bluuebunny/crossref_metadata_2025_split huggingface dataset:
CoREST has a conserved role in facilitating SPR-5/LSD1 maternal reprogramming of histone methylation
Authors: Carpenter Brandon S. , Scott Alyssa , Goldin Robert , Chavez Sindy R. , Myrick Dexter A. , Curlee Marcus , Schmeichel Karen , Katz David J. 
Published: May 2021

ABSTRACTMaternal reprogramming of histone methylation is critical for reestablishing totipotency in the zygote, but how histone modifying enzymes are regulated during maternal reprogramming is not well characterized. To address this gap, we asked whether maternal reprogramming by the H3K4me1/2 demethylase SPR-5/LSD1/KDM1A, is regulated by the co-repressor protein, SPR-1/CoREST in C. elegans and mice. In C. elegans, SPR-5 functions as part of a reprogramming switch together with the H3K9 methyltransferase MET-2. By examining germline development, fertility and gene expression in double mutants between spr-1 and met-2, we find that spr-1 mutants are partially compromised for spr-5; met-2 reprogramming. In mice, we generated a separation of function Lsd1 M448V point mutation that compromises CoREST binding, but only slightly affects LSD1 demethylase activity. When maternal LSD1 in the oocyte is derived exclusively from this allele, the progeny phenocopy the increased perinatal lethality that we previously observed when LSD1 was reduced maternally. Together, these data are consistent with CoREST having a conserved function in facilitating maternal LSD1 epigenetic reprogramming.
In mice and humans, the brain’s blood vessels mature postnatally to acquire barrier and contractile properties
Authors: Slaoui Leila , Gilbert Alice , Federici Laetitia , Rancillac Armelle , Gelot Antoinette , Favier Maryline , Robil Noémie , Letort Gaëlle , Dias Karine , Jourdren Laurent , Mailly Philippe , Auvity Sylvain , Cisternino Salvatore , Cohen-Salmon Martine , Boulay Anne-Cécile 
Published: May 2021

AbstractThe brain dense vascular network is essential for distributing oxygen and nutrients to neural cells. The network develops during embryogenesis and leads to the formation of the endothelial blood-brain barrier (BBB). This barrier is surrounded by mural cells (pericytes and vascular smooth muscle cells (VSMCs)) and fibroblasts. Here, we compared the molecular and functional properties of brain vascular cells on postnatal day (P)5 vs. P15, via a transcriptomic analysis of purified mouse cortical microvessels (MVs) and the identification of vascular-cell-type-specific or -preferentially expressed transcripts. We found that endothelial cells (ECs), VSMCs and fibroblasts follow specific molecular maturation programs over this time period. In particular, ECs acquire P-glycoprotein (P-gP)-mediated efflux capacities. The arterial VSMC network expands, acquires contractile proteins (such as smooth muscle actin (SMA) and myosin heavy chain 11 (Myh11)) and becomes contractile. We also analyzed samples of human brain cortex from the early prenatal stage through to adulthood: the expression of endothelial P-gP increased at birth and Myh11 in VSMCs acts as a developmental switch (as in the mouse) at birth and up to the age of 2 of 5 years. Thus, in both mice and humans, the early postnatal phase is a critical period during which the essential properties of cerebral blood vessels (i.e. the endothelial efflux of xenobiotics and other molecules, and the VSMC contractility required for vessel tone and brain perfusion) are acquired and mature.
Runaway evolution from male-male competition
Authors: Moore Allen J. , McGlothlin Joel W. , Wolf Jason B. 
Published: May 2021

AbstractWondrously elaborate weapons and displays that appear to be counter to ecological optima are widespread features of male contests for mates across the animal kingdom. To understand how such diverse traits evolve, here we develop a quantitative genetic model of sexual selection for a male signaling trait that mediates aggression in male-male contests and show that an honest indicator of aggression can generate selection on itself by altering the social environment. This can cause selection to accelerate as the trait is elaborated, leading to runaway evolution. Thus, an evolving source of selection provided by the social environment is the fundamental unifying feature of runaway sexual selection driven by either male-male competition or female mate choice. However, a key difference is that runaway driven by male-male competition requires signal honesty. Our model identifies simple conditions that provide clear, testable predictions for empirical studies using standard quantitative genetic methods.
Retention dependences support highly confident identification of lipid species in human plasma by reversed-phase UHPLC/MS
Authors: Vaňková Zuzana , Peterka Ondřej , Chocholoušková Michaela , Wolrab Denise , Jirásko Robert , Holčapek Michal 
Published: May 2021

