bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dorsal skull meningeal lymphatic vessels drain blood-solutes after intracerebral hemorrhage
Authors: Virenque Anaïs , Balin Raz , Noe Francesco M. 
Published: March 2021

AbstractDrainage of intraparenchymal hematoma is crucial for the treatment of intracerebral hemorrhage (ICH). We investigated here the possible function of the meningeal lymphatic vessels (mLVs) in ICH resolution. Meningeal lymphatics have been reported to be involved in cerebrospinal fluid drainage, but their role in the drainage and clearance of brain parenchyma has not been characterized in details. Using two preclinical models of ICH, mimicking focal cortical ischemic hemorrhage and subcortical extended hemorrhage, we characterized the dynamics of blood drainage through the dorsal mLVs by two-photon real time imaging in awake mice. After ICH induction, we observe the flow of blood-derived components within the mLVs, suggesting that meningeal lymphatics can play a role in facilitating the drainage of the hemorrhage. We also found that local formation of new mLVs is directly correlated with ICH-related neuroinflammation levels. These findings suggest that meningeal lymphatics could provide a valuable therapeutic target for ICH resolution.SummaryIn vivo awake imaging reveals the direct drainage of extravasated blood-solutes from brain parenchyma into dorsal meningeal lymphatic vessels, following focal or diffuse intracranial hemorrhage
Location, location, location– choice of Voxel-Based Morphometry processing pipeline drives variability in the location of neuroanatomical brain markers
Authors: Zhou Xinqi , Wu Renjing , Zeng Yixu , Qi Ziyu , Ferraro Stefania , Yao Shuxia , Kendrick Keith M. , Becker Benjamin 
Published: March 2021

AbstractFundamental and clinical neuroscience has benefited from the development of automated computational analyses of Magnetic Resonance Imaging (MRI) data, such as Voxel-based Morphometry (VBM). VBM determines regional gray matter variations with high spatial resolution and results are commonly interpreted in a regional-specific manner, for instance with respect to which specific brain regions differ in volume between women and men. In excess of 600 papers using VBM are now published every year and a number of different automated VBM processing pipelines are frequently used in analyses although it remains to be fully and systematically assessed whether they come up with the same answers. Here we have therefore examined variability between four commonly used VBM pipelines in two large brain structural datasets. Spatial similarity, reproducibility and reliability of the processed gray matter brain maps was generally low between pipelines. Examination of sex-differences and age-related changes in gray matter volumes revealed considerable differences between the pipelines in terms of the specific regions identified as well as meta-analytic characterization of their function. In contrast, applying machine learning-based multivariate analyses allowed an accurate prediction of sex or age based on the gray matter maps across pipelines, although prediction accuracy differed strongly between them. Together the findings suggest that the choice of pipeline alone leads to considerable variability in brain structural analyses which poses a serious challenge for reproducibility as well as interpretation.
Genome structure ofBrachionus asplanchnoidis, a Eukaryote with intrapopulation variation in genome size
Authors: Stelzer C.P. , Blommaert J. , Waldvogel A.M. , Pichler M. , Hecox-Lea B. , Mark Welch D.B. 
Published: March 2021

