bluuebunny/crossref_metadata_2025_split huggingface dataset:
Balanced mitochondrial and cytosolic translatomes underlie the biogenesis of human respiratory complexes
Authors: Soto Iliana , Couvillion Mary , McShane Erik , Hansen Katja G. , Moran J. Conor , Barrientos Antoni , Churchman L. Stirling 
Published: June 2021

AbstractOxidative phosphorylation (OXPHOS) complexes consist of nuclear and mitochondrial DNA-encoded subunits. Their biogenesis requires cross-compartment gene regulation to mitigate the accumulation of disproportionate subunits. To determine how human cells coordinate mitochondrial and nuclear gene expression processes, we established an optimized ribosome profiling approach tailored for the unique features of the human mitoribosome. Analysis of ribosome footprints in five cell types revealed that average mitochondrial synthesis rates corresponded precisely to cytosolic rates across OXPHOS complexes. Balanced mitochondrial and cytosolic synthesis did not rely on rapid feedback between the two translation systems. Rather, LRPPRC, a gene associated with Leigh’s syndrome, is required for the reciprocal translatomes and maintains cellular proteostasis. Based on our findings, we propose that human mitonuclear balance is enabled by matching OXPHOS subunit synthesis rates across cellular compartments, which may represent a vulnerability for cellular proteostasis.
Hematologic and systemic metabolic alterations due to Mediterranean type II G6PD deficiency in mice
Authors: D’Alessandro Angelo , Howie Heather L , Hay Ariel M. , Dziewulska Karolina H. , Brown Benjamin , Wither Matthew J , Karafin Matthew , Stone Elizabeth F. , Spitalnik Steven L , Hod Eldad A , Francis Richard O , Fu Xiaoyun , Thomas Tiffany , Zimring James C 
Published: June 2021

AbstractDeficiency of Glucose 6 phosphate dehydrogenase (G6PD) is the single most common enzymopathy, present in approximately 400 million humans (e.g. 5% of humans). Its prevalence is hypothesized to be due to conferring resistance to malaria. However, G6PD deficiency also results in hemolytic sequelae from oxidant stress. Moreover, G6PD deficiency is associated with kidney disease, diabetes, pulmonary hypertension, immunological defects, and neurodegenerative diseases. To date, the only available mouse models have decreased levels of G6PD due to promoter mutations, but with stable G6PD. However, human G6PD mutations are missense mutations that result in decreased enzymatic stability. As such, this results in very low activity in red blood cells and platelets that cannot synthesize new protein. To generate a more accurate model, the human sequence for a severe form of G6PD deficiency (Med -) was knocked into the murine G6PD locus. As predicted, G6PD levels were extremely low in RBCs and deficient mice have increased hemolytic sequalae to oxidant stress. G6PD levels were mildly decreased in non-erythroid organs, consistent with what has been observed in humans. Juxtaposition of G6PD deficient and wild-type mice revealed altered lipid metabolism in multiple organ systems. Together, these findings both establish a new mouse model of G6PD deficiency that more accurately reflects human G6PD deficiency and also advance our basic understanding of altered metabolism in this setting.
Resurrected Rubisco suggests uniform carbon isotope signatures over geologic time
Authors: Kedzior Mateusz , Garcia Amanda K. , Li Meng , Taton Arnaud , Adam Zachary R. , Young Jodi N. , Kacar Betul 
Published: June 2021

