bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agrammatism and paragrammatism: a cortical double dissociation revealed by lesion-symptom mapping
Authors: Matchin William , Basilakos Alexandra , Stark Brielle C. , Ouden Dirk-Bart den , Fridriksson Julius , Hickok Gregory 
Published: March 2020

AbstractThe fundamental distinction of grammatical deficits in aphasia, agrammatism and paragrammatism, was made over a century ago. However, the extent to which the agrammatism/paragrammatism distinction exists independently of differences in speech fluency has not clearly been investigated. Despite much research on agrammatism, the lesion correlates of paragrammatism are essentially unknown. Lesion-symptom mapping was used to investigate the degree to which the lesion correlates of agrammatism and paragrammatism overlap or dissociate. Four expert raters assessed videos of 53 right-handed patients with aphasia following chronic left hemisphere stroke retelling the Cinderella story. Consensus discussion determined each subject’s classification with respect to grammatical deficits as Agrammatic, Paragrammatic, Both, or No Grammatical Deficit. Each subject’s lesion was manually drawn on a high-resolution MRI and warped to standard space for group analyses. Lesion-symptom mapping analyses were performed in NiiStat including lesion volume as a covariate. Secondary analyses included speech rate (words per minute) as an additional covariate. Region of interest analyses identified a double dissociation between these syndromes: damage to Broca’s area was significantly associated with agrammatism, p = 0.001 (but not paragrammatism, p = 0.930), while damage to the left posterior superior and middle temporal gyri was significantly associated with paragrammatism, p < 0.001 (but not agrammatism, p = 0.873). The same results obtained when regressing out the effect of speech rate, and non-overlapping lesion distributions between the syndromes were confirmed by uncorrected whole brain analyses. Our results support a fundamental distinction between agrammatism and paragrammatism.
The mouse cortico-tectal projectome
Authors: Benavidez Nora L. , Bienkowski Michael S. , Khanjani Neda , Bowman Ian , Fayzullina Marina , Garcia Luis , Gao Lei , Korobkova Laura , Gou Lin , Cotter Kaelan , Becerra Marlene , Aquino Sarvia , Cao Chunru , Foster Nicholas N. , Song Monica Y. , Zhang Bin , Yamashita Seita , Zhu Muye , Lo Darrick , Boesen Tyler , Zingg Brian , Santarelli Anthony , Wickersham Ian R. , Ascoli Giorgio A. , Hintiryan Houri , Dong Hong-Wei 
Published: March 2020

SUMMARYThe superior colliculus (SC) is a midbrain structure that receives diverse and robust cortical inputs to drive a range of cognitive and sensorimotor behaviors. However, it remains unclear how descending cortical inputs arising from higher-order associative areas coordinate with SC sensorimotor networks to influence its outputs. In this study, we constructed a comprehensive map of all cortico-tectal projections and identified four collicular zones with differential cortical inputs: medial (SC.m), centromedial (SC.cm), centrolateral (SC.cl) and lateral (SC.l). Computational analyses revealed that cortico-tectal projections are organized as multiple subnetworks that are consistent with previously identified cortico-cortical and cortico-striatal subnetworks. Furthermore, we delineated the brain-wide input/output organization of each collicular zone and described a subset of their constituent neuronal cell types based on distinct connectional and morphological features. Altogether, this work provides a novel structural foundation for the integrative role of the SC in controlling cognition, orientation, and other sensorimotor behaviors.
Draft Genome Sequence of pyschrotolerantClostridiumsp. M14 Isolated from Spoiled Uncooked Venison
Authors: Palevich Nikola , Palevich Faith P. , Maclean Paul H. , Jauregui Ruy , Altermann Eric , Mills John , Brightwell Gale 
Published: March 2020

