bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding Cu+2binding with DNA: A molecular dynamics study comparing Cu2+and Mg2+binding to the Dickerson DNA
Authors: Sharma Angad , Yadav Hari O. S. , Bandyopadhyay Pradipta 
Published: July 2024

ABSTRACTCu2+ions led DNA damage by reactive oxygen species (ROS) is widely known biological phenomena. The ionic radii of Cu2+and Mg2+being similar, the binding of Cu2+ions to DNA is expected to be similar to that of the Mg2+ions. However, little is known how Cu2+ions bind in different parts (phosphate, major and minor grooves) of a double-strand (ds) DNA, especially at atomic level. In the present study, we employ molecular dynamic (MD) simulations to investigate the binding of Cu2+ions with the Dickerson DNA, a B-type dodecamer double stranded (ds) DNA. The binding characteristics of Cu2+and Mg2+ions with this dsDNA are compared to get an insight into the differences and similarities in binding behavior of both ions. Unlike Mg2+ions, the first hydration shell of Cu2+is found to be labile, thus it shows both direct and indirect binding with the dsDNA, i.e., binding through displacement of water from the hydration shell or through the hydration shell. Though the binding propensity of Cu2+ions with dsDNA is observed relatively stronger, the binding order to phosphates, major groove, and minor groove is found qualitatively similar (phosphates > major groove > minor groove) for both ions. The study gives a deep understanding of Cu2+binding to DNA, which could be helpful in rationalizing the Cu2+led ROS-mediated DNA damage.
Glioma-associated tertiary lymphoid structures are sites of lymphocyte clonal expansion and plasma cell formation
Authors: Cakmak Pinar , Lun Jennifer H. , Singh Aakanksha , Macas Jadranka , Schupp Jonathan , Köhler Miriam , Starzetz Tatjana , Burger Michael C. , Steidl Eike , Hasse Lucie Marie , Hattingen Elke , Plate Karl H. , Reiss Yvonne , Imkeller Katharina 
Published: July 2024

SummaryAdult-type diffuse gliomas, the most common primary brain tumors, pose significant clinical challenges due to limited treatment options, restricted anti-tumor immune response and dismal patient prognosis. In this study, we elucidate the immunological function and clinical relevance of intra-tumoral tertiary lymphoid structures (TLS) in adaptive anti-glioma immunity. We conducted a comprehensive, unbiased analysis of lymphoid aggregation in 642 gliomas using a multi-modal approach that combines RNA sequencing with spatial transcriptome and proteome profiling. Our findings reveal that TLS are present in 15% of tumors and correlate with improved overall survival. Gliomas with TLS exhibit a remodeled perivascular space, marked by transcriptional upregulation and spatial redistribution of collagens associated with barrier functions. Furthermore, we demonstrate that TLS maturation into sites of dynamic adaptive immune responses, characterized by clonal T and B cell expansion and IgA+ and IgG+ plasma-cell formation, is driven by efficient early T cell recruitment to the perivascular space.
Physical constraints on the positions and dimensions of the zebrafish swim bladder by surrounding bones
Authors: Satoh Koumi , Maeno Akiteru , Adachi Urara , Ishizaka Mizuki , Yamada Kazuya , Koita Rina , Nakazawa Hidemichi , Oikawa Sae , Fujii Renka , Furudate Hiroyuki , Kawamura Akinori 
Published: July 2024

AbstractPrecise regulation of organ size and position is crucial for optimal organ function. Since the swim bladder is primarily responsible for buoyancy in teleosts, early development and subsequent inflation of the swim bladder should be appropriately controlled with the body growth. However, the underlying mechanism remains unclear. In this study, we show that the size and position of the swim bladder are physically constrained by the surrounding bones in zebrafish. Non-invasive micro-CT scanning revealed that the anterior edge of the swim bladder is largely attached to the os suspensorium, which is an ossicle extending medioventrally from the 4th vertebra. Additionally, we observed thathoxc6amutants, which lack the os suspensorium, exhibited an anterior projection of the swim bladder beyond the 4th vertebra. During the swim bladder development, we found that the counterclockwise rotation of the os suspensorium correlates with posterior regression of the swim bladder, suggesting that the os suspensorium pushes the swim bladder posteriorly into its proper position. Furthermore, our results revealed a close association between the posterior region of the swim bladder and the pleural ribs. Inhoxaacluster mutants with additional ribs, the swim bladder expanded posteriorly, accompanied by an enlarged body cavity. Taken together, our results demonstrate the importance of the surrounding bones in the robust regulation of swim bladder size and position in zebrafish.
Methamphetamine-induced adaptation of learning rate dynamics depend on baseline performance
Authors: Kirschner Hans , Molla Hanna M. , Nassar Matthew R. , de Wit Harriet , Ullsperger Markus 
Published: July 2024

