bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Meta-Analysis of Executive Functions in Frontal Cortex: Comparing Healthy and Neuropsychiatric Groups
Authors: Waters Abigail B. , Swenson Lance P. , Gansler David A. 
Published: May 2018

AbstractBackgroundThe neural architecture of executive functions remains a topic of considerable clinical and academic interest in the clinical neurosciences, given its strength as a transdiagnostic predictor of adaptive functioning with high heritability. In recent years, meta-analyses have shown a consistent relationship between prefrontal cortex size and executive functioning task performance in healthy adults and lesion patients, with increases in measures of cortical size (i.e., volume or thickness) associated with better executive functioning performance. There is a gap in meta-analytic literature assessing these relationships in neuropsychiatric populations, their effects relative to healthy controls, and differential contributions of brains regions and neuropsychological paradigms.MethodsWe conducted a meta-analysis of published studies (k =30) that assessed the relationship between executive functions and frontal regions in vivo (N = 1935) for both healthy (20 samples) and neuropsychiatric (21 samples) adults. Random effects modeling was used to calculate mean effect sizes and CIs.ResultsLarger volumes and thickness were associated with better executive functioning in both healthy (r =.35, 95% CI =.29 -.39) and neuropsychiatric populations (r =.47, 95% CI =.40 -.51), with the effect size for neuropsychiatric populations being significantly larger compared to healthy controls. While there was variability between tasks, there were no significant differences in effect size between neuropsychological paradigms or brain region classification.ConclusionsThese results indicate the relationship between healthy adult performance on neuropsychological testing is less associated with cortical size compared to neuropsychiatric adults.
Speciation with gene flow via cycles of isolation and migration: Insights from multiple mangrove taxa
Authors: He Ziwen , Li Xinnian , Yang Ming , Wang Xinfeng , Zhong Cairong , Duke Norman C. , Shi Suhua , Wu Chung-I 
Published: May 2018

AbstractAllopatric speciation requiring an unbroken period of geographical isolation has been the standard model of neo-Darwinism. While doubts have been repeatedly raised, strict allopatry without any gene flow remains a plausible mechanism in most cases. To rigorously reject strict allopatry, genomic sequences superimposed on the geological records of a well-delineated geographical barrier will be necessary. The Strait of Malacca, narrowly connecting the Pacific and Indian Ocean coasts, serves at different times either as a geographical barrier or a conduit of gene flow for coastal/marine species. We surveyed 1,700 plants from 29 populations of five common mangrove species by large scale DNA sequencing and added several whole-genome assemblies. Speciation between the two oceans is driven by cycles of isolation and gene flow due to the fluctuations in sea level leading to the opening/closing of the Strait to ocean currents. Because the time required for speciation in mangroves is longer than the isolation phases, speciation in these mangroves has proceeded through many cycles of mixing-isolation-mixing, or MIM cycles. The MIM mechanism, by relaxing the condition of no gene flow, can promote speciation in many more geographical features than strict allopatry can. Finally, the MIM mechanism of speciation is also efficient, potentially yielding mn(m>1) species after n cycles.Significance statementMechanisms of species formation have always been a conundrum. Speciation between populations that are fully geographically isolated, or allopatric speciation, has been the standard solution in the last 50 years. Complete geographical isolation with no possibility of gene flow, however, is often untenable and is inefficient in generating the enormous biodiversity. By studying mangroves on the Indo-Malayan coasts, a global hotspot of coastal biodiversity, we were able to combine genomic data with geographical records on the Indo-Pacific barrier that separates Pacific and Indian Ocean coasts. We discovered a novel mechanism of speciation, that we call mixing-isolation-mixing (MIM) cycles. By permitting intermittent gene flow during speciation, MIM can potentially generate species at an exponential rate, thus combining speciation and biodiversity in a unified framework.
M-current regulates firing mode and spike reliability in a collision detecting neuron
Authors: Dewell Richard B. , Gabbiani Fabrizio 
Published: May 2018

