bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging Pretrained Deep Protein Language Model to Predict Peptide Collision Cross Section
Authors: Nakai-Kasai Ayano , Ogata Kosuke , Ishihama Yasushi , Tanaka Toshiyuki 
Published: September 2024

AbstractCollision cross section (CCS) of peptide ions provides an important separation dimension in liquid chromatography/tandem mass spectrometry-based proteomics that incorporates ion mobility spectrometry (IMS), and its accurate prediction is the basis for advanced proteomics workflows. This paper describes novel experimental data and a novel prediction model for challenging CCS prediction tasks including longer peptides that tend to have higher charge states. The proposed model is based on a pretrained deep protein language model. While the conventional prediction model requires training from scratch, the proposed model enables training with less amount of time owing to the use of the pretrained model as a feature extractor. Results of experiments with the novel experimental data show that the proposed model succeeds in drastically reducing the training time while maintaining the same or even better prediction performance compared with the conventional method. Our approach presents the possibility of prediction in a “greener” manner of various peptide properties in proteomic liquid chromatography/tandem mass spectrometry experiments.
LoVis4u: Locus Visualisation tool for comparative genomics
Authors: Egorov Artyom A. , Atkinson Gemma C. 
Published: September 2024

AbstractSummaryComparative genomic analysis often involves visualisation of alignments of genomic loci. While several software tools are available for this task, ranging from Python and R libraries to standalone graphical user interfaces, there is lack of a tool that offers fast, automated usage and the production of publication-ready vector images.Here we present LoVis4u, a command-line tool and Python API designed for highly customizable and fast visualisation of multiple genomic loci. LoVis4u generates vector images in PDF format based on annotation data from GenBank or GFF files. It is capable of visualising entire genomes of bacteriophages as well as plasmids and user-defined regions of longer prokaryotic genomes. Additionally, LoVis4u offers optional data processing steps to identify and highlight accessory and core genes in input sequences.Availability and ImplementationLoVis4u is implemented in Python3 and runs on Linux and MacOS. The command-line interface covers most practical use cases, while the provided Python API allows usage within a Python program, integration into external tools, and additional customisation. Source code is available at the GitHub page:github.com/art-egorov/lovis4u. Detailed documentation that includes an example-driven guide is available from the software home page:art-egorov.github.io/lovis4u.
SOX2 drives fetal reprogramming and reversible dormancy in colorectal cancer
Authors: Baulies Anna , Moncho-Amor Veronica , Drago-Garcia Diana , Kucharska Ania , Chakravarty Probir , Moreno-Valladares Manuel , Cruces-Salguero Sara , Hubl Florian , Hutton Colin , Kim Hanue , Matheu Ander , Lovell-Badge Robin , Li Vivian S. W. 
Published: September 2024

AbstractCellular plasticity plays critical roles in tissue regeneration, tumour progression and therapeutic resistance. However, the mechanism underlying this cell state transition remains elusive. Here, we show that the transcription factor SOX2 induces fetal reprogramming and reversible dormancy in colorectal cancer (CRC). SOX2 expression correlates with fetal reprogramming and poor prognosis in human primary and metastatic colorectal adenocarcinomas. In mouse CRC models, rare slow-cycling SOX2+SCA1+cells are detected in earlyApc-deleted mouse tumours that undergo slow clonal expansion over time. In contrast, the SOX2+clones were found proliferative in advancedApc-/-;KrasG12D/+;p53-/-;Tgfbr2-/-(AKPT) tumours, accompanied by dynamic cell state reprogramming from LGR5+to LGR5-SCA1+cells. Using transgenic mouse models, we demonstrate that ectopic expression of SOX2 inhibits intestinal lineage differentiation and induces fetal reprogramming. SOX2+ cells adopt dynamic cell cycle states depending on its expression level. High SOX2 expression results in hyperproliferation, whereas low SOX2 levels induce senescence-mediated dormancy. We find that loss of p53 can reverse SOX2-induced senescence, in line with the dormant cell state exit of the SOX2+ cells observed in advanced tumours. Finally, SOX2 expression is induced by 5-FU treatment in CRC. SOX2-expressing organoids exhibit increased tolerance to chemotherapy treatment, whilst deletion of SOX2 in AKPT tumour organoids sensitises drug responses. We propose that SOX2-induced plasticity and reversible dormancy promotes tumour progression and drug tolerance in CRC.
Inheritance bias of deletion-harbouring mtDNA in yeast: the role of copy number and intracellular selection
Authors: Kashko Nataliia D. , Karavaeva Iuliia , Glagoleva Elena S. , Logacheva Maria D. , Garushyants Sofya K. , Knorre Dmitry A. 
Published: September 2024