AbstractThe ability to calibrate learning according to new information is a fundamental component of an organism’s ability to adapt to changing conditions. Yet, the exact neural mechanisms guiding dynamic learning rate adjustments remain unclear. Catecholamines appear to play a critical role in adjusting the degree to which we use new information over time, but individuals vary widely in the manner in which they adjust to changes. Here, we studied the effects of a low dose of methamphetamine (MA), and individual differences in these effects, on probabilistic reversal learning dynamics in a within-subject, double-blind, randomized design. Participants first completed a reversal learning task during a drug-free baseline session to provide a measure of baseline performance. Then they completed the task during two sessions, one with MA (20 mg oral) and one with placebo (PL). First, we showed that, relative to PL, MA modulates the ability to dynamically adjust learning from prediction errors. Second, this effect was more pronounced in participants who performed poorly at baseline. These results present novel evidence for the involvement of catecholaminergic transmission on learning flexibility and highlights that baseline performance modulates the effect of the drug.
Implementing a Behaviour Change Communication interaction for enhancing male involvement in maternity care among the Saharia Tribes in Gwalior District, Madhya Pradesh: a feasibility study
Authors: Adhikari Tulsi , Nair Saritha , Grover Ashpinder kaur 
Published: July 2024

ABSTRACTBackgroundThe Indian tribal population is diverse, with a wide range of customs, ways of life, and cultural practices. However, there is one thing that all Indian tribal communities have in common: they have worse health indicators, a higher rate of illness and mortality, and very restricted access to medical care. Their health issues require extra consideration in the right setting.[1] Growth in the utilization of reproductive and maternal health services will not only curtail down the reproductive morbidities, but it will also reduce the child mortality.[2] Men’s participation in prenatal care, delivery and postpartum period is rarely found, especially among tribal communities, due to their economic instabilities and priorities. Also our health system does not promote the involvement of men in the maternal and child health care. Hence, there was a need felt for development of gender and community sensitive interventions package that could address the individual and the community health care facility level barriers of male involvement in utilisation of the maternal care services. Our study was an endeavour to determine the feasibility of implementing a behaviour Change Communication Interaction developed for improvement in utilisation of maternity care services through male participation among the Saharia Tribes in Gwalior District, Madhya Pradesh.MethodsThe Study utilised a qualitative approach. Various activities were organised as a part of BCC, viz, Community mobilization, Campaign/Rallies, Interpersonal Communication-Drama & Mock Sessions, Face to Face counselling and Quiz etc. Action technique called Transect was used in order to know more about the environment and living of the people of Saharia Tribes in Gwalior District, Madhya Pradesh. Feasibility of the model was assessed by focusing on three main principles i.e., acceptability, integration and limited-efficacy testing.ResultAcceptability testing study reveal that BCC intervention was successfully accepted by intended individual-both targeted individuals and those involved in implementing programs. Integration approach reveal that no major change in infrastructure of Govt. Programmes and facilities is required; only the participation of key people in society and workers local health services is required. Limited-efficacy testing reveals that there is a behavioural change in men’s perception of accompanying their spouse to the health centre; same was observed on the vaccination day in the village.ConclusionsThe BCC intervention proved to be feasible to implement. The Proposed BCC interaction is feasible and accepted by both Programme stake holders and beneficiaries.
MIST: an interpretable and flexible deep learning framework for single-T cell transcriptome and receptor analysis
Authors: Lai Wenpu , Li Yangqiu , Luo Oscar Junhong 
Published: July 2024