AbstractEukaryotic genomes vary greatly in size due to variation in the proportion of non-coding DNA, a pattern that emerges both in comparisons at a larger taxonomic scale and at the level of individuals within a species. The rotiferBrachionus asplanchnoidisrepresents one of the most extreme cases of intraspecific genome size variation among Eukaryotes, displaying almost 2-fold variation within a geographic population. Here we used a whole-genome sequencing approach to identify the underlying DNA sequence differences by assembling a high-quality reference genome draft for one individual of the population and aligning short-reads of 15 individuals from the same geographic population. We identified large, contiguous copy number variable regions (CNVs), which exhibited significant coverage differences among individuals, and whose coverage overall scaled with genome size. CNVs were mainly composed of tandemly repeated satellite DNA, with only few interspersed genes or other sequences, and were characterized by an elevated GC-content. Judging from their distributions across contigs, some CNVs are fragments of accessory (B-)chromosomes while others resemble large insertions to normal chromosomes. CNV patterns in offspring of two parents with divergent genome size, and CNV patterns in several individuals from an inbred line differing in genome size demonstrated inheritance and accumulation of CNVs across generations. Our study provides unprecedented insights into genome size evolution at microevolutionary time scales and thus paves the way for studying genome size evolution in contemporary populations rather than inferring patterns and processesa posteriorifrom species comparisons.
Inner hair cell dysfunction inKlhl18mutant mice leads to low frequency progressive hearing loss
Authors: Ingham Neil J , Banafshe Navid , Panganiban Clarisse , Crunden Julia L , Chen Jing , Steel Karen P 
Published: March 2021

ABSTRACTAge-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency hearing impairment in two mutant mouse lines, carrying different mutant alleles of theKlhl18gene: a spontaneous missense mutation (Klhl18lowf) and a targeted mutation (Klhl18tm1a(KOMP)Wtsi). Both males and females were studied, and the two mutant lines showed similar phenotypes. Auditory brainstem response (ABR) thresholds (a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window ofKlhl18lowfmutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed thatKlhl18lowfmutant mice had abnormally tapering inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies.Klhl18mutant mice exhibit an uncommon low frequency hearing impairment with physiological features consistent with Auditory Neuropathy Spectrum Disorder (ANSD).SIGNIFICANCE STATEMENTWe describe a novel progressive hearing loss inKlhl18mutant mice that affects the lower frequencies of its’ hearing range. Investigation of two mutant alleles of this gene revealed primary inner hair cell defects affecting the neural output of the cochlea while outer hair cell function appeared normal. The tallest stereocilia of inner hair cells showed an abnormal tapering shape, especially notable in the apical half of the cochlear duct corresponding to the low frequency hearing loss. Our finding of a primary inner hair cell defect associated with raised thresholds for auditory brainstem responses combined with normal outer hair cell function suggests that Klhl18 deficiency and inner hair cell pathology may contribute to Auditory Neuropathy Spectrum Disorder in humans.
Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2-autoreceptor activity
Authors: Lycas Matthew D. , Ejdrup Aske L. , Sørensen Andreas T. , Haahr Nicolai O. , Jørgensen Søren H. , Guthrie Daryl A. , Støier Jonatan F. , Werner Christian , Newman Amy Hauck , Sauer Markus , Herborg Freja , Gether Ulrik 
Published: March 2021

SUMMARYThe nanoscopic organization and regulation of individual molecular components in presynaptic varicosities of neurons releasing modulatory volume neurotransmitters like dopamine (DA) remain largely elusive. Here we show by application of several super-resolution microscopy techniques to cultured neurons and mouse striatal slices, that the dopamine transporter (DAT), a key protein in varicosities of dopaminergic neurons, exists in the membrane in dynamic equilibrium between an inward-facing nanodomain-localized and outward-facing unclustered configuration. The balance between these configurations is inversely regulated by excitatory drive and by DA D2-autoreceptor activation in manner dependent on Ca2+-influx via N-type voltage-gated Ca2+-channels. The DAT nanodomains contain tens of transporters molecules and overlap with nanodomains of PIP2 (phosphatidylinositol-4,5-bisphosphate) but show little overlap with D2-autoreceptor, syntaxin-1 and clathrin nanodomains. Summarized, the data reveal a mechanism for rapid alterations in nanoscopic DAT distribution and show a striking link of this to the conformational state of the transporter.
Endogenous retrovirus rewired the gene regulatory network shared between primordial germ cells and naïve pluripotent cells in hominoids
Authors: Ito Jumpei , Seita Yasunari , Kojima Shohei , Parrish Nicholas F. , Sasaki Kotaro , Sato Kei 
Published: March 2021

