bluuebunny/crossref_metadata_2025_split huggingface dataset:
G4mer: An RNA language model for transcriptome-wide identification of G-quadruplexes and disease variants from population-scale genetic data
Authors: Zhuang Farica , Gutman Danielle , Islas Nathaniel , Guzman Bryan B , Jimenez Alli , Jewell San , Hand Nicholas J , Nathanson Katherine , Dominguez Daniel , Barash Yoseph 
Published: October 2024

ABSTRACTRNA G-quadruplexes (rG4s) are key regulatory elements in gene expression, yet the effects of genetic variants on rG4 formation remain underexplored. Here, we introduce G4mer, an RNA language model that predicts rG4 formation and evaluates the effects of genetic variants across the transcriptome. G4mer significantly improves accuracy over existing methods, highlighting sequence length and flanking motifs as important rG4 features. Applying G4mer to 5’ untranslated region (UTR) variations, we identify variants in breast cancer-associated genes that alter rG4 formation and validate their impact on structure and gene expression. These results demonstrate the potential of integrating computational models with experimental approaches to study rG4 function, especially in diseases where non-coding variants are often overlooked. To support broader applications, G4mer is available as both a web tool and a downloadable model.
An inducible and reversible system to regulate unsaturated fatty acid biosynthesis inC. elegans
Authors: Battista Bernabe , Cravero Bruno Hernadez , Colaiácovo Monica P , Cochella Luisa , Binolfi Andres , de Mendoza Diego 
Published: October 2024

AbstractUnsaturated fatty acids (UFAs) play crucial roles in various physiological and pathological processes. In animals, these lipids are synthesized from saturated fatty acids through the action of delta 9 (Δ9) desaturases. InC. elegans, three Δ9 desaturases are encoded by the genesfat-5,fat-6, andfat-7. The presence of multiple Δ9 desaturases has posed a significant challenge in developing a rapid and efficient approach to control UFA production inC. elegansand other model organisms. Utilizing the auxin-inducible degradation system, we specifically targeted theC. elegans fat-7gene, responsible for the major stearoyl-CoA desaturase (SCD), while deletingfat-5andfat-6. This design resulted in a strain that can be reversibly depleted of UFAs in the cells of interest. Conditional depletion in all somatic cells exhibited a pronounced auxin-dependent defect in UFA production. Using this system, we uncovered an essential requirement for de novo UFA production during L1 and L2 stage. Moreover, our results support a direct connection between UFA levels, fat storage and increased lipid turnover. This system will enable further studies exploring the cellular and physiological consequences of impairing UFA biosynthesis at different developmental stages or in specific tissues.SummaryUnsaturated fatty acids (UFAs) are essential for life. In animals, UFAs are synthesized by Δ9 desaturase enzymes.Caenorhabditis eleganspossesses three Δ9 desaturase genes: fat-5, fat-6, and fat-7. We engineered a strain where fat-7 can be reversibly switched off while fat-5 and fat-6 are deleted, allowing precise control of UFA levels throughout the life cycle. Our findings demonstrate the critical role of UFA biosynthesis in early development and its direct link to fat storage and lipid turnover. This strain enables the study of UFA-related physiological and pathological processes in animals.
Filtered Point Processes Tractably Capture Rhythmic And Broadband Power Spectral Structure in Neural Electrophysiological Recordings
Authors: Bloniasz Patrick F. , Oyama Shohei , Stephen Emily P. 
Published: October 2024