AbstractEukaryotic cells contain multiple copies of mitochondrial DNA (mtDNA) molecules that replicate independently. Cell mtDNA content and variability contributes to the overall cell fitness. During sexual reproduction, fungi usually inherit mtDNA from both parents, however, the distribution of the mtDNA in the progeny can be biased toward some mtDNA variants. For example, crossingSaccharomyces cerevisiaestrain carrying wild type (rho+) mtDNA with the strain carrying mutant mtDNA variant with large deletion (rho−) can produce up to 99-100% ofrho−diploid progeny. Two factors could contribute to this phenomenon. First,rho−cells may accumulate more copies of mtDNA molecules per cell than wild-type cells, makingrho−mtDNA a prevalent mtDNA molecule in zygotes. This consequently leads to a high portion ofrho−diploid cells in the offspring. Second,rho−mtDNA may have a competitive advantage within heteroplasmic cells, and therefore could displacerho+mtDNA in a series of generations, regardless of their initial ratio. To assess the contribution of these factors, we investigated the genotypes and phenotypes of twenty tworho−yeast strains. We found that indeedrho−cells have a higher mtDNA copy number per cell thanrho+strains. Using anin silicomodelling of mtDNA selection and random drift in heteroplasmic yeast cells, we assessed the intracellular fitness of mutant mtDNA variants. Our model indicates that both higher copy numbers and intracellular fitness advantage of therho-mtDNA contribute to the biased inheritance ofrho−mtDNA.
Biofabrication of Small Vascular Graft with Acellular Human Amniotic Membrane: A Proof-of-Concept Study in Pig
Authors: Aung O , Rossi Peter J , Dyer Mitchell R , Stellpflug Austin , Zhai Yingnan , Kenneth Allen , Wang Xiaolong , Chang Jackie , Chen Yiliang , Tefft Brandon , Wu Rongxue , Gu Lingxia , Wang Bo 
Published: September 2024

AbstractSynthetic vascular grafts, such as expanded polytetrafluoroethylene (ePTFE), are commonly used for large vessel surgeries [internal diameter (ID) ≥ 10 mm] but present significant challenges in medium to small vessels (ID < 10 mm) due to increased risks of thrombosis, stenosis, and infection. In this study, we developed a small-diameter vascular graft using decellularized human amniotic membrane (DAM graft) (ID = 6 mm) and transplanted it into porcine carotid arteries, comparing it with ePTFE grafts to assess inflammation, biocompatibility, patency, and overall function. One-week post-implantation, ultrasound imaging confirmed blood patency in both graft types. However, after one-month, gross examination revealed pronounced neointimal hyperplasia in ePTFE grafts, while DAM grafts maintained open lumens without signs of stenosis or thrombosis. Histological analysis showed extensive fibrous tissue formation in ePTFE grafts, resulting in luminal narrowing, whereas DAM grafts displayed sustained lumen patency and vascular integration. Immunofluorescence confirmed reduced inflammation and improved tissue organization in DAM grafts, characterized by lower macrophage infiltration and better cellular architecture. These findings suggest that DAM grafts offer superior biocompatibility and significantly lower risks of neointimal hyperplasia, making them a promising alternative for small-diameter vascular surgeries compared to ePTFE grafts.
A ChatGPT Assisted Reading Protocol for Undergraduate Research Students
Authors: Sambar Marcus , Vázquez Gonzalo R. , Vázquez Anne V. , Vázquez Frank X. 
Published: September 2024

