bluuebunny/crossref_metadata_2025_split huggingface dataset:
A previously-unrecognized motif of transcription factor RYBP, hotspot of cancer-related mutations, is essential for the integrity ofPolycombrepressive complex 1
Authors: Silva Catarina S. , Pérez Laura Mariño , Ferrer Irene Garcia , Dieryck Ines , Pessey Ombeline , Erba Elisabetta Boeri , Jensen Malene Ringkjøbing , Marcia Marco 
Published: October 2023

ABSTRACTPolycombrepressive complex 1 (PRC1) catalyzes monoubiquitination of histone H2A on Lys119, promoting gene silencing. Cells at different developmental stages and in different tissues express different PRC1 isoforms. All isoforms share the same catalytic core (subunits RING1B and PCGF) and vary in the composition of regulatory subunits, clustering in two major classes. Canonical isoforms (cPRC1) are regulated by CBX-like subunits, while variant isoforms (vPRC1) are regulated by RYBP-like subunits. The molecular bases for how regulatory subunits affect the structural assembly of the complex and its catalytic activity are still largely unknown. To fill this knowledge gap, here we have specifically studied how RYBP regulates vPRC1 structure and function. Integrating the machine-learning algorithm AlphaFold2 and NMR, we have identified novel vPRC1 structural motifs in RING1B and RYBP. While the new RING1B motif is dispensable for vPRC1 assembly, the RYBP motif is essential for mediating inter-subunit interactions between RYBP and the catalytic RING1B-PCGF4 heterodimer. Importantly, the RYBP motif harbors cancer-related mutations systematically positioned on the same face of a putative transiently-forming α-helix. Biochemical, biophysical and enzymatic characterization of purified cancer-related mutants confirm that this region is crucial for the structural stability of the complex. Overall, our data offer novel insights into the molecular architecture of vPRC1 and the effects of its regulatory subunit on the biochemical, structural, enzymatic, and physio-pathological properties of the complex.
A new abundant nitrite-oxidizing phylum in oligotrophic marine sediments
Authors: Zhao Rui , Jørgensen Steffen L. , Babbin Andrew R. 
Published: October 2023

AbstractNitrite-oxidizing bacteria (NOB) are important nitrifiers whose activity regulates the availability of nitrite and links reduced ammonium and oxidized nitrate in ecosystems. In oxic marine sediments, ammonia-oxidizing archaea (AOA) and NOB together catalyze the oxidation of ammonium to nitrate, but the observed abundance ratios of AOA to canonical NOB are significantly higher than the theoretical ratio predicted from microbial physiology, indicating that many novel NOBs are yet to be discovered. Here we report a new bacterial phylumCandidatusNitrosediminicolota, members of which are more abundant than canonical NOBs and are widespread across global oligotrophic sediments.Ca.Nitrosediminicolota members have the functional potential to oxidize nitrite, in addition to other accessory functions such as urea hydrolysis and thiosulfate reduction. While one recovered species (Ca.Nitrosediminicola aerophilis) is generally confined within the oxic zone, another (Ca.Nitrosediminicola anaerotolerans) can additionally thrive in anoxic sediments. CountingCa.Nitrosediminicolota as a nitrite-oxidizer resolves the apparent abundance imbalance between AOA and NOB in oxic marine sediments, and thus its activity may exert a critical control on the nitrite budget.
Transposable elements acquire time- and sex-specific transcriptional and epigenetic signatures along mouse fetal gonad development
Authors: Stévant Isabelle , Gonen Nitzan , Poulat Francis 
Published: October 2023