AbstractAll animals must detect impending collisions to escape them, and they must reliably discriminate them from non-threatening stimuli to prevent false alarms. Therefore, it is no surprise that animals have evolved highly selective and sensitive neurons dedicated to such tasks. We examined a well-studied collision detection neuron in the grasshopperSchistocerca americanausingin vivoelectrophysiology, pharmacology, and computational modeling. This lobula giant movement detector (LGMD) neuron is excitable by inputs originating from each ommatidia of the compound eye, and it has many intrinsic properties that increase its selectivity to objects approaching on a collision course, including switching between burst and non-burst firing. Here, we demonstrate that the LGMD neuron exhibits a large M current, generated by non-inactivating K+channels, that narrows the window of dendritic integration, regulates a firing mode switch between burst and isolated spiking, increases the precision of spike timing, and increases the reliability of spike propagation to downstream motor centers. By revealing how the M current increases the LGMD’s ability to detect impending collisions our results suggest that it may play an analogous role in other collision detection circuits.New & NoteworthyThe ability to reliably detect impending collisions is a critical survival skill. The nervous systems of many animals have developed dedicated neurons for accomplishing this task. We used a mix ofin vivoelectrophysiology and computational modeling to investigate the role of M potassium channels within one such collision detecting neuron and showed that through regulation of burst firing and increasing spiking reliability the M current increases the ability to detect impending collisions.
Epidemiologal investigation of anAcinetobacter baumanniioutbreak using Core Genome Multilocus Sequence Typing
Authors: Venditti Carolina , Vulcano Antonella , D’Arezzo Silvia , Maria Gruber Cesare Ester , Selleri Marina , Antonini Mario , Lanini Simone , Marani Alessandra , Puro Vincenzo , Nisii Carla , Caro Antonino Di 
Published: May 2018

ABSTRACTCarbapenem-resistant (CR)Acinetobacter baumanniiis a serious nosocomial pathogen able to cause a variety of serious, often life-threatening infections and outbreaks. We aimed to investigate the molecular epidemiology of clinical isolates of CR-A. baumanniifrom an outbreak occurred in the intensive care unit (ICU) of our hospital.From January to April 2017, 13 CR-A. baumanniiisolates were collected at the “L. Spallanzani” hospital, Rome, Italy; typing was performed by repetitive extragenetic palindromic-based (rep)- PCR-based DiversiLab system and WGS data were used for insilicoanalysis of traditional MLST types, for identifying resistance genes and for core genome multi locus sequence typing (cgMLST) analysis. Epidemiological data were obtained from hospital records.Strains were cultured from 7 patients treated in the ICU of our hospital; all isolates showed a multi-drug resistant (MDR) profile, carrying theblaOXA-23carbapenemase. Typing performed by rep-PCR and MLST showed that the isolates clustered into one group while the cgMLST approach, which uses 2690 gene targets to characterize the gene-by-gene allelic profile ofA. baumannii,highlighted the presence of two cluster types. These results allowed us to identify two patients who entered the ICU already colonized by two different strains of CR-A. baumannii; we hypothesize that these two patients could be the source of two separate transmission chains.Our results show that whole-genome-DNA sequencing by cgMLST is a valuable tool, better suited for prompt epidemiological investigations than traditional typing methods because of its higher discriminatory ability in determining clonal relatedness.
Characterizing the Effects of Glutathione as an Immunoadjuvant in the Treatment of Tuberculosis
Authors: Cao Ruoqiong , Teskey Garrett , Islamoglu Hicret , Abrahem Rachel , Gyurjian Karo , Zhong Li , Venketaraman Vishwanath 
Published: May 2018

AbstractMycobacteriumtuberculosis(M.tb) is the etiological agent that is responsible for causing tuberculosis (TB), which continues to affect millions of people worldwide, with an ever-increasing resistance to antibiotics. We tested the synergistic effects of N-acetyl cysteine (NAC, the precursor molecule for the synthesis of glutathione) and individual first-line antibiotics typically given for the treatment of TB such as Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Pyrazinamide (PZA) to improve the ability of macrophages to control intracellularM.tbinfection. Glutathione (GSH), a pleiotropic antioxidant molecule has been previously shown to display both antimycobacterial and immune-enhancing effects. Our results indicate that there was not only an increase in beneficial immunomodulatory effects, but a greater reduction in the intracellular viability ofM. tbwhen macrophages were treated with the combination of antibiotics (INH/RIF/EMB or PZA) and NAC.
Computational analysis of the Plasmodiophora brassicae genome: mitochondrial sequence description and metabolic pathway database design
Authors: Daval S. , Belcour A. , Gazengel K. , Legrand L. , Gouzy J. , Cottret L. , Lebreton L. , Aigu Y. , Mougel C. , Manzanares-Dauleux M.J. 
Published: May 2018