AbstractA major challenge for undergraduate students is reading scientific literature. This is especially true in biophysics, where many of the concepts may not have been covered in undergraduate courses. Students can become overwhelmed, which may lead to less overall engagement with the scientific literature. In response, we have developed a guided reading protocol that combines pre-reading strategies, structured notetaking, and ChatGPT to help students clarify unfamiliar concepts in an interactive way. To test the protocol, participants in this study were given an initial survey to determine their experience with reading scientific literature. After this they were given an abridged biophysics paper and the protocol. The ChatGPT transcripts were analyzed using open coding and the students were given a post-study survey. We found most students did not appear to regularly engage with the literature, possibly due to content barriers they encountered. Analyzing their transcripts, we observed that students asked for definitions, explanations, summaries, and simplifications. Overall, students reported that using ChatGPT was a positive experience and they expected to use ChatGPT in the future. From this work, we expect this new protocol may be a way to keep novice students from becoming discouraged when reading scientific papers and keep them engaged with the current literature.
Multiple Functions of Cerebello-Thalamic Neurons in Learning and Offline Consolidation of a Motor Skill in mice
Authors: Varani Andres P , Mailhes-Hamon Caroline , Sala Romain W , Fouda Sarah , Frontera Jimena L , Léna Clément , Popa Daniela 
Published: September 2024

ABSTRACTMotor skill learning is a complex and gradual process that involves the cortex and basal ganglia, both crucial for the acquisition and long-term retention of skills. The cerebellum, which rapidly learns to adjust the movement, connects to the motor cortex and the striatum via the ventral and intralaminar thalamus respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. Using a targeted chemogenetic inhibition that preserves the motor abilities, we found that cerebellar nuclei neurons projecting to the intralaminar thalamus contribute to learning and expression, while cerebellar nuclei neurons projecting to the ventral thalamus contribute to offline consolidation. Asymptotic performance, however, required each type of neurons. Thus, our results show that cerebellar neurons belonging to two parallel cerebello-thalamic pathways play distinct, but complementary, roles functioning on different timescales and both necessary for motor skill learning.
An updated AL-Base reveals ranked enrichment of immunoglobulin light chain variable genes in AL amyloidosis
Authors: Morgan Gareth , Nau Allison N. , Wong Sherry , Spencer Brian H. , Shen Yun , Hua Axin , Bullard Matthew J. , Sanchorawala Vaishali , Prokaeva Tatiana 
Published: September 2024

AbstractBackgroundEach monoclonal antibody light chain associated with AL amyloidosis has a unique sequence. Defining how these sequences lead to amyloid deposition could facilitate faster diagnosis and lead to new treatments.MethodsLight chain sequences are collected in the Boston University AL-Base repository. Monoclonal sequences from AL amyloidosis, multiple myeloma and the healthy polyclonal immune repertoire were compared to identify differences in precursor gene use, mutation frequency and physicochemical properties.ResultsAL-Base now contains 2,193 monoclonal light chain sequences from plasma cell dyscrasias. Sixteen germline precursor genes were enriched in AL amyloidosis, relative to multiple myeloma and the polyclonal repertoire. Two genes,IGKV1-16andIGLV1-36, were infrequently observed but highly enriched in AL amyloidosis. The number of mutations varied widely between light chains. AL-associated κ light chains harbored significantly more mutations compared to multiple myeloma and polyclonal sequences, whereas AL-associated λ light chains had fewer mutations. Machine learning tools designed to predict amyloid propensity were less accurate for new sequences than their original training data.ConclusionsRarely-observed light chain variable genes may carry a high risk of AL amyloidosis. New approaches are needed to define sequence-associated risk factors for AL amyloidosis. AL-Base is a foundational resource for such studies.
Cross-sectional brain age assessments are limited in predicting future brain change
Authors: Korbmacher Max , Vidal-Pineiro Didac , Wang Meng-Yun , van der Meer Dennis , Wolfers Thomas , Nakua Hajer , Eikefjord Eli , Andreassen Ole A. , Westlye Lars T. , Maximov Ivan I. 
Published: September 2024

