bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding peptide generation for MHC Class I proteins with deep reinforcement learning
Authors: Chen Ziqi , Zhang Baoyi , Guo Hongyu , Emani Prashant , Clancy Trevor , Jiang Chongming , Gerstein Mark , Ning Xia , Cheng Chao , Min Martin Renqiang 
Published: January 2023

Abstract

Motivation
MHC Class I protein plays an important role in immunotherapy by presenting immunogenic peptides to anti-tumor immune cells. The repertoires of peptides for various MHC Class I proteins are distinct, which can be reflected by their diverse binding motifs. To characterize binding motifs for MHC Class I proteins, in vitro experiments have been conducted to screen peptides with high binding affinities to hundreds of given MHC Class I proteins. However, considering tens of thousands of known MHC Class I proteins, conducting in vitro experiments for extensive MHC proteins is infeasible, and thus a more efficient and scalable way to characterize binding motifs is needed.

Results
We presented a de novo generation framework, coined PepPPO, to characterize binding motif for any given MHC Class I proteins via generating repertoires of peptides presented by them. PepPPO leverages a reinforcement learning agent with a mutation policy to mutate random input peptides into positive presented ones. Using PepPPO, we characterized binding motifs for around 10 000 known human MHC Class I proteins with and without experimental data. These computed motifs demonstrated high similarities with those derived from experimental data. In addition, we found that the motifs could be used for the rapid screening of neoantigens at a much lower time cost than previous deep-learning methods.

Availability and implementation
The software can be found in https://github.com/minrq/pMHC.

Supplementary information
Supplementary data are available at Bioinformatics online.
Selection of p53 pathway in adaptive evolution and reproductive isolation in incipient sympatric speciation ofDrosophilaat Evolution Canyon
Authors: Zhao Yang , Song Li , Wang Junying , Fang Xiaodong , Li Kexin , Han Lijuan , Beiles Avigdor , Cao Yi-Bin , Nevo Eviatar 
Published: January 2023

AbstractSympatric speciation (SS) refers to the origin of new species within a freely breeding population. The ‘Evolution Canyon’ (EC) in Israel is a natural microsite model for SS of species across phylogenies from viruses and bacteria to mammals, adapting to, and speciating in, interslope microclimates. The cosmopolitan Drosophila melanogaster at EC I, Mount Carmel, is undergoing incipient SS in response to sharply divergent interslope microclimate stresses, including solar radiation, temperature, humidity and pathogenicity. We demonstrated here a selective interslope divergence of single nucleotide polymorphism (SNP) distribution in the Drosophila p53 pathway. This involves a total of 71 genes, which are associated with DNA repair, heat response, and fungal and bacterial resistant pathways. This distribution pattern links the previously observed thermotolerance and ageing divergence of D. melanogaster between the opposite canyon slopes: the south-facing slope (SFS, or African slope: tropical, savannoid and dry) and the abutting north-facing slope (NFS, or European slope; temperate, forested, cool and humid). The genes with interslope-significant differential SNPs link the p53 pathway with pathways related to the responses to microclimates through protein-protein interaction. Moreover, for the first time we provide evidence that the p53 pathway is linked to reproductive isolation, and is thus actively participating in incipient SS of D. melanogaster. This is the first demonstration of a link between the p53 pathway and reproductive isolation, thereby contributing to adaptive incipient sympatric speciation.
Recent natural hybridization inElymusandCampeiostachysof Triticeae: evidence from morphological, cytological and molecular analyses
Authors: Wu Dan-Dan , Liu Xiao-Yan , Yu Zheng-Hao , Tan Lu , Lu Jia-Le , Cheng Yi-Ran , Sha Li-Na , Fan Xing , Kang Hou-Yang , Wang Yi , Zhou Yong-Hong , Zhang Chang-Bing , Zhang Hai-Qin 
Published: January 2023

