, ATP-bound, and BiP-bound states revealed significant conformational
variability in the tetratricopeptide repeat (TPR) motifs. In this study, we
investigate the conformational dynamics of FicD’s TPR motifs using two-color
single-molecule Förster resonance energy transfer (smFRET). We demonstrate that
the TPR motifs exhibit conformational dynamics between the TPR-out and TPR-in
conformations on timescales ranging from milliseconds to microseconds. In
addition, we extend our investigation on multiple labeling positions within
FicD, revealing how conformational dynamics vary depending on the location
within the TPR motif. We quantify the motions with dynamic photon distribution
analysis (PDA) for the FRET constructs and propose a conformational landscape
model for FicD where the TPR-in/out states exist in an equilibrium that is
altered due to the presence of ATP and BiP.
Sustained efficacy of CRISPR-Cas13b gene therapy for FSHD is challenged by immune response to Cas13b
Authors: Rashnonejad Afrooz , Farea Manal , Amini-Chermahini Gholamhossein , Coulis Gerald , Taylor Noah , Fowler Allison , Villalta Armando , King Oliver D. , Harper Scott Q.
Published: January 2025

Facioscapulohumeral muscular dystrophy (FSHD) is a potentially devastating muscle disease caused by de-repression of the toxicDUX4gene in skeletal muscle. FSHD patients may benefit fromDUX4inhibition therapies, and although several experimental strategies to reduceDUX4levels in skeletal muscle are being developed, no approved disease modifying therapies currently exist. We developed a CRISPR-Cas13b system that cleavesDUX4mRNA and reduces DUX4 protein level, protects cells from DUX4-mediated death, and reduces FSHD-associated biomarkersin vitro.In vivodelivery of the CRISPR-Cas13b system with adeno-associated viral vectors reduced acute damage caused by highDUX4levels in a mouse model of severe FSHD. However, protection was not sustained over time, with decreases in Cas13b and guide RNA levels between 8 weeks and 6 months after injection. In addition, wild-type mice injected with AAV6.Cas13b showed muscle inflammation with infiltrates containing Cas13b-responsive CD8+ cytotoxic T cells. Our RNA-seq data confirmed that several immune response pathways were significantly increased in human FSHD myoblasts transfected with Cas13b. Overall, our findings suggest that CRISPR-Cas13b is highly effective forDUX4silencing but successful implementation of CRISPR/Cas13-based gene therapies may require strategies to mitigate immune responses.
A simple silicone elastomer colonisation model highlights complexities ofCandida albicansandStaphylococcus aureusinteractions in biofilm formation
Authors: McConnell Gail , Rooney Liam M. , Sandison Mairi E. , Hoskisson Paul A. , Baxter Katherine J.
Published: January 2025

Healthcare-associated infections (HAIs) significantly contribute to the burden of antimicrobial resistance (AMR). A major factor in HAIs is the colonisation of indwelling medical devices by biofilm-forming opportunistic pathogens such asCandida albicansandStaphylococcus aureus. These organisms frequently co-infect, resulting in synergistic interactions with enhanced virulence and resistance to treatment.C. albicansandS. aureusreadily form dual-species biofilms on silicone elastomers, a commonly used medical device material, yet the colonisation phenotypes of these organisms on such surfaces remains poorly understood.

We developed a simple, optically tractable model to mimic the colonisation of indwelling medical devices to investigateC. albicansandS. aureusbiofilm formation. The system utilises discs of a silicone elastomer embedded in agar, reflecting device-associated conditions and enabling high-resolution imaging of biofilms formed byC. albicansandS. aureusco-culture. Initial results using the silicone elastomer colonisation model reveal robust biofilm formation. These biofilms exhibited morphological differences between dual species biofilms formed byS. aureusco-cultures with either yeast- or hyphal-formC. albicans, indicating the impact of differingC. albicanscell morphotypes in biofilm-associated medical device colonization on silicone elastomers. Quantification of biofilm formation by crystal violet staining provided further validation of the system. These findings underscore the importance of developing tools for biofilm study which more closely resemble the infectious microenvironment, with our work detailing such a system which can be employed in further study to improve strategies against device-related HAIs.
A secreted helminth microRNA suppresses gastrointestinal cell differentiation
required for innate immunity
Authors: Perez Matias G. , Gillan Victoria , Anderson William M. , Gerbe François , Herbert Fabien , McNeilly Tom N. , Maizels Rick M. , Jay Philippe , Devaney Eileen , Britton Collette
Published: January 2025

