bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wheat stripe rust resistance geneYr9, derived from rye, is aCC-NBS-LRRgene in a highly conservedNLRcluster
Authors: Yu Yang , Liu Jiajun , Lan Shengjie , Chen Qihang , Li Jinlong , Song Haoyuan , Pan Chen , Qi Juan , Ni Fei , Epstein Lynn , Fu Daolin , Wu Jiajie 
Published: October 2024

AbstractWheat stripe rust, caused byPuccinia striiformisf. sp.tritici(Pst), is a significant threat to global wheat production. Genetic resistance plays a crucial role in controlling this disease. Among wheat breeding innovations, the wheat-rye 1BL.1RS translocations are notable for introducing alien genetic diversity, partly due to the presence of the stripe rust resistance geneYr9on 1RS. To cloneYr9, we first identified fourPst-susceptible mutants from Lumai 15, which carries the 1BL.1RS translocation andYr9. Using these mutants, we performed Sequencing Trait-Associated Mutations (STAM). A single candidate gene,YrChr1B, was identified within theYr9locus and later confirmed asYr9through genetic complementation and gene editing. TheYr9gene encodes a coiled-coil nucleotide-binding site leucine-rich repeat (CC-NBS-LRR or NLR) protein and is part of a 14-memberNLRgene cluster. This cluster is conserved among Triticeae species and is an ortholog of the barleyMlalocus. CloningYr9expands the genetic resources available for molecular wheat breeding aimed at durable and broad-spectrum disease resistance.
pLM-DBPs: Enhanced DNA-Binding Protein Prediction in Plants Using Embeddings From Protein Language Models
Authors: Pokharel Suresh , Barasa Kepha , Pratyush Pawel , Kc Dukka 
Published: October 2024

AbstractDNA-binding proteins (DBPs) play critical roles in gene regulation, development, and environmental response across various species, including plants, animals, and microorganisms. While various machine learning and deep learning models have been developed to distinguish DNA-binding proteins (DBPs) from non-DNA-binding proteins (NDBPs), most available tools have focused on human and mouse datasets. As a result, there are limited studies specifically addressing plant-based DNA-binding proteins, which restricts our understanding of their unique roles and functions in plant biology. Developing an efficient framework for improving DBP prediction in plants would enhance our knowledge and enable precise gene expression control, accelerate crop improvement, enhance stress resilience, and optimize metabolic engineering for agricultural advancement. In this work, we developed a tool that uses a protein language model (pLM) pre-trained on millions of sequences. We evaluated several leading models, including ProtT5, Ankh, and ESM-2, and leveraged their high-dimensional, information-rich representations to improve the accuracy of DNA-binding protein prediction in plants significantly. Our final model, pLM-DBPs, a feed-forward neural network classifier utilizing ProtT5-based representations, outperformed existing approaches with a Matthews Correlation Coefficient (MCC) of 83.8% on the independent test set. This represents a 10% improvement over the previous state-of-the-art model for plant-based DBP prediction, highlighting its superior performance compared to the existing approaches.
MicroBayesAge: A Maximum Likelihood Approach to Predict Epigenetic Age Using Microarray Data
Authors: Nolan Nicole , Mitchell Megan , Mboning Lajoyce , Bouchard Louis-S. , Pellegrini Matteo 
Published: October 2024

AbstractCertain epigenetic modifications, such as the methylation of CpG sites, can serve as biomarkers for chronological age. Previously, we introduced our BayesAge frameworks for accurate age prediction through the use of locally weighted scatterplot smoothing (LOWESS) to capture the non-linear relationship between methylation or gene expression and age, and Maximum Likelihood Estimation (MLE) for bulk bisulfite and RNA sequencing data. Here we now introduce MicroBayesAge, a framework that enhances prediction accuracy by subdividing input data into age-specific co-horts and employing a new two-stage process for training and testing. Age prediction for younger patients was significantly improved. MicroBayesAge also exhibited minimal bias in its age predictions. Additionally, we explored the performance of our model for sex-specific age prediction which revealed slight improvements in accuracy for male patients, while no changes were observed for female patients. MicroBayesAge provides more accurate age predictions by accounting for variations in epigenetic markers of aging among different subgroups, which have been over-looked by commonly used models.
Portable In-Field DNA Sequencing for Rapid Detection of Pathogens and Antimicrobial Resistance: A Proof-of-Concept Study
Authors: Pillay Stephanie , Calderón-Franco David , Abeel Thomas 
Published: October 2024