ABSTRACTThe concept of brain age (BA) describes an integrative imaging marker of brain health, often suggested to reflect ageing processes. However, the degree to which cross-sectional MRI features, including BA, reflect past, ongoing and future brain changes across different tissue types from macro-to microstructure remains controversial (Vidal-Pineiro et al. 2021). Here, we advance these findings by using multimodal imaging data of39, 325UK Biobank participants, aged44 − 82years at baseline and2, 520follow-ups within1.12 − 6.90years. In concordance with the original findings, we find insufficient evidence that BA reflects the rate of brain ageing. However, modality-specific differences in brain ages reflected the state of the brain, highlighting diffusion and multimodal MRI brain age as potentially useful cross-sectional markers.
Tissue-specific metabolomic signatures for adoublesexmodel of reduced sexual dimorphism
Authors: Coig Rene , Harrison Benjamin R. , Johnson Richard S. , MacCoss Michael J. , Promislow Daniel E.L. 
Published: September 2024

AbstractSex has a major effect on the metabolome. However, we do not yet understand the degree to which these quantitative sex differences in metabolism are associated with anatomical dimorphism and modulated by sex-specific tissues. In the fruit fly,Drosophila melanogaster, knocking out thedoublesex(dsx) gene gives rise to adults with intermediate sex characteristics. Here we sought to determine the degree to which this key node in sexual development leads to sex differences in the fly metabolome. We measured 91 metabolites across head, thorax and abdomen inDrosophila, comparing the differences between distinctly sex-dimorphic flies with those of reduced sexual dimorphism:dsxnull flies. Notably, in the reduced dimorphism flies, we observed a sex difference in only 1 of 91 metabolites, kynurenate, whereas 51% of metabolites (46/91) were significantly different between wildtype XX and XY flies in at least one tissue, suggesting thatdsxplays a major role in sex differences in fly metabolism. Kynurenate was consistently higher in XX flies in both the presence and absence of functioningdsx. We observed tissue-specific consequences of knocking outdsx. Metabolites affected by sex were significantly enriched in branched chain amino acid metabolism and the mTOR pathway. This highlights the importance of considering variation in genes that cause anatomical sexual dimorphism when analyzing sex differences in metabolic profiles and interpreting their biological significance.
Tenascin C Deletion Impairs Tendon Healing and Functional Recovery After Rotator Cuff Repair
Authors: Tashjian Robert Z. , Zitnay Jared , Kazmers Nikolas H. , Veerabhadraiah Shivakumar R. , Zelada Antonio C. , Honeggar Matthew , Smith Matthew C. , Chalmers Peter N. , Henninger Heath B. , Jurynec Michael J. 
Published: September 2024

AbstractThe biological factors that affect healing after rotator cuff repair (RCR) are not well understood. Genetic variants in the extracellular matrix protein Tenascin C (TNC) are associated with impaired tendon healing and it is expressed in rotator cuff tendon tissue after injury, suggesting it may have a role in the repair process. The purpose of the current study was to determine the role of TNC on tendon healing after RCR in a murine model. The supraspinatus tendon was transected and repaired on the left shoulder of Wild-Type (WT-RCR),Tenascin Cnull (Tnc−-RCR) andTncheterozygous (Tnc+/−-RCR) mice. Controls included the unoperated, contralateral shoulder of WT-RCR,Tnc—RCR,Tnc+/−-RCR mice and unoperated shoulders from age and genotype matched controls. We performed histologic, activity testing, RNA-seq, and biomechanical analyses. At 8-weeks post-RCR,Tnc−andTnc+/−mice had severe bone and tendon defects following rotator cuff repair.Tnc−-RCR mice had reduced activity after rotator cuff repair including reduced wheel rotations, wheel duration, and wheel episode average velocity compared with WT-RCR. Loss ofTncfollowing RCR altered gene expression in the shoulder, including upregulation of sex hormone and WNT pathways and a downregulation of inflammation and cell cycle pathways.Tnc−mice had similar biomechanical properties after repair as WT. Further research is required to evaluate tissue specific alterations ofTnc, the interactions ofTncand sex hormone and inflammation pathways as well as possible adjuvants to improve enthesis healing in the setting of reduced TNC function.
Challenging the Chronic Perverse Bias in Prosthetic Valve Design: A Pathway Opens for Advanced Mechanical Valves
Authors: Scotten Lawrence N. , Goode Dylan , Siegel Rolland , Blundon David J. , Dutton James W. , Mohammadi Hadi 
Published: September 2024