Pathogens have developed multiple strategies to modulate host immune defense
mechanisms. Understanding how this is achieved has potential to inform novel
therapeutics for diseases caused by immune dysfunction. Parasitic helminths are
masters of immune evasion, via release of secreted products, resulting in
chronic infection. Helminths secrete small regulatory microRNA (miRNAs), which
can interact with host cells. Here we show that a single parasite miRNA
(miR-5352), conserved across gastrointestinal (GI) nematodes, suppresses
IL-13-induced GI epithelial cell differentiation and cytokine responses, and
promotes stem cell maintenance. Mechanistically, this is achieved through
targeted repression of critical host factors, including Klf-4 and the IL-22
receptor, together with modulation of Wnt and Notch signalling pathways.
Nematode miR-5352 shows seed sequence conservation with mammalian miR-92a family
members, indicating that through convergent evolution, GI nematodes exploit a
host miRNA regulatory network to suppress host innate responses, promote tissue
regeneration and establish a favourable environment for chronic
infection.
Genomic feature of filled regions of telomere-to-telomere genomes in five model species
Authors: Xiong Chu , Zheng Jun , Zhang Hui , Zhang Yunpeng , Hao Lihong , Wang Min , Liang Zhen
Published: January 2025

T2T genome is a telomere-to-telomere high-quality genome with exceptional accuracy, continuity and integrity. It significantly filled some gaps of chromosome. However, the genomic features unique to the filled regions assembled in the T2T genome across species remain unclear. Here, we collected and compared T2T genomes with their older version from human (Homo sapiens), animal (Mus musculus), and plants (Arabidopsis thaliana,Musa acuminata, andFragaria vesca). We explored the newly filled regions generated by the T2T genome in comparison to the old one, and focused on: (1) the comparison of their locations, (2) the distribution of genomic features, and (3) gene annotation and gene function for filled regions. Research indicated that the filled regions of the T2T genome ordinarily appear in the centromere and telomere regions, contain a great number of repetitive sequences. The T2T genome revealed the identification of a certain number of newly annotated genes, alongside significant variations in common annotated genes. Interestingly, the genomic features of filled regions exhibit distinct patterns between plants and human/animal. T2T genomes feature analysis serves as a crucial resource for studying pattern characteristics across diverse species and advancing the in-depth development of genomics.
Molecular mechanisms underlying p62-dependent secretion of the Alzheimer-associated ubiquitin variant, UBB+1
Authors: Wagh Ajay R. , Glickman Michael H.
Published: January 2025