AbstractNeural electrophysiological recordings arise from interacting rhythmic (oscillatory) and broadband (aperiodic) biological subprocesses. Both rhythmic and broadband processes contribute to the neural power spectrum, which decomposes the variance of a neural recording across frequencies. Although an extensive body of literature has successfully studied rhythms in various diseases and brain states, researchers only recently have systematically studied the characteristics of broadband effects in the power spectrum. Broadband effects can generally be categorized as 1) shifts in power across all frequencies, which correlate with changes in local firing rates and 2) changes in the overall shape of the power spectrum, such as the spectral slope or power law exponent. Shape changes are evident in various conditions and brain states, influenced by factors such as excitation to inhibition balance, age, and various diseases. It is increasingly recognized that broadband and rhythmic effects can interact on a sub-second timescale. For example, broadband power is time-locked to the phase of <1 Hz rhythms in propofol induced unconsciousness. Modeling tools that explicitly deal with both rhythmic and broadband contributors to the power spectrum and that capture their interactions are essential to help improve the interpretability of power spectral effects. Here, we introduce a tractable stochastic forward modeling framework designed to capture both narrowband and broadband spectral effects when prior knowledge or theory about the primary biophysical processes involved is available. Population-level neural recordings are modeled as the sum of filtered point processes (FPPs), each representing the contribution of a different biophysical process such as action potentials or postsynaptic potentials of different types. Our approach builds on prior neuroscience FPP work by allowing multiple interacting processes and time-varying firing rates and by deriving theoretical power spectra and cross-spectra. We demonstrate several properties of the models, including that they divide the power spectrum into frequency ranges dominated by rhythmic and broadband effects, and that they can capture spectral effects across multiple timescales, including sub-second cross-frequency coupling. The framework can be used to interpret empirically observed power spectra and cross-frequency coupling effects in biophysical terms, which bridges the gap between theoretical models and experimental results.
Artificial lighting affects the predation performance of the predatory bugOrius insidiosus(Say) against the Western flower thripsFrankliniella occidentalis(Pergande)
Authors: Canovas Morgane L. , Abram Paul K. , Cormier Jean-François , Galstian Tigran , Dorais Martine 
Published: October 2024

AbstractProtected crops, such as greenhouses and indoor farming environments, using light-emitting diodes (LEDs) enable the modulation of the light spectrum, intensity, and photoperiod for agronomic purposes. This creates dynamic artificial light conditions for insects and arachnids, including predators used in biological control. Despite increasing interest, the effects of LEDs on predator behavior and control performance remain poorly understood. In the laboratory, we examined the locomotion and predation behaviors of the generalist predatorOrius insidiosusagainst the pestFrankliniella occidentalisunder various light spectra and intensities. We tested narrowband blue, green, and red spectra, three ratios of red and blue light, and a spectrum combining all three colors across a gradient of light intensity in microcosms.Orius insidiosuswas active and successfully attacked prey under all lighting conditions, with 70% of individuals engaging in predation during the observation period. The light spectrum significantly influenced all recorded behaviors, while light intensity had negligible effects. Narrowband spectra led to the highest attack probabilities, but the mixed blue-red spectrum with a higher proportion of red light yielded the highest prey capture rates. The spectrum with all three colors showed intermediate capture success. These trends were consistent regarding capture probability in more complex environments with cucumber plants, where thrips were exposed to 24-hour artificial light sequences before and during predator releases. However, thrips survival rates remained similar across all lighting treatments. Our results demonstrated that while lighting treatments affect predator behavior,Orius insidiosusretains its ability to capture prey under various light conditions. This paves the way for developing lighting strategies that balance plant productivity with effective biological control in protected crop environments.
Injury-induced transcription in the planarian outer epithelium is critical for tissue regeneration
Authors: Barai Pallob , Kibtiya Mariya S. , Maggard Nathan G. , Biswas Shishir , Duncan Elizabeth M. 
Published: October 2024

AbstractPlanarian flatworms have an extraordinary regenerative capacity; even a small, asymmetrical fragment of amputated planarian tissue can recreate an entirely new animal. The planarian field has made significant progress in identifying specific genes and cell types required for this complex process, but substantially less is known about the molecular mechanisms that convert a significant physical injury (e.g., head amputation) into the expression of specific genes in particular cell types. One tissue in which this question is particularly relevant is the planarian epidermis, a single-layer, mucociliary epithelium with similarities to the epithelia of mammalian airways. This epithelium plays an essential, early role in planarian regeneration as the cells surrounding the wound site must quickly stretch and extend to cover the wound area after injury. We hypothesized that these injury-induced morphological changes activate the transcription of genes with essential functions in the regenerative process. To best detect these transcriptional changes, we developed a rapid method for isolating the planarian outer epithelium and prepared ribodepleted RNA-sequencing libraries from samples isolated at multiple time points after tissue amputation. One gene we both identified using these methods and found to be functionally important for regeneration is a putative planarian homolog of vertebrateShoc2. SHOC2 is an essential scaffolding protein that mediates specific, context-dependent activation of the ERK1/2 signaling pathway (JangandGalperin2016). Notably, the ERK1/2 pathway is known to be activated after injury and required for regeneration in multiple species (Manuelet al. 2006; Owlarnet al. 2017; Tomassoet al. 2023). These findings suggest that these epithelial datasets have the potential to uncover many functionally relevant and possibly highly conserved genes that play fundamental roles in animal regeneration.
Erbin interacts with NHERF1 and Ezrin to stabilize a membrane ErbB2 signaling complex in HER2-positive breast cancer
Authors: Jeong Jaekwang , Yoo Kwangmin , Lee Jongwon , Shin Jae Hun , Choi Jungmin , Wysolmerski John 
Published: October 2024