ABSTRACTThe non-proteolytic, non-toxigenic and pyschrotolerantClostridiumsp. M14 was isolated from vacuum-packaged refrigerated spoiled venison. This report describes the generation and annotation of the 3.9 Mb draft genome sequence ofClostridiumsp. M14.
Severe and multifaceted systemic immunosuppression caused by experimental cancers of the central nervous system requires release of non-steroid soluble mediators
Authors: Ayasoufi K , Pfaller CK , Evgin L , Khadka RH , Tritz ZP , Goddery EN , Fain CE , Yokanovich LT , Himes BT , Jin F , Zheng J , Schuelke MR , Hansen MJ , Tung W , Pease LR , Vile RG , Johnson AJ 
Published: March 2020

AbstractImmunosuppression of unknown etiology is a hallmark feature of glioblastoma (GBM) and is characterized by decreased CD4 T cell counts and down regulation of MHC class II expression on peripheral blood monocytes in patients. This immunosuppression is a critical barrier to the successful development of immunotherapies for GBM. We recapitulated the immunosuppression observed in GBM patients in the C57BL/6 mouse and investigated the etiology of low CD4 T cell counts. We determined that thymic involution was a hallmark feature of immunosuppression in three distinct models of CNS cancer, including mice harboring GL261 glioma, B16 melanoma, and in a spontaneous model of Diffuse Intrinsic Pontine Glioma (DIPG). In addition to thymic involution, we determined that tumor growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC class II expression on hematopoietic cells, and a modest increase in bone marrow resident CD4 T cells with a naïve phenotype. Using parabiosis we report that thymic involution, declines in peripheral T cell counts, and reduced MHC class II expression levels were mediated through circulating blood-derived factors. Conversely, T cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells bothin vitroandin vivo. Interestingly, the factor responsible for immunosuppression in serum is nonsteroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the aforementioned immunosuppression was not unique to cancer itself, but rather occurs in response to CNS injury. Noncancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that CNS cancers cause multifaceted immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity.Short SummaryCNS cancers and other brain-injuries suppress immunity through release of non-steroid soluble factors that disrupt immune homeostasis and dampen responses of the peripheral immune system.Graphical Abstract
Access to PCNA by Srs2 and Elg1 controls the choice between alternative repair pathways in yeast
Authors: Arbel Matan , Bronstein Alex , Sau Soumitra , Liefshitz Batia , Kupiec Martin 
Published: March 2020

ABSTRACTDuring DNA replication stalling can occur when the replicative DNA polymerases encounter lesions or hard-to replicate regions. Under these circumstances the processivity factor PCNA gets ubiquitylated at lysine 164, inducing the DNA damage tolerance (DDT) mechanisms that can bypass lesions encountered during DNA replication. PCNA can also be SUMOylated at the same residue or at lysine 127. Surprisingly,pol30-K164Rmutants display a higher degree of sensitivity to DNA damaging agents thanpol30-KK127,164RRstrains, unable to modify any of the lysines. Here we show that in addition to trans-lesion synthesis and strand-transfer DTT mechanisms, an alternative repair mechanism (“salvage recombination”) that copies information from the sister chromatid, is repressed by the recruitment of Srs2 to SUMOylated PCNA. Overexpression of Elg1, the PCNA unloader, or of the recombination protein Rad52 allows its activation. We dissect the genetic requirements for this pathway, as well as the interactions between Srs2 and Elg1.
Metabolic disturbances and inflammatory dysfunction predict severity of coronavirus disease 2019 (COVID-19): a retrospective study
Authors: Nie Shuke , Zhao Xueqing , Zhao Kang , Zhang Zhaohui , Zhang Zhentao , Zhang Zhan 
Published: March 2020