AbstractGonadal sex determination in mice is a complex and dynamic process, crucial for the development of functional reproductive organs. The expression of genes involved in this process is regulated by a variety of genetic and epigenetic mechanisms. Recently, there has been increasing evidence that transposable elements (TEs), which are a class of mobile genetic elements, play a significant role in regulating gene expression during embryogenesis and organ development. In this study, we aimed to investigate the involvement of TEs in the regulation of gene expression during mouse embryonic gonadal development. Through bioinformatic analysis, we aimed to identify and characterize specific TEs acting as regulatory elements for sex-specific genes, as well as their potential mechanisms of regulation. We identified TE loci expressed in a time- and sex-specific manner along fetal gonad development that correlate positively and negatively with nearby gene expression, suggesting that their expression is integrated to the gonadal regulatory network. Moreover, chromatin accessibility and histone post-transcriptional modification analyses in the differentiating supporting cells revealed that TEs are acquiring sex-specific signature for promoter-, enhancer-, and silencer-like elements with some of them being proximal to critical sex determining genes. Altogether, our study introduces TEs as new potential players of the gene regulatory network controlling gonadal development in mammals.
Micrococcin cysteine-to-thiazole conversion through transient interactions between a scaffolding protein and two modification enzymes
Authors: Calvopina-Chavez Diana G , Bursey Devan M , Tseng Yi-Jie , Patil Leena M , Bewley Kathryn D , Bennallack Philip R , McPhie Josh M , Wagstaff Kimberly B , Daley Anisha , Miller Susan M , Moody James D , Price John C , Griffitts Joel S 
Published: October 2023

ABSTRACTRibosomally synthesized and post-translationally modified peptides (RiPPs) are a broad group of compounds mediating microbial competition in nature. Azole/azoline heterocycle formation in the peptide backbone is a key step in the biosynthesis of many RiPPs. Heterocycle formation in RiPP precursors is often carried out by a scaffold protein, an ATP-dependent cyclodehydratase, and an FMN-dependent dehydrogenase. It has generally been assumed that the orchestration of these modifications is carried out by a stable complex including the scaffold, cyclodehydratase and dehydrogenase. The antimicrobial RiPP micrococcin begins as a precursor peptide (TclE) with a 35-amino acid N-terminal leader and a 14-amino acid C-terminal core containing six Cys residues that are converted to thiazoles. The putative scaffold protein (TclI) presumably presents the TclE substrate to a cyclodehydratase (TclJ) and a dehydrogenase (TclN) to accomplish the two-step installation of the six thiazoles. In this study, we identify a minimal TclE leader region required for thiazole formation, we demonstrate complex formation between TclI, TclJ and TclN, and further define regions of these proteins required for complex formation. Our results point to a mechanism of thiazole installation in which TclI associates with the two enzymes in a mutually exclusive fashion, such that each enzyme competes for access to the peptide substrate in a dynamic equilibrium, thus ensuring complete modification of each Cys residue in the TclE core.IMPORTANCEThiopeptides are a family of antimicrobial peptides characterized for having sulfur-containing heterocycles and for being highly post-translationally modified. Numerous thiopeptides have been identified; almost all of which inhibit protein synthesis in gram-positive bacteria. These intrinsic antimicrobial properties make thiopeptides promising candidates for the development of new antibiotics. The thiopeptide micrococcin is synthesized by the ribosome and undergoes several post-translational modifications (PTMs) to acquire its bioactivity. In this study, we identify key interactions within the enzymatic complex that carries out cysteine to thiazole conversion in the biosynthesis of micrococcin.
Honey varietals differentially impactBifidobacterium animalisssplactissurvivability in yogurt through simulatedin vitrodigestion
Authors: Alvarado David A. , Ibarra-Sánchez Luis Alberto , Mysonhimer Annemarie R. , Khan Tauseef A. , Cao Rong , Miller Michael J. , Holscher Hannah D. 
Published: October 2023