AbstractApproximately 20% of breast cancers overexpress ErbB2/HER2/Neu, a receptor tyrosine kinase. Our previous studies demonstrated that HER2 interacts with the calcium pump, PMCA2, and the scaffolding molecules, NHERF1 and Ezrin to stabilize HER2/HSP90 interactions and contribute to the retention of active HER2 at the plasma membrane. In the normal mammary epithelium where apical/basal polarity is tightly regulated by junctional proteins, HER2 is expressed at the basolateral membrane and interacts with the LAP family member, Erbin, whereas PMCA2, NHERF1, and Ezrin localize to the apical membrane. Here, we show that loss of apical membrane polarity in hyperplastic lesions of MMTV-Neu mammary glands or in human DCIS leads to intermixing of these molecules and allows Erbin to interact with NHERF1, Ezrin and HER2 initially within the basolateral membrane and then more diffusely within the plasma membrane. In SKBR3 cells, Erbin physically interacts with NHERF1, Ezrin and HER2 in actin-rich membrane protrusions that we have previously described to be sites of active HER2 signaling. Knockdown of Erbin in these cells reduced HER2 signaling by disrupting the formation of a HER2/NHERF1/Ezrin/HSP90 protein complex in the membrane protrusions. Furthermore, inhibition of Ezrin or knock-down of NHERF1 expression disrupted the ability of Erbin to interact with HER2. Taken together, our data suggest that Erbin supports HER2 stability, HER2 membrane retention and HER2 transforming ability by interacting with Ezrin and NHERF1 to maintain a multi-protein signaling complex necessary for HER2-mediated transformation.
Unveiling the chemical and behavioural ecology ofTribolium castaneum(Herbst, 1797) in wheat flour: Alterations in flour metabolic content and the role of chemical cues in modulating beetles’ behaviour and regulating population growth
Authors: Das Subhadeep , Manna Sourav , Chatterjee Oishika , Saha Riya , Sarkar Oishee Janet 
Published: October 2024

AbstractTribolium castaneum(Herbst, 1797) (Coleoptera: Tenebrionidae) is a notorious secondary pest of stored grains and flours, accounting for 10–15% of global annual losses in stored products. This study first evaluated the impact ofT. castaneuminfestation on the nutritional parameters of stored wheat flour. Infested flour exhibited reductions in total soluble sugars, triacylglycerol levels, and unsaturated fatty acids, particularly Oleic and Linoleic acid, while secondary metabolites such as phenolics, flavonoids, and tannins were increased. Behavioural assays revealed that adult beetles were significantly more attracted towards infested flour odour due to the presence of 4,8-Dimethyldecanal (4,8-DMD), an aggregation pheromone of T. castaneum. Another key compound in infested flour, 1-Pentadecene, derived from the beetles’ cuticular wax, was found to influence adult beetle behaviour. At higher concentrations, 1-Pentadecene acted as a repellent for the species. Molecular docking studies suggested that 1-Pentadecene competes with 4,8-DMD for binding to the odorant receptor TcOR1, which could potentially inhibit aggregation behaviour and reduce population growth. The docking analysis revealed that 1-Pentadecene interacts with the same binding pocket on TcOR1, sharing key amino acids (MET49, PHE69, THR72, GLN73, THR134, VAL135, TYR138, LEU154, ILE177, GLY180, ALA181, TYR286) and forming similar intermolecular bonds, such as a pi-alkyl bond, with a binding affinity (ΔG = -5.7) comparable to 4,8-DMD (ΔG = -5.8). Additionally, beetles reared in wheat flour containing higher concentrations of 1-Pentadecene exhibited lower population growth compared to those reared in flour with lower concentrations of this compound.
GLA-3 Mediates Stress Response inCaenorhabditis elegansGerm Cells: A key role of the Tristetraprolin (TTP) Family
Authors: Salinas Laura Silvia , Dámazo-Hernández Angel Armando , Morales-Oliva Enrique , Láscarez-Lagunas Laura Ivón , Navarro Rosa Estela 
Published: October 2024