UBB⁺¹, a ubiquitin variant protein arising from a frameshift in the ubiquitin-B gene, is a pathological marker in the brains of Alzheimer disease (AD) patients. At the cellular level, UBB⁺¹ disrupts the ubiquitin-proteasome system while simultaneously activating autophagy. UBB⁺¹ is itself secreted in autophagosome-like vesicles. Secretory autophagy mediates the release of cytosolic proteins via the fusion of autophagosomes with the plasma membrane, bypassing lysosomal degradation. We demonstrate that SQSTM1/p62 plays a pivotal role in UBB⁺¹ secretion by acting as a ubiquitin receptor for its ubiquitin domain thereby facilitating UBB⁺¹ loading into autophagosome-like vesicles. Gain- and loss-of-function studies reveal that SQSTM1/p62 is critical for regulating both intracellular and extracellular UBB⁺¹ levels. Knockout of SQSTM1/p62 resulted in the accumulation of UBB⁺¹ in insoluble aggregates, while its overexpression promoted the formation of p62-UBB⁺¹ bodies. Notably, under both conditions, UBB⁺¹ secretion was suppressed, leading to its intracellular retention. This study reveals distinct roles for SNARE-mediated membrane fusion in degradative and secretory autophagy pathways. Specifically, SEC22B (an R-SNARE) and Syntaxin-4 (STX4) (a Q-SNARE) are identified as key mediators of UBB⁺¹ exocytosis. Disruption of these SNAREs impaired the fusion of UBB⁺¹-containing autophagosomes with the plasma membrane, significantly reducing UBB⁺¹ secretion while leaving intracellular turnover unaffected. This study highlights a dual role for autophagy in managing neurotoxic proteins, with SQSTM1/p62 serving as a critical ubiquitin receptor for UBB⁺¹ trafficking and secretion. These findings offer new insights into the cellular mechanisms underlying the clearance of misfolded proteins in neurodegenerative diseases.
Resolving vs. Non-resolving Sphingolipid Dynamics During Macrophage Activation: A Time-resolved Metabolic Analysis
Authors: Chiappa Nathan A. , Lal Nidhi , Botchwey Edward A.
Published: January 2025

Sphingolipids are increasingly recognized as critical regulators of inflammation and cell fate decisions, with metabolites such as ceramide and sphingosine 1-phosphate exerting contrasting effects on survival and pro-inflammatory signaling. In macrophages, this balance is especially important, given their central role in host defense, pathogenesis and wound healing. Here, we present a time-resolved model of sphingolipid metabolism in RAW 264.7 macrophages stimulated with KdO₂–Lipid A. By integrating measured metabolite concentrations with flux balance analysis and established enzyme kinetics, we systematically map dynamic changes in the sphingolipid network during inflammation. Our results reveal a three-phase pattern of sphingolipid remodeling that correlates with distinct functional states of the cell. Moreover, metabolites can be classified into “resolving” or “non-resolving” lipids based on whether they return to basal levels or remain dysregulated through the later phases of the inflammatory response. This partitioning suggests that targeted modulation of specific metabolic nodes may influence the resolution of inflammation. Importantly, our computational approach can assist in the rational design of experimental studies by pinpointing putative drug targets with maximal impact on sphingolipid homeostasis. Such targeted interventions may prevent the pathological amplification of inflammatory signals without globally suppressing essential sphingolipid functions. These findings highlight the utility of an integrative systems-level analysis for elucidating sphingolipid dynamics in macrophages and underscore its potential to guide therapeutic strategies against conditions involving dysregulated inflammation.
Pushing the limits of structure prediction in regions of disorder using ColabFold: Progress and insights
Authors: Rieth Monica D.
Published: January 2025

Understanding the impact of amino acid substitutions on protein structure is critical for unraveling mechanisms of protein function and disease. ColabFold, a user-friendly implementation of AlphaFold2, offers an efficient and accessible platform for high-accuracy protein structure predictions. In this study, we explore the utility of ColabFold in predicting structural changes arising from specific amino acid substitutions. Using a structurally well-characterized model protein, mutations were selectively introduced and resulting structural deviations compared to the wild-type conformations. By employing a confidence score embedded in the program called the predicted local distance difference test (pLDDT), which is used to assess a model’s accuracy, together with what is known about the protein’s structure, we identify mutation-induced alterations and determine their potential implications on structural integrity. The results reported here demonstrate that ColabFold is capable of capturing subtle structural perturbations, offering insights into structural stability and the propensity for specific amino acid residues to induce or disrupt secondary structure conformations. We anticipate these studies and others like it will pave the way for high-throughput mutation screening and provide a valuable tool for protein engineering along with hypothesis-driven experimental studies to facilitate our understanding of the behavior of disease-associated mutations.
PicornaviridaeandCaliciviridaediversity in Madagascar fruit bats is driven by cross-continental genetic exchange
Authors: Kettenburg Gwenddolen , Ranaivoson Hafaliana C. , Andrianianina Angelo , Andry Santino , Henry Amy R. , Davis Rachel L. , Laboune Farida , Longtine Elizabeth R. , Godbole Sucheta , Horigan Sophia , Ruhs Emily Cornelius , Raharinosy Vololoniaina , Randriambolamanantsoa Tsiry Hasina , Lacoste Vincent , Heraud Jean-Michel , Dussart Philippe , Douek Daniel C. , Brook Cara E.
Published: January 2025

