bluuebunny/crossref_metadata_2025_split huggingface dataset:
A critique of the hypothesis that CA repeats are primary targets of neuronal MeCP2
Authors: Chhatbar Kashyap , Connelly John , Webb Shaun , Kriaucionis Skirmantas , Bird Adrian 
Published: May 2022

AbstractThe DNA binding protein MeCP2 is reported to bind methylated cytosine in CG and CA motifs in genomic DNA, but it was recently proposed that arrays of tandemly repeated CA containing either methylated or hydroxymethylated cytosine are the primary targets for MeCP2 binding and function. Here we investigated the predictions of this hypothesis using a range of published datasets. We failed to detect enrichment of cytosine modification at genomic CA repeat arrays in mouse brain regions and found no evidence for preferential MeCP2 binding at CA repeats. Moreover, we did not observe a correlation between the CA repeat density near genes and their degree of transcriptional deregulation when MeCP2 was absent. Our results do not provide support for the hypothesis that CA repeats are key mediators of MeCP2 function. Instead, we found that CA repeats are subject to CAC methylation to a degree that is typical of the surrounding genome and contribute modestly to MeCP2-mediated modulation of gene expression in accordance with their content of this canonical target motif.
AA-amyloidosis in cats (Felis catus) housed in shelters
Authors: Ferri Filippo , Ferro Silvia , Porporato Federico , Callegari Carolina , Guglielmetti Chiara , Mazza Maria , Ferrero Marta , Crinò Chiara , Gallo Enrico , Drigo Michele , Coppola Luigi M. , Gerardi Gabriele , Schulte Tim Paul , Ricagno Stefano , Vogel Monique , Storni Federico , Bachmann Martin F. , Vogt Anne-Cathrine , Caminito Serena , Mazzini Giulia , Lavatelli Francesca , Palladini Giovanni , Merlini Giampaolo , Zini Eric 
Published: May 2022

AbstractSystemic AA-amyloidosis is a protein-misfolding disease that is characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. In domestic short-hair cats, AA-amyloidosis has only been anecdotally reported and is considered a rare disease. Here we report that an astonishing 57-73% of early deceased short-hair cats kept in three independent shelters suffer from amyloid deposition in the liver, spleen, or kidney. Histopathology and mass spectrometry of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B=0.026, CI95%=0.007-0.046; p=0.010). Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease.
The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data
Authors: Leonard Hampton L. , Murtadha Ruqaya , Martinez-Carrasco Alejandro , Muller-Nedebock Amica , Gil-Martinez Ana-Luisa , Illarionova Anastasia , Moore Anni , Bustos Bernabe I. , Jadhav Bharati , Huxford Brook , Storm Catherine , Towns Clodagh , Vitale Dan , Chetty Devina , Yu Eric , Jama Fatumah , Grenn Francis P. , Salazar Gabriela , Rateau Geoffrey , Iwaki Hirotaka , Elsayed Inas , Foote Isabelle , van Rensburg Zuné Jansen , Kim Jonggeol Jeff , Yuan Jie , Lake Julie , Brolin Kajsa , Senkevich Konstantin , Wu Lesley , Tan Manuela M.X. , Periñán María Teresa , Makarious Mary B , Ta Michael , Pillay Nikita Simone , Betancor Oswaldo Lorenzo , Reyes-Pérez Paula R. , Jerez Pilar Alvarez , Saini Prabhjyot , al-Ouran Rami , Sivakumar Ramiya , Real Raquel , Reynolds Regina H. , Hu Ruifneg , Abrahams Shameemah , Rao Shilpa C. , Antar Tarek , Leal Thiago Peixoto , Iankova Vassilena , Scotton William J. , Song Yeajin , Singleton Andrew , Nalls Mike A. , Dey Sumit , Bandres-Ciga Sara , Blauwendraat Cornelis , Noyce Alastair J. 
Published: May 2022