SummaryThe earliest geochemical indicators of microbes—and the enzymes that powered them—extend back almost 3.8 billion years on our planet. Paleobiologists often attempt to understand these indicators by assuming that the behaviors of modern microbes and enzymes are consistent (uniform) with those of their predecessors. A uniformitarian assumption (i.e., the idea that fundamental geobiological processes have occurred in much the same manner over Earth history) seems at odds with our understanding of the inherent variability of living systems. Here, we examine whether a uniformitarian assumption for an enzyme thought to generate carbon isotope indicators of biological activity, RuBisCO, can be corroborated by independently studying the history of changes recorded within RuBisCO’s genetic sequences. Specifically, we resurrected a Precambrian-age, ancient RuBisCO by engineering its ancient DNA inside a modern cyanobacterium genome and measured the engineered organism’s fitness and carbon-isotope-discrimination profile. The envelope of ancestral RuBisCO isotopic fractionation observed here indicates that uniformitarian assumptions may be warranted, but with important caveats. Our results suggest that further inquiries that link molecule-level evolutionary changes with planet-level geochemical conditions are needed to discern whether enzyme-affected isotope fractionation trends extend deeper into the early Precambrian. Experimental studies illuminating life’s early molecular innovations are crucial to explore the foundations of Precambrian uniformitarian assumptions.
Differential microRNA expression analyses across two brain regions in Alzheimer’s disease
Authors: Dobricic Valerija , Schilling Marcel , Schulz Jessica , Zhu Ling-Shuang , Zhou Chao-Wen , Fuß Janina , Franzenburg Sören , Zhu Ling-Qiang , Parkkinen Laura , Lill Christina M. , Bertram Lars 
Published: June 2021

AbstractBackgroundDysregulation of microRNAs (miRNAs) is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). Hitherto, sample sizes from differential miRNA expression studies in AD are exceedingly small aggravating any biological inference. To overcome this limitation, we investigated six candidate miRNAs in a large collection of brain samples.MethodsBrain tissue was derived from superior temporal gyrus (STG) and entorhinal cortex (EC) from 99 AD patients and 91 controls. Expression of six miRNAs was examined by qPCR (STG) or small RNA sequencing (EC). Brain region-dependent differential miRNA expression was investigated in a transgenic AD mouse model using qPCR and FISH. Total RNA sequencing was used to assess differential expression of miRNA target genes.ResultsMiR-129-5p, miR-132-5p, and miR-138-5p were significantly downregulated in AD vs. controls both in STG and EC, while miR-125b-5p and miR-501-3p showed no evidence for differential expression in this dataset. In addition, miR-195-5p was significantly upregulated in EC but not STG in AD patients. The brain region-specific pattern of miR-195-5p expression was corroboratedin vivoin transgenic AD mice. Total RNA sequencing identified several novel and functionally interesting target genes of these miRNAs involved in synaptic transmission (GABRB1), the immune-system response (HCFC2) or AD-associated differential methylation (SLC16A3).ConclusionsUsing two different methods (qPCR and small RNA-seq) in two separate brain regions in 190 individuals we more than doubled the available sample size for most miRNAs tested. Differential gene expression analyses confirm the likely involvement of miR-129-5p, miR-132-5p, miR-138-5p, and miR-195-5p in AD pathogenesis and highlight several novel potentially relevant target mRNAs.FundingThis work was supported by the Deutsche Forschungsgemeinschaft (DFG) and the National Science Foundation China (NSFC) as a Joint Sino-German research project (“MiRNet-AD”, #391523883). Additional support was provided by the DFG Research Infrastructure NGS_CC (project 407495230) as part of the Next Generation Sequencing Competence Network (#423957469) and the Cure Alzheimer’ s Fund (CAF) as part of the CIRCUITS consortium project.
Nuclear and plastid phylogenomic analyses provide insights into the reticulate evolution, species delimitation and biogeography of the Sino-Japanese disjunctive Diabelia (Caprifoliaceae)
Authors: Ke Xiu-Rong , Morales-Briones Diego F. , Wang Hong-Xin , Sun Qing-Hui , Landis Jacob B. , Wen Jun , Wang Hua-Feng 
Published: June 2021