AbstractPurposeInfectious diseases represent a major global health threat due to the rapid spread of pathogens, leading to widespread outbreaks. Concurrently, antimicrobial resistance (AMR) is increasing, making standard treatments less effective and complicating infection management. Effective surveillance systems are essential to address these challenges.MethodsWe conducted a proof-of-concept study to evaluate a portable in-field microbial lab against a traditional molecular lab for DNA isolation, sequencing, microbial detection, antibiotic resistance gene identification, and plasmid classification. Samples from lake water, wastewater treatment plant sludge, and retail meat were selected to reflect relevant surveillance vectors. This approach provides valuable data for environmental monitoring, public health, and food safety, aiding in outbreak preparedness. We compared results using five metrics: DNA yield and purity, read N50, taxonomic classification, antibiotic resistance gene identification (ARGs), and plasmid classification.ResultsOur study found that metagenomic bacterial DNA isolation from environmental and food sources is feasible with portable lab technology, producing ≥800ng of DNA, suitable for Nanopore sequencing. DNA from retail meat, lake, and sludge samples resulted in similar read numbers and read N50 values. Taxonomic classification was achieved at the genus and species levels. A Jaccard similarity of over 50% was observed in the top 20 most abundant species between chicken samples, and lake samples. ESKAPE pathogens were detected in chicken and lake samples. ARGs and plasmids were also identified in both retail meat and lake samples.ConclusionThis study demonstrates that in-field DNA isolation and sequencing are feasible with minimal equipment, yielding results comparable to traditional lab methods.
Nutri Complex 150+: a new and effective approach to facial rejuvenation
Authors: Privitera Anna , Ferruggia Greta , Contino Martina , Maugeri Salvatore , Zimbone Massimo , Cardile Venera , Caruso Giuseppe , Brundo Maria Violetta 
Published: October 2024

AbstractSkin is the largest multifunctional human organ and possesses a complex multilayered structure with the ability to regenerate and renew. The key role in skin regeneration is played by fibroblasts, also playing an important role in wound healing process. We used different methods to evaluate on human fibroblasts thein vitroeffects of a new compound called Nutri Complex 150+ (NC150+), containing a mixture of 20 different biologically active factors (GF20) and exosomes isolated and purified from bovine colostrum. NC150+ was able to significantly enhance cell proliferation/metabolic status of fibroblasts at both 24 and 48 hours compared to untreated (control) cells. NC150+ was also able to enhance the ability of human fibroblasts to close the wound scratch. Our findings demonstrate the ability of NC150+, based on a new technology called AMPLEX plus, to enhance cell proliferation/metabolic status of fibroblasts. The obtained results also suggest how NC150+ could be potentially effective in treating skin injury.
The GLP-1 analogue, exendin-4, improves bone material properties and strength through a central relay in ovariectomized mice
Authors: Mermet Morgane , Denom Jessica , Mieczkowska Aleksandra , Biggs Emma , Gribble Fiona M. , Reimann Frank , Magnan Christophe , Cruciani-Guglielmacci Celine , Mabilleau Guillaume 
Published: October 2024

ABSTRACTGlucagon-like peptide-1 (GLP-1) has previously been shown to be indispensable for optimal bone strength by acting at the bone material level. However, it was not fully clear whether the effects of GLP-1 were mediated by direct or indirect actions on bone cells. In the present study, we were unable to demonstrate the expression of the GLP-1 receptor (GLP-1r) in bone tissue at the gene expression level using qPCR and in situ hybridization, or at the protein level. Furthermore, the peripheral administration of exendin-4, a specific GLP-1r agonist, in ovariectomized (OVX) BALB/c mice enhanced post-yield displacement (18%) and energy-to-fracture (24%), as well as bone volume/total volume (BV/TV) (11%), trabecular number (Tb.N) (6%), and collagen maturity (18%). These bone effects were still observed when exendin-4 was centrally administered into the lateral cerebral ventricle. On the other hand, the peripheral administration of exendin-4 coupled to bovine serum albumin, a GLP-1r agonist that cannot penetrate the brain, failed to replicate the positive effects on bone despite increased calcitonin secretion. Altogether, these data confirm that GLP-1r agonists represent an interesting approach for managing bone fragility due to ovariectomy, but also suggest that GLP-1r agonists require a central relay yet to be identified to exert positive effects on bone physiology. Further studies are needed to decipher the mechanisms of action of GLP-1 and GLP-1r agonists on bone physiology.
Soil microbiome perturbation impedes growth ofBouteloua curtipendulaand increases relative abundance of soil microbial pathogens
Authors: Hobbs Alisiara , Ochoa-Rojas Daisy , Humphrey Christine E. , Kyndt John A. , Moore Tyler C. 
Published: October 2024