Bats are reservoir hosts for numerous well-known zoonotic viruses, but their broader virus-hosting capacities remain understudied.Picornaviralesare an order of enteric viruses known to cause disease across a wide range of mammalian hosts, including Hepatitis A in humans and foot-and-mouth disease in ungulates. Host-switching and recombination drive the diversification ofPicornaviralesworldwide. DivergentCaliciviridaeandPicornaviridae(families within thePicornavirales) have been described in bats across mainland Africa, but surveillance for these viruses has been rare in the Southwest Indian Ocean Islands. Bats live in close proximity to and are consumed widely as a food source by humans in Madagascar, providing opportunities for zoonotic transmission. Prior work in Madagascar has described numerous evolutionarily divergent bat viruses, some with zoonotic potential. Using metagenomic Next Generation Sequencing of urine and fecal samples obtained from three species of endemic Malagasy fruit bats (Eidolon dupreanum,Pteropus rufus, andRousettus madagascariensis), we recovered 13 full-length and 37 partial-length genomic sequences within the orderPicornavirales(36Picornaviridaeand 14Caliciviridaesequences), which we identify and describe here. We find evidence that genetic exchange between mainland African bat and Madagascar batPicornaviraleslikely shaped the diversification patterns of these novel sequences through recombination events between closely relatedPicornavirales; thus far, high host fidelity appears to have limited these viruses from spilling over into other species.
Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases
Authors: Finney Joel , Kuraoka Masayuki , Song Shengli , Watanabe Akiko , Liang Xiaoe , Liao Dongmei , Moody M. Anthony , Walter Emmanuel B. , Harrison Stephen C. , Kelsoe Garnett
Published: January 2025

The discovery of broadly protective antibodies to the influenza virus neuraminidase (NA) has raised interest in NA as a vaccine target. However, recombinant, solubilized tetrameric NA ectodomains are often challenging to express and isolate, hindering the study of anti-NA humoral responses. To address this obstacle, we established a panel of 22 non-adherent cell lines stably expressing native, historical N1, N2, N3, N9, and NB NAs anchored on the cell surface. The cell lines are barcoded with fluorescent proteins, enabling high-throughput, 16-plex analyses of antibody binding with commonly available flow cytometers. The cell lines were at least as efficient as a Luminex multiplex binding assay at identifying NA antibodies from a library of unselected clonal IgGs derived from human memory B cells. The membrane-anchored NAs are catalytically active and are compatible with established small-molecule catalytic activity assays. NA-expressing K530 cell lines therefore represent a useful tool for studying NA immunity and evaluating influenza vaccine efficacy.
Impact of Low-Dose Narrowband UV Radiation on Skin Tissue and Mast Cells in a Canine Model
Authors: Maeda Yusuke , Kubota Shota , Kawarai Shinpei , Kamimura Mai , Okuyama Hiroki , Ono Moeko , Nishida Moe , Moriya Shigeharu , Onoda Yushi , Tsurumoto Tomohiro , Nagata Koichi , Ansai Shin-ichi , Fujikawa Yasuo , Tsukamoto Atsushi
Published: January 2025

