bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for the absence of low-energy chlorophylls responsible for photoprotection from a primitive cyanobacterial PSI
Authors: Kato Koji , Hamaguchi Tasuku , Nagao Ryo , Kawakami Keisuke , Ueno Yoshifumi , Suzuki Takehiro , Uchida Hiroko , Murakami Akio , Nakajima Yoshiki , Yokono Makio , Akimoto Seiji , Dohmae Naoshi , Yonekura Koji , Shen Jian-Ren 
Published: October 2021

AbstractPhotosystem I (PSI) of photosynthetic organisms is a multi-subunit pigment-protein complex and functions in light harvesting and photochemical charge-separation reactions, followed by reduction of NADP to NADPH required for CO2 fixation. PSI from different photosynthetic organisms has a variety of chlorophylls (Chls), some of which are at lower-energy levels than its reaction center P700, a special pair of Chls, and are called low-energy Chls. However, the site of low-energy Chls is still under debate. Here, we solved a 2.04-Å resolution structure of a PSI trimer by cryo-electron microscopy from a primitive cyanobacterium Gloeobacter violaceus PCC 7421, which has no low-energy Chls. The structure showed absence of some subunits commonly found in other cyanobacteria, confirming the primitive nature of this cyanobacterium. Comparison with the known structures of PSI from other cyanobacteria and eukaryotic organisms reveals that one dimeric and one trimeric Chls are lacking in the Gloeobacter PSI. The dimeric and trimeric Chls are named Low1 and Low2, respectively. Low2 does not exist in some cyanobacterial and eukaryotic PSIs, whereas Low1 is absent only in Gloeobacter. Since Gloeobacter is susceptible to light, this indicates that Low1 serves as a main photoprotection site in most oxyphototrophs, whereas Low2 is involved in either energy transfer or energy quenching in some of the oxyphototrophs. Thus, these findings provide insights into not only the functional significance of low-energy Chls in PSI, but also the evolutionary changes of low-energy Chls responsible for the photoprotection machinery from photosynthetic prokaryotes to eukaryotes.
Optogenetic EB1 inactivation shortens metaphase spindles by disrupting cortical force-producing interactions with astral microtubules
Authors: Dema Alessandro , van Haren Jeffrey , Wittmann Torsten 
Published: October 2021

SUMMARYChromosome segregation is accomplished by the mitotic spindle, a bipolar micromachine built primarily from microtubules. Different microtubule populations contribute to spindle function: Kinetochore microtubules attach and transmit forces to chromosomes, antiparallel interpolar microtubules support spindle structure, and astral microtubules connect spindle poles to the cell cortex [1,2]. In mammalian cells, End Binding (EB) proteins associate with all growing microtubule plus ends throughout the cell cycle and serve as adaptors for a diverse group of +TIPs that control microtubule dynamics and interactions with other intracellular structures [3]. Because binding of many +TIPs to EB1 and thus microtubule-end association is switched off by mitotic phosphorylation [4–6] the mitotic function of EBs remains poorly understood. To analyze how EB1 and associated +TIPs on different spindle microtubule populations contribute to mitotic spindle dynamics, we use a light sensitive EB1 variant, π-EB1, that allows local, acute and reversible inactivation of +TIP association with growing microtubule ends in live cells [7]. We find that acute π-EB1 photoinactivation results in rapid and reversible metaphase spindle shortening and transient relaxation of tension across the central spindle. However, in contrast to interphase, π-EB1 photoinactivation does not inhibit microtubule growth in metaphase, but instead increases astral microtubule length and number. Yet, in the absence of EB1 activity astral microtubules fail to engage the cortical dynein/dynactin machinery and spindle poles move away from regions of π-EB1 photoinactivation. In conclusion, our optogenetic approach reveals mitotic EB1 functions that remain hidden in genetic experiments likely due to compensatory molecular systems regulating vertebrate spindle dynamics.
The perceptual categorization of multidimensional stimuli is hierarchically organized
Authors: Chen Chi , de Hoz Livia 
Published: October 2021