AbstractBackgroundBifidobacterium animalis ssp. lactisDN-173 010/CNCM I-2494 (B. animalis) is a probiotic strain commonly added to yogurt. Yogurt and honey are a popular culinary pairing. Honey improves bifidobacteria survivalin vitro. However, probiotic survival in yogurt with honey duringin vitrodigestion has not been investigated.ObjectiveThe study aimed to evaluate the effects of different honey varietals and concentrations onB. animalissurvivability in yogurt throughin vitrodigestion.MethodsYogurt with honey or control-treated samples underwentin vitrosimulated oral, gastric, and intestinal digestion.B. animaliscells were enumerated on MRS medium followed by an overlay with a modified selective MRS medium; all underwent anaerobic incubation.B. animaliswere enumerated pre-digestion and after oral, gastric, and intestinal digestion. There were two study phases: phase 1 tested four honey varietals at 20% w/w per 170g yogurt, and phase 2 tested seven dosages of clover honey (20, 14, 10, 9, 8, 6, and 4% w/w) per 170g yogurt.ResultsSimilarB. animaliscounts were observed between all treatments after oral and gastric digestion (<1 Log CFU/g probiotic reduction). HigherB. animalissurvivability was observed in yogurt with clover honey after exposure to simulated intestinal fluids (∼3.5 Log CFU/g reduction;P< 0.05) compared to all control treatments (∼5.5 Log CFU/g reduction;P< 0.05). Yogurt with 10 to 20% w/w clover honey increasedB. animalissurvivability after simulatedin vitrodigestion (up to ∼4.7 Log CFU/g survival;P< 0.05).ConclusionYogurt with added honey improves probiotic survivability duringin vitrodigestion. The effective dose of clover honey in yogurt was 10 to 20% w/w per serving (1 – 2 tablespoons per 170g yogurt) for increased probiotic survivability duringin vitrodigestion.
Genome Editing Outcomes Reveal Mycobacterial NucS Participates in a Short-Patch Repair of DNA Mismatches
Authors: Islam Tanjina , Josephs Eric A. 
Published: October 2023

SUMMARYIn the canonical DNA mismatch repair (MMR) mechanism in bacteria, if during replication a nucleotide is incorrectly mis-paired with the template strand, the resulting repair of this mis-pair can result in the degradation and re-synthesis of hundreds or thousands of nucleotides on the newly-replicated strand (long-patch repair). While mycobacteria, which include important pathogens such asMycobacterium tuberculosis, lack the otherwise highly-conserved enzymes required for the canonical MMR reaction, it was found that disruption of a mycobacterial mismatch-sensitive endonuclease NucS results in a hyper-mutative phenotype, which has led to the idea that NucS might be involved in a cryptic, independently-evolved DNA MMR mechanism. It has been proposed that nuclease activity at a mismatch might result in correction by homologous recombination (HR) with a sister chromatid. Using oligonucleotide recombination, which allows us to introduce mismatches during replication specifically into the genomes of a model forM. tuberculosis, Mycobacterium smegmatis, we find that NucS participates in a direct repair of DNA mismatches where the patch of excised nucleotides is largely confined to within ∼5 - 6 bp of the mis-paired nucleotides, which is inconsistent with mechanistic models of canonical mycobacterial HR or other double-strand break (DSB) repair reactions. The results presented provide evidence of a novel NucS-associated mycobacterial MMR mechanism occurringin vivoto regulate genetic mutations in mycobacteria.
HumanO-linked Glycosylation Site Prediction Using Pretrained Protein Language Model
Authors: Pakhrin Subash C. , Chauhan Neha , Khan Salman , Upadhyaya Jamie , Keller Charles , Neuman Laurie N. , Beck Moriah R. , Blanco Eduardo 
Published: October 2023

AbstractO-linked glycosylation of proteins is an essential post-translational modification process inHomo sapiens, where the attachment of a sugar moiety occurs at the oxygen atom of serine and/or threonine residues. This modification plays a pivotal role in various biological and cellular functions. While threonine or serine residues in a protein sequence are potential sites forO-linked glycosylation, not all threonine or serine residues areO-linked glycosylated. Furthermore, the modification is reversible. Hence, it is of vital importance to characterize if and whenO-linked glycosylation occurs. We propose a multi-layer perceptron-based approach termed OglyPred-PLM which leverages the contextualized embeddings produced from the ProtT5-XL-UniRef50 protein language model that significantly improves the prediction performance of humanO-linked glycosylation sites. OglyPred-PLM surpassed the performance of other indispensableO-linked glycosylation predictors on the independent benchmark dataset. This demonstrates that OglyPred-PLM is a powerful and unique computational tool to predictO-linked glycosylation sites in proteins and thus will accelerate the discovery of unknownO-linked glycosylation sites in proteins.
Recurrent gene flow events shaped the diversification of the clownfish skunk complex
Authors: Marcionetti Anna , Bertrand Joris A. M. , Cortesi Fabio , Donati Giulia F. A. , Heim Sara , Huyghe Filip , Kochzius Marc , Pellissier Loïc , Salamin Nicolas 
Published: October 2023