AbstractReversed-phase ultrahigh-performance liquid chromatography q mass spectrometry (RP-UHPLC/MS) method was developed with the aim to unambiguously identify a large number of lipid species from multiple lipid classes in human plasma. The optimized RP-UHPLC/MS method employed the C18 column with sub-2 μm particles with the total run time of 25 min. The chromatographic resolution was investigated with 42 standards from 18 lipid classes. The UHPLC system was coupled to high-resolution quadrupole – time-of-flight (QTOF) mass analyzer using electrospray ionization (ESI) measuring full scan and tandem mass spectra (MS/MS) in positive- and negative-ion modes with high mass accuracy. Our identification approach was based onm/zvalues measured with mass accuracy within 5 ppm tolerance in the full scan mode, characteristic fragment ions in MS/MS, and regularity in chromatographic retention dependences for individual lipid species, which provides the highest level of confidence for reported identifications of lipid species including regioisomeric and other isobaric forms. The graphs of dependences of retention times on the carbon number or on the number of double bond(s) in fatty acyl chains were constructed to support the identification of lipid species in homologous lipid series. Our list of identified lipid species is also compared with previous publications investigating human blood samples by various MS based approaches. In total, we have reported more than 500 lipid species representing 26 polar and nonpolar lipid classes detected in NIST Standard reference material 1950 human plasma.
DiversityScanner: Robotic discovery of small invertebrates with machine learning methods
Authors: Wührl Lorenz , Pylatiuk Christian , Giersch Matthias , Lapp Florian , von Rintelen Thomas , Balke Michael , Schmidt Stefan , Cerretti Pierfilippo , Meier Rudolf 
Published: May 2021

ABSTRACTInvertebrate biodiversity remains poorly explored although it comprises much of the terrestrial animal biomass, more than 90% of the species-level diversity and supplies many ecosystem services. The main obstacle is specimen- and species-rich samples. Traditional sorting techniques require manual handling and are slow while molecular techniques based on metabarcoding struggle with obtaining reliable abundance information. Here we present a fully automated sorting robot, which detects each specimen, images and measures it before moving it from a mixed invertebrate sample to the well of a 96-well microplate in preparation for DNA barcoding. The images are then used by a newly trained convolutional neural network (CNN) to assign the specimens to 14 particularly common, usually family-level “classes” of insects in Malaise trap samples and an “other-class” (N=15). The average assignment precision for the classes is 91.4% (75-100%). In order to obtain biomass information, the specimen images are also used to measure specimen length and estimate body volume. We outline how the DiversityScanner robot can be a key component for tackling and monitoring invertebrate diversity. The robot generates large numbers of images that become training sets for CNNs once the images are labelled with identifications based on DNA barcodes. In addition, the robot allows for taxon-specific subsampling of large invertebrate samples by only removing the specimens that belong to one of the 14 classes. We conclude that a combination of automation, machine learning, and DNA barcoding has the potential to tackle invertebrate diversity at an unprecedented scale.
Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress
Authors: Fu Yong , Brown Kevin M. , Jones Nathaniel G. , Moreno Silvia N. J. , Sibley L. David 
Published: May 2021