AbstractAs we interact with our surroundings, we encounter the same or similar objects from different perspectives and are compelled to generalize. For example, we recognize dog barks as a distinct class of sound, despite the variety of individual barks. While we have some understanding of how generalization is done along a single stimulus dimension, such as frequency or color, natural stimuli are identifiable by a combination of dimensions. To understand perception, measuring the interaction across stimulus dimensions is essential. For example, when identifying a sound, does our brain focus on a specific dimension or a combination, such as its frequency and duration? Furthermore, does the relative relevance of each dimension reflect its contribution to the natural sensory environment? Using a 2- dimension discrimination task for mice we tested untrained generalization across several pairs of auditory dimensions in a naturalistic and automatized behavioral paradigm. We uncovered a perceptual hierarchy over the tested dimensions that was dominated by the sound’s spectral composition. This hierarchy could reflect the relevance of the different dimensions in natural stimuli and their potentially associated differential shaping of neuronal tuning. Mice could learn to pay more attention to dimensions low in the hierarchy, but this learning was more rigid and did not generalize as flexibly. Stimuli are thus not perceived as a whole but as a combination of their features, each of which weights differently on the dentification of the stimulus according to an established hierarchy.
Odor motion sensing enables complex plume navigation
Authors: Kadakia Nirag , Demir Mahmut , Michaelis Brenden T. , Reidenbach Matthew A. , Clark Damon A. , Emonet Thierry 
Published: October 2021

ABSTRACTStudies dating back a century (Flügge, 1934) have stressed the critical role of the wind as the primary directional cue in odor plume navigation. Here, we show that Drosophila shape their navigational decisions using a second directional cue – the direction of motion of odors – which they detect from the temporal correlations of the odor signal between their two antennae. Using a high-resolution virtual reality paradigm to deliver spatiotemporally complex fictive odors to freely-walking flies, we demonstrate that such odor direction sensing is computationally equivalent to motion detection algorithms underlying motion detection in vision. Simulations and theoretical analysis of turbulent plumes reveal that odor motion contains valuable directional information absent from the airflow; indeed, this information is used by both Drosophila and virtual agents to navigate naturalistic odor environments. The generality of our findings suggests that odor direction sensing is likely used throughout the animal kingdom, and could significantly improve olfactory robot navigation in harsh chemical environments.
Roles of PKCdelta in Photoperiod and Circadian Regulations in Drosophila melanogaster
Authors: Khaira Harjit , Patro Somya , Lee Kwangwon 
Published: October 2021

AbstractMany organisms are known to regulate seasonal behaviors and physiological processes in response to day length changes through photoperiodism. Extreme changes in photoperiods have detrimental effects on human health, which can impair development and serve as the origin of adult diseases. Since the seminal work by Bünning in 1936, there are studies supporting the view that organisms can measure the day length through an endogenous 24-hour cellular circadian clock. However, the mechanisms involved in measuring seasonal or day-length changes are not understood. In the current study, we performed a genome-wide association study (GWAS) on photoperiodism using the Drosophila Genetic Reference Panel. The GWAS identified 4 top candidate genes responsible for photoperiodic regulations. The knockout mutants of the four candidate genes (Protein Kinase C delta (Pkcdelta), Glucuronyltransferase-P (GlcAT-P), Brain-specific homeobox (Bsh), and Diuretic hormone 31 Receptor (Dh31-R1)) were analyzed for their photoperiod and circadian period phenotypes. PKCdelta and GlcAT-P mutants show a significantly different photoperiod response compared to that of the wild type strain, and also had an altered circadian period phenotype. Further molecular characterization revealed two independent mutant alleles of PKCdelta with a defective catalytic domain had distinct photoperiod responses. Taken these data together, we concluded that there is overlap between the circadian clock and photoperiodic regulations in Drosophila, and PKCdelta is a component that is involved in both circadian and photoperiodic regulations. By identifying novel molecular components of photoperiod, the current study provides new insights into the genetic mechanisms of determining the seasonal changes.Author SummaryExtreme changes in photoperiods have detrimental effects on human health, which can impair development and serve as the origin of adult diseases. The molecular and genetic mechanisms of how an organism interprets and adapts to seasonal environmental changes are not well understood. Drosophila Genetic Reference Panel (DGRP) is a community resource of 205 inbred lines created for studying population genomics and quantitative traits. Using DGRP we performed a genome-wide association study (GWAS) to find potential photoperiod candidate genes. PKCdelta, a candidate gene from the GWAS study was identified to have both photoperiod and circadian effects. This data supports the view that circadian clock and photoperiodism have a shared regulatory circuit. Our study sheds light onto potential genes that could be further studied to characterize the mechanisms of photoperiodism, and its relationship to the circadian clock.
Variation in the response to malaria in Diversity Outbred mice
Authors: Gupta Avni S. , Chevée Victoria , Kirosingh Adam S. , Davis Nicole M. , Schneider David S. 
Published: October 2021