AbstractUnderstanding biological diversity and the mechanisms of the Sino-Japanese disjunctions are major challenges in eastern Asia biogeography. The Sino-Japanese flora has been broadly studied as an ideal model for plant phylogeography. Diabelia (Caprifoliaceae) is an East Asian genus, with a disjunctive distribution across the Sino-Japanese region. However, relationships within Diabelia remain elusive. In this study, we reconstructed the phylogeny of Diabelia and inferred historical biogeography and evolutionary patterns based on nuclear and plastid sequences from target enrichment and genome skimming approaches, respectively. We found that the main clades within Diabelia were discordant between nuclear and plastid trees. Both nuclear and plastid phylogenetic analyses supported five main clades: D. serrata, D. tetrasepala, D. sanguinea, D. spathulata var. stenophylla and D. spathulata var. spathulata. Species network analyses revealed that Diabelia tetrasepala is likely the result of a hybridization event. Divergence time estimation and ancestral area reconstructions showed that Diabelia originated in Japan during the early Miocene, with subsequent vicariance and dispersal events between Japan and Korea, and between Japan and China. Overall, our results support the division of Diabelia into five main clades and the recognition of five species in the genus. This research provides new insights in the species delimitation and speciation processes of taxonomically complex lineages such as Diabelia.
Serial Dependence in Temporal Perception Reveals the Dynamics of Constructing an Internal Reference Frame
Authors: Wang Tianhe , Luo Yingrui , Pöppel Ernst , Bao Yan 
Published: June 2021

AbstractTemporal perception is crucial to cognitive functions. To better estimate temporal durations, the observers need to construct an internal reference frame based on past experience and apply it to guide future perception. However, how this internal reference frame is constructed remains largely unclear. Here we showed the dynamics of the internal reference construction from the perspective of serial dependence in temporal reproduction tasks. We found the current duration estimation is biased towards both perceived and reproduced durations in previous trials. Moreover, this effect is regulated by the variability of sample durations. The influence of previous trials was stronger when the observers were exposed to context with more variable durations, which is inconsistent with previous theories that the similarity between successive stimuli induces serial dependence. We proposed a Bayesian model with an adaptive reference updated continuously after each observation, which can better explain the serial dependence observed in temporal perception.
Anatomical Structures, Cell Types, and Biomarkers Tables Plus 3D Reference Organs in Support of a Human Reference Atlas
Authors: Börner Katy , Teichmann Sarah A. , Quardokus Ellen M. , Gee James , Browne Kristen , Osumi-Sutherland David , Herr Bruce W. , Bueckle Andreas , Paul Hrishikesh , Haniffa Muzlifah A. , Jardine Laura , Bernard Amy , Ding Song-Lin , Miller Jeremy A. , Lin Shin , Halushka Marc , Boppana Avinash , Longacre Teri A. , Hickey John , Lin Yiing , Valerius M. Todd , He Yongqun , Pryhuber Gloria , Sun Xin , Jorgensen Marda , Radtke Andrea J. , Wasserfall Clive , Ginty Fiona , Ho Jonhan , Sunshine Joel , Beuschel Rebecca T. , Brusko Maigan , Lee Sujin , Malhotra Rajeev , Jain Sanjay , Weber Griffin 
Published: June 2021

1.AbstractThis paper reviews efforts across 16 international consortia to construct human anatomical structures, cell types, and biomarkers (ASCT+B) tables and three-dimensional reference organs in support of a Human Reference Atlas. We detail the ontological descriptions and spatial three-dimensional anatomical representations together with user interfaces that support the registration and exploration of human tissue data. Four use cases are presented to demonstrate the utility of ASCT+B tables for advancing biomedical research and improving health.
Lessons from 20 years of plant genome sequencing: an unprecedented resource in need of more diverse representation
Authors: Marks Rose A. , Hotaling Scott , Frandsen Paul B. , VanBuren Robert 
Published: June 2021

AbstractThe field of plant genomics has grown rapidly in the past 20 years, leading to dramatic increases in both the quantity and quality of publicly available genomic resources. With this ever-expanding wealth of genomic data from an increasingly diverse set of taxa, unprecedented potential exists to better understand the genome biology and evolution of plants. Here, we provide a contemporary view of plant genomics, including analyses on the quality of existing plant genome assemblies, the taxonomic distribution of sequenced species, and how national participation has influenced the field’s development. We show that genome quality has increased dramatically in recent years, that substantial taxonomic gaps exist, and that the field has been dominated by affluent nations in the Global North and China, despite a wide geographic distribution of sequenced species. We identify multiple disconnects between the native range of focal species and the national affiliation of the researchers studying the plants, which we argue are rooted in colonialism--both past and present. However, falling sequencing costs paired with widening availability of analytical tools and an increasingly connected scientific community provide key opportunities to improve existing assemblies, fill sampling gaps, and, most importantly, empower a more global plant genomics community.
Phylogenetic context using phylogenetic outlines
Authors: Bagci Caner , Bryant David , Cetinkaya Banu , Huson Daniel H. 
Published: June 2021