AbstractBackgroundThe coronavirus disease 2019 (COVID-19) is spreading worldwide with 16,558 deaths till date. Serum albumin, high-density lipoprotein (HDL-C), and C-reactive protein have been known to be associated with the severity and mortality of community-acquired pneumonia. However, the characteristics and role of metabolic and inflammatory indicators in COVID-19 is unclear.MethodsWe included 97 hospitalized patients with laboratory-confirmed COVID-19. Epidemiological, clinical, and laboratory indices; radiological features; and treatment were analysed. The differences in the clinical and laboratory parameters between mild and severe COVID-19 patients and the role of these indicators in severity prediction of COVID-19 were investigated.ResultsAll were Wuhan residents with contact with confirmed COVID-19 cases. The median age was 39 years (IQR: 30–59). The most common presenting symptoms were fever (58.8%), cough (55.7%), and fatigue (33%). Other features were lymphopenia, impaired fasting glucose, hypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia. Decrease in lymphocyte count, serum total protein, serum albumin, high-density lipoprotein cholesterol (HDL-C), ApoA1, CD3+T%, and CD8+T% were found to be valuable in predicting the transition of COVID-19 from mild to severe illness. Chest computed tomography (CT) images showed that the absorption of bilateral lung lesions synchronized with the recovery of metabolic and inflammatory indicators.ConclusionsHypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia, and decreased ApoA1, CD3+T%, and CD8+T% could predict severity of COVID-19. Lymphocyte count, total serum protein, and HDL-C may be potentially useful for the evaluation of COVID-19.
Home collection of nasal swabs for detection of influenza in the Household Influenza Vaccine Evaluation Study
Authors: Malosh Ryan E. , Petrie Joshua G. , Callear Amy P. , Monto Arnold S. , Martin Emily T. 
Published: March 2020

AbstractBackgroundCommunity based studies of influenza and other respiratory viruses (e.g. SARS-COV-2) require laboratory confirmation of infection. During the current COVID-19 pandemic, social distancing guidelines require alternative data collection in order protect both research staff and participants.Home-collected respiratory specimens are less resource intensive, can be collected earlier after symptom onset, and provide a low-contact means of data collection. A prospective, multi-year, community-based cohort study is an ideal setting to examine the utility of home-collected specimens for identification of influenza.MethodsWe describe the feasibility and reliability of home-collected specimens for the detection of influenza. We collected data and specimens between October 2014 and June 2017 from the Household Influenza Vaccine Evaluation (HIVE) Study. Cohort participants were asked to collect a nasal swab at home upon onset of acute respiratory illness. Research staff also collected nose and throat swab specimens in the study clinic within 7 days of onset. We estimated agreement using Cohen’s kappa and calculated sensitivity and specificity of home-collected compared to staff-collected specimens.ResultsWe tested 336 paired staff- and home-collected respiratory specimens for influenza by RT-PCR; 150 staff-collected specimens were positive for influenza A/H3N2, 23 for influenza A/H1N1, 14 for influenza B/Victoria, and 31 for influenza B/Yamagata. We found moderate agreement between collection methods for influenza A/H3N2 (0.70) and B/Yamagata (0.69) and high agreement for influenza A/H1N1 (0.87) and B/Victoria (0.86). Sensitivity ranged from 78-86% for all influenza types and subtypes. Specificity was high for influenza A/H1N1 and both influenza B lineages with a range from 96-100%, and slightly lower for A/H3N2 infections (88%).ConclusionsCollection of nasal swab specimens at home is both feasible and reliable for identification of influenza virus infections.
Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma
Authors: Roberts Hannah E , Lopopolo Maria , Pagnamenta Alistair T , Sharma Eshita , Parkes Duncan , Lonie Lorne , Freeman Colin , Knight Samantha J L , Lunter Gerton , Dreau Helene , Lockstone Helen , Taylor Jenny C , Schuh Anna , Bowden Rory , Buck David 
Published: March 2020

AbstractRecent advances in throughput and accuracy mean that the Oxford Nanopore Technologies (ONT) PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables genome-wide detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialized joint calling algorithms. We find the comparative performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6Mb deletion and a p.(Arg249Met) mutation involvingTP53are orientedin trans.
MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity
Authors: Lu Ya-Lin , Liu Yangjian , McCoy Matthew J. , Yoo Andrew S. 
Published: March 2020