AbstractWe infected Diversity Outbred mice with Plasmodium chabaudi to better understand how the host response to infection can vary and to try to identify genetic loci responsible for this variation. We identified two loci correlating with binary traits: one on chromosome two was linked to undetectable parasite loads and another on chromosome ten which was linked to death. Though we tested many variable traits, none of those reached statistical significance using the 489 mice we tested.
Drivers and Determinants of Strain Dynamics Following Faecal Microbiota Transplantation
Authors: Schmidt Thomas SB , Li Simone S , Maistrenko Oleksandr M , Akanni Wasiu , Coelho Luis Pedro , Dolai Sibasish , Fullam Anthony , Glazek Anna M , Hercog Rajna , Herrema Hilde , Jung Ferris , Kandels Stefanie , Orakov Askarbek , Van Rossum Thea , Benes Vladimir , Borody Thomas J , de Vos Willem M , Ponsioen Cyriel Y , Nieuwdorp Max , Bork Peer 
Published: October 2021

AbstractFaecal microbiota transplantation (FMT) is an efficacious therapeutic intervention, but its clinical mode of action and underlying microbiome dynamics remain poorly understood. Here, we analysed the metagenomes associated with 142 FMTs, in a time series-based meta-study across five disease indications. We quantified strain-level dynamics of 1,089 microbial species based on their pangenome, complemented with 47,548 newly constructed metagenome-assembled genomes. Using subsets of procedural-, host- and microbiome-based variables, LASSO-regularised regression models accurately predicted the colonisation and resilience of donor and recipient microbes, as well as turnover of individual species. Linking this to putative ecological mechanisms, we found these sets of variables to be informative of the underlying processes that shape the post-FMT gut microbiome. Recipient factors and complementarity of donor and recipient microbiomes, encompassing entire communities to individual strains, were the main determinants of individual strain population dynamics, and mostly independent of clinical outcomes. Recipient community state and the degree of residual strain depletion provided a neutral baseline for donor strain colonisation success, in addition to inhibitive priority effects between species and conspecific strains, as well as putatively adaptive processes. Our results suggest promising tunable parameters to enhance donor flora colonisation or recipient flora displacement in clinical practice, towards the development of more targeted and personalised therapies.
The unforeseen intracellular lifestyle of Enterococcus faecalis in hepatocytes
Authors: Nunez Natalia , Derré-Bobillot Aurélie , Lakisic Goran , Lecomte Alexandre , Mercier-Nomé Françoise , Cassard Anne-Marie , Bierne Hélène , Serror Pascale , Archambaud Cristel 
Published: October 2021

AbstractEnterococcus faecalis is a bacterial species present at a sub-dominant level in the human gut microbiota. This commensal turns into an opportunistic pathogen under specific conditions involving dysbiosis and host immune deficiency. E. faecalis is also the only intestinal pathobiont identified to date as contributing to liver damage in alcoholic liver disease. We have previously observed that E. faecalis is internalized in hepatocytes. Here, the survival and fate of E. faecalis was examined in hepatocytes, the main epithelial cell type in the liver. Although referred to as an extracellular pathogen, we demonstrate that E. faecalis is able to survive and divide in hepatocytes, and form intracellular clusters in two distinct hepatocyte cell lines, in primary mouse hepatocytes, as well as in vivo. This novel process extends to kidney cells. Unravelling the intracellular lifestyle of E. faecalis, our findings contribute to the understanding of pathobiont-driven diseases.
An Evolutionarily Conserved Regulatory Pathway of Muscle Mitochondrial Network Organization
Authors: Katti Prasanna , Ajayi Peter T. , Aponte Angel , Bleck Christopher K.E. , Glancy Brian 
Published: October 2021