AbstractToxoplasma gondiihas evolved different developmental stages for disseminating during acute infection (i.e. tachyzoites) and for establishing chronic infection (i.e. bradyzoites). Calcium ion (Ca2+) signaling tightly regulates the lytic cycle of tachyzoites by controlling microneme secretion and motility to drive egress and cell invasion. However, the roles of Ca2+signaling pathways in bradyzoites remain largely unexplored. Here we show that Ca2+responses are highly restricted in bradyzoites and that they fail to egress in response to agonists. Development of dual-reporter parasites revealed dampened calcium responses and minimal microneme secretion by bradyzoites induced in vitro or harvested from infected mice and tested ex vivo. Ratiometric Ca2+imaging demonstrated lower Ca2+basal levels, reduced magnitude, and slower Ca2+kinetics in bradyzoites compared with tachyzoites stimulated with agonists. Diminished responses in bradyzoites were associated with down-regulation of calcium ATPases involved in intracellular Ca2+storage in the endoplasmic reticulum (ER) and acidocalcisomes. Once liberated from cysts by trypsin digestion, bradyzoites incubated in glucose plus calcium rapidly restored their intracellular Ca2+and ATP stores leading to enhanced gliding. Collectively, our findings indicate that intracellular bradyzoites exhibit dampened Ca2+signaling and lower energy levels that restrict egress, and yet upon release they rapidly respond to changes in the environment to regain motility.
Spatiotemporal context modulates encoding and retrieval of overlapping events
Authors: Smith Devyn E. , Moore Isabelle L. , Long Nicole M. 
Published: May 2021

AbstractOverlap between events can lead to interference due to a tradeoff between encoding the present event and retrieving the past event. Temporal context information – ‘when’ something occurred, a defining feature of episodic memory – can cue retrieval of a past event. However, the influence of temporal overlap, or proximity in time, on the mechanisms of interference are unclear. Here, by identifying brain states using scalp electroencephalography (EEG) from male and female human subjects, we show the extent to which temporal overlap promotes interference and induces retrieval. In this experiment, subjects were explicitly directed to either encode the present event or retrieve a past, overlapping event while perceptual input was held constant. We find that the degree of temporal overlap between events leads to selective interference. Specifically, greater temporal overlap between two events leads to impaired memory for the past event selectively when the top-down goal is to encode the present event. Using pattern classification analyses to measure neural evidence for a retrieval state, we find that greater temporal overlap leads to automatic retrieval of a past event, independent of top-down goals. Critically, the retrieval evidence we observe likely reflects a general retrieval mode, rather than retrieval success or effort. Collectively, our findings provide insight into the role of temporal overlap on interference and memory formation.
Structure Activity Relationship of USP5 Allosteric Inhibitors
Authors: Mann Mandeep K. , Zepeda-Velázquez Carlos A. , Alvarez Hector G. , Dong Aiping , Kiyota Taira , Aman Ahmed , Arrowsmith Cheryl H. , Al-Awar Rima , Harding Rachel J. , Schapira Matthieu 
Published: May 2021

ABSTRACTUSP5 is a deubiquitinase that has been implicated in a range of diseases, including cancer, but no USP5-targeting chemical probe has been reported to date. Here, we present the progression of a chemical series that occupies the C-terminal ubiquitin-binding site of a poorly characterized zinc-finger ubiquitin binding domain (ZnF-UBD) of USP5 and allosterically inhibits the catalytic activity of the enzyme. Systematic exploration of the structure-activity relationship, complemented with crystallographic characterization of the ZnF-UBD bound to multiple ligands, led to the identification of 64, which binds to the USP5 ZnF-UBD with a KD of 2.8 µM. 64 is selective over the structurally similar ZnF-UBD domain of HDAC6 and inhibits USP5 catalytic activity in vitro with an IC50 of 26 µM. This study provides a chemical and structural framework for the discovery of a chemical probe to delineate USP5 function in cells.
Table of Contents Graphic
Feral and managed honey bees,Apis mellifera(Hymenoptera: Apidae), in southern California have similar levels of viral pathogens
Authors: Geffre Amy , Travis Dillon , Kohn Joshua , Nieh James 
Published: May 2021