AbstractPlasmodiophora brassicae is an obligate biotrophic pathogenic protist responsible for clubroot, a root gall disease of Brassicaceae species. In addition to the reference genome of the P. brassicae European e3 isolate and the draft genomes of Canadian or Chinese isolates, we present the genome of eH, a second European isolate. Refinement of the annotation of the eH genome led to the identification of the mitochondrial genome sequence, which was found to be bigger than that of Spongospora subterranea, another plant parasitic Plasmodiophorid phylogenetically related to P. brassicae. New pathways were also predicted, such as those for the synthesis of spermidine, a polyamine up-regulated in clubbed regions of roots. A P. brassicae pathway genome database was created to facilitate the functional study of metabolic pathways in transcriptomics approaches. These available tools can help in our understanding of the regulation of P. brassicae metabolism during infection and in response to diverse constraints.
CRISPR/Cas9-mediated knock-out of dUTPase in mice leads to early embryonic lethality
Authors: Pálinkás Hajnalka Laura , Rácz Gergely , Gál Zoltán , Hoffmann Orsolya , Tihanyi Gergely , Gócza Elen , Hiripi László , Vértessy Beáta G. 
Published: May 2018

AbstractSanitization of nucleotide pools is essential for genome maintenance. Among the enzymes significant in this mechanism, deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) performs cleavage of dUTP into dUMP and inorganic pyrophosphate. By this reaction the enzyme efficiently prevents uracil incorporation into DNA and provides dUMP, the substrate for de novo thymidylate biosynthesis. Despite its physiological significance, knock-out models of dUTPase have not yet been investigated in mammals, only in unicellular organisms, such as bacteria and yeast. Here we generate CRISPR/Cas9-mediated dUTPase knock-out in mice. We find that heterozygous dut +/-animals are viable while the decreased dUTPase level is clearly observable. We also show that the enzyme is essential for embryonic development. Based on the present results, early dut -/-embryos can still reach the blastocyst stage, however, they die shortly after implantation. Analysis of preimplantion embryos indicate perturbed growth of both inner cell mass (ICM) and trophectoderm (TE). We conclude that dUTPase is indispensable for post-implantation development in mice. The gene targeting model generated in the present study will allow further detailed studies in combination with additional gene knock-outs.
Humanized Mcl-1 mice enable accurate pre-clinical evaluation of MCL-1 inhibitors destined for clinical use
Authors: Brennan Margs S. , Chang Catherine , Dewson Grant , Tai Lin , Lessene Guillaume , Strasser Andreas , Kelly Gemma L. , Herold Marco J. 
Published: May 2018

SUMMARYMCL-1 is a pro-survival BCL-2 protein required for the sustained growth of many cancers. Recently a highly specific MCL-1-inhibitor, S63845, showing 6-fold higher affinity to human compared to mouse MCL-1 has been described. To accurately test efficacy and tolerability of this BH3 mimetic drug in pre-clinical cancer models, we developed a humanized Mcl-1 (huMcl-1) mouse in which MCL-1 was replaced with its human homologue. HuMcl-1 mice are phenotypically indistinguishable from wild-type mice but are more sensitive to MCL-1 inhibition. Importantly, non-transformed cells and lymphomas from huMcl-1;Eμ-Myc mice are more sensitive to S63845 in vitro than their control counterparts. When huMcl-1;Eμ-Myc lymphoma cells are transplanted into huMcl-1 mice, treatment with S63845 alone or alongside cyclophosphamide leads to long-term remission in ~60% or almost 100% of mice, respectively. These results demonstrate the potential of our huMCL-1 mouse model to test MCL-1 inhibitors, allowing precise predictions of efficacy and tolerability for clinical translation.
Integrated Cognitive Assessment: Speed and Accuracy of Visual Processing as a Reliable Proxy to Cognitive Performance
Authors: Khaligh-Razavi Seyed-Mahdi , Habibi Sina , Sadeghi Maryam , Marefat Haniye , Khanbagi Mahdiyeh , Nabavi Seyed Massood , Sadeghi Elham , Kalafatis Chris 
Published: May 2018