AbstractMitochondrial networks provide coordinated energy distribution throughout muscle cells. However, pathways specifying mitochondrial network-type separately from contractile fiber-type remain unclear. Here, we show that natural energetic demands placed onDrosophila melanogastermuscles yield native cell-types among which contractile and mitochondrial network-types are regulated independently. Proteomic analyses of indirect flight, jump, and leg muscles together with muscles misexpressing known fiber-type specification factorsalmidentified transcription factorsH15andcutas potential mitochondrial network regulators. We demonstrateH15operates downstream ofsalmregulating flight muscle contractile and mitochondrial network-type. Conversely,H15regulates mitochondrial network configuration but not contractile type in jump and leg muscles. Further, we find thatcutregulatessalmexpression in flight muscles and mitochondrial network configuration in leg muscles. These data indicate cell type-specific regulation of muscle mitochondrial network organization separately from contractile type, mitochondrial content, and mitochondrial size through an evolutionarily conserved pathway involvingcut, salm, andH15.
Structures of core eukaryotic protein complexes
Authors: Humphreys Ian R. , Pei Jimin , Baek Minkyung , Krishnakumar Aditya , Anishchenko Ivan , Ovchinnikov Sergey , Zhang Jing , Ness Travis J. , Banjade Sudeep , Bagde Saket , Stancheva Viktoriya G. , Li Xiao-Han , Liu Kaixian , Zheng Zhi , Barrero Daniel J. , Roy Upasana , Fernández Israel S. , Szakal Barnabas , Branzei Dana , Greene Eric C. , Biggins Sue , Keeney Scott , Miller Elizabeth A. , Fromme J. Christopher , Hendrickson Tamara L. , Cong Qian , Baker David 
Published: October 2021

AbstractProtein-protein interactions play critical roles in biology, but despite decades of effort, the structures of many eukaryotic protein complexes are unknown, and there are likely many interactions that have not yet been identified. Here, we take advantage of recent advances in proteome-wide amino acid coevolution analysis and deep-learning-based structure modeling to systematically identify and build accurate models of core eukaryotic protein complexes, as represented within the Saccharomyces cerevisiae proteome. We use a combination of RoseTTAFold and AlphaFold to screen through paired multiple sequence alignments for 8.3 million pairs of S. cerevisiae proteins and build models for strongly predicted protein assemblies with two to five components. Comparison to existing interaction and structural data suggests that these predictions are likely to be quite accurate. We provide structure models spanning almost all key processes in Eukaryotic cells for 104 protein assemblies which have not been previously identified, and 608 which have not been structurally characterized.One-sentence summaryWe take advantage of recent advances in proteome-wide amino acid coevolution analysis and deep-learning-based structure modeling to systematically identify and build accurate models of core eukaryotic protein complexes.
Combined Lineage Tracing and scRNA-seq Reveals Unexpected First Heart Field Predominance of Human iPSC Differentiation
Authors: Galdos Francisco X. , Lee Carissa , Lee Soah , Goodyer William , Paige Sharon , Escobar Gabriela V. , Darsha Adrija , Beck Aimee , Xu Sidra , Bak Rasmus O. , Porteus Matthew , Wu Sean M. 
Published: October 2021