ABSTRACTClownfish (subfamily Amphiprioninae) are an iconic group of coral reef fish that evolved a mutualistic interaction with sea anemones, which was shown to have triggered the adaptive radiation of the group. Within clownfishes, the skunk complex is particularly interesting as, besides ecological speciation, gene flow between species and hybrid speciation are suggested to have shaped the diversification of the group. We investigated, for the first time, the mechanisms underlying the diversification of this complex. By taking advantage of their disjunct geographical distribution, we obtained whole-genome data of sympatric and allopatric populations of the three main species of the complex (Amphiprion akallopisos,A. perideraionandA. sandaracinos). We examined the population structure, genomic divergence patterns and introgression signals, and performed demographic modeling to identify the most realistic diversification scenario. We excluded scenarios of strict isolation, of hybrid origin ofA. sandaracinos, and ruled out the presence of extensive gene flow in sympatry. We discovered moderate gene flow fromA. perideraionto the ancestor ofA. akallopisos + A. sandaracinosand weak gene flow between the species in the Indo-Australian Archipelago throughout the diversification process of the group. We identified introgressed regions inA. sandaracinosand detected two large regions of high divergence inA. perideraion, likely maintained by the disruption of recombination. Altogether, our results show that ancestral hybridization events shaped the group’s diversification. However, more recent gene flow is less pervasive than initially thought and suggests a role of host repartition or behavioral barriers in maintaining the genetic identity of the species in sympatry.
Resource configurations among digital academic spin-offs: finding the technology-market fit
Authors: Evertsen Phuc Huynh , Rasmussen Einar 
Published: October 2023

PurposeManaging resources is crucial for firms to gain competitive advantages and succeed, particularly for startups with limited resources. It is important to understand how digital startups in general and digital academic spin-offs (ASOs) in particular may orchestrate their resources to optimize value. This paper integrates the resource-based perspective with digital entrepreneurship to analyze the resource configurations leading to success of digital ASOs.Design/methodology/approachThe paper adopts an inductive approach and applies qualitative comparative analysis (QCA) on a longitudinal dataset of digital ASOs to identify the resource configurations for a successful outcome.FindingsThe authors' paper identifies two main paths to success among digital ASOs, consisting of five distinct resource configurations. The first path is termed “market exploiters” that operate in favorable market conditions where specific technological resources and research collaboration resources are lacking. The second path involves “technology explorers” that combines both technological and commercial resources to achieve success.Research limitations/implicationsBy outlining distinct pathways to the success of digital ASOs, this paper contributes to the digital academic entrepreneurship literature and the resource-based view of entrepreneurial firms. The paper also suggests implications for policymakers and managers in managing resources for the success of digital ventures.Originality/valueBy exploring the resource configurations leading to the success of ASOs commercializing digital technologies, the paper shows that favorable market conditions and complementary resource configurations can be alternative pathways to success.
Numerical investigations on the lubrication characteristics of involute harmonic gears
Authors: Shen Yi , He Tao , Gong Xiaoya 
Published: October 2023

Purpose
Harmonic gears always work under different operating conditions and may usually break down due to lubrication failures, while its lubrication mechanism is still not clearly understood. This paper aims to present a lubrication model comprehensively considering the influence of contact geometry, lubrication properties and three-dimensional (3D) real surface roughness to analyze the lubrication performance under different conditions.

Design/methodology/approach
Based on the discrete convolution-fast Fourier transformation with duplicated padding and quasi-system numerical methods, the lubrication model for harmonic gears is developed, which is verified by comparing results with available lubrication data.

Findings
The effects of meshing process, working conditions and 3D roughness on the lubrication characteristics are discussed. From the calculated cases, the increase in rotational speed and decrease of applied torque may increase the film thickness, enhancing the lubrication performance of harmonic gears. It is also observed that proper surface roughness can be used for lubrication design.

