bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic post-stroke aphasia severity is determined by fragmentation of residual white matter networks
Authors: Marebwa Barbara K. , Fridriksson Julius , Yourganov Grigori , Feenaughty Lynda , Rorden Chris , Bonilha Leonardo 
Published: August 2017

AbstractMany stroke survivors with aphasia in the acute period experience spontaneous recovery within the first six months after the stroke. However, approximately 30–40% sustain permanent aphasia and the factors determining incomplete recovery are unclear. Suboptimal recovery may be influenced by disruption of areas seemingly spared by the stroke due to loss of white matter connectivity and network integrity. We reconstructed individual anatomical whole-brain connectomes from 90 left hemisphere stroke survivors using diffusion MR images. We measured the modularity of the residual white matter network organization, the probability of brain regions clustering together, and the degree of fragmentation of left hemisphere networks. Greater post-stroke left hemisphere network fragmentation and higher modularity index were associated with more severe chronic aphasia, controlling for the size of the stroke lesion. Even when the left hemisphere was relatively spared, subjects with disorganized community structure had significantly worse aphasia, particularly when key temporal lobe regions were isolated into segregated modules. These results suggest that white matter integrity and disorganization of neuronal networks could be important determinants of chronic aphasia severity. Connectome white matter organization measured through modularity and other topological features could be used as a personalized variable for clinical staging and aphasia treatment planning.
Global mapping of miRNA-target interactions in cattle (Bos taurus)
Authors: Scheel Troels K. H. , Moore Michael J. , Luna Joseph M. , Nishiuchi Eiko , Fak John , Darnell Robert B. , Rice Charles M. 
Published: August 2017

AbstractWith roles in development, cell proliferation and disease, micro-RNA (miRNA) biology is of great importance and a potential therapeutic target. Here we used cross-linking immunoprecipitation (CLIP) and ligation of miRNA-target chimeras on the Argonaute (AGO) protein to globally map miRNA interactions in the cow. The interactome is the deepest reported to date. miRNA targeting principles are consistent with observations in other species, but with expanded pairing rules. Experimental mapping robustly predicted functional miR-17 regulatory sites. From miRNA-specific targeting for >5000 mRNAs we determined gene ontologies (GO). This confirmed repression of genes important for embryonic development and cell cycle progress by the let-7 family, and repression of those involved in cell cycle arrest by the miR-17 family, but also suggested a number of unappreciated miRNA functions. Our results provide a significant resource for understanding of bovine and species-conserved miRNA regulation, and demonstrate the power of experimental methods for establishing comprehensive interaction maps.
An amphibian chemical defense phenotype is inducible across life history stages
Authors: Bucciarelli Gary M. , Shaffer H. Bradley , Green David B. , Kats Lee B. 
Published: August 2017

AbstractInducible phenotypic responses to environmental variation are ubiquitous across the tree of life, but it remains an open question whether amphibian chemical defense phenotypes are inducible. Tetrodotoxin (TTX) is a key chemical defense trait in North American and Eurasian newts (Salamandridae). We tested if TTX can be induced by exposing populations of adult and larval California newts (Taricha torosa) to sustained stressful conditions while longitudinally quantifying TTX concentrations. Adult newts rapidly increased chemical defenses in response to simulated predator attacks and consistently maintained elevated TTX concentrations relative to wild, non-captive individuals. We also found that laboratory-reared larvae maintained chemical defenses nearly three-fold greater than those of siblings reared in streams. Collectively, our results indicate that amphibian chemical defenses are not fixed. Instead, toxins are maintained at a baseline concentration that can quickly be increased in response to perceived risk with substantial increases to toxicity. Therefore, it is crucial that inducible variation be accounted for when considering ecological dynamics of chemically defended animals and coevolutionary predator-prey and mimic-model relationships.
Heritability of the Symbiodinium community in vertically- and horizontally-transmitting broadcast spawning corals
Authors: Quigley Kate M. , Willis Bette L. , Bay Line K. 
Published: August 2017

