bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heart Transplantation, Either Alone or Combined With Liver and Kidney, a Viable Treatment Option for Selected Patients With Severe Cardiac Amyloidosis
Authors: Guendouz Soulef , Grimbert Philippe , Radu Costin , Cherqui Daniel , Salloum Chady , Mongardon Nicolas , Maghrebi Sami , Belhadj Karim , Le Bras Fabien , Teiger Emmanuel , Couetil Jean-Paul , Balan Adriana , Kharoubi Mounira , Bézard Mélanie , Oghina Silvia , Bodez Diane , Hittinger Luc , Audard Vincent , Planté-Bordeneuve Violaine , De la Taille Alexandre , Bergoend Eric , Frenkel Valerie , Fanen Pascale , Leroy Vincent , Duvoux Christophe , Carmagnat Maryvonnick , Folliguet Thierry , Damy Thibaud 
Published: June 2022

Background.
Heart transplantation in cardiac amyloidosis (CA) patients is possible and generally considered for transplantation if other organs are not affected. In this study, we aimed to describe and assess outcome in patients following heart transplantations at our CA referral center.

Methods.
We assessed all CA patients that had heart transplantations at our center between 2005 and 2018. Patients with New York Heart Association status 3 out of 4, with poor short-term prognosis due to heart failure, despite treatment, and without multiple myeloma, systemic disease, severe neuropathic/digestive comorbidities, cancer, or worsening infections were eligible for transplantation. Hearts were transplanted by bicaval technique. Standard induction and immunosuppressive therapies were used. Survival outcome of CA patients after transplantation was compared with recipients with nonamyloid pathologies in France.

Results.
Between 2005 and 2018, 23 CA patients had heart transplants: 17 (74%) had light chain (light chain amyloidosis [AL]) and 6 (26%) had hereditary transthyretin (hereditary transthyretin amyloidosis [ATTRv]) CA. Also, 13 (57%) were male, and the mean age at diagnosis was 56.5 y (range, 47.7–62.8). Among AL patients, 13 had heart-only and 5 had heart-kidney transplantations. Among ATTRv patients, 1 had heart-only and 5 had heart-liver transplantations. The 1-y survival rate after transplantation was 78%, 70% with AL, and 100% with ATTRv. At 2 y, 74% were alive: 65% with AL and 100% with ATTRv.

Conclusion.
After heart transplantation, French CA and nonamyloid patients have similar survival outcomes. Among CA patients, ATTRv patients have better prognosis than those with AL, possibly due to the combined heart-liver transplantation. Selected CA patients should be considered for heart transplantations.
Prediction of adolescent suicide attempt by integrating clinical, neurocognitive and geocoded neighborhood environment data
Authors: Visoki Elina , Moore Tyler M. , Gur Ruben C. , Ruiz Victor M. , Fein Joel A. , Benton Tami D. , Gur Raquel E. , Tsui Fuchiang R. , Barzilay Ran 
Published: June 2022

AbstractObjectiveThe authors used multimodal data collected during pre/early-adolescence in research settings to predict self-report of past suicide attempt (SA) by mid-late adolescence in pediatric care settings. The study further aimed to determine types of data that contribute to the prediction; and to test generalizability of the prediction in an independent sample.MethodsThe authors applied machine learning methods on clinical, neurocognitive and geocoded neighborhood environmental data from the Philadelphia Neurodevelopmental Cohort study (PNC, Mean age 11.1, SD=2.2, 52.3% female and 51.4% Black participants) to predict SA reported ∼5 years later in a community pediatric clinic (n=922, 5.3% SA) or emergency department (n=497, 8.2% SA). The authors compared prediction performance when using all data versus individual data types, then used feature selection algorithms (Lasso, Relief and Random Forest) to identify important predictors and compared performance of models relying on feature subsets.ResultsIn the training dataset, SA prediction was good, reaching AUC=0.75, sensitivity/specificity 0.76/0.77 when relying on feature subsets identified using feature selection pipelines. Use of highest-ranking feature subsets from the training dataset yielded similar prediction in the testing dataset with AUC=0.74, sensitivity/specificity 0.66/0.70. Different algorithms showed different high-ranking features, but overall multiple data domains were represented among the highest-ranking predictors selected by each algorithm.ConclusionsThese findings provide evidence for feasibility of predicting youth SA using data collected at a single timepoint early in life in a diverse cohort. Results encourage incorporation of multiple data types including neurocognitive and geocoded environmental measures in machine learning SA prediction pipelines.
TopEnzyme: A framework and database for structural coverage of the functional enzyme space
Authors: van der Weg Karel , Gohlke Holger 
Published: June 2022