AbstractTristetraprolin or TTP is an RNA-binding protein that possesses two CCCH-like zinc-finger domains that bind AU-rich elements to promote their degradation. One of its targets is the mRNA of tumor necrosis factor alpha (TNF-α). When TTP is absence, the TNF-α factor accumulates causing severe, generalized inflammation in knockout mice. TTP is also considered a tumor suppressor protein because regulates the expression of several mRNAs that encode for proteins involve in cell cycle regulation and it is downregulated in various types of human cancers. Under stress, TTP associates with stress granules (SGs), dynamic cytoplasmic condensates formed by liquid-liquid phase separation (LLPS) that protect mRNAs from harmful conditions. Despite TTP’s important role in mRNA turnover, much remains to explore about its participation in stress resistance in life animals that is why, we explored the role of GLA-3, one of the TTP’s homolog, in the nematodeCaenorhabditis elegans. Nematodes lackinggla-3/TTP exhibit phenotypes such as progressive loss of motility, reduced brood size, and increased embryonic lethality. As well as defects in meiotic progression, and increased germ-cell apoptosis. Here we showed that the GFP::GLA-3 reporter is expressed mainly in theC. elegansgermline, where associates with different condensates like germ granules, processing bodies, and stress granules suggesting that, like TTP, GLA-3 plays an important role in mRNA regulation in theC. elegansgermline. Furthermore we demonstrated that GLA-3 is important for stress granules’ and processing bodies’ formation. We also show that oogenic germ cells of GLA-3 mutant animals that were exposed to heat shock resulted embryos that did not survive showing that GLA-3 plays an important role protecting germ cells from this condition. Our results demonstrate that the role of GLA-3 is conserved inC. elegans, and this model can be very useful for further investigating the role of this protein on the future.
INVESTIGATING TRAIT IMPULSIVITY IN OBSESSIVE-COMPULSIVE DISORDER: A SCOPING REVIEW
Authors: Banwell M.J. , Scheffler F. , Lochner C. , Chamberlain S.R. , Stein D.J. 
Published: October 2024

AbstractBackground/AimsWhile obsessive-compulsive disorder (OCD) is specifically characterised by compulsivity, considerable literature suggests impulsivity also plays an important role in the disorder. However, impulsivity is a multi-faceted construct and the exact relationship of trait impulsivity to OCD remains unclear. Therefore, this scoping review aimed to collate and review studies of trait impulsivity in OCD by an investigation of: 1. How trait impulsivity in OCD is measured in the research literature; 2. How people with OCD perform on these measures and compare to healthy and other psychiatric groups; and 3. What correlations with trait impulsivity are observed in OCD.MethodsThis study was pre-registered on PROSPERO (CRD42023481781). Electronic search of PubMed, Scopus, and PsycINFO databases using keywords ‘(impuls*) AND (OCD)’ was undertaken without date restrictions for peer-reviewed articles available in English. After exclusion of duplicates and screening of 1476 abstracts, 114 articles were identified for full-text review.Results54 articles were reviewed after excluding studies assessing neurocognitive impulsivity only (i.e. no inclusion of trait impulsivity), sub-clinical OCD symptoms, and review articles. The literature reports cross-sectional clinician-rated and self-rated trait impulsivity data, with the Barratt Impulsivity Scale (BIS) being used most frequently. Broadly, people with OCD scored higher than healthy controls on at least one aspect of trait impulsivity. However, comparisons of OCD groups to other psychiatric groups demonstrated equal or lower trait impulsivity in OCD. Individuals with OCD with comorbid diagnoses (ADHD, behavioural addictions, tic disorder, borderline personality disorder, bipolar disorder) had relatively higher levels of trait impulsivity than those without. In OCD, trait impulsivity scores were associated with various psychiatric symptomatology (OCD severity, anxiety, depression, compulsivity, hoarding levels, behavioural addictions, anhedonia, aggressive and sexual impulses). Trait impulsivity did not correlate with neurocognitive measures of impulsivity.ConclusionsKey findings are that trait impulsivity research in OCD was predominantly observational, with cross-sectional studies using the BIS. While higher levels of trait impulsivity were seen in patients with OCD compared to healthy controls, this finding was not specific to OCD. OCD demonstrated equal or lower trait impulsivity than other psychiatric groups that the literature had examined to date; trait impulsivity in OCD was positively correlated with a number of psychiatric factors; and neurocognitive measures of impulsivity did not correlate with trait impulsivity. Future work on OCD should include interventional and neuroimaging methods that utilise several different measures of impulsivity.
Programmatic diagnostic accuracy and clinical utility of Xpert MTB/XDR in patients with rifampicin-resistant tuberculosis in Georgia
Authors: Pfurtscheller Theresa , Tsutsunava Ana , Maghradze Nino , Gujabidze Mariam , Bablishvili Nino , Yerlikaya Seda , Denkinger Claudia M. , Tukvadze Nestani , Gupta-Wright Ankur 
Published: October 2024