AbstractThe dinoflagellate-coral partnership influences the coral holobiont’s tolerance to thermal stress and bleaching. However, the comparative roles of host genetic versus environmental factors in determining the composition of this symbiosis are largely unknown. Here we quantify the heritability of the initialSymbiodiniumcommunities for two broadcast-spawning corals with different symbiont transmission modes:Acropora tenuishas environmental acquisition, whereasMontipora digitatahas maternal transmission. Using high throughput sequencing of the ITS-2 region to characterize communities in parents, juveniles and eggs, we describe previously undocumentedSymbiodiniumdiversity and dynamics in both corals. After one month of uptake in the field,Symbiodiniumcommunities associated withA.tenuisjuveniles were dominated by A3, C1, D1, A-type CCMP828, and D1a in proportional abundances conserved between experiments in two years.M.digitataeggs were predominantly characterized by C15, D1, and A3. In contrast to current paradigms, host genetic influences accounted for a surprising 29% of phenotypic variation inSymbiodiniumcommunities in the horizontally-transmittingA.tenuis, but only 62% in the vertically-transmittingM.digitata. Our results reveal hitherto unknown flexibility in the acquisition ofSymbiodiniumcommunities and substantial heritability in both species, providing material for selection to produce partnerships that are locally adapted to changing environmental conditions.
Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia
Authors: Cavallari Claudia , Ranghino Andrea , Tapparo Marta , Cedrino Massimo , Figliolini Federico , Grange Cristina , Giannachi Valentina , Garneri Paolo , Deregibus Maria Chiara , Collino Federica , Rispoli Pietro , Camussi Giovanni , Brizzi Maria Felice 
Published: August 2017

AbstractSerum is an abundant and accessible source of circulating extracellular vesicles (EVs). Serum-EV (sEV) pro-angiogenic capability and mechanisms are herein analyzed using an in vitro assay which predicts sEV angiogenic potential in vivo. Effective sEVs (e-sEVs) also improved vascular remodeling and prevented muscle damage in a mouse model of acute hind limb ischemia. e-sEV angiogenic proteomic and transcriptomic analyses show a positive correlation with matrix-metalloproteinase activation and extracellular matrix organization, cytokine and chemokine signaling pathways, Insulin-like Growth Factor and platelet pathways, and Vascular Endothelial Growth Factor signaling. A discrete gene signature, which highlights differences in e-sEV and ineffective-EV biological activity, was identified using gene ontology (GO) functional analysis. An enrichment of genes associated with the Transforming Growth Factor beta 1 (TGFβ1) signaling cascade is associated with e-sEV administration but not with ineffective-EVs. Chromatin immunoprecipitation analysis on the inhibitor of DNA binding I (ID1) promoter region, and the knock-down of small mother against decapentaplegic (SMAD)1–5 proteins confirmed GO functional analyses. This study demonstrates sEV pro-angiogenic activity, validates a simple, sEV pro-angiogenic assay which predicts their biological activity in vivo, and identifies the TGFβ1 cascade as a relevant mediator. We propose serum as a readily available source of EVs for therapeutic purposes.
Temporal changes in the radiocesium distribution in forests over the five years after the Fukushima Daiichi Nuclear Power Plant accident
Authors: Imamura Naohiro , Komatsu Masabumi , Ohashi Shinta , Hashimoto Shoji , Kajimoto Takuya , Kaneko Shinji , Takano Tsutomu 
Published: August 2017

AbstractTo elucidate the temporal changes in the radiocesium distribution in forests contaminated by the Fukushima Daiichi Nuclear Power Plant accident, we monitored the 137Cs concentration and inventory within forests from 2011 to 2015 across nine plots containing variable tree species and different contamination levels. The 137Cs concentrations in needles and branches decreased exponentially at all coniferous plots, with effective ecological half-lives of 0.45–1.55 yr for needles and 0.83–1.69 yr for branches. By contrast, the 137Cs concentration in deciduous konara oak leaves did not change over the five years. The concentration of 137Cs in oak wood increased by 37–75%, whereas that in Japanese red pine decreased by 63% over the five years. In Japanese cedar and hinoki cypress, the 137Cs concentration in wood showed an increasing trend in half of the plots. The changes in 137Cs in the organic and mineral soil layers were not strongly related to the tree species or contamination level. Our multi-site, multi-species monitoring results revealed that the pattern of temporal changes in radiocesium in the 9 forest plots was similar overall; however, changes in 137Cs in needles/leaves and wood differed among tree species.
Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma
Authors: Li Shau-Hsuan , Chien Chih-Yen , Huang Wan-Ting , Luo Sheng-Dean , Su Yan-Ye , Tien Wan-Yu , Lan Ya-Chun , Chen Chang-Han 
Published: August 2017