AbstractTopEnzyme is a database of structural enzyme models created with TopModel and is linked to the SWISS-MODEL and AlphaFold Protein Structure Database to provide an overview of structural coverage of the functional enzyme space for over 200,000 enzyme models. It allows the user to quickly obtain representative structural models for 60% of all known enzyme functions. We assessed the models with TopScore and contributed 9039 good-quality and 1297 high-quality structures. Furthermore, we compared these models to AlphaFold2 models with TopScore and found that the TopScore differs only by 0.04 on average in favor of AlphaFold2. We tested TopModel and AlphaFold2 for targets not seen in the respective training databases and found that both methods create qualitatively similar structures. When no experimental structures are available, this database will facilitate quick access to structural models across the currently most extensive structural coverage of the functional enzyme space.
Sex-specific niche signaling contributes to sexual dimorphism following stem cell transplantation
Authors: Smith Julianne N.P. , Cordova Brittany A. , Richardson Brian , Christo Kelsey F. , Campanelli Jordan , Broncano Alyssia V. , Chen Jonathan , Lee Juyeun , Cameron Scott J. , Lathia Justin D. , Goodman Wendy A. , Cameron Mark J. , Desai Amar B. 
Published: June 2022

AbstractHematopoietic stem cell (HSC) transplantation (HST) is a curative treatment for many hematopoietic cancers and bone marrow (BM) disorders but is currently limited by numerous complications including a lengthy recovery period, prolonged neutropenia resulting in severe infections and bleeding, and a high incidence of graft vs. host disease (GVHD). While clinical studies have demonstrated that sex mismatch, notably male recipients with female donor cells, results in increased risk of GVHD (likely due to male recipient minor histocompatibility antigens targeted by donor female T-cells 1), increased non-relapse mortality, and decreased overall survival, the mechanisms underlying sex-determinants on hematopoiesis and post-transplant recovery are not clear. In this manuscript we have identified: 1) unique expression of hematopoietic niche factors in the BM and spleens of male and female mice, 2) altered kinetics of hematopoietic reconstitution following transplantation when male vs. female BM is used as the donor cell source, 3) a sex-specific role for the recipient niche in promoting post HST recovery, and 4) a dose-dependent role for exogenous sex hormones in maintaining hematopoietic stem and progenitor cells (HSPCs). Taken together, these data demonstrate that sex-specific cellular and molecular signaling occurs during hematopoietic regeneration. Further identifying novel sex-dependent determinants of regeneration following transplantation will not only enhance understanding of steady state versus regeneration hematopoiesis but may also reveal unique (and potentially sex-specific) therapeutic targets to accelerate hematologic recovery.Key PointsMale and female mice display altered kinetics of regeneration following HST due to unique niche factors in hematopoietic compartments.Exogenous steroid sex hormones uniquely regulate the pool of hematopoietic stem and progenitor cells and may impact transplantation outcomes.
Cancer-keeping genes as therapeutic targets
Authors: Zhang Xizhe , Pan Chunyu , Wei Xinru , Yu Meng , Liu Shuangjie , An Jun , Yang Jieping , Wei Baojun , Hao Wenjun , Yao Yang , Zhu Yuyan , Zhang Weixiong 
Published: June 2022