AbstractMicrobial studies typically involve the sequencing and assembly of draft genomes for individual microbes or whole microbiomes. Given a draft genome, one first task is to determine its phylogenetic context, that is, to place it relative to the set of related reference genomes. We provide a new interactive graphical tool that addresses this task using Mash sketches to compare against all bacterial and archaeal representative genomes in the GTDB taxonomy, all within the framework of SplitsTree5. The phylogenetic context of the query sequences is then displayed as a phylogenetic outline, a new type of phylogenetic network that is more general that a phylogenetic tree, but significantly less complex than other types of phylogenetic networks. We propose to use such networks, rather than trees, to represent phylogenetic context, because they can express uncertainty in the placement of taxa, whereas a tree must always commit to a specific branching pattern. We illustrate the new method using a number of draft genomes of different assembly quality.
Cryo-EM structures of human RNA polymerase I
Authors: Misiaszek Agata D. , Girbig Mathias , Grötsch Helga , Baudin Florence , Lafita Aleix , Murciano Brice , Müller Christoph W. 
Published: June 2021

AbstractRNA polymerase I (Pol I) specifically synthesizes ribosomal RNA. Pol I upregulation is linked to cancer, while mutations in the Pol I machinery lead to developmental disorders. Here, we report the cryo-EM structure of elongating human Pol I at 2.7 Å resolution. In the exit tunnel, we observe a double-stranded RNA helix that may support Pol I processivity. Our structure confirms that human Pol I consists of 13 subunits with only one subunit forming the Pol I stalk. Additionally, the structure of human Pol I in complex with the initiation factor RRN3 at 3.1 Å resolution reveals stalk flipping upon RRN3 binding. We also observe an inactivated state of human Pol I bound to an open DNA scaffold at 3.3 Å resolution. Lastly, the high-resolution structure of human Pol I allows mapping of disease-related mutations that can aid understanding of disease etiology.
EnTrance: Exploration of Entropy Scaling Ball Cover Search in Protein Sequences
Authors: Kim Yoonjin , Guo Zhen , Robertson Jeffrey A. , Reidys Benjamin , Zhang Ziyan , Heath Lenwood S. 
Published: June 2021

AbstractBiological sequence alignment using computational power has received increasing attention as technology develops. It is important to predict if a novel DNA sequence is potentially dangerous by determining its taxonomic identity and functional characteristics through sequence identification. This task can be facilitated by the rapidly increasing amounts of biological data in DNA and protein databases thanks to the corresponding increase in computational and storage costs. Unfortunately, the growth in biological databases has caused difficulty in exploiting this information. EnTrance presents an approach that can expedite the analysis of this large database by employing entropy scaling. This allows scaling with the amount of entropy in the database instead of scaling with the absolute size of the database. Since DNA and protein sequences are biologically meaningful, the space of biological sequences demonstrates the structure exploited by entropy scaling. As biological sequence databases grow, taking advantage of this structure can be extremely beneficial for reducing query times. EnTrance, the entropy scaling search algorithm introduced here, accelerates the biological sequence search exemplified by tools such as BLAST. EnTrance does this by utilizing a two step search approach. In this fashion, EnTrance quickly reduces the number of potential matches before more exhaustively searching the remaining sequences. Tests of EnTrance show that this approach can lead to improved query times. However, constructing the required entropy scaling indices beforehand can be challenging. To improve performance, EnTrance investigates several ideas for accelerating index build time that supports entropy scaling searches. In particular, EnTrance makes full use of the concurrency features of Go language greatly reducing the index build time. Our results identify key tradeoffs and demonstrate that there is potential in using these techniques for sequence similarity searches. Finally, EnTrance returns more matches and higher percentage identity matches when compared with existing tools.
Functional organization of frontoparietal cortex in the marmoset investigated with awake resting-state fMRI
Authors: Hori Yuki , Cléry Justine C. , Schaeffer David J. , Menon Ravi S. , Everling Stefan 
Published: June 2021