AbstractBackgroundOpen science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities.ObjectiveTo coordinate a virtual hackathon to develop novel PD research tools.Methods49 early career scientists from 12 countries collaborated in a virtual 3-day hackathon event in May 2021, during which they built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools.ResultsEach team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools.ConclusionHackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early career researchers. The resources generated can be used to accelerate research on the genetics of PD.
The trade-off function of photorespiration in a changing environment
Authors: Hernandez Jakob Sebastian , Nägele Thomas 
Published: May 2022

AbstractThe photorespiratory pathway in plants comprises metabolic reactions distributed across several cellular compartments. It emerges from the dual catalytic function of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) which either carboxylates or oxygenates ribulose-1,5-bisphosphate (RuBP). Carboxylation reactions produce 3-phospho-glycerate (3PGA) molecules which are substrate for central carbohydrate metabolism while oxygenation forms 2-phosphoglycolate (2PG) molecules which are substrate for the multicompartmental recovery process of photorespiration. Further, 2PG is a strong inhibitor of several enzymes involved in the Calvin-Benson-Bassham cycle which challenges the experimental and theoretical study of carbon assimilation, photorespiration and metabolic regulationin vivo. Here, an approach of structural kinetic modeling (SKM) is presented to investigate the extend of stabilization of CBC and carbohydrate metabolism by photorespiration. Further, our approach highlights the importance of feedback regulation by 2-PG for alleviation of environmental perturbation. Our findings indicate that oxygenation of RuBP by Rubisco significantly stabilizes CBC activity and, thus, carbohydrate metabolism. Based on our findings, we suggest a trade-off function of photorespiration which reduces carbon assimilation rates but simultaneously stabilizes metabolism by increasing plasticity of metabolic regulation within the chloroplast. Furthermore, our analysis suggests a stabilizing effect of increasing the partition of newly assimilated carbon going towards sucrose biosynthesis. With this, our analysis sheds light on the role of a multicompartmental metabolic pathway in stabilizing plant metabolism within a changing environment.
Spontaneously produced lysogenic phages are an important component of the soybean Bradyrhizobium mobilome
Authors: Joglekar Prasanna , Ferrell Barbra D. , Jarvis Tessa , Haramoto Kona , Place Nicole , Dums Jacob T , Polson Shawn W. , Wommack K. Eric , Fuhrmann Jeffry J. 
Published: May 2022

AbstractThe ability to nodulate and fix atmospheric nitrogen in soybean root nodules makes soybean Bradyrhizobium spp. (SB) critical in supplying humanity’s nutritional needs. The intricacies of SB-plant interactions have been studied extensively; however, bradyrhizobial ecology as influenced by phages has received somewhat less attention even though these interactions may significantly impact soybean yield. In batch culture four SB strains, S06B (B. japonicum, S06B-Bj), S10J (B. japonicum, S10J-Bj), USDA 122 (B. diazoefficiens, USDA 122-Bd), and USDA 76T (B. elkanii, USDA 76-Be), spontaneously (without apparent exogenous chemical or physical induction) produced phages throughout the growth cycle; for three strains, phage concentrations exceeded cell numbers by ca. 3-fold after 48 h incubation. Observed spontaneously produced phages (SPP) were tailed. Phage terminase large-subunit protein phylogeny revealed possible differences in phage packaging and replication mechanisms. Bioinformatic analyses predicted multiple prophage regions within each SB genome preventing accurate identification of SPP genomes. A DNA sequencing approach was developed that accurately delineated the boundaries of four SPP genomes within three of the SB chromosomes. Read mapping suggested that the SPP are capable of transduction. In addition to the phages, bacterial strains S06B-Bj and USDA 76-Be were rich in mobile elements consisting of insertion sequences (IS) and large, conjugable, broad host range plasmids. The prevalence of SPP along with IS and plasmids indicate that horizontal gene transfer likely plays an outsized role in SB ecology and may subsequently impact soybean productivity.ImportancePrevious studies have shown that IS and plasmids mediate horizontal gene transfer (HGT) of symbiotic nodulation (nod) genes in SB; however, these events require close cell to cell contact which could be limited in soil environments. Bacteriophage assisted gene transduction through spontaneously produced prophages could provide stable means of HGT not limited by the constraints of proximal cell to cell contact. Phage mediated HGT events could be important in SB population ecology with concomitant impacts on soybean agriculture.
A Standardized Ontology for Naming tRNA-derived RNAs Based on Molecular Origin
Authors: Holmes Andrew D. , Chan Patricia P. , Chen Qi , Ivanov Pavel , Drouard Laurence , Polacek Norbert , Kay Mark A. , Lowe Todd M. 
Published: May 2022