AbstractFinding cancer-driver genes – the genes whose mutations may transform normal cells into cancerous ones – remains a central theme of cancer research. We took a different perspective; instead of considering normal cells, we focused on cancerous cells and genes that maintained abnormal cell growth which we namedcancer-keeping genes(CKGs). Intervention in CKGs may rectify aberrant cell growth so that they can be adopted as therapeutic targets for cancer treatment. We developed a novel approach to identifying CKGs by extending the well-established theory of network structural controllability, which aims at finding a control scheme (i.e., a minimal set of non-overlapping control paths covering all nodes) and control nodes (driver genes) that can steer the cell from any state to the designated state. Going beyond driver genes defined by one control scheme, we introducedcontrol-hubgenes located in the middle of a control path ofeverycontrol scheme. Control hubs are essential for maintaining cancerous states and thus can be taken as CKGs. We applied our CKG-based approach to bladder cancer (BLCA) as a case study. All the genes on the cell cycle and p53 pathways in BLCA were identified as CKGs, showing the importance of these genes in cancer and demonstrating the power of our new method. Furthermore, sensitive CKGs that could be easily changed by structural perturbation were better suited as therapeutic targets. Six sensitive CKGs (RPS6KA3, FGFR3, N-cadherin (CDH2), EP300, caspase-1, and FN1) were subjected to small-interferencing-RNA knockdown in two BLCA cell lines to validate their cancer-suppressing effects. Knocking down RPS6KA3 in a mouse model of BLCA significantly inhibited the growth of tumor xenografts in mice. Combined, our results demonstrated the value of CKGs as therapeutic targets for cancer therapy.Key pointsFocus on genes that maintain aberrant cell growth, namedcancer-keeping genes(CKGs).Develop a novel approach for finding CKGs by extending the well-estabilished theory of network structural controllability to total network controllability.Apply the new method to bladder cancer and experimentally validated the cancer-suppressing function of six CKGs in two bladder cancer cell lines and that of one CKG in bladder cancer mice.
Study and Modeling of Biological Noise-Filtering Properties of Conserved Gene Regulatory Networks Motifs in Animal Development
Authors: Ruiz G. Lina M. , Gloria Machado R , Rodriguez R Boris A. 
Published: June 2022

ABSTRACTBiological noise results from heterogeneous gene expression levels among a group of cells [1]. This heterogeneity is due to the variation in gene expression that occurs over time at the single-cell level. Some noise-filtering mechanisms like redundancy in genetic circuits have been identified. Likewise, the feed-forward loop network motif has been found to have noise-filtering capacities in animal development. On the other hand, previous studies have contradictory conclusions about the noise-filtering capacities of the feedback loop and none of them have studied this capacity in the activator-inhibitor regulatory system. Here we studied some dynamical properties, such as noise and expression levels, in self-activated and activator-inhibitor regulatory systems, both at the unicellular and multicellular levels. These systems are essential in the self-patterning and community effect processes occurring in development and differentiation. We used the three-stage model to represent the expression of a gene with promoter regulation and Hill functions to represent the regulatory connections between genes. We used Gillespie’s Algorithm and the Chemical Langevin Equation for simulations. The regulatory systems evaluated do not reduce the biological noise. On the contrary, the noise remains at the same level or increases in comparison with an unregulated gene. The noise levels in these systems depend on the gene expression type of both the regulator and the regulated gene. In this way, the particular forms in which genes connect to each other in these regulatory systems do not explain the noise in expression. However, the noise has a propagation pattern different for activation and inactivation types of regulation. Finally, the diffusion and colony size could be mechanisms of noise filtering in gene expression in a colony of cells. The increase in diffusion rate and colony size are necessary to synchronize gene expression and perform the community effect in embryonic development.
The homeodomain transcription factor Ventx2 regulates respiratory progenitor cell number and differentiation timing duringXenopuslung development
Authors: Rankin Scott A. , Zorn Aaron M. 
Published: June 2022

AbstractVentx2 is anantennapediasuperfamily / NKL subclass homeodomain transcription factor best known for its role in the regulation of early dorsal-ventral pattern during Xenopus gastrulation and in the maintenance of neural crest multipotency. In this work we characterize an unappreciated spatial-temporal expression domain ofventx2in Xenopus respiratory system epithelial progenitors. We findventx2is directly induced by BMP signaling in the ventral foregut prior tonkx2-1, the earliest epithelial marker of the respiratory lineage. Functional studies demonstrate that Ventx2 regulates the number of Nkx2-1/Sox9+ respiratory progenitors induced during foregut development, the timing and level of surfactant protein gene expression, and proper tracheal-esophageal separation. Our data suggest that Ventx2 regulates the balance of respiratory progenitor expansion and differentiation. While theventxgene family has been lost from the mouse genome during evolution, humans have retained aventx2-like gene(VENTX)and we lastly discuss how our findings might suggest a possible function ofVENTXin human respiratory progenitors.
Mechanical Deformation Behaviors and Structural Properties of Ligated DNA Crystals
Authors: Li Ruixin , Zheng Mengxi , Madhvacharyula Anirudh Sampath , Du Yancheng , Mao Chengde , Choi Jong Hyun 
Published: June 2022