AbstractNatural hybrids in Triticeae have been frequently reported from the Qinghai–Tibet plateau, but minor variation in morphological features and homoploid hybridization have made it difficult to identify the origin and genome constitution of hybrids between Elymus and Campeiostachys. Specimens were investigated using morphology, cytogenetics and phylogenetic analyses to uncover the genome constitution and origin of ten putative natural hybrids (SH01-SH10) from the Qinghai–Tibet plateau. SH01, SH02, SH03, SH05 and SH06 (2n = 5x = 35, StStHHY) originated from Campeiostachys breviaristata (2n = 6x = 42, StStHHYY) and Elymus sibiricus (2n = 4x = 28, StStHH); SH04 and SH07 (2n = 5x = 35, StStHHY) originated from C. nutans (2n = 6x = 42, StStHHYY) and E. sibiricus; SH08 (2n = 5x = 35, StStHHY) originated from C. dahurica var. tangutorum (2n = 6x = 42, StStHHYY) and E. sibiricus; and SH09 and SH10 (2n = 4x = 28, StStHH) were the homoploid hybrids of E. sibiricus and an unknown Elymus sp. (2n = 4x = 28, StStHH). Karyotype variations in SH04 and SH07 might originate from the maternal progenitor. Frequent hybridization in the Qinghai–Tibet plateau might result from factors such as genome constitution, pollination habits, overlapping flowering stage, sympatric distribution and unique ecological conditions.
Phylogeographic patterns ofDeschampsia cespitosa(Poaceae) in Europe inferred from genomic data
Authors: Xue Zhiqing , Chiapella Jorge O , Paun Ovidiu , Volkova Polina , Peintinger Markus , Wasowicz Pawel , Tikhomirov Nikita , Grigoryan Maksim , Barfuss Michael H J , Greimler Josef 
Published: January 2023

AbstractThe highly variable tufted hairgrass Deschampsia cespitosa is a tussock-forming plant especially of cool and humid environments. Although common and widespread, its phylogeographic structure and the significance of polyploidy for its evolution are poorly understood. Here we used a phylogenomic approach to study the genetic structure of this species in Europe and how the polyploid cytotypes/subspecies are related to the diploids. Using genomic data (RADseq and whole plastid sequencing) we found a highly divergent Iberian group, including the Spanish Deschampsia cespitosa subsp. cespitosa (diploid and tetraploid) and the Macaronesian island endemic diploid Deschampsia argentea. Moreover, we found substantial divergence of pseudoviviparous tetraploids (Deschampsia cespitosa subspp. neoalpina and rhenana) from seminiferous tetraploids (except Deschampsia cespitosa subsp. littoralis) and all diploids of the remaining European samples. The divergent pseudoviviparous tetraploids (D. cespitosa subspp. neoalpina and rhenana) and the seminiferous tetraploid D. cespitosa subsp. littoralis probably represent periglacial and relict lineages of unknown origin regarding auto- and/or allo-polyploidy, whereas other seminiferous tetraploid variants of D. cespitosa are always nested in the diploid D. cespitosa, suggesting multiple autopolyploid origins. An analysis after excluding the Iberian Group and the highly divergent tetraploids revealed five genetic groups with overlapping geographical patterns. However, the recovered geographical structure, the overall low genetic divergence and the diffuse genetic structure point to recolonization from various refugial areas and secondary contact. Effective wind dispersal of pollen and seeds in an open early post-glacial tundra landscape and, finally, increasing human impact on dispersal of this grass since the Neolithic, may have enhanced admixture and resulted in the complex patterns detected today.
Phylogenetics of the Andean tree genusRuagea(Meliaceae): implications for taxonomy
Authors: Rojas-Andrés Blanca M , Lihanova Yuliia , Pennington Terence D , Muellner-Riehl Alexandra N 
Published: January 2023