AbstractJoint analysis of transcriptomic and T cell receptor (TCR) features at single-cell resolution provides a powerful approach for in-depth T cell immune function research. Here, we introduce a deep learning framework for single-T cell transcriptome and receptor analysis, MIST (Multi-Insight for T cell). MIST features three latent spaces: gene expression, TCR, and a joint latent space. Through analyses of antigen- specific T cells and T cells related to lung cancer immunotherapy, we demonstrate MIST’s interpretability and flexibility. MIST easily and accurately resolves cell function and antigen-specificity by vectorizing and integrating transcriptome and TCR data of T cells. In addition, using MIST, we identified the heterogeneity of CXCL13+subsets in lung cancer infiltrating CD8+T cells and their association with immunotherapy, providing additional insights into the functional transition of CXCL13+T cells related to anti-PD-1 therapy that were not reported in the original study. MIST is available athttps://github.com/aapupu/MIST.
Cell sorting based on single nucleotide variation enables characterization of mutation-dependent transcriptome and chromatin states
Authors: Salatino Roberto , Franco Marianna , Romero-Toledo Arantxa , Wang Yi , Tsuda Shanel , Szentirmai Oszkar , Janiszewska Michalina 
Published: July 2024

ABSTRACTSingle nucleotide variants (SNVs) contribute to cancer by altering the coding and the non-coding regions of the genome. Connecting SNVs to transcriptomic and epigenetic changes at the single-cell level remains challenging. To enable studies of rare cell populations harboring specific point mutations, we developed STAR-FACS, Specific-To-Allele PCR-FACS, to sort cells based on genomic allele alterations. We show that STAR-FACS can separate cells based on TERT promoter mutation status and is compatible with bulk and single-cell transcriptomic and epigenetic profiling. We demonstrate that glioblastoma cell lines derived from the same tumor but harboring distinct TERT promoter SNVs have different transcriptional programs.
Development and Characterization of 50 nanometer diameter Genetically Encoded Multimeric Nanoparticles
Authors: Hernandez Cindy M. , Duran-Chaparro David C. , van Eeuwen Trevor , Rout Michael P. , Holt Liam J. 
Published: July 2024

AbstractThe mechanisms that regulate the physical properties of the cell interior remain poorly understood, especially at the mesoscale (10nm-100nm). Changes in these properties have been suggested to be crucial for both normal physiology and disease. Many crucial macromolecules and molecular assemblies such as ribosomes, RNA polymerase, and biomolecular condensates span the mesoscale size range. Therefore, we need better tools to study the cellular environment at this scale. A recent approach has been to use genetically encoded multimeric nanoparticles (GEMs), which consist of self-assembling scaffold proteins fused to fluorescent tags. After translation of the fusion protein, the monomers self-assemble into bright and stable nanoparticles of defined geometry that can be visualized by fluorescence microscopy. Physical properties of the cell can then be inferred through analysis of the motion of these particles, an approach called nanorheology. Previously, 40nm-GEMs elucidated TORC1 kinase as a regulator of cytoplasmic crowding. However, extremely sensitive microscopes were required. Here, we describe the development and characterization of a 50 nm diameter GEM that is brighter and probes a larger length scale. 50nm-GEMs will make high-throughput nanorheology accessible to a broader range of researchers and reveal new insights into the biophysical properties of cells.
Shikimate pathway-Dependent Catabolism: enabling near-to-maximum production yield of aromatics
Authors: Bruinsma Lyon , Batianis Christos , Moreno Paz Sara , Kurnia Kesi , Dirkmaat Job. J , Müller Alexandra , Juncosa Nunez Jose , Weusthuis Ruud A. , Martins dos Santos Vitor A. P. 
Published: July 2024