ABSTRACTDNA self-assembly has emerged as a powerful strategy for constructing complex nanostructures. While the mechanics of individual DNA strands have been studied extensively, the deformation behaviors and structural properties of self-assembled architectures are not well understood. This is partly due to the small dimensions and limited experimental methods available. DNA crystals are macroscopic crystalline structures assembled from nanoscale motifs via sticky-end association. The large DNA constructs may thus be an ideal platform to study structural mechanics. Here we have investigated the fundamental mechanical properties and behaviors of ligated DNA crystals made of tensegrity triangular motifs. We performed coarse-grained molecular dynamics simulations and confirmed the results with nanoindentation experiments using atomic force microscopy. We observed various deformation modes including un-tension, linear elasticity, duplex dissociation, and single-stranded component stretch. We found that the mechanical properties of a DNA architecture are correlated with those of its components, however the structure shows complex behaviors which may not be predicted by components alone.
Human threat learning is associated with gut microbiota composition
Authors: Oyarzun Javiera P. , Kuntz Thomas M. , Stussi Yoann , Karaman Olivia T. , Vranos Sophia , Callaghan Bridget L. , Huttenhower Curtis , LeDoux Joseph E. , Phelps Elizabeth A. 
Published: June 2022

AbstractRodent studies have shown that the gut microbiota can influence threat and safety learning, which has been linked to anxiety phenotypes. In humans, it has been demonstrated that microbiota composition varies with anxiety disorders, but evidence showing an association with threat learning is lacking. Here, we tested whether individual variability in threat and safety learning was related to gut microbiota composition in healthy adults. We found that threat, but not safety learning varies with individuals’ microbiome composition. Our results provide evidence that the gut microbiota is associated with excitatory threat learning across species.Significance StatementLearning from threats and safety is a core mechanism of anxiety disorders, and studies in rodent models have shown that the gut microbiota can modulate such behaviors. Although previous literature on humans shows a relationship between emotional circuits and gut microbiota, the evidence linking learning and microbiota is lacking. In a Pavlovian threat conditioning paradigm, we show that patterns of gut microbiota composition in healthy humans relate to their patterns of threat learning, but not safety learning. Our findings suggest one mechanism by which the human gut microbiota is associated with anxiety-related behaviors.
A model for generating differences in microtubules between axonal branches depending on the distance from terminals
Authors: Imanaka Chiaki , Simada Satoshi , Ito Shino , Kamada Marina , Iguchi Tokuichi , Konishi Yoshiyuki 
Published: June 2022

AbstractIn the remodeling of axonal arbor, the growth and retraction of branches are differentially regulated within a single axon. Although cell-autonomously generated differences in microtubule (MT) turnover are thought to be involved in selective branch regulation, the cellular system whereby neurons generate differences of MTs between axonal branches has not been clarified. Because MT turnover tends to be slower in longer branches compared with neighboring shorter branches, feedback regulation depending on branch length is thought to be involved. In the present study, we generated a model of MT lifetime in axonal terminal branches by adapting a length-dependent model in which parameters for MT dynamics were constant in the arbor. The model predicted that differences in MT lifetime between neighboring branches could be generated depending on the distance from terminals. In addition, the following points were predicted. Firstly, destabilization of MTs throughout the arbor decreased the differences in MT lifetime between branches. Secondly, differences of MT lifetime existed even before MTs entered the branch point. In axonal MTs in primary neurons, treatment with a low concentration of nocodazole significantly decreased the differences of detyrosination (deTyr) and tyrosination (Tyr) of tubulins, indicators of MT turnover. Expansion microscopy of the axonal shaft before the branch point revealed differences in deTyr/Tyr modification on MTs. Our model recapitulates the differences in MT turnover between branches and provides a feedback mechanism for MT regulation that depends on the axonal arbor geometry.
Early selection of the amino acid alphabet was adaptively shaped by biophysical constraints of foldability
Authors: Makarov Mikhail , Sanchez Rocha Alma C. , Krystufek Robin , Cherepashuk Ivan , Dzmitruk Volha , Charnavets Tatsiana , Faustino Anneliese M. , Lebl Michal , Fujishima Kosuke , Fried Stephen D. , Hlouchova Klara 
Published: June 2022