AbstractRuagea (Meliaceae) comprises c. 15 species of small or medium-sized trees distributed in Central and South America, predominantly in montane rain forest and cloud forest of the Andes. The taxonomic position of Ruagea has changed several times in the past, and it was previously included in Guarea. Ruagea is currently accepted as a separate genus based on morphology and molecular phylogenetic analyses at the family level. However, its monophyly has not been accurately tested, and phylogenetic relationships among species are still largely unknown. In addition, delimitation of species boundaries is not straightforward due to morphological diversity within species. Here, we present the first phylogenetic reconstruction of Ruagea based on two nuclear ribosomal (ITS, ETS) and two plastid DNA regions (rps4-trnT, psbA-trnH). Our results show that Ruagea is monophyletic and composed of four main clades (A, B, C and D). Clade D, comprising the Ecuadorian endemic R. membranacea and a potentially new species from Colombia, is sister to the rest of the genus. Our results demonstrate that R. membranacea and R. insignis are monophyletic and provide support for the recognition of two new species with divergent morphologies. The delimitation of the remaining species remains unresolved as they are recovered as either poly- or paraphyletic. Our results highlight the complexity of the taxonomy of Ruagea, as found in other rainforest taxa, and the need for further detailed analyses to delimit these taxa. This study provides the first and most extensive phylogenetic analysis of the genus so far, representing a contribution towards understanding the evolutionary history of Ruagea.
Association analysis of 10 candidate genes causing Mendelian calcium nephrolithiasis in the INCIPE study: a South European general population cohort
Authors: Santoro Gloria , Lombardi Gianmarco , Andreola Stefano , Salvagno Gian Luca , Treccani Mirko , Locatelli Elena , Ferraro Pietro Manuel , Lippi Giuseppe , Malerba Giovanni , Gambaro Giovanni 
Published: January 2023

ABSTRACTBackgroundIdiopathic calcium nephrolithiasis (ICN) is a common condition with a complex phenotype influenced by both environmental and genetic factors. In our study we investigated the association of allelic variants with the history of nephrolithiasis.MethodsWe genotyped and selected 10 candidate genes potentially related to ICN from 3046 subjects participating in the INCIPE survey cohort (Initiative on Nephropathy, of relevance to public health, which is Chronic, possibly in its Initial stages, and carries a Potential risk of major clinical End-points), a study enrolling subjects from the general population in the Veneto region in Italy.ResultsOverall, 66 224 variants mapping on the 10 candidate genes were studied. A total of 69 and 18 variants in INCIPE-1 and INCIPE-2, respectively, were significantly associated with stone history (SH). Only two variants, rs36106327 (chr20:54 171 755, intron variant) and rs35792925 (chr20:54 173 157, intron variant) of the CYP24A1 gene were observed to be consistently associated with ICN. Neither variant has been previously reported in association with renal stones or other conditions. Carriers of CYP24A1 variants showed a significant increase in the ratio of 1,25 (OH)2 vitamin D to 25 (OH) vitamin D compared with controls (P = .043). Although not associated with ICN in this study, the rs4811494 CYP24A1 variant that was reported to be causative of nephrolithiasis was very prevalent in heterozygosity (20%).ConclusionOur data suggest a possible role for CYP24A1 variants in the risk of nephrolithiasis. Genetic validation studies in larger sample sets will be necessary to confirm our findings.
Evaluating the Clinical Utility of a Long-Read Sequencing-Based Approach in Prenatal Diagnosis of Thalassemia
Authors: Liang Qiaowei , He Jun , Li Qing , Zhou Yulin , Liu Yanqiu , Li Youqiong , Tang Lingfang , Huang Shengwen , Li Rong , Zeng Fanqian , Mao Aiping , Liu Yinyin , Liang Desheng , Wu Lingqian 
Published: January 2023

AbstractBackgroundThe aim is to evaluate the clinical utility of a long-read sequencing-based approach termed comprehensive analysis of thalassemia alleles (CATSA) in prenatal diagnosis of thalassemia.MethodsA total of 278 fetuses from at-risk pregnancies identified in thalassemia carrier screening by PCR-based methods were recruited from 9 hospitals, and PCR-based methods were employed for prenatal diagnosis. CATSA was performed retrospectively and blindly for all 278 fetuses.ResultsAmong the 278 fetuses, 263 (94.6%) had concordant results and 15 (5.4%) had discordant results between the 2 methods. Of the 15 fetuses, 4 had discordant thalassemia variants within the PCR detection range and 11 had additional variants identified by CATSA. Independent PCR and Sanger sequencing confirmed the CATSA results. In total, CATSA and PCR-based methods correctly detected 206 and 191 fetuses with variants, respectively. Thus, CATSA yielded a 7.9% (15 of 191) increment as compared with PCR-based methods. CATSA also corrected the predicted phenotype in 8 fetuses. Specifically, a PCR-based method showed one fetus had homozygous HBB c.52A &gt; T variants, while CATSA determined the variant was heterozygous, which corrected the predicted phenotype from β-thalassemia major to trait, potentially impacting the pregnancy outcome. CATSA additionally identified α-globin triplicates in 2 fetuses with the heterozygous HBB c.316-197C &gt; T variant, which corrected the predicted phenotype from β-thalassemia trait to intermedia and changed the disease prognosis.ConclusionsCATSA represents a more comprehensive and accurate approach that potentially enables more informed genetic counseling and improved clinical outcomes compared to PCR-based methods.
Irreducible Fuzzy Multiset Finite Automaton
Authors: Shamsizadeh Marzieh , Mehdi Zahedi Mohammad , Abolpour Khadijeh 
Published: January 2023