AbstractDespite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and survival. However, the significance of mTOR on the prognosis of tongue SCC remains largely undefined. In the present study, immunohistochemistry was performed to evaluate the expression of phosphorylated mTOR (p-mTOR) in 160 surgically resected tongue SCC, and correlated with survival. Univariate analysis revealed that p-mTOR overexpression (P = 0.006) was associated with inferior overall survival. In multivariate comparison, p-mTOR overexpression (P = 0.002, hazard ratio = 2.082) remained independently associated with worse overall survival. In vitro study, tongue cancer cells treated with everolimus, the specific mTOR inhibitor, or transfected with mTOR-mediated siRNAs dramatically attenuated the abilities of cell proliferation by MTT and BrdU assays. In 4-NQO-induced tongue cancer murine model, mTOR inhibitors significantly decreased the incidence of tongue SCC. In conclusion, p-mTOR overexpression was independently associated with poor prognosis of patients with tongue SCC. In vitro and vivo, mTOR inhibition showed the promising activity in tongue SCC. Our results suggest that inhibition of mTOR signaling pathway may be a novel therapeutic target for tongue SCC.
Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis
Authors: Li Shuxia , Christiansen Lene , Christensen Kaare , Kruse Torben A. , Redmond Paul , Marioni Riccardo E. , Deary Ian J. , Tan Qihua 
Published: August 2017

AbstractAging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging. We identified 67,604 age-associated CpG sites reaching genome-wide significance of FWER <0.05, 86% demethylated with increasing age. Double-replication resulted in 5,168 CpGs (39% age-methylated and 61% age-demethylated) which were characterized by high concentration of age-methylated CpGs at 1stExon and TSS200 and a dominant pattern of age-demethylated CpGs at other gene regions, and by overwhelming age-related methylation in CpG islands and demethylation at shore/shelf and open sea. The differential distribution patterns over gene regions for methylated and demethylated CpGs both relate to reduced gene activity during aging. Pathway analysis showed that age-dependent methylations were especially involved in cellular signalling activities while demethylations particularly linked to functions of the extracellular matrix, all implicated in the aging process and age-related disease risk.
Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA
Authors: Németh Andrea , Orgovan Norbert , Sódar Barbara W , Osteikoetxea Xabier , Pálóczi Krisztina , Szabó-Taylor Katalin É. , Vukman Krisztina V. , Kittel Ágnes , Turiák Lilla , Wiener Zoltán , Tóth Sára , Drahos László , Vékey Károly , Horvath Robert , Buzás Edit I. 
Published: August 2017

AbstractRecently, biological roles of extracellular vesicles (which include among others exosomes, microvesicles and apoptotic bodies) have attracted substantial attention in various fields of biomedicine. Here we investigated the impact of sustained exposure of cells to the fluoroquinolone antibiotic ciprofloxacin on the released extracellular vesicles. Ciprofloxacin is widely used in humans against bacterial infections as well as in cell cultures against Mycoplasma contamination. However, ciprofloxacin is an inducer of oxidative stress and mitochondrial dysfunction of mammalian cells. Unexpectedly, here we found that ciprofloxacin induced the release of both DNA (mitochondrial and chromosomal sequences) and DNA-binding proteins on the exofacial surfaces of small extracellular vesicles referred to in this paper as exosomes. Furthermore, a label-free optical biosensor analysis revealed DNA-dependent binding of exosomes to fibronectin. DNA release on the surface of exosomes was not affected any further by cellular activation or apoptosis induction. Our results reveal for the first time that prolonged low-dose ciprofloxacin exposure leads to the release of DNA associated with the external surface of exosomes.
Forces and Disease: Electrostatic force differences caused by mutations in kinesin motor domains can distinguish between disease-causing and non-disease-causing mutations
Authors: Li Lin , Jia Zhe , Peng Yunhui , Godar Subash , Getov Ivan , Teng Shaolei , Alper Joshua , Alexov Emil 
Published: August 2017