SummaryNeuron-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), direct cell fate switching of human fibroblasts to neurons when ectopically expressed by repressing anti-neurogenic genes. How these miRNAs function after the onset of the transcriptome switch to a neuronal fate remains unclear. Here, we identified direct targets of miRNAs by Argonaute (AGO) HITS-CLIP as reprogramming cells activate the neuronal program and reveal the role of miR-124 that directly promotes the expression of its target genes associated with neuronal development and function. The mode of miR-124 as a positive regulator is determined by a neuron-enriched RNA-binding protein, ELAVL3, that interacts with AGO and binds target transcripts, whereas the non-neuronal ELAVL1 counterpart fails to elevate the miRNA-target gene expression. Although existing literature indicate that miRNA-ELAVL1 interaction can result in either target gene upregulation or downregulation in a context-dependent manner, we specifically identified neuronal ELAVL3 as the driver for miRNA target gene upregulation in neurons. In primary human neurons, repressing miR-124 and ELAVL3 led to the downregulation of genes involved in neuronal function and process outgrowth, and cellular phenotypes of reduced inward currents and neurite outgrowth. Results from our study support the role of miR-124 promoting neuronal function through positive regulation of its target genes.
Acute social isolation evokes midbrain craving responses similar to hunger
Authors: Tomova Livia , Wang Kimberly L. , Thompson Todd , Matthews Gillian A. , Takahashi Atsushi , Tye Kay M. , Saxe Rebecca 
Published: March 2020

AbstractWhen people are forced to be isolated from one another, do they crave social interactions? To address this question, we used functional magnetic resonance imaging (fMRI) to measure neural responses evoked by food and social cues after participants (n=40) experienced ten hours of mandated fasting or total social isolation. After isolation, people felt lonely and craved social interaction. Midbrain regions showed selective activation to food cues after fasting and to social cues after isolation; these responses were correlated with self-reported craving. By contrast, striatal and cortical regions differentiated between craving food versus social interaction. Across deprivation sessions, we find that deprivation narrows and focuses the brain’s motivational responses to the deprived target. Our results support the intuitive idea that acute isolation causes social craving, similar to the way fasting causes hunger.
Metformin improves cognition of aged mice by promoting cerebral angiogenesis and neurogenesis
Authors: Zhu Xiaoqi , Shen Junyan , Feng Shengyu , Huang Ce , Liu Zhongmin , Sun Yi. Eve. , Liu Hailiang 
Published: March 2020

AbstractThe cerebral microvasculature is essential for preservation of normal cerebral function. Age-related decreases of neurogenesis and cognitive function are accompanied by reduced blood flow and a decline in neural stem cell (NSC) number. Here, we report that metformin administered by tail vein injection enhanced cognition in aged but not young mice in a dose-dependent manner. Further, metformin restored cerebral blood flow and brain vascular density and promoted neurogenic potential of the subependymal zone/subventricular zone both in vivo and in vitro. RNA-Seq result indicated that metformin could enhance glycolysis in blood, with an increase in relative mRNA expression of the enzyme in the glycolysis pathway from hippocampal tissue of metformin-treated mice. Mechanistically, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in the glycolysis pathway, may contribute to angiogenic and neurogenic potentials of NSCs. Interestingly, examination of peripheral blood mononuclear cells from people of various ages showed that mRNA expression of GAPDH gradually decreased with age, while its expression level positively correlated with cognitive levels. Our results indicate that metformin represents a candidate pharmacological approach for recruitment of NSCs in aged mouse brain by enhancing glycolysis and promoting neurovascular generation, a strategy that might be of therapeutic value for anti-aging in humans.Graphical Abstract
Brainstem development requires galactosylceramidase and is critical for the pathogenesis of Krabbe Disease
Authors: Weinstock Nadav I. , Kreher Conlan , Favret Jacob , Bongarzone Ernesto , Wrabetz Lawrence , Feltri M. Laura , Shin Daesung 
Published: March 2020