AbstractVarious mental disorders are accompanied by some degree of cognitive impairment. Particularly in neurodegenerative disorders, cognitive impairment is the phenotypical hallmark of the disease. Effective, accurate and timely cognitive assessment is key to early diagnosis of this family of mental disorders. Current standard-of-care techniques for cognitive assessment are primarily paper-based, and need to be administered by a healthcare professional; they are additionally language and education-dependent and typically suffer from a learning bias. These tests are thus not ideal for large-scale pro-active cognitive screening and disease progression monitoring. We developed the Integrated Cognitive Assessment (ICA), a 5-minute computerized cognitive assessment tool based on a rapid visual categorization task, in which a series of carefully selected natural images of varied difficulty are presented to participants. Overall 448 participants, across a wide age-range with different levels of education took the ICA test. We compared participants’ ICA test results with a variety of standard pen-and-paper tests that are routinely used to assess cognitive performance. ICA had excellent test-retest reliability, and was significantly correlated with all the reference cognitive tests used here, demonstrating ICA’s ability as one unified test that can assess various cognitive domains.
Tissue growth factor β stimulates fibroblast-like synovial cells to produce extra domain A fibronectin in osteoarthritis
Authors: Kragstrup TW , Sohn DH , Lepus CM , Onuma K , Wang Q , Robinson WH , Sokolove J 
Published: May 2018

AbstractIntroductionThe pathophysiology of osteoarthritis (OA) involves wear and tear, and a state of low-grade inflammation. Wear and tear leads to tissue degradation and tissue repair responses, including tissue growth factor beta (TGFβ)-induced myofibroblast production of extracellular matrix (ECM). Fibronectins are an essential part of the ECM, and injection of fibronectin fragments into rabbit joints is a previously established animal model of OA. Alternatively-spliced fibronectin contains the ED-A domain (ED-A FN) and has been shown to activate Toll-like receptor 4. In this study, we tested the hypothesis that FN fragments containing the ED-A domain could be one mechanism transducing mechanical events into inflammatory signals in OA.MethodsSamples of synovial membrane and cartilage were obtained from patients with knee OA undergoing joint replacement surgery. Immunostaining for ED-A FN and the myofibroblast marker alpha smooth muscle actin (αSMA) was performed on synovial membranes and fibroblast-like synovial cells (FLS). FLS were stimulated with TGFβ, TNFα, lipopolysaccharide, IL-6, OA synovial fluid, or chondrocyte lysate, and analyzed for ED-A FN. Synovial cells isolated by enzymatic digestion and human monocyte-derived macrophages (MDM) were incubated with recombinant ED-A FN, plasmin, cellular FN, or cellular FN digested with plasmin; and culture supernatants were analyzed for MCP-1 and TNFα.ResultsWe hypothesized that ED-A FN is produced by OA FLS in response to factors found in the OA synovial joint. Indeed, the production of ED-A FN by OA FLS was increased by TGFβ, OA synovial fluid, and lysed chondrocytes in all experiments (n=3). ED-A FN co- localized with the myofibroblast marker αSMA in both the OA FLS (n=3) and in the OA synovial membranes (n=8). We further hypothesized that ED-A FN expression is associated with cellular density and expression of inflammatory molecules in OA. ED-A FN staining was associated with both number of lining layer cells (rho=0.85 and p=0.011) and sublining cells (rho=0.88 and p=0.007) in the OA synovium (n=8), and co-localized with both MCP-1 and TNFα (n=5). Recombinant ED-A FN increased the production of both MCP-1 and TNFα by MDM (n=3) and OA FLS (n=3). Finally, we demonstrated that the FN fragments containing the ED-A domain generated the same production of both MCP-1 and TNFα as recombinant ED-A FN.ConclusionThe disease process in OA shares features with the chronic wound healing response including myofibroblast differentiation and production of mediators that promote myofibroblast production of ED-A FN. We show that recombinant and plasmin-derived ED-A fragments stimulate FLS and MDM to produce pro-inflammatory mediators. Our findings support utilizing ED-A FN for drug delivery or therapeutic targeting of the formation of ED- A FN or the enzymatic fragmentation of FN to reduce pro-inflammatory responses in OA.
Proteome and microbiota analysis reveals alterations of liver-gut axis under different stocking density of Peking ducks
Authors: Wu Yuqin , Li Jianhui , Qin Xin , Sun Shiqiang , Xiao Zhibin , Dong Xiaoyu , Shahid Muhammad Suhaib , Yin Dafei , Lei Zhao , Guo Yuming , Yuan Jianmin 
Published: May 2018