ABSTRACTWhereas modern proteins rely on a quasi-universal repertoire of 20 canonical amino acids (AAs), numerous lines of evidence suggest that ancient proteins relied on a limited alphabet of 10 ‘early’ AAs, and that the 10 ‘late’ AAs were products of biosynthetic pathways. However, many non-proteinogenic AAs were also prebiotically available, which begs two fundamental questions: Why do we have the current modern amino acid alphabet, and Would proteins be able to fold into globular structures as well if different amino acids comprised the genetic code? Here, we experimentally evaluated the solubility and secondary structure propensities of several prebiotically relevant amino acids in the context of synthetic combinatorial 25-mer peptide libraries. The most prebiotically abundant linear aliphatic and basic residues were incorporated along with or in place of other early amino acids to explore these alternative sequence spaces. We show that foldability was a critical factor in the selection of the canonical alphabet. Unbranched aliphatic and short-chain basic amino acids were purged from the proteinogenic alphabet despite their high prebiotic abundance because they generate polypeptides that are over-solubilized and have low packing efficiency. Surprisingly, we find that the inclusion of a short-chain basic amino acid also decreases polypeptides’ secondary structure potential. Our results support the view that despite lacking basic residues, the early canonical alphabet was remarkably adaptive at supporting protein folding and explain why basic residues were only incorporated at a later stage of the alphabet evolution.
Condition-Specific Mapping of Operons (COSMO) using dynamic and static genome data
Authors: Calvert-Joshua Tracey , Bendou Hocine , Heusden Peter van , Grobbelaar Melanie , Warren Rob , Christoffels Alan 
Published: June 2022

AbstractAn operon is a set of adjacent genes which are transcribed into a single messenger RNA. Operons allow prokaryotes to efficiently circumvent environmental stresses. It is estimated that about 60% of theMycobacterium tuberculosisgenome is arranged into operons, which makes them interesting drug targets in the face of emerging drug resistance. We therefore developed COSMO - a tool for operon prediction inM. tuberculosisusing RNA-seq data. We analyzed four algorithmic parameters and benchmarked COSMO against two top performing operon predictors. COSMO outperformed both predictors in its accuracy and in its ability to distinguish operons activated under distinct conditions.Author SummaryOperons may be important drug targets for the development of effective anti-microbials to combat the emerging, global drug resistance challenge. However, there is a shortage of knownMycobacterium tuberculosis (Mtb)operons. This is exacerbated by the fact that current operon predictors are not optimized for the unique genome of Mtb. COSMO removes the limitations imposed by using the constraints of a specific organism’s genome and exploits RNA-seq data instead. This allows COSMO to more accurately predict full-length operons in Mtb, and it also avails COSMO to other microorganisms for the same purpose.
Cell fusion upregulates PD-L1 expression and promotes tumor formation
Authors: Tajima Youichi , Shibasaki Futoshi , Masai Hisao 
Published: June 2022

AbstractMSCs (mesenchymal stem cells), responsible for tissue repair, rarely undergo cell fusion with somatic cells. Here, we show that approximately 5% of bladder cancer cells (UMUC-3) fuses with bone marrow-derived MSC (BM-MSC) in co-culture and exhibits increased tumorigenicity. Eleven fusion cell clones are established, and 116 genes are identified whose expression is specifically altered in the fusion cells. Many of them are interferon-stimulated genes (ISG), but are activated in a manner independent of interferon. Among them, we show that PD-L1 is induced in fusion cells, and its knockout decreases tumorigenesis in a xenograft model. PD-L1 is induced in a manner independent of STAT1 known to regulate PD-L1 expression, but is regulated by histone modification, and is likely to inhibit phagocytosis by PD1-expressing macrophages, thus protecting cancer cells from immunological attacks. The fusion cells overexpress multiple cytokines including CCL2 that causes tumor progression by converting infiltrating macrophages to tumor-associated-macrophage (TAM). The results present mechanisms of how cell fusion promotes tumorigenesis, revealing a novel link between cell fusion and PD-L1, and underscores the efficacy of cancer immunotherapy.