AbstractBackgroundXpert MTB/XDR (Cepheid, USA) is recommended for drug susceptiblity testing in patients with tuberculosis (TB) by the World Health Organization (WHO) with potential for rapid detection of isoniazid and fluoroquinolones resistance. However, diagnostic accuracy and clinical utility in a programmatic setting are unknown.MethodsWe evaluated accuracy and clinical utility of Xpert XDR in patients with rifampicin-resistant pulmonary TB during programmatic implementation in Georgia between July 2022 and August 2024, using phenotypic drug susceptibility testing (pDST) as reference standard.Results140 patients were tested with Xpert MTB/XDR and pDST, and 94.9% and 33.8% had isoniazid and fluoroquinolone resistance by pDST respectively. Xpert MTB/XDR showed 99.2% sensitivity (95% CI 95.5-100%) and 100% specificity (95% CI 54.1-100%) for isoniazid resistance. Sensitivity and specificity for fluoroquinolone resistance were 88.4% (95% CI 74.9-96.1%) and 100% (95% CI 95.6-100%). Including indeterminate/invalid Xpert MTB/XDR results, 17.4% (8/46) and 6.4% (8/129) of patients with phenotypic fluoroquinolone and isoniazid resistance were missed, respectively. Median turn-around time for Xpert MTB/XDR was 1 day (IQR 1-3) and median time to treatment was 4 days (IQR 1-7). Phenotypic DST results took a median of 43 days (IQR 29-63) longer than Xpert MTB/XDR results. 95% (115/121, 95% CI 89.5-98.2%) of patients had fluoroquinolones appropriately prescribed based on Xpert XDR result.ConclusionsProgammatic data confirms high accuracy of Xpert MTB/XDR, although below WHO TPP targets for fluoroquinolones, with significantly faster time-to-results than pDST. However, there is a strong need for rapid tests to detect resistance to bedaquiline and other newer TB drugs.
Spatial analysis of HPV associated cervical intraepithelial neoplastic tissues demonstrate distinct immune signatures associated with cervical cancer progression
Authors: Pavilion Gianna , Vu Hani , Xiong Zherui , Dang Thi Viet Trinh , Walsh Michael , Causer Andrew , Chandra Janin , Nguyen Quan , Frazer Ian H 
Published: October 2024

AbstractCervical cancer remains the fourth most common cancer affecting women worldwide, and incidences of other HPV-related cancers continue to rise. For the development of effective prevention strategies in high-risk patients, we aimed to better understand the roles of inflammatory pathways and the tumour microenvironment as the main driver of progression to malignancy in HPV-infected tissues. We analysed the spatial organisation of seven samples of HPV+ high-grade squamous intraepithelial lesion (HSIL) and cervical intraepithelial neoplasia 3 (CIN3), comparing tumour heterogeneity and immune microenvironments between pre-malignant (neoplastic) and adjacent cervical tissues. We observed evidence of immune suppression within the neoplastic regions across all samples and identified distinct immune clusters for each dysplastic lesion. Previous single-cell data analyses in an HPV16 E7 oncoprotein-driven transgenic mouse model suggested a potential role for IL34-CSF1R signalling in immune modulation, where low IL34 expression was associated with Langerhans cell dysfunction, and, in cervical cancer, with poor patient outcome. Here, we observed that IL34-CSF1R co-expression was absent within HPV-associated neoplastic tissues but present in adjacent normal tissue regions. Additionally, we identified enrichment of an M2 gene signature in neoplastic tissue, while adjacent tissue was enriched with a pro-inflammatory M1 gene signature. Our findings provide bio-pathological insights into the spatial cellular and molecular mechanisms underlying HPV-associated cervical cancer immune regulation and suggest a strategy to modulate the immune system in HPV-positive neoplastic cervical and other tissues.