ABSTRACTDuring mammalian development, the left and right ventricles arise from early populations of cardiac progenitors known as the first and second heart fields, respectively. While these populations have been extensively studied in non-human model systems, their identification and studyin vivohuman tissues have been limited due to the ethical and technical limitations of accessing gastrulation stage human embryos. Human induced pluripotent stem cells (hiPSCs) present an exciting alternative for modeling early human embryogenesis due to their well-established ability to differentiate into all embryonic germ layers. Here, we describe the development of a TBX5/MYL2 lineage tracing reporter system that allows for the identification of FHF-progenitors and their descendants including left ventricular cardiomyocytes.Furthermore, using single cell RNA sequencing (scRNA-seq) with oligonucleotide-based sample multiplexing, we extensively profiled differentiating hiPSCs across 12 timepoints in two independent iPSC lines. Surprisingly, our reporter system and scRNA-seq analysis revealed a predominance of FHF differentiation using the small molecule Wnt-based 2D differentiation protocol. We compared this data with existing murine and 3D cardiac organoid scRNA-seq data and confirmed the dominance of left ventricular cardiomyocytes (>90%) in our hiPSC-derived progeny. Together, our work provides the scientific community with a powerful new genetic lineage tracing approach as well as a single cell transcriptomic atlas of hiPSCs undergoing cardiac differentiation.
Revisiting colorectal cancer tumorigenesis with spatially-resolved gene expression profiling
Authors: Roelands Jessica , van der Ploeg Manon , Dang Hao , Boonstra Jurjen J. , Hardwick James C.H. , Hawinkels Lukas J.A.C. , Morreau Hans , de Miranda Noel F.C.C. 
Published: October 2021

AbstractEarly detection and treatment are paramount to the clinical outcome of patients with colorectal cancer (CRC). Deciphering the dynamic interactions that occur between epithelial cells and stromal cells during tumorigenesis requires in-depth analyses of early-stage CRC lesions in spatial context. Here we employed spatially-resolved gene expression profiling to dissect molecular processes that associate with malignant transformation in CRC. We provide the transcriptional landscapes of colorectal cancer tumorigenesis from healthy mucosa, through different degrees of dysplasia, to cancer. The complementary examination of epithelial and stromal fractions allowed us to define whether specific oncogenic processes involved cancer cells, stromal cells, or the tumor microenvironment as a whole. We identified several genes that were consistently deregulated during CRC onset that could serve as clinical biomarkers for early-stage CRC. Furthermore, we uncovered an essential role for the innate immune system during CRC tumorigenesis.Abstract Figure
A nuclear function for an oncogenic microRNA as a modulator of snRNA and splicing
Authors: Fatimy Rachid EI , Zhang Yanhong , Deforzh Evgeny , Ramadas Mahalakshmi , Saravanan Harini , Wei Zhiyun , Rabinovsky Rosalia , Teplyuk Nadiya M. , Uhlmann Erik J. , Krichevsky Anna M. 
Published: October 2021

ABSTRACTmiRNAs are regulatory transcripts established as repressors of mRNA stability and translation. Here we demonstrate that a key onco-miRNA, miR-10b, binds to U6 snRNA, a core component of the spliceosomal machinery. We provide evidence of direct binding between miR-10b and U6, in situ visualizations of miR-10b and U6 co-localization in glioma cells and patient-derived tumor tissues, and biochemical co-isolation of miR-10b with the components of the spliceosome. We further demonstrate that miR-10b modulates U6 N-6-adenosine methylation and pseudouridylation, U6 binding to splicing factors SART3 and PRPF8, and regulates U6 stability, conformation, and levels. These effects on U6 result in splicing alterations, illustrated by the altered ratio of the isoforms of a small GTPase CDC42, reduced overall CDC42 levels, and downstream CDC42 -mediated effects on cell viability. We, therefore, present an unexpected intersection of the miRNA and splicing machineries and a new nuclear function for a major cancer-associated miRNA.
arakno - An R Package for Effective Spider Nomenclature, Distribution and Trait Data Retrieval from Online Resources
Authors: Cardoso Pedro , Pekar Stano 
Published: October 2021

AbstractOnline open databases are increasing in number, usefulness, and ease of use. There are currently two main global databases exclusive for spiders, the World Spider Catalogue (WSC) and the World Spider Trait (WST) database. Both are regularly used by thousands of researchers. Computational tools that allow effective processing of large data are now part of the workflow of any researcher and R is becoming ade factostandard for data manipulation, analysis, and presentation. Here we present an R package,arakno, that allows interface with the two databases. Implemented tools include checking species names against nomenclature of the WSC, obtaining and mapping data on distribution of species from both WST and the Global Biodiversity Information Facility (GBIF), and downloading trait data from the WST. A set of tools are also provided to prepare data for further statistical analysis.