AbstractBouteloua curtipendula(sideoats grama) is a valuable prairie grass for livestock forage, supporting food webs of herbivorous insects, reducing soil erosion, and limiting weed infiltration in urban grasslands. Efficient establishment ofB. curtipendulain prairie restorations and urban plantings could drastically improve long-term functionality of the space. Soil microbial communities have been linked to plant germination, growth, and drought tolerance in many plant species, however little is known about the factors contributing toB. curtipendulagermination and early growth. In this study, we used sterilized soil to examine the impact of soil microbes onB. curtipendulagrowth under greenhouse conditions. We foundBouteloua curtipendulaemergence and growth to be impaired in sterilized soil compared to non-sterilized soil. Using high throughput sequencing of the soil, we found thatB. curtipendulagrown in sterilized soil induced a greater proportion of plant pathogens and fewer nitrifying bacteria when grown in non- sterilized soil. For example, there was a significantly higher proportion ofAcidovorax,Cellvibrio, andXanthomonaswhich are known to contain plant pathogens, while plant- growth promoting bacteria, likeRhodopseudomonas,were significantly higher in the non-sterile conditions. We found that soil sterilization and growth ofB. curtipendulachanged the relative abundance of metabolic subsystem genes in the soil, however, by seven weeks after seeding,B. curtipendulatransformed the bacterial community of sterile soil such that it was indiscernible from non-sterile soil. In contrast, fungal communities in sterilized soil were still different from non-sterilized soil seven weeks post-seeding. It appears that the bacteria are involved in the initial establishment of beneficial conditions that set the stage for a robust fungal and plant seedling development.
Hydrothermal pretreatment renders peat susceptible to enzymatic saccharification
Authors: Thomsen Jonas , Lett Signe , Martens Helle , Sørensen Helle , Kelleher Darragh , Tryfona Theodora , Dupree Paul , Johansen Katja S. 
Published: October 2024

AbstractSphagnumpeat bogs store a large fraction of biologically-bound carbon, due to a steady accumulation of plant material over millennia. The resistance ofSphagnumbiomass to decay is poorly understood but of high importance for preservation efforts and climate models. It is shown that peat cellulose and other glucose-rich polysaccharides are readily degradable by a commercial enzyme cocktail designed for the industrial saccharification of lignocellulose of vascular plants. However, prior hydrothermal pretreatment of peat was required for the enzymes to gain access to the polysaccharides. The pretreatment itself released monosaccharides and glucose-containing soluble oligosaccharides. The monosaccharide profile released from hydrothermal pretreatment was consistent with the expected hemicellulose content ofSphagnumand was clearly different from that seen for pretreated tissue from vascular plants, such as pretreated wheat straw. Cellulose retained in the insoluble part of peat was cleaved at a similar or higher rate compared to cellulose from vascular plant tissues. Confocal laser scanning microscopy showed that the hydrothermal pretreatment disrupted the cells and relocated lignin-like compounds. Peat contains a high concentration of iron, which likely explains the pronounced acidification observed for the pretreated peat slurry at ambient conditions during saccharification assays. The acidification is due to abiotic oxidative reactions that also inactivate the enzymes. Adding catalase to the reactions alleviated enzyme inactivation and essentially stopped acidification during saccharification. This study confirms the importance of considering those abiotic oxidative reactions that take place in drained peat material.
Cytokine-Driven NF-κB Activation in Retinal Cells and Its Impact on the Pathogenesis of Age-Related Macular Degeneration: A Systematic Review
Authors: Shafi Viqas , Khan Nabeel Ahmad , Kazmi Javeria , Siddiqui Ifrah 
Published: October 2024