ABSTRACTObjective-In vitro evaluation of several prototype mechanical valves compared to present-day controls.Method-simulated normal cardiac pressures and flows-gravity pressure head column tester flows.-recorded valve hydrodynamics and kinematicsResults-valves superior in performance to clinical controlsConclusions-Prototype MHV candidates outperform the closing performance of present day SAVR prosthetic valves, including bioprosthetic control.Competing InterestsNone declaredFinancial DisclosureThis research was performed on a pro bono basis by indicted coauthors*, in part, to assist coauthor and Ph.D. candidate Dylan Goode.CENTRAL MESSAGEIn-vitro dynamics of optimized prototype mechanical heart valves (MHVs) outperformed those of current clinical prosthetic SAVR valves. -Achieving the objective of an anticoagulation-free and durable MHV is directly related to mitigation of detrimental valve closing hydrodynamics and kinematics.PERSPECTIVEImprovements in prosthetic valve performance and durability notwithstanding, the objective of an anti-coagulation free device with durability exceeding the projected life expectancy of all recipients has not been achieved. Our work identifies a design and development void that may have significantly delayed progress toward this objective.SIGNIFICANCEOur results challenge a longstanding bias in valve design, shifting the focus towards crucial behavior during valve closure. This study paves the way for advanced mechanical valves bringing us closer to the elusive goal of anticoagulation-free performance—a long-awaited milestone in the evolution of prosthetic valves.
Gut-Brain Nexus: Mapping Multi-Modal Links to Neurodegeneration at Biobank Scale
Authors: Shafieinouri Mohammad , Hong Samantha , Schuh Artur , Makarious Mary B. , Sandon Rodrigo , Lee Paul Suhwan , Simmonds Emily , Iwaki Hirotaka , Hill Gracelyn , Blauwendraat Cornelis , Escott-Price Valentina , Qi Yue A. , Noyce Alastair J. , Reyes-Palomares Armando , Leonard Hampton L. , Tansey Malu , Singleton Andrew , Nalls Mike A. , Levine Kristin S , Bandres-Ciga Sara 
Published: September 2024

AbstractAlzheimer’s disease (AD) and Parkinson’s disease (PD) are influenced by genetic and environmental factors. Using data from UK Biobank, SAIL Biobank, and FinnGen, we conducted an unbiased, population-scale study to: 1) Investigate how 155 endocrine, nutritional, metabolic, and digestive system disorders are associated with AD and PD risk prior to their diagnosis, considering known genetic influences; 2) Assess plasma biomarkers’ specificity for AD or PD in individuals with these conditions; 3) Develop a multi-modal classification model integrating genetics, proteomics, and clinical data relevant to conditions affecting the gut-brain axis. Our findings show that certain disorders elevate AD and PD risk before AD and PD diagnosis including: insulin and non-insulin dependent diabetes mellitus, noninfective gastro-enteritis and colitis, functional intestinal disorders, and bacterial intestinal infections, among others. Polygenic risk scores revealed lower genetic predisposition to AD and PD in individuals with co-occurring disorders in the study categories, underscoring the importance of regulating the gut-brain axis to potentially prevent or delay the onset of neurodegenerative diseases. The proteomic profile of AD/PD cases was influenced by comorbid endocrine, nutritional, metabolic, and digestive systems conditions. Importantly, we developed multi-modal prediction models integrating clinical, genetic, proteomic and demographic data, the combination of which performs better than any single paradigm approach in disease classification. This work aims to illuminate the intricate interplay between various physiological factors involved in the gut-brain axis and the development of AD and PD, providing a multifactorial systemic understanding that goes beyond traditional approaches. Further, we have developed an interactive resource for the scientific community [https://gut-brain-nexus.streamlit.app/] where researchers can investigate components of the predictive model and can investigate feature effects on a sample level.TeaserCo-occurring disorders of the gut-brain axis combined with genetic and proteomic data can better predict neurodegenerative risk.