Originality/value
The research results can provide theoretical guidance for improving lubrication performance and reducing friction/wear of the harmonic gear interfaces. This study can be promoted to various engineering scenarios of harmonic gears, such as industrial robots, space-driven agencies and precision measuring instruments.
Recent developments in freezing of fruits and vegetables: Striving for controlled ice nucleation and crystallization with enhanced freezing rates
Authors: Grover Yashmita , Negi Pradeep Singh 
Published: October 2023

AbstractFruits and vegetables are rich in essential nutrients such as minerals, vitamins, and antioxidants; however, they have short shelf life. Freezing is a superior method of preservation compared to other techniques with respect to nutrient retention and maintenance of sensory attributes. However, several physical and textural quality changes associated with freezing and thawing pose a serious problem to the quality of frozen products. Some of the disadvantages associated with the currently employed methods for freezing fruits and vegetables include low rates of heat exchange in blast freezers, shape limitation in plate freezers, high cost of operation in cryogenic freezing, and freezing solution dilution in immersion freezing. Therefore, novel freezing technologies have been developed to achieve controlled ice nucleation and crystallization, enhanced freezing rate, decreased phase transition time, and maintained temperature stability. This review discusses some of the most recent approaches employed in freezing and points to their adoption for maintaining the quality of fruits and vegetables with extended storage.
Practical application of the linkage disequilibrium method for estimating contemporary effective population size: A review
Authors: Waples Robin S. 
Published: October 2023

AbstractThe method to estimate contemporary effective population size (Ne) based on patterns of linkage disequilibrium (LD) at unlinked loci has been widely applied to natural and managed populations. The underlying model makes many simplifying assumptions, most of which have been evaluated in numerous studies published over the last two decades. Here, these performance evaluations are reviewed and summarized, with a focus on information that facilitates practical application to real populations in nature. Potential sources of bias that are discussed include calculation of r2 (a measure of LD), adjustments for sampling error, physical linkage, age structure, migration and spatial structure, mutation and selection, mating systems, changes in abundance, rare alleles, missing data, genotyping errors, data filtering choices and methods for combining multiple Ne estimates. Factors that affect precision are reviewed, including pseudoreplication that limits the information gained from large genomics datasets, constraints imposed by small samples of individuals, and the challenges in obtaining robust estimates for large populations. Topics that merit further research include the potential to weight r2 values by allele frequency, lump samples of individuals, use genotypic likelihoods rather than called genotypes, prune large LD values and apply the method to species practising partial monogamy.
The heritages of forced opening: The treaty‐port history and institutions in modern China
Authors: Liu Yuan , Zhang Lei 
Published: October 2023

AbstractTreaty ports attracted most of colonial China's foreign enterprise and introduced western institutions that would shape property rights and the judicial system. Political change and economic reconstruction after 1949 depressed this tradition, but its effects lingered and became more active after reform and opening. Using cross‐sectional data for cities combining the treaty‐port history and the investment climate, we document the impact of this heritage on the institutional quality and economic development of modern China.
Retinal vein occlusion as an age‐dependent marker of incident dementia in a long‐term Danish national cohort
Authors: Clausen Anna Rebien , Stokholm Lonny , Frederiksen Katrine Hartmund , Möller Sören , Blaabjerg Morten , Pedersen Frederik Nørregaard , Grauslund Jakob 
Published: October 2023

AbstractPurposeThe aim of this study was to investigate retinal vein occlusion (RVO) as an independent marker of incident dementia.MethodsIn a prospective nationwide cohort study, we identified 2 225 568 individuals through the Danish national health registers. Individuals older than 65 years, without unspecified retinal vascular occlusion or dementia were included from 1998 to 2020 and followed until 2022. We calculated the incidence rate (IR) and performed a Cox regression analysis with a hazard ratio (HR) and 95% confidence interval (CI) for RVO (exposure) as a marker of all‐cause dementia adjusted for systemic comorbidity.ResultsWe identified 19 669 individuals with RVO who had a higher prevalence of systemic comorbidity at inclusion compared to those without RVO (n = 2 185 483). We performed a Cox regression analysis for age‐dependent exposure due to non‐proportional hazards in the pre‐planned analysis. Exposed individuals younger than 75 years had an increased risk of all‐cause dementia (adjusted HR 1.09, 95% CI 1.01–1.18), whereas individuals older than 75 years had a decreased risk of all‐cause dementia (adjusted HR 0.92, 95% CI 0.86–0.98).ConclusionIndividuals with RVO had an age‐dependent risk of dementia, with a 9% increased risk in individuals with RVO younger than 75 years and an 8% decreased risk in individuals older than 75 years at the time of exposure.