Abstract
This study aims to investigate the algebraic properties of fuzzy multiset finite automaton (FMFA), giving a congruence relation. Using the equivalence classes, a minimal accessible complete FMFA is then presented. In addition, we define the concepts of admissible relation, admissible partition for FMFA and quotient FMFA. Further, we present an algorithm which determines an admissible partition for an FMFA and we suggest the time complexity of the algorithm. In particular, we introduce a connection between the admissible partition and the quotient FMFA and we show that any quotient of a given FMFA and the FMFA itself have the same language. Furthermore, using the quotient FMFA, we obtain an irreducible FMFA with the same language.
Improved (Related-Key) Differential-Based Neural Distinguishers for SIMON and SIMECK Block Ciphers
Authors: Lu Jinyu , Liu Guoqiang , Sun Bing , Li Chao , Liu Li 
Published: January 2023

Abstract
In CRYPTO 2019, Gohr made a pioneering attempt and successfully applied deep learning to the differential cryptanalysis against NSA block cipher Speck 32/64, achieving higher accuracy than the pure differential distinguishers. By its very nature, mining effective features in data plays a crucial role in data-driven deep learning. In this paper, in addition to considering the integrity of the information from the training data of the ciphertext pair, domain knowledge about the structure of differential cryptanalysis is also considered into the training process of deep learning to improve the performance. Meanwhile, taking the performance of the differential-neural distinguisher of Simon 32/64 as an entry point, we investigate the impact of input difference on the performance of the hybrid distinguishers to choose the proper input difference. Eventually, we improve the accuracy of the neural distinguishers of Simon 32/64, Simon 64/128, Simeck 32/64 and Simeck 64/128. We also obtain related-key differential-based neural distinguishers on round-reduced versions of Simon 32/64, Simon 64/128, Simeck 32/64 and Simeck 64/128 for the first time.
Can scale cortisol concentration be quantified non-lethally in wild fish species?
Authors: Kennedy Emily K C , Janz David M 
Published: January 2023

Abstract
Cortisol, the primary glucocorticoid in fishes, is secreted into the bloodstream in response to stress. Circulating cortisol accumulates in scales, a durable calcified structure that can be easily sampled from many fish species. As such, the use of scale cortisol concentration (SCC) is currently being explored as a means of chronic stress biomonitoring in wild fishes. Scales serve an important role in fish physiology and thus the number of scales required for reliable cortisol analysis is a limiting factor in the non-lethal collection of such samples. To date, scale cortisol quantification has also only been performed non-lethally in captive fishes and due to differences in stress responsiveness SCCs likely differ in wild species. As such, this study aimed to (1) apply our fish scale processing and analysis protocol to wild fish species and (2) apply it to five north temperate fish species to provide information useful to future non-lethal scale sampling regimes. Cortisol was successfully measured in scales collected from wild northern pike (Esox lucius), walleye (Sander vitreus), whitefish (Coregonus clupeaformis), white sucker (Catostomus commersonii) and captive rainbow trout (Oncorhynchus mykiss). SCCs were significantly different between species and thus the sample mass required for reliable cortisol analysis differed as well. In addition to the size of the fish and the mass of their scales this is an important consideration for future scale cortisol analyses as these factors could make SCC an attainable non-lethal sample matrix in some species of fish but impractical in others.
Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease
Authors: Shubhakar Archana , Jansen Bas C , Adams Alex T , Reiding Karli R , Ventham Nicholas T , Kalla Rahul , Bergemalm Daniel , Urbanowicz Paulina A , Gardner Richard A ,   IBD-BIOM Consortium, Wuhrer Manfred , Wuhrer Manfred , Halfvarson Jonas , Satsangi Jack , Fernandes Daryl L , Spencer Daniel I R 
Published: January 2023