Narrowband ultraviolet radiation (NB-UVR) therapy is widely utilized in dermatology worldwide. While the immunosuppressive effects of ultraviolet radiation are well-documented, its non-inflammatory effects remain poorly understood. This study evaluated the effects of sub-minimal erythema dose (MED) narrowband ultraviolet radiation using a canine model. The effects of narrowband-ultraviolet B (310 nm) and A2 wavelengths (320 and 330 nm) were compared. Initially, we demonstrated the therapeutic potential of NB-UVR in dogs with spontaneous atopic dermatitis (n = 6, p < 0.05). Following 300 mJ/cm² sub-MED ultraviolet radiation exposure, intradermal skin testing, skin mast cell counts, and RNA sequencing analysis were conducted. Additionally, cell viability (WST assay) and apoptosis (DAPI staining) were assessed in vitro using a canine mast cell line. Ultraviolet radiation exposure significantly reduced intradermal skin test scores across all wavelengths and decreased skin mast cell counts at 310 nm (n = 3, p < 0.05). In vitro, cell viability was significantly reduced at 310 and 320 nm (p < 0.05), and 310 nm irradiation specifically increased apoptotic cell numbers (p < 0.05). RNA sequencing identified 71 differentially expressed genes at 320 nm, with enrichment analysis highlighting muscle cell components and functions, potentially associated with arrector pili muscle activity. These findings suggest that 310 nm irradiation induces apoptosis, while 320 nm elicits non-inflammatory modulatory effects, highlighting distinct wavelength-specific therapeutic mechanisms of narrowband ultraviolet radiation.
REM sleep microstructure alterations in REM sleep behavior disorder: beyond muscle tone
Authors: Nicolas Judith , Comperat Louis , Fort Patrice , Cheylus Anne , Ricordeau François , Bastuji Hélène , Simor Péter , Leclair-Visonneau Laurène , Peter-Derex Laure
Published: January 2025

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by dream enactment behaviors and loss of physiological atonia during REM sleep. It is considered a prodromal stage of alpha-synucleinopathies and may result from dysfunction of brainstem structures regulating muscle tone in REM sleep. Whether other REM sleep features are simultaneously affected remains unclear. Here, we investigated alterations in REM sleep microstructure, including phasic REM sleep, sawtooth waves (STW) and non-REM/REM sleep transitions, in iRBD and RBD associated with Parkinson’s disease (PD+RBD). We retrospectively included 20 patients with iRBD (85% male, 66.5[63–68]years), 20 patients with PD+RBD (75% male, 62.5[57.5-65]years) and 20 controls (75% male, 67[61–70]years). REM sleep without atonia (RSWA), bursts of REMs and STW bursts were manually scored. Phasic REM sleep proportion (derived from REMs), STW density/duration/frequency and the duration of NREM/REM transitions were compared between groups with a general linear mixed-effects model. Phasic REM sleep proportion was higher in the iRBD group (26.5[21–33]%) than in control (16.4[12.5-22.3]%, p-corrected=0.005) and PD+RBD (17.6[13.9-21.7]%, p-corrected=0.005) ones. Non-REM/REM transitions showed a duration gradient, increasing from controls (119.0[58.5-186.1]sec) to iRBD (212.1[68.5-391.4]sec, p-corrected=0.0038) and PD+RBD (375.8[217.6-514.6]sec, p-corrected<0.001) patients. STW density and duration were reduced in the PD+RBD group only (1.33[1.1-1.54]/min; 2.13[1.70-2.69]sec) vs controls (1.74[1.52-2.05]/min, p-corrected=0.005; 2.98[2.18-4.11], p-corrected<0.001), whereas altered STW spectral content was observed in both patient’s groups with a power shift toward higher frequencies (both p<0.001 vs controls). These results reinforce the hypothesis that REM sleep dysregulation in RBD extends to REM-specific electrophysiological features beyond loss of muscle atonia and dream enactments.

Statement of Significance

This study compared rapid eye movement (REM) sleep microstructure between patients with isolated REM sleep behavior disorder (iRBD) or RBD associated with Parkinson’s disease (PD+RBD), and controls. We found some altered REM sleep features in patient groups versus controls, as increased phasic REM sleep proportion in iRBD and reduced sawtooth waves (STW) density and duration in PD+RBD. Both groups exhibited altered STW spectral characteristics with a shift toward higher frequencies. Additionally, we observed a gradient in the duration of NREM/REM sleep transitions, increasing from controls to patients with iRBD and peaking in patients with PD+RBD, who exhibited the longest transitions. These findings highlight that REM sleep anomalies in RBD extends beyond atonia loss and dream enactments, encompassing broader microstructural changes.