AbstractObjectiveTo investigate the role of cytokine-induced NF-κB activation in retinal pigment epithelium (RPE) and photoreceptor cells, elucidating its contribution to the pathogenesis of Age-related Macular Degeneration (AMD) and identifying potential therapeutic targets.BackgroundAMD is a leading cause of vision loss in older adults, driven by inflammation, oxidative stress, and immune dysregulation, particularly in RPE and photoreceptor cells. The NF-κB signaling pathway, activated by cytokines such as TNF-α, IL-6, and IL-1β, regulates these pathological processes. Understanding cytokine-induced NF-κB activation may provide insight into AMD progression and facilitate the development of novel therapeutic strategies.MethodsA systematic review of literature from databases including PubMed, MEDLINE, and Google Scholar was conducted to evaluate the involvement of TNF-α, IL-6, IL-1β, IL-8, IFN-γ, IL-17, IL-12, IL-18, IL-33, and IL-25 in activating NF-κB in RPE and photoreceptor cells, contributing to AMD pathogenesis. The search was performed with no date restrictions and followed PRISMA guidelines. Eligible studies were selected based on predefined criteria assessing NF-κB activation mechanisms and its effects on inflammation, oxidative stress, and retinal degeneration.ResultsThe investigation revealed that cytokines TNF-α, IL-6, IL-1β, IL-8, IFN-γ, IL-17, IL-12, IL-18, IL-33, and IL-25 activate the NF-κB signaling pathway in retinal pigment epithelium (RPE) and photoreceptor cells. This activation triggers the transcription of genes involved in inflammation, oxidative stress, and immune responses. Chronic NF-κB activation leads to persistent inflammation, increased oxidative stress, and immune cell recruitment, contributing to retinal cell dysfunction and degeneration. Additionally, NF-κB-driven upregulation of angiogenic factors such as VEGF promotes neovascularization in wet AMD. These findings highlight the central role of NF-κB in AMD pathogenesis and suggest that targeting this pathway could mitigate inflammatory and oxidative damage, offering potential therapeutic benefits for AMD patients.ConclusionCytokine-induced NF-κB activation plays a central role in AMD pathogenesis by promoting chronic inflammation, oxidative stress, and angiogenesis in retinal cells. Targeting NF-κB could present a therapeutic strategy to reduce inflammatory and oxidative damage, preserving retinal function and preventing vision loss in AMD. Further research is required to develop effective NF-κB-targeted interventions.
Lutetium-177 hydroxyapatite radiosynovectomy in refractory chronic inflammatory arthritis of the knee joint
Authors: Sarwal Tanvi , Kumar Rajesh , Taywade Sameer , Gopalakrishnan Maya , Elhence Abhay , Didel Siyaram , Gaur Ravi 
Published: October 2024

ABSTRACTObjectiveTo determine the efficacy of177Lutetium hydroxyapatite radiosynovectomy (RSV) in patients with refractory chronic inflammatory arthritis of the knee joint.Materials and MethodsOverall, 24 knees in 22 patients with refractory chronic inflammatory arthritis were enrolled in this prospective study. All patients were assessed clinically for pain, tenderness, range of motion, analgesic intake, Oxford knee score and blood pool activity on three phase bone scan. Various scores were assigned to clinical these parameters. RSV of the knee joint was done using intra-articular injection of177Lutetium hydroxyapatite. Patients were assessed clinically at 1 and 3 months, and scintigraphically at 3 months using blood pool index on three phase bone scan. Patients were categorised as responders and non-responders on the basis of change in percentage of cumulative scores.ResultsOut of 24 knees, 18 knees were responders and 6 knees were non-responders at 3 months. There was a significant improvement in clinical scores at 1 month post RSV, which persisted at 3 months post RSV (p < 0.05). However, the change in blood pool activity on three phase bone scan was not significant. Reported adverse effects were mild and not significant.ConclusionThis study confirmed the safety and efficacy of177Lutetium hydroxyapatite radiosynovectomy for patients with chronic inflammatory knee joint arthritis refractory to conventional medical treatment.
Biomarkers of insulin resistance and their performance as predictors of treatment response in adults with risk factors for type 2 diabetes
Authors: Brogan RJ , Rooyackers O , Phillips BE , Twelkmeyer B , Ross LM , Atherton PJ , Kraus WE , Timmons JA , Gallagher IJ 
Published: October 2024