AbstractThe aim of this study was to determine the impact of stocking density on the liver proteome and cecal microbiota of Peking ducks. A total of 1,200 ducks with 21-day old were randomly allotted into 5 stocking density groups of 5, 6, 7, 8 and 9 ducks/m2, with 6 replicates for each group. At 40 days of age, duck serum and pectorals were collected for biochemical tests; liver and cecal contents of ducks were gathered for proteome and microbiota analysis, respectively. Serum MDA increased while pectorals T-AOC reduced linearly with enhancing stocking density. Duck lipid metabolism was altered under different stocking density as well. Serum LDL-C increased linearly with increasing stocking density. Proteome analysis revealed fatty acid biosynthesis proteins such as acyl-CoA synthetase family member 2 and fatty acid oxidation related proteins including acyl-CoA dehydrogenase long chain and acyl-coenzyme A oxidase were enriched in high stocking density group. Additionally, high stocking density increased oxidative response related proteins such as DDRGK domain containing 1 while diminished anti-oxidant capacity related proteins including regucalcin and catalase. 16S rDNA analysis revealed that higher stocking density was accompanied with decreased microbial diversity, as well as depletion of anti-inflammatory bacterial taxa, including Bacteroidales, Butyricimonas and Alistipe. In addition, decreased bile acid metabolism-associated bacteria such as Ruminococcaceae, Clostridiales and Desulfovibrionaceae were found in the high-density group. Both proteome and 16S rDNA results showed inflammation and chronic liver disease trend in the high-density group, which suggests the involvement of the liver-gut axis in oxidative stress.
Longitudinal increase in sleep problems is related to amyloid deposition in cortical regions with high HOMER1 gene expression
Authors: Fjell Anders M , Sederevicius Donatas , Sneve Markus H , de Lange Ann-Marie Glasø , Sjøli Bråthen Anne Cecilie , Walhovd Kristine B ,   for The Alzheimer’s Disease Neuroimaging Initiative
Published: May 2018

AbstractOlder adults who report more sleep problems tend to have elevated levels of the Alzheimer’s disease (AD) biomarker β-amyloid (Aβ), but the mechanisms responsible for this relationship are largely unknown. Molecular markers of sleep problems are now emerging from rodent research, yielding opportunities to generate hypotheses about the causes of the sleep-Aβ relationship. A major molecular marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, involved in control of sleep homeostasis and also implied in Aβ accumulation. Here, in a sample of 109 cognitively healthy middle-aged and older adults, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over three years, was stronger in cortical regions with high HOMER1 mRNA expression levels. Aβ correlated with poorer sleep quality cross-sectionally and longitudinally. This relationship was stronger in the younger (50-67 years) than the older (68-81 years) participants. Effects were mainly found in regions with high expression of HOMER1, suggesting a possible molecular pathway between sleep problems and Aβ accumulation. The anatomical distribution of the sleep-Aβ relationships followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment (MCI) or AD. Thus, the results indicate that the relationship between sleep problems and Aβ-accumulation may involve Homer1 activity in the cortical regions that harbor Aβ in AD. Analysis of cortical gene expression patterns represent a promising avenue to unveil molecular mechanisms behind the relationship between sleep problems and AD risk.