AbstractKrabbe disease (KD) is caused by a deficiency of galactosylceramidase (GALC), which induces demyelination and neurodegeneration due to accumulation of cytotoxic psychosine. Hematopoietic stem cell transplantation (HSCT) improves clinical outcomes in KD patients only if delivered pre-symptomatically. We hypothesized that the restricted temporal efficacy of HSCT reflects a requirement for GALC in early brain development. Using a novelGalcfloxed allele, we induced ubiquitous GALC ablation (Galc-iKO) at various postnatal timepoints and identified a critical period of vulnerability to GALC ablation between P4-6. EarlyGalc-iKO induction caused a worse KD phenotype, higher psychosine levels, and a significantly shorter life-span. Intriguingly, GALC expression peaks during this critical developmental period. Further analysis revealed a novel cell autonomous role for GALC in the development and maturation of immature T-box-brain-1 positive brainstem neurons. These data identify a perinatal developmental period, in which neuronal GALC expression influences brainstem development that is critical for KD pathogenesis.
The Effect of the Glossary on the Reliability and Performance of the Reading the Mind in the Eyes Test (RMET)
Authors: Toloza-Muñoz José , González-Mendoza Jean , Castillo Ramón D. , Morales-Bader Diego 
Published: March 2020

AbstractThe Reading the Mind in the Eyes Test (RMET) is used to measure high-level Theory of Mind. RMET consists of images of the regions surrounding the eyes and a glossary of terms that defines words associated with the gazes depicted in the images. People must identify the meaning associated with each gaze and can consult the glossary as they respond. The results indicate that typically developed adults perform better than adults with neurodevelopmental disorders. However, the evidence regarding the validity and reliability of the test is contradictory. This study evaluated the effect of the glossary on the performance, internal consistency, and temporal stability of the test. A total of 89 undergraduate students were randomly assigned to three conditions. The first group used the original glossary (Ori-G). The second group developed a self-generated glossary of gazes (Self-G). Finally, the third group developed a glossary that did not define gazes, but unrelated words instead (No-G). The test was administered before and after participants drew a randomly assigned image as a secondary task. The findings show that the number of correct answers was similar among the three conditions before and after the secondary task. However, the Self-G and No-G groups took less time to finish the test. The type of glossary affected the consistency and stability of the test. In our case, the Self-G condition made the responses faster, more consistent, and more stable. The results are discussed in terms of levels of processing and the detection of mental states based on gazes.
Analysis of p67 allelic sequences reveals a subtype of allele type 1 unique to buffalo-derivedTheileria parvaparasites from southern Africa
Authors: Mukolwe Lubembe D. , Odongo David O. , Byaruhanga Charles , Snyman Louwtjie P. , Sibeko-Matjila Kgomotso P. 
Published: March 2020

AbstractEast Coast fever (ECF) and Corridor disease (CD) caused by cattle- and buffalo-derivedT. parvarespectively are the most economically important tick-borne diseases of cattle in the affected African countries. The p67 gene has been evaluated as a recombinant subunit vaccine against East Coast fever (ECF), and for discrimination ofT. parvaparasites causing ECF and Corridor disease (CD). The p67 allele type 1 was first identified in cattle-derivedT. parvaparasites from east Africa, where parasites possessing this allele type have been associated with ECF. Subsequent characterization of buffalo-derivedT. parvaparasites from South Africa where ECF was eradicated, revealed the presence of a similar allele type, raising concerns as to whether or not allele type 1 from parasites from the two regions is identical. A 900 bp central fragment of the gene encoding p67 was PCR amplified fromT. parvaDNA extracted from blood collected from cattle and buffalo in South Africa, Mozambique, Kenya, Tanzania and Uganda, followed by DNA sequence analysis. Four p67 allele types previously described were identified. A subtype of p67 allele type 1 was identified in parasites from clinical cases of CD and buffalo from southern Africa. Notably, p67 allele type 1 sequences from parasites associated with ECF in East Africa and CD in Kenya were identical. Analysis of two p67 B-cell epitopes (TpM12 and AR22.7) revealed amino acid substitutions in allele type 1 from buffalo-derivedT. parvaparasites from southern Africa. However, both epitopes were conserved in allele type 1 from cattle- and buffalo-derivedT. parvaparasites from East Africa. These findings reveal detection of a subtype of p67 allele type 1 associated withT. parvaparasites transmissible from buffalo to cattle in southern Africa.