AbstractFrontoparietal networks contribute to complex cognitive functions in humans and macaques such as working memory, attention, task-switching, response suppression, grasping, reaching, and eye movement control. However, little is known about the organization of frontoparietal networks in the New World common marmoset monkey (Callithrix jacchus) which is now widely recognized as a powerful nonhuman primate experimental animal. In this study, we employed hierarchical clustering of interareal BOLD signals to investigate the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. We found that the posterior part of the lateral frontal cortex (premotor regions) was functionally connected to the anterior parietal areas while more anterior frontal regions (frontal eye field (FEF)) were connected to more posterior parietal areas (the area around lateral intraparietal area (LIP)). These overarching patterns of inter-areal organization are consistent with a recent macaque study. These findings demonstrate parallel frontoparietal processing streams in marmosets and support the functional homologies of FEF-LIP and premotor-anterior parietal pathways between marmoset and macaque.Significant StatementFrontoparietal networks contribute to many cognitive functions in humans and macaques, but little is known about the organization of frontoparietal networks in the New World common marmoset monkey. Here, we investigated the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. These frontoparietal connection showed overarching pattern of interareal organization consistent with Old world monkeys. These findings demonstrate parallel frontoparietal processing streams in marmosets.
Genome characterization of ‘Candidatus Phytoplasma meliae’ (isolate ChTYXIII)
Authors: Fernández Franco Daniel , Conci Luis Rogelio 
Published: June 2021

Abstract‘Candidatus Phytoplasma meliae’ (subgroups 16SrXIII-G and XIII-C) has been reported in association to chinaberry yellowing disease in Argentina, Bolivia and Paraguay. In Argentina, this disease constitutes a major phytosanitary problem for chinaberry forestry production. To date, no genome information of this phytoplasma and others from 16SrXIII-group has been published, hindered its characterization at genomic level. Here we analyze the draft genome of ‘Candidatus Phytoplasma meliae’ strain ChTYXIII obtained from a chinaberry-infected plant using a metagenomics approach. The draft assembly consists of twenty-one contigs with a total length of 751.949 bp. The annotation contains 669 CDSs, 34tRNA and one set of rRNA operons. Metabolic pathways analysis indicated that the ChTYXIII contains the complete core genes for glycolysis and functional sec system for translocation of proteins. The phylogenetic relationships inferred 132 single copy genes (orthologues core) analysis revealed that ‘Ca. P. meliae’ constitutes a clade closely related to the ‘Ca. australiense’ and ‘Ca. P. solani’. Thirty-one putative effectors were identified, among which a homologue to SAP11 was found and others that have only been described in this pathogen. This work provides relevant genomic information for ‘Ca. P. meliae’ and constitutes the first genome described for the group 16SrXIII (MPV).
Genomic evidence for a chemical link between redox conditions and microbial community composition
Authors: Dick Jeffrey M. , Tan Jingqiang 
Published: June 2021

AbstractEnvironmental influences on community structure are often assessed through multivariate analyses in order to relate microbial abundances to separately measured physicochemical variables. However, genes and proteins are themselves chemical entities; in combination with genome databases, differences in microbial abundances directly encode for chemical variability. We predicted that the carbon oxidation state of inferred community proteomes, obtained by combining taxonomic abundances from published 16S rRNA gene sequencing datasets with predicted microbial proteomes from the NCBI Reference Sequence (RefSeq) database, would reflect environmental oxidation-reduction conditions in various natural and engineered settings including shale gas wells. Our analysis confirms the geobiochemical predictions for environmental redox gradients within and between hydrothermal systems and stratified lakes and marine environments. Where they are present, a common set of taxonomic groups (Gamma- and Deltaproteobacteria and Clostridia) act as drivers of the community-level differences in oxidation state, whereas Flavobacteria most often oppose the overall changes. The geobiochemical signal is largest for the steep redox gradients associated with hydrothermal systems and between surface water and produced fluids from shale gas wells, demonstrating the ability to determine the magnitude of redox effects on microbial communities from 16S sequencing alone.