AbstractSmall RNAs processed from transfer RNA are recognized to have regulatory functions distinct from protein synthesis. This rapidly advancing field has led to a constellation of transcript nomenclatures. Building upon the accepted tRNA naming system and linking tRNA-derived small RNAs to their molecular sources, we propose an improved nomenclature. Facilitated by the tDRnamer system, it will promote inter-study comparisons leveraging a biologically-rooted nomenclature for this emerging class of intriguing regulators.
A comprehensive list of the replication promoters of Bunyavirales reveals a unique promoter structure in Nairoviridae differing from other virus families
Authors: Neriya Yutaro , Kojima Shohei , Sakiyama Arata , Kishimoto Mai , Iketani Takao , Watanabe Tadashi , Abe Yuichi , Shimoda Hiroshi , Nakagawa Keisuke , Koma Takaaki , Matsumoto Yusuke 
Published: May 2022

AbstractBunyaviruses belong to the order Bunyavirales, the largest group of RNA viruses. They infect a wide variety of host species around the world, including plants, animals and humans, and pose a major threat to public health. Major families in the order Bunyavirales have tri-segmented negative-sense RNA genomes, the 5’ and 3’ ends of which form complementary strands that serve as a replication promoter. Elucidation of the mechanisms by which viral RNA-dependent RNA polymerase recognizes the promoter to initiates RNA synthesis is important for understanding viral replication and pathogenesis, and for developing antivirals. A list of replication promoter configuration patterns may provide details on the differences in the replication mechanisms among bunyaviruses. Here, by using public sequence data of all known bunyavirus species, we constructed a comprehensive list of the replication promoters comprising 40 nucleotides in both the 5’ and 3’ ends of the genome that form a specific complementary strand. We showed that among tri-segmented bunyaviruses, viruses belonging to the family Nairoviridae, including the highly pathogenic Crimean-Congo hemorrhagic fever virus, have evolved a GC-rich promoter structure that differs from that of other bunyaviruses. The unique promoter structure might be related to the large genome size of the family Nairoviridae among bunyaviruses. It is possible that the large genome architecture confers a pathogenic advantage. The promoter list provided in this report is expected to be useful for predicting virus family-specific replication mechanisms of segmented negative-sense RNA viruses.
Splashed E-box and AP-1 motifs cooperatively drive regeneration-response and shape regeneration abilities
Authors: Tamaki Teruhisa , Yoshida Takafumi , Shibata Eri , Nishihara Hidenori , Ochi Haruki , Kawakami Atsushi 
Published: May 2022

ABSTRACTInjury triggers genetic program to induce gene expression for regeneration. Several studies have recently reported the identification of regeneration-response enhancers (RREs) in zebrafish; however, it remains unclear whether a common mechanism operates in RREs. Here, we show that E-box and activator protein 1 (AP-1) motifs cooperatively function as RREs. We identified three RREs from the fn1b promoter by a search of conserved sequences and an in vivo transgenic assay for regeneration-response in zebrafish. Two of them derived from transposons displayed RRE activity only when combined with the −0.7 kb fn1b promoter, while another non-transposable element functioned as a standalone enhancer. A search for transcription factor-binding motifs and validation by transgenic assay revealed that both of E-box and AP-1 motifs are necessary and sufficient for RREs. Such RREs responded to variety of tissue injuries including zebrafish heart and Xenopus limb bud regenerations. Our findings highlight that regeneration is regulated by merging two activating signals evoked by tissue injuries. It is speculated that a large pool of potential enhancers in the genome shaped regenerative capacities during evolution.SUMMARY STATEMENTThe study revealed that regeneration-response enhancer is composed of two transcription factor-binding motifs. The fidelity of regeneration-dependent gene expression is ensured by merging two activating signals evoked by injuries.
Defining the HIV Capsid Binding Site of Nucleoporin 153
Authors: Li Shunji , Patel Jagdish Suresh , Yang Jordan , Crabtree Angela Marie , Rubenstein Brenda M. , Lund-Andersen Peik Karl , Ytreberg Frederick Marty , Rowley Paul Andrew 
Published: May 2022