AbstractAlthough the gene regulatory network controlling germ cell development is critical for gamete integrity, this network has been substantially diversified during mammalian evolution. Here, we show that several hundred loci of LTR5_Hs, a hominoid-specific endogenous retrovirus (ERV), function as enhancers in both human primordial germ cells (PGCs) and naïve pluripotent cells. PGCs and naïve pluripotent cells exhibit a similar transcriptome signature, and the enhancers derived from LTR5_Hs contribute to establishing such similarity. LTR5_Hs appears to be activated by transcription factors critical in both cell types (KLF4, TFAP2C, NANOG, and CBFA2T2). Comparative transcriptome analysis between humans and macaques suggested that the expression of many genes in PGCs and naïve pluripotent cells has been upregulated by LTR5_Hs insertions in the hominoid lineage. Together, this study suggests that LTR5_Hs insertions have rewired and finetuned the gene regulatory network shared between PGCs and naïve pluripotent cells during hominoid evolution.TeaserA hominoid-specific ERV has rewired the gene regulatory network shared between PGCs and naïve pluripotent cells.
Mutations in a barley cytochrome P450 gene enhances pathogen induced programmed cell death and cutin layer instability
Authors: Ameen G. , Solanki S. , Sager-Bittara L. , Richards J. , Tamang P. , Friesen T.L. , Brueggeman R.S. 
Published: March 2021

ABSTRACTDisease lesion mimic mutants (DLMMs) are characterized by spontaneous development of necrotic spots with various phenotypes designated as necrotic (nec) mutants in barley. Thenecmutants were traditionally considered to have aberrant regulation of programmed cell death (PCD) pathways, which have roles in plant immunity and development. Most barleynec3mutants express cream to orange necrotic lesions contrasting them from typical spontaneous DLMMs that develop dark pigmented lesions indicative of serotonin/phenolics deposition. Also, barleynec3mutants grown under sterile conditions did not exhibit necrotic phenotypes until inoculated with adapted pathogens suggesting that they are not typical DLMMs. The F2progeny of a cross betweennec3-γ1 and variety Quest segregated as a single recessive gene post inoculation withBipolaris sorokiniana, the causal agent of the disease spot blotch.Nec3was genetically delimited to 0.14 cM representing 16.5 megabases of physical sequence containing 149 annotated high confidence genes. RNAseq and comparative analysis of wild type and five independentnec3mutants identified a single candidate cytochrome P450 gene (HORVU.MOREX.r2.6HG0460850) that was validated asnec3by independent mutations that result in predicted nonfunctional proteins. Histology studies determined thatnec3mutants had an unstable cutin layer that disrupted normalBipolaris sorokinianagerm tube development.AUTHOR SUMMARYAt the site of pathogen infection, plant defense mechanisms rely on controlled programmed cell death (PCD) to sequester biotrophic pathogens that require living cells to extract nutrient from the host. However, these defense mechanisms are hijacked by necrotrophic plant pathogens that purposefully induce PCD mechanism to feed from the dead cells facilitating further disease development. Thus, understanding PCD responses is important for resistance to both classes of pathogens. We characterized five independent disease lesion mimic mutants of barley designated necrotic 3 (nec3) that show aberrant regulation of PCD responses upon pathogen challenge. A cytochrome P450 gene was identified asNec3encoding a Tryptamine 5-Hydroxylase that functions as a terminal serotonin biosynthetic enzyme in the Tryptophan pathway of plants. Thenec3mutants have disrupted serotonin biosynthesis resulting in expansive PCD, necrotrophic pathogen susceptibility and cutin layer instability. Thenec3mutants lacking serotonin deposition in pathogen induced necrotic lesions show expansive PCD and disease susceptibility suggesting a role of serotonin to sequester PCD and suppress pathogen colonization. The identification ofNec3will facilitate functional analysis to elucidate the role serotonin plays in the elicitation or suppression of PCD immunity responses to diverse pathogens and effects it has on cutin layer biosynthesis.
Effects of invasion level ofProsopis julifloraon native species diversity and regeneration in Afar region, Northeast Ethiopia
Authors: Shiferaw Wakshum 
Published: March 2021