ABSTRACTCatabolism is a complex network of tightly regulated metabolic reactions that provides energy and carbon to fuel anabolism in all living organisms. Rewiring catabolism is essential for harnessing industrial biotechnology but remains a substantial metabolic engineering challenge due to its high genetic stability and tight regulation acquired through evolution. In this study, by combining metabolic modeling, rational engineering, and adaptive laboratory evolution, we fundamentally redesigned bacterial catabolism. We created a new-to-nature shikimate pathway-dependent catabolism (SDC) inPseudomonas putidaby reprogramming the shikimate pathway as the primary catabolic route. SDC supports growth by supplying the glycerol catabolic end-product pyruvate, enabling superior production of shikimate pathway-derived molecules. Through SDC, aromatics production reached over 89% of the pathway’s maximum theoretical yield, setting a new benchmark for their microbial synthesis. Our study successfully repurposed an anabolic pathway for catabolism, exemplifying the high metabolic plasticity of microbes and providing a bacterial chassis for the efficient production of high-added value compounds.
Low coverage whole genome sequencing of low-grade dysplasia strongly predicts colorectal cancer risk in ulcerative colitis
Authors: Bakir Ibrahim Al , Curtius Kit , Cresswell George D , Grant Heather E , Nasreddin Nadia , Smith Kane , Nowinski Salpie , Guo Qingli , Belnoue-Davis Hayley L , Fisher Jennifer , Clarke Theo , Kimberley Christopher , Mossner Maximilian , Dunne Philip D , Loughrey Maurice B , Speight Ally , East James E , Wright Nicholas A , Rodriguez-Justo Manuel , Jansen Marnix , Moorghen Morgan , Baker Ann-Marie , Leedham Simon J , Hart Ailsa L , Graham Trevor A 
Published: July 2024

AbstractPatients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC), and this risk increases dramatically in those who develop low-grade dysplasia (LGD). However, there is currently no accurate way to risk-stratify patients with LGD, leading to both over- and under-treatment of cancer risk. Here we show that the burden of somatic copy number alterations (CNAs) within resected LGD lesions strongly predicts future cancer development. We performed a retrospective multi-centre validated case-control study of n=122 patients (40 progressors, 82 non-progressors, 270 LGD regions). Low coverage whole genome sequencing revealed CNA burden was significantly higher in progressors than non-progressors (p=2x10-6in discovery cohort) and was a very significant predictor of CRC risk in univariate analysis (odds ratio = 36; p=9x10-7), outperforming existing clinical risk factors such as lesion size, shape and focality. Optimal risk prediction was achieved with a multivariate model combining CNA burden with the known clinical risk factor of incomplete LGD resection. The measurement of CNAs in LGD lesions is a robust, low-cost and rapidly translatable predictor of CRC risk in IBD that can be used to direct management and so prevent CRC in high-risk individuals whilst sparing those at low-risk from unnecessary intervention.
Exposure to and engagement with digital psychoeducational content and community related to maternal mental health by perinatal persons and mothers: design of an online survey with optional follow-up and participant characteristics
Authors: Waring Molly E. , McManus-Shipp Katherine E. , Field Christiana M. , Bhusal Sandesh , Perez Asley , Shapiro Olivia , Gaspard Sophia A. , Dennis Cindy-Lee 
Published: July 2024

AbstractBackgroundLeveraging digital platforms may be an effective strategy for connecting perinatal persons and mothers with evidence-based information and support related to maternal mental health and peers. Momwell is a mom-centered model of care that provides psychoeducational content through several digital platforms including social media, podcasts, and blog posts.ObjectiveTo describe the design of a study of perinatal persons and mothers who are exposed to or engage with psychoeducation content and community related to maternal mental health on social media or other digital platforms (Momwell), and to describe characteristics of the sample.MethodsAdults who engaged with Momwell on any of their digital platforms were recruited to participate in an online survey study in summer/fall 2023. Participants completed either a longer or shorter survey. Two to 3 months after completing this survey, participants who provided permission to be re-contacted were invited to complete a second survey. The surveys included validated psychological measures, study-specific quantitative questions, and open-ended questions that assessed participant demographics, exposure to and engagement with Momwell psychoeducation content and community, maternal mental health, parenting relationships, parenting self-efficacy, and additional psychosocial and health measures.ResultsParticipants (N=584; n=298 longer survey, n=286 shorter survey) were >99% mothers, 46% perinatal (10% pregnant, 36% post-partum), and on average 32.4 (SD: 3.9) years old. Fifty-nine percent were from the United States, 36% from Canada, and 5% from other countries. The vast majority (95%) followed Momwell on Instagram, 44% listened to the Momwell podcast and 41% received their newsletter. Most participants had been exposed to Momwell’s psychoeducation content for at least 6 months across the different platforms (range: 40% TikTok to 87% Instagram). Two to 3 months later, 246 participants completed a second survey (n=149 longer survey, n=97 shorter survey).ConclusionsData from this study will provide insights into how perinatal persons and mothers leverage digital psychoeducational content and peer communities to support their mental health across the perinatal period and into the early years of motherhood. Leveraging digital platforms to disseminate evidence-based digital psychoeducational content related to maternal mental health and connect peers has the potential to change how we care for perinatal persons and mothers.
Enhanced MC1R-signalling and pH modulation facilitate melanogenesis within late endosomes of BLOC-1-deficient melanocytes
Authors: Goff Philip S. , Patel Shyamal , Carter Tom , Marks Michael S. , Sviderskaya Elena V. 
Published: July 2024