AbstractThe interaction between the HIV-1 capsid (CA) and human nucleoporin 153 (NUP153) is vital for delivering the HIV-1 preintegration complex into the nucleus via the nuclear pore complex. The interaction with CA requires a phenylalanine/glycine-containing motif in the C-terminus of NUP153. This study used molecular modeling and biochemical assays to determine the amino acids of NUP153 that are essential for its interactions with CA. Molecular dynamics, FoldX, and PyRosetta simulations delineated the minimal CA binding motif of NUP153 based on the known structure of NUP153 bound to the HIV-1 CA hexamer. Computational predictions were experimentally validated by testing the interaction of NUP153 with CA using an in vitro binding assay and a cell-based TRIM-NUP153C restriction assay. This multidisciplinary approach identified eight amino acids from P1411 to G1418 that stably engage with CA, with significant correlations between molecular models and empirical experiments. Specifically, P1411, V1414, F1415, T1416, F1417, and G1418 were confirmed as critical amino acids required to interact NUP153 with CA.IMPORTANCEHuman immunodeficiency virus (HIV) can infect non-dividing cells by interacting with host nuclear pores. The host nuclear pore protein NUP153 directly interacts with the HIV capsid to promote viral nuclear entry. This study used a multidisciplinary approach combining computational and experimental techniques to map the essential amino acids of NUP153 required for HIV capsid interaction. This approach revealed that the HIV capsid interacts specifically with only six amino acids of NUP153, suggesting other FG-containing motifs could also interact with the capsid. Based on molecular modeling, naturally occurring polymorphisms in human and non-human primates would be predicted to prevent NUP153 interaction with capsid, potentially protecting from HIV infection.
The proteomic and transcriptomic landscapes altered by Rgg2/3 activity in Streptococcus pyogenes
Authors: Rued Britta E. , Anderson Caleb M. , Federle Michael J. 
Published: May 2022

ABSTRACTStreptococcus pyogenes, otherwise known as Group A Streptococcus (GAS), is an important and highly adaptable human pathogen with the ability to cause both superficial and severe diseases. Understanding how S. pyogenes senses and responds to its environment will likely aid in determining how it causes a breadth of diseases. One regulatory network involved in GAS’s ability to sense and respond to the changing environment is the Rgg2/3 quorum sensing (QS) system, which responds to metal and carbohydrate availability and regulates changes to the bacterial surface. To better understand the impact of Rgg2/3 QS on S. pyogenes physiology, we performed RNA-seq and TMT-LC-MS/MS analysis on cells in which this system was induced or disrupted. Primary findings confirmed that pheromone stimulation in wildtype cultures is limited to the induction of operons whose promoters contain previously determined Rgg2/3 binding sequences. However, supplementing exogenous pheromone to a deletion mutant of rgg3, a strain that endogenously produces elevated amounts of pheromone, led to extended alterations of the transcriptome and proteome, ostensibly by stress-induced pathways. Under such exaggerated pheromone conditions (Δrgg3+SHP), a connection was identified between Rgg2/3 and the stringent response. Mutation of relA, the bifunctional guanosine tetra- and penta-phosphate nucleoside synthetase/hydrolase, and alarmone synthase genes sasA and sasB, impacted culture doubling times and disabled induction of Rgg2/3 in response to mannose, while manipulation of Rgg2/3 signaling modestly altered nucleotide levels. Our findings indicate that excessive pheromone production or exposure places stress on GAS resulting in an indirect altered proteome and transcriptome beyond primary pheromone signaling.IMPORTANCEStreptococcus pyogenes causes several important human diseases. This study evaluates how the induction or disruption of a cell-cell communication system alters S. pyogenes’s gene expression and, in extreme conditions, its physiology. Using transcriptomic and proteomic approaches, the results define the pheromone-dependent regulon of the Rgg2/3 quorum sensing system. In addition, we find that excessive pheromone stimulation, generated by genetic disruption of the system, leads to stress responses that are associated with the stringent response. Disruption of this stress response affects the ability of the cell-cell communication system to respond under certain conditions. These findings assist in the determination of how S. pyogenes is impacted by and responds to non-traditional sources of stress.
PHi-C2: interpreting Hi-C data as the dynamic 3D genome state
Authors: Shinkai Soya , Itoga Hiroya , Kyoda Koji , Onami Shuichi 
Published: May 2022