AbstractThe study aimed to assess (i) the effects ofProsopis juliflorainvasion on the diversity of plant species, and floristic composition at Awash Fentale and the Amibara districts of the Afar region and (ii) the effects ofP. juliflorainvasion on the regeneration potential of native woody species. Sample collection was performed in habitats ofP. juliflorathicket,P. julifloramixed with native species stands, non-invaded woodlands, and open grazing lands. A stratified random sampling technique was used for data collection. Among species of plants, the highest proportion of species, 87 (27.4%), was recorded under non-invaded woodlands, but the lowest proportion of species, 70 (22%), was recorded under open grazing lands. The invasion level ofP. julifloracaused significantly reduced Shannon diversity index. The mean values of Shannon diversity index and species richness underP. julifloramixed with native species (H’=2.22, R=14) and non-invaded woodlands (H’=2.23, R=13) were significantly higher thanP. juliflorathicket (H’=1.96, R=12) and open grazing lands (H’=1.84, R=10). In this study, 102 trees ha-1native woody species were recorded underP. juliflorathicket, but 1252 trees ha-1native species were recorded under non-invaded woodlands. If the present effects of the invasion ofP. julifloraon native species diversity were to continue coupled with a drier climate, plant diversity of the Afar flora region will be highly affected. As a result the ecosystem services will be under threat. Thus, the participation of all stakeholders and multidisciplinary research approaches should be designed for the management of invaded rangelands to reverse the situation.
Expression and protein sequence analyses of zebrafishimpg2aandimpg2b, two proteoglycans of the interphotoreceptor matrix
Authors: Castellini M.E. , Spagnolli G. , Biasini E. , Casarosa S. , Messina A. 
Published: March 2021

AbstractPhotoreceptor outer segments projecting from the surface of the neural retina toward the retinal pigment epithelium (RPE) are surrounded by a carbohydrate-rich matrix, the interphotoreceptor matrix (IPM) [1,2]. This extracellular compartment is necessary for physiological retinal function. However, specific roles for molecules characterizing the IPM have not been clearly defined [3]. Recent studies have found the presence of nonsense mutations in the interphotoreceptor matrix proteoglycan 2 (IMPG2)gene in patients affected by autosomal recessive Retinitis Pigmentosa (arRP) [4,5] and autosomal dominant and recessive vitelliform macular dystrophy (VMD) [6,7]. The gene encodes for a proteoglycan synthesized by photoreceptors and secreted in the IPM. However, little is known about the function and structure of this protein. We used the teleost zebrafish (D.rerio) as a model to studyIMPG2expression both during development and in adulthood, as its retina is very similar in humans [8]. In zebrafish, there are two IMPG2 proteins, IMPG2a and IMPG2b. We generated a phylogenetic tree based on IMPG2 protein sequence similarity among different vertebrate species, showing a significant similarity despite the evolutionary distance between humans and teleosts. In fact, human IMPG2 andD.rerioIMPG2a and IMPG2b share conserved SEA and EGF-like domains. Homology models of these domains were obtained by using the iTasser server. Finally, expression analyses ofimpg2aandimpg2bduring development and in the adult fish showed expression of both mRNAs starting from 3 days post fertilization (dpf) in the outer nuclear layer of zebrafish retina that continues throughout adulthood. This data lays the groundwork for the generation of novel and most needed animal models for the study of IMPG2-related inherited retinal dystrophies.
Social learning about rewards – how information from others helps to adapt to changing environment
Authors: Winiarski M. , Borowska J. , Wołyniak R. M. , Jędrzejewska-Szmek J. , Kondrakiewicz L. , Mankiewicz L. , Chaturvedi M. , Turzyński K. , Wójcik D.K. , Puścian A. , Knapska E. 
Published: March 2021