AbstractBees provide critical pollination services but are threatened by multiple stressors, including viral pathogens. Most studies of pollinator health focus on managed honey bees (Apis mellifera Linnaeus) (MHB) or native bee species, but a third player, the feral honey bee (FHB), requires further study. Spillover and spillback of viral pathogens between these managed, feral, and native bees is generating increasing interest. In this case study, we provide evidence suggesting that FHB colonies play an important role in viral pathogen dynamics of southern California pollinator communities because they act as reservoirs, of viral pathogens such as acute bee paralysis virus (ABPV), black queen cell virus (BQCV), and deformed wing virus (DWV). Surprisingly, even though FHB are not treated for diseases or parasites, they harbor similar pathogen loads to MHB, which are usually highly treated, suggesting the need for future studies to determine if FHB resist or are more resilient to viruses.
Glucose-dependent miR-125b is a negative regulator of β-cell function
Authors: Cheung Rebecca , Pizza Grazia , Chabosseau Pauline , Rolando Delphine , Tomas Alejandra , Burgoyne Thomas , Wu Zhiyi , Salowka Anna , Thapa Anusha , Macklin Annabel , Cao Yufei , Nguyen-Tu Marie-Sophie , Dickerson Matthew T. , Jacobson David A. , Marchetti Piero , Shapiro James , Piemonti Lorenzo , de Koning Eelco , Leclerc Isabelle , Bouzakri Karim , Sakamoto Kei , Smith David M. , Rutter Guy A. , Martinez-Sanchez Aida 
Published: May 2021

ABSTRACTImpaired pancreatic β-cell function and insulin secretion are hallmarks of type 2 diabetes. MicroRNAs are short non-coding RNAs that silence gene expression, vital for the development and function of β-cells. We have previously shown that β-cell specific deletion of the important energy sensor AMP-activated protein kinase (AMPK) results in increased miR-125b-5p levels. Nevertheless, the function of this miRNA in β-cells is unclear. We hypothesized that miR-125b-5p expression is regulated by glucose and that this miRNA mediates some of the deleterious effects of hyperglycaemia in β-cells. Here we show that islet miR-125b-5p expression is up-regulated by glucose in an AMPK-dependent manner and that short-term miR-125b-5p overexpression impairs glucose stimulated insulin secretion (GSIS) in the mouse insulinoma MIN6 cells and in human islets. An unbiased high-throughput screen in MIN6 cells identified multiple miR-125b-5p targets, including the transporter of lysosomal hydrolases M6pr and the mitochondrial fission regulator Mtfp1. Inactivation of miR-125b-5p in the human β-cell line EndoCβ-H1 shortened mitochondria and enhanced GSIS, whilst mice overexpressing miR-125b-5p selectively in β-cells (MIR125B-Tg) were hyperglycaemic and glucose intolerant. MIR125B-Tg β-cells contained enlarged lysosomal structures and showed reduced insulin content and secretion. Collectively, we identify miR-125b as a glucose-controlled regulator of organelle dynamics that modulates insulin secretion.Graphical abstract
Mobile Footprinting: Linking Individual Distinctiveness in Mobility Patterns to Mood, Sleep, and Brain Functional Connectivity
Authors: Xia Cedric Huchuan , Barnett Ian , Tapera Tinashe M. , Cui Zaixu , Moore Tyler M. , Adebimpe Azeez , Rush-Goebel Sage , Piiwaa Kayla , Murtha Kristin , Linguiti Sophia , Leibenluft Ellen , Brotman Melissa A. , Martin Melissa Lynne , Calkins Monica E. , Roalf David R. , Wolf Daniel H. , Bassett Danielle S. , Lydon-Staley David M. , Baker Justin T. , Ungar Lyle , Satterthwaite Theodore D. 
Published: May 2021

ABSTRACTMapping individual differences in behavior is fundamental to personalized neuroscience. Here, we establish that statistical patterns of smartphone-based mobility features represent unique “footprints” that allow individual identification. Critically, mobility footprints exhibit varying levels of person-specific distinctiveness and are associated with individual differences in affective instability, circadian irregularity, and brain functional connectivity. Together, this work suggests that real-world mobility patterns may provide an individual-specific signature linking brain, behavior, and mood.
The association of human astrovirus with extracellular vesicles facilitates cell infection and protects the virus from neutralizing antibodies
Authors: Carlos Baez-N , Quevedo Iván R. , López Susana , Arias Carlos F. , Iša Pavel 
Published: May 2021