Abstract
Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio [HR] 25.9, p = 1.1 × 10-12; 95% confidence interval [CI], 8.52–78.78). Application to an independent replication cohort of 54 IBD patients yielded an HR of 5.1 [p = 1.1 × 10-5; 95% CI, 2.54–10.1]. These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalised medicine in IBD.
Racial and Ethnic Trajectories of Sleep Disturbances: Variations by Age and Cohort
Authors: Chen Jen-Hao 
Published: January 2023

Abstract

Background
The racial and ethnic differences in trajectories of sleep disturbances in later life are crucial for addressing health disparities, but are not well understood. This study examines (a) how trajectories of sleep disturbances vary by race and ethnicity and birth cohort and (b) whether social and health risk factors explain such variations.

Methods
The study uses longitudinal data from the 2002–2018 Health and Retirement Study (N = 21 963) and the multilevel growth curve model to assess trajectories of sleep disturbances and their variations across 6 cohorts of White, Black, and Hispanic older adults. Sleep disturbances are measured using a modified Jenkins Sleep Scale.

Results
Without controls, sleep disturbances increased with aging for all racial and ethnic groups, but more rapidly among minorities, particularly younger cohorts of Hispanic older adults. When controlling for social and health risks, sleep disturbances did not change with aging for Whites and Blacks and increased for younger cohorts of Hispanics. Cohort effects were observed among White older adults, with higher sleep disturbances in younger cohorts. Importantly, the racial and ethnic disparities in age and cohort effects were not fully explained by social and health risks. Of the symptoms, the most salient racial and ethnic disparities were found in “waking up at night” and “not feeling rested.”

Conclusions
Findings reveal several differences by race and ethnicity and birth cohort in trajectories of sleep disturbances. Efforts should be made to improve sleep health for older adults as they age, especially for younger cohorts of Blacks and Hispanics.
Fundamental Invariants of Tensors, Latin Hypercubes, and Rectangular Kronecker Coefficients
Authors: Amanov Alimzhan , Yeliussizov Damir 
Published: January 2023

Abstract
We study polynomial SL-invariants of tensors, mainly focusing on fundamental invariants that are of smallest degrees. In particular, we prove that certain 3-dimensional analogue of the Alon–Tarsi conjecture on Latin cubes considered previously by Bürgisser and Ikenmeyer implies positivity of (generalized) Kronecker coefficients at rectangular partitions and as a result provides values for degree sequences of fundamental invariants.
B cell-intrinsic DNase1L3 is essential for the T cell-independent type II response in mice
Authors: Kato Kei , Haniuda Kei , Fukao Saori , Kitamura Daisuke 
Published: January 2023

Abstract
T cell independent type II (TI-II) antigens, such as capsular polysaccharides, have multivalent epitopes, which induce B cell activation, plasma cell differentiation and antibody production by strongly cross-linking B cell receptors. However, the mechanism of B cell activation by TI-II antigens remains unclear. In this study, we demonstrate that DNA endonuclease DNase1L3 (also termed DNase γ) is required for the TI-II response. The production of antigen-specific antibodies was severely diminished in DNase1L3-deficient mice upon immunization with TI-II antigens, but not with T cell dependent (TD) antigens. Bone marrow chimeric mice and B cell transfer experiments revealed that B cell-intrinsic DNase1L3 was required for the TI-II response. DNase1L3-deficient B cells were defective in cell proliferation and plasma cell differentiation in the TI-II response in vivo as well as in vitro, which was not rescued by co-culture with DNase1L3-sufficient B cells in vitro, disproving an involvement of a secretory DNase1L3. In vitro stimulation with TI-II antigen transiently increased expression of DNase1L3 and its translocation into the nucleus. RNA-seq analysis of ex vivo B cells that had responded to TI-II antigen in vivo revealed a marked reduction of Myc-target gene sets in DNase1L3-deficient B cells. Expression of IRF4, a gene that Myc targets, was diminished in the ex vivo DNase1L3-deficient B cells, in which forced expression of IRF4 restored the TI-II response in vivo. These data revealed an unexpected role of DNase1L3 in a missing link between B cell receptor signaling and B cell activation in the TI-II response, giving a valuable clue to molecularly dissect this response.