AbstractInsulin Resistance (IR) is a component of the pathogenesis of type 2 diabetes mellitus (T2DM), and risk factor for cardiovascular and neurodegenerative diseases. Amino acid and lipid metabolomic IR diagnostics associate with future T2DM risk in epidemiological cohorts. Whether these assays can accurately detect altered IR following treatment has not been established. In the present study we evaluated the ability of metabolomic diagnostics to predict altered IR following exercise treatment. We evaluated the performance of two distinct insulin assays and built combined clinical and metabolomic IR diagnostics. These were utilised to stratify IR status in the pre-intervention fasting samples in three independent cohorts (META-PREDICT (MP, n=179), STRRIDE-AT/RT (S-2, n=116) and STRRIDE-PD (S-PD, n=149)). Linear and Bayesian projective prediction strategies were used to evaluate biomarkers for fasting insulin and HOMA2- IR and change in fasting insulin with treatment. Both insulin assays accurately quantified international standard insulin (R2>0.99), yet agreement for fasting insulin was less congruent (R2=0.65). Only the high-sensitivity ELISA assay could identify the mean effect of treatment on fasting insulin. Clinical-metabolomic models were statistically related to fasting insulin (R20.33 – 0.39) but had modest capacity to classify HOMA2-IR at a clinically relevant threshold. Furthermore, no model predicted treatment responses in any cohort. Thus, we demonstrate that the choice of insulin assay is critical when quantifying the influence of life-style on fasting insulin, while none of the clinical-metabolomic biomarkers, validated in cross-sectional data, are suitable for monitoring longitudinally changes in IR status.
Hippocampal ripples during offline periods predict human motor sequence learning
Authors: Chen Pin-Chun , Stritzelberger Jenny , Walther Katrin , Hamer Hajo , Staresina Bernhard P. 
Published: October 2024

AbstractHigh-frequency bursts in the hippocampus, known as ripples (80-120 Hz in humans), have been shown to support episodic memory processes. However, converging recent evidence in rodent models as well as human neuroimaging suggests that the hippocampus may be involved in a wider range of memory domains, including motor sequence learning (MSL). Nevertheless, no direct link between hippocampal ripples and MSL has yet been established. Here, we recorded intracranial electroencephalography from the hippocampus in 20 epilepsy patients during a MSL task in which participants showed steady improvement across nine 30-second training blocks interspersed with 30-second rest (‘offline’) periods. We first demonstrate that ripple rates strongly increase during rest periods relative to training blocks. Importantly, ripple rates during rest periods tracked learning behaviour, both across blocks and across participants. These results suggest that hippocampal ripples during offline periods play a functional role in motor sequence learning and that the hippocampus may be involved in offline learning beyond episodic memory.
The Impact of Host Genetics and/or its Microbiota on the Severity ofCorynebacterium-Associated Hyperkeratosis in Outbred Athymic Nude Mice
Authors: Michelson Abigail , Cheleuitte-Nieves Christopher , Miranda Ileana C. , Dobtsis Irina , Lipman Neil S 
Published: October 2024

AbstractCorynebacterium bovis(Cb), the etiology ofCorynebacterium-associated hyperkeratosis (CAH) in nude mice, may impact research outcomes. Little is known about the differences in the course and severity of CAH in different outbred athymic nude mice stocks. Three genetic stocks (designated A, B, and C), 1 of which was obtained from 2 geographically separate colonies with distinct microbiota (A1 and A2), were inoculated topically with 1 × 108CFUs of a pathogenic Cb field isolate (#7894; n = 6/stock) or sterile media (n=2/stock; controls). Clinical signs were assessed daily and scored 0 – 5 based on lesion severity. Mice were euthanized at 14 (A1, A2, B, and C) or 28 (B) days-post-inoculation (dpi), macroscopic changes documented, and 6 skin samples per mouse were obtained and histologically scored 0 – 4 based on the presence and severity of hyperkeratosis, acanthosis, inflammation, and bacterial colonies. No stock A1 or control mice developed clinical disease; 1 of 6 stock B mice developed mild CAH (mean peak clinical score [MPCS] – 0.33) at 14 dpi (14 day group) and 2 of 6 stock B (28 day group) developed mild CAH at 15 dpi (MPCS -0.33); and, all stock C and A2 mice developed significant clinical signs at 5 dpi (MPCS – 2.5 and 3, respectively) which resolved by 11 dpi. Despite differences in clinical presentation, all Cb-infected mice had hyperkeratosis and/or acanthosis with associated bacterial colonies. Stocks A1 and B, which had minimal or no clinical signs, were colonized withCorynebacterium amycolatum(Ca). In contrast, stocks C and A2 were not colonized with Ca, raising the possibility that Ca and/or other components of the skin microbiota may mitigate clinical signs but not necessarily all histopathologic changes associated with infection. These findings suggest host genetics and/or the skin microbiota can markedly influence the presentation of CAH in nude mice.