AbstractViral gastroenteritis has a global distribution and represents a high risk for vulnerable population and children under 5 years because of acute diarrhea, fever and dehydration. Human astroviruses (HAstV) have been identified as the third most important cause of viral gastroenteritis in pediatric and immunocompromised patients. Furthermore, HAstV has been reported in biopsies taken from patients with encephalitis, meningitis and acute respiratory infection, yet it is not clear how the virus reaches these organs. In this work we tested the possibility that the released astrovirus particles could be associated with extracellular vesicles. Comparison between vesicles purified from astrovirus- and mock-infected cells showed that infection with HAstV Yuc8 enhances production of vesicles larger than 150 nm. These vesicles contain CD63 and Alix, two markers of vesicular structures. Some of the extracellular virus was found associated with vesicular membranes, and this association facilitates cell infection in the absence of trypsin activation and protects virions from neutralizing antibodies. Our findings suggest a new pathway for HAstV spread and might represent an explanation for the extraintestinal presence of some astrovirus strains.ImportanceAstroviruses are an important cause of diarrhea in children; recently some reports have found these viruses in extra-intestinal organs, including the central nervous system, causing unexpected clinical disease. In this work we found that human astrovirus strain Yuc8 associates with extracellular vesicles, possibly during or after their cell egress. The association with vesicles seems to increase astrovirus infectivity in less susceptible cells, and renders virus particles insensitive to neutralization by antibodies. These data suggest that extracellular vesicles could represent a novel pathway for astrovirus to disseminate outside the gastrointestinal tract.
Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases
Authors: Valli Adrian A. , López Rafael García , Ribaya María , Martínez Francisco Javier , Gómez Diego García , García Beatriz , Gonzalo Irene , de Prádena Alfonso Gonzalez , Pasin Fabio , Montanuy Inmaculada , Rodríguez-Gonzalo Encarnación , García Juan Antonio 
Published: May 2021

AbstractCassava brown streak disease (CBSD), dubbed the “Ebola of plants”, is a serious threat to food security in Africa caused by two viruses of the familyPotyviridae: cassava brown streak virus (CBSV) and Ugandan (U)CBSV. Intriguingly, U/CBSV, along with another member of this family and one secoviridae, are the only known RNA viruses encoding a protein of the Maf/ham1-like family, a group of widespread pyrophosphatase of non-canonical nucleotides (ITPase) expressed by all living organisms. Despite the socio-economic impact of CDSD, the relevance and role of this atypical viral factor has not been yet established. Here, using an infectious cDNA clone and reverse genetics, we demonstrate that UCBSV requires the ITPase activity for infectivity in cassava, but not in the model plantNicotiana benthamiana. HPLC MS/MS experiments showed that, quite likely, this host-specific constraint is due to an unexpected high concentration of non-canonical nucleotides in cassava. Finally, protein analyses and experimental evolution of mutant viruses indicated that keeping a fraction of the yielded UCBSV ITPase covalently bound to the viral RNA-dependent RNA polymerase (RdRP) optimizes viral fitness, and this seems to be a feature shared by the other members of thePotyviridaefamily expressing Maf/ham1-like proteins. All in all, our work (i) reveals that the over-accumulation of non-canonical nucleotides in the host might have a key role in antiviral defense, and (ii) provides the first example of an RdRP-ITPase partnership, reinforcing the idea that RNA viruses are incredibly versatile at adaptation to different host setups.
BleTIES: Annotation of natural genome editing in ciliates using long read sequencing
Authors: Seah Brandon K. B. , Swart Estienne C. 
Published: May 2021

AbstractSummaryCiliates are single-celled eukaryotes that eliminate specific, interspersed DNA sequences (internally eliminated sequences, IESs) from their genomes during development. These are challenging to annotate and assemble because IES-containing sequences are much less abundant in the cell than those without, and IES sequences themselves often contain repetitive and low-complexity sequences. Long read sequencing technologies from Pacific Biosciences and Oxford Nanopore have the potential to reconstruct longer IESs than has been possible with short reads, and also the ability to detect correlations of neighboring element elimination. Here we present BleTIES, a software toolkit for detecting, assembling, and analyzing IESs using mapped long reads.Availability and implementationBleTIES is implemented in Python 3. Source code is available at https://github.com/Swart-lab/bleties (MIT license), and also distributed via Bioconda.ContactContact: kb.seah@tuebingen.mpg.deSupplementary informationBenchmarking of BleTIES with published sequence data.