SummaryPhotoprotective melanins in the skin are synthesised by epidermal melanocytes within specialised lysosome-related organelles called melanosomes. Melanosomes coexist with lysosomes; thus, melanocytes employ specific trafficking machineries to ensure correct cargo delivery to either the endolysosomal system or maturing melanosomes. Mutations in some of the protein complexes required for melanogenic cargo delivery, such as biogenesis of lysosome-related organelles complex 1 (BLOC-1), result in hypopigmentation due to mistrafficking of cargo to endolysosomes. We show that hypopigmented BLOC-1-deficient melanocytes retain melanogenic capacity that can be enhanced by treatment with cAMP elevating agents despite the mislocalisation of melanogenic proteins. The melanin formed in BLOC-1-deficient melanocytes is not generated in melanosomes but rather within late endosomes/lysosomes to which some cargoes mislocalise. Although these organelles generally are acidic, a cohort of late endosomes/lysosomes have a sufficiently neutral pH to facilitate melanogenesis, perhaps due to mislocalised melanosomal transporters and melanogenic enzymes. Modulation of the pH of late endosomes/lysosomes by genetic manipulation or via treatment with lysosomotropic agents significantly enhances the melanin content of BLOC-1-deficient melanocytes. Our data suggest that upregulation of mistargeted cargoes can facilitate reprogramming of a subset of endolysosomes to generate some functions of lysosome-related organelles.
Bulk medium properties of heavy-ion collisions from the beam energy scan with a multistage hydrodynamic model
Authors: Du Lipei 
Published: July 2024

I introduce a method to reconstruct full rapidity distributions of charged particle multiplicity and net proton yields, crucial for constraining the longitudinal dynamics of nuclear matter created in the beam energy scan program. Employing rapidity distributions within a multistage hydrodynamic model calibrated for Au+Au collisions at sNN=7.7–200GeV, I estimate the total energy and baryon number deposited into the collision fireball, offering insights into initial dynamics and the identification of nuclear remnants. I explore the potential of rapidity-dependent measurements in probing equations of state at finite chemical potentials. Furthermore, I compare the freeze-out parameters derived from both hydrodynamics and thermal models, highlighting that the parameters extracted via thermal models represent averaged properties across rapidities.

Published by the American Physical Society
2024
Amplitude analysis of
B0→KS0K+K−
decays in a quasi-two-body QCD factorization approach
Authors: Dedonder J.-P. , Kamiński R. , Leśniak L. , Loiseau B. , Żenczykowski P. 
Published: July 2024

The B0→KS0K+K− decay amplitude is derived within a quasi-two-body QCD factorization framework in terms of kaon form factors and B0 to two-kaon-transition functions. The final state kaon-kaon interactions in the S, P, and D waves are taken into account. The unitarity constraints are satisfied for the two kaons in scalar states. It is shown that with few terms of the full decay amplitude one may reach a fair agreement with the total branching fraction and Dalitz-plot projections published in 2010 by the Belle Collaboration and in 2012 by the Collaboration. With 13 free parameters, our model fits the corresponding 422 data with a χ2 of 583.6 which leads to a χ2 per degree of freedom equal to 1.43. The dominant branching fraction arises from the f0(K+K−)KS0 mode with 83.0% of the total branching. The next important mode is dominated by ϕKS0 plus small ωKS0 and ρ0KS0 modes with 18.3% of the total. Then follows the a0±K∓ mode with 6.2%. Adding the other smaller modes, the total percentage sum is 107.7% which indicates a small interference contribution. In most regions of the Dalitz plot, our model gives rather small CP asymmetry, but in some parts its values can be large and positive or negative. Its predicted total value is equal to −0.11%. The calculated time dependent CP-asymmetry parameters agree, within errors, with those obtained by the analysis. Our model amplitude can be the basis for a parametrization in experimental Dalitz plot analyses of LHCb and Belle II Collaborations.

Published by the American Physical Society
2024