AbstractBeing a part of a social structure is key for survival and reproduction. Living with conspecifics boosts evolutionary fitness, by providing essential information about the environment. Nonetheless, studying neural mechanisms of social learning has not yet been established under laboratory conditions. To examine how socially passed information about the reward affects the behavior of individuals we used Eco-HAB, an automated system for tracing voluntary behavior of group-housed mice living under semi-naturalistic conditions. We show that a scent of a rewarded individual has profound effects on the conspecifics’ ability to find the reward in both familiar and novel environments. Importantly, the animals display clear and stable individual differences in social behavior. As a result, socially conveyed information has different effects on individual mice. Further, we show that disrupting neuronal plasticity in the prelimbic cortex with nanoparticles gradually releasing TIMP metallopeptidase inhibitor 1, disrupts animals’ social behavior and results in decreased ability to adapt to environmental changes. The experimental paradigm we developed can be further used to study neuronal mechanisms of social learning.
Local association ofTrypanosoma cruzichronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale
Authors: Khan Archie A. , Langston Harry C. , Costa Fernanda C. , Olmo Francisco , Taylor Martin C. , McCann Conor J. , Kelly John M. , Lewis Michael D. 
Published: March 2021

AbstractGastrointestinal (GI) disease affects a substantial subset of chronic Chagas disease (CD) patients, but the mechanism of pathogenesis is poorly understood. The lack of a robust, predictive animal model of chronicT. cruziinfection that exhibits functional digestive disease has held back research. To address this, we combined GI tracer assays and bioluminescencein vivoinfection imaging systems for diverse parasite strains to discover models exhibiting chronic digestive transit dysfunction. We identified the colon as a specific site of both tissue parasite persistence and delayed transit. Digestive CD mice exhibited significant retention of faeces in both sated and fasted conditions. Histological and immunofluorescence analysis of the enteric nervous system (ENS) revealed a dramatic reduction in the number of neurons and a loss of immunoreactivity of the enteric neural network in the colon. This model therefore recapitulates key clinical manifestations of human digestive CD. We also exploited dual bioluminescent-fluorescent parasites to analyse rare chronic infection foci in the colon at the single cell level, revealing co-localisation with ENS lesions. This indicates that long-termT. cruzi-host interactions in the colon drive pathogenesis and thus chronic disease may be preventable using anti-parasitic chemotherapy.
Identification and characterization of two transmembrane proteins required for virulence of Ustilago maydis
Authors: Weiland Paul , Altegoer Florian 
Published: March 2021

AbstractSmut fungi comprise a large group of biotrophic phytopathogens infecting important crops such as wheat and corn. Through the secretion of effector proteins, the fungus actively suppresses plant immune reactions and modulates its host’s metabolism. Consequently, how soluble effector proteins contribute to virulence is already characterized in a range of phytopathogens. However, membrane-associated virulence factors have been much less studied to date. Here, we investigated six transmembrane (TM) proteins that show elevated gene expression during biotrophic development of the maize pathogen Ustilago maydis. We show that two of the six proteins, named Vmp1 and Vmp2 (virulence-associated membrane protein), are essential for the full virulence of U. maydis. The deletion of the corresponding genes lead to a substantial attenuation in the virulence of U. maydis. Furthermore, both are conserved in various related smuts and contain no domains of known function. Our biochemical analysis clearly shows that Vmp1 and Vmp2 are membrane-associated proteins, potentially localizing to the U. maydis plasma membrane. Mass photometry and light scattering suggest that Vmp1 mainly occurs as a monomer, while Vmp2 is dimeric. Notably, the large and partially unstructured C-terminal domain of Vmp2 is crucial for virulence while not contributing to dimerization. Taken together, we here provide an initial characterization of two membrane proteins as virulence factors of U. maydis.