SummaryHi-C is a widely used assay for studying three-dimensional (3D) genome organization across the whole genome. Here, we present PHi-C2, a Python package supported by mathematical and biophysical polymer modeling, that converts an input Hi-C matrix data into the polymer model’s dynamics, structural conformations, and rheological features. The updated optimization algorithm to regenerate a highly similar Hi-C matrix provides a fast and accurate optimal solution compared to the previous version by eliminating a computational bottleneck in the iterative optimization process. Besides, we newly set up the availability on Google Colab workflow to run, easily change parameters and check the results in the notebook. Overall, PHi-C2 can be a valuable tool to mine the dynamic 3D genome state embedded in Hi-C data.Availability and ImplementationPHi-C2 as the phic Python package is freely available under the GPL license and can be installed from the Python package index. The source code is available from GitHub at https://github.com/soyashinkai/PHi-C2. Without preparing a Python environment, PHi-C2 can run on Google Colab (https://bit.ly/3rlptGI).Contactsoya.shinkai@riken.jp or sonami@riken.jp
Highly specialized carbohydrate metabolism capability in Bifidobacterium strain associated with intestinal barrier maturation in early preterm infants
Authors: Ma Bing , Sundararajan Sripriya , Nadimpalli Gita , France Michael , McComb Elias , Rutt Lindsay , Lemme-Dumit Jose M , Janofsky Elise , Roskes Lisa S. , Gajer Pawel , Fu Li , Yang Hongqiu , Humphrys Mike , Tallon Luke J , Sadzewicz Lisa , Pasetti Marcela F , Ravel Jacques , Viscardi Rose M 
Published: May 2022

ABSTRACT“Leaky gut”, or high intestinal barrier permeability, is common in preterm newborns. The role of microbiota in this process remains largely uncharacterized. We employed both short- and long-read sequencing of the 16S rRNA gene and metagenomes to characterize the intestinal microbiome of a longitudinal cohort of 113 preterm infants born between 240/7-326/7 weeks of gestation. Enabled by enhanced taxonomic resolution, we found significantly increased abundance of Bifidobacterium breve and a diet rich in mother’s breastmilk to be associated with intestinal barrier maturation during the first week of life. We combined these factors using genome- resolved metagenomics and identified a highly specialized genetic capability of the Bifidobacterium strains to assimilate human milk oligosaccharides and host-derived glycoproteins. Our study proposed mechanistic roles of breastmilk feeding and intestinal microbial colonization in postnatal intestinal barrier maturation; these observations are critical towards advancing therapeutics to prevent and treat hyperpermeable gut- associated conditions, including necrotizing enterocolitis.IMPORTANCEDespite improvements in neonatal intensive care, necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality. “Leaky gut”, or intestinal barrier immaturity with elevated intestinal permeability, is the proximate cause of susceptibility to NEC. Early detection and intervention to prevent leaky gut in “at-risk” preterm neonates is critical to lower the risk for potentially life-threatening complications like NEC. However, the complex interactions between the developing gut microbial community, nutrition, and intestinal barrier function, remain largely uncharacterized. In this study, we revealed the critical role of sufficient breastmilk feeding volume and specialized carbohydrate metabolism capability of Bifidobacterium in coordinated postnatal improvement of intestinal barrier. Determining the clinical and microbial biomarkers that drive the intestinal developmental disparity will inform early detection and novel therapeutic strategies to promote appropriate intestinal barrier maturation, prevent NEC and other adverse health conditions in preterm infants.