AbstractThe ability to predict if a given mutation is disease-causing or not has enormous potential to impact human health. Typically, these predictions are made by assessing the effects of mutation on macromolecular stability and amino acid conservation. Here we report a novel feature: the electrostatic component of the force acting between a kinesin motor domain and tubulin. We demonstrate that changes in the electrostatic component of the binding force are able to discriminate between disease-causing and non-disease-causing mutations found in human kinesin motor domains using the receiver operating characteristic (ROC). Because diseases may originate from multiple effects not related to kinesin-microtubule binding, the prediction rate of 0.843 area under the ROC plot due to the change in magnitude of the electrostatic force alone is remarkable. These results reflect the dependence of kinesin’s function on motility along the microtubule, which suggests a precise balance of microtubule binding forces is required.
Fine Structure of Posterior Alpha Rhythm in Human EEG: Frequency Components, Their Cortical Sources, and Temporal Behavior
Authors: Barzegaran Elham , Vildavski Vladimir Y. , Knyazeva Maria G. 
Published: August 2017

AbstractHeterogeneity of the posterior alpha rhythm (AR) is a widely assumed but rarely tested phenomenon. We decomposed the posterior AR in the cortical source space with a 3-way PARAFAC technique, taking into account the spatial, frequency, and temporal aspects of mid-density EEG. We found a multicomponent AR structure in 90% of a group of 29 healthy adults. The typical resting-state structure consisted of a high-frequency occipito-parietal component of the AR (ARC1) and a low-frequency occipito-temporal component (ARC2), characterized by individual dynamics in time. In a few cases, we found a 3-component structure, with two ARC1s and one ARC2. The AR structures were stable in their frequency and spatial features over weeks to months, thus representing individual EEG alpha phenotypes. Cortical topography, individual stability, and similarity to the primate AR organization link ARC1 to the dorsal visual stream and ARC2 to the ventral one. Understanding how many and what kind of posterior AR components contribute to the EEG is essential for clinical neuroscience as an objective basis for AR segmentation and for interpreting AR dynamics under various conditions, both normal and pathological, which can selectively affect individual components.
Inhibin-A and Decorin Secreted by Human Adult Renal Stem/Progenitor Cells Through the TLR2 Engagement Induce Renal Tubular Cell Regeneration
Authors: Sallustio Fabio , Curci Claudia , Aloisi Alessandra , Toma Chiara Cristina , Marulli Elisabetta , Serino Grazia , Cox Sharon Natasha , De Palma Giuseppe , Stasi Alessandra , Divella Chiara , Rinaldi Rosaria , Schena Francesco Paolo 
Published: August 2017

AbstractAcute kidney injury (AKI) is a public health problem worldwide. Several therapeutic strategies have been made to accelerate recovery and improve renal survival. Recent studies have shown that human adult renal progenitor cells (ARPCs) participate in kidney repair processes, and may be used as a possible treatment to promote regeneration in acute kidney injury. Here, we show that human tubular ARPCs (tARPCs) protect physically injured or chemically damaged renal proximal tubular epithelial cells (RPTECs) by preventing cisplatin-induced apoptosis and enhancing proliferation of survived cells. tARPCs without toll-like receptor 2 (TLR2) expression or TLR2 blocking completely abrogated this regenerative effect. Only tARPCs, and not glomerular ARPCs, were able to induce tubular cell regeneration process and it occurred only after damage detection. Moreover, we have found that ARPCs secreted inhibin-A and decorin following the RPTEC damage and that these secreted factors were directly involved in cell regeneration process. Polysaccharide synthetic vesicles containing these molecules were constructed and co-cultured with cisplatin damaged RPTECs. These synthetic vesicles were not only incorporated into the cells, but they were also able to induce a substantial increase in cell number and viability. The findings of this study increase the knowledge of renal repair processes and may be the first step in the development of new specific therapeutic strategies for renal repair.
Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals
Authors: Wölnerhanssen Bettina K. , Moran Andrew W. , Burdyga Galina , Meyer-Gerspach Anne Christin , Peterli Ralph , Manz Michael , Thumshirn Miriam , Daly Kristian , Beglinger Christoph , Shirazi-Beechey Soraya P. 
Published: August 2017

AbstractMorbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidly obese subjects before and 3 months after laparoscopic sleeve gastrectomy (LSG). Tissue morphology, abundance of chromogranin A, gut hormones, α-defensin, mucin 2, Na+/glucose co-transporter 1 (SGLT1) and transcription factors, Hes1, HATH1, NeuroD1, and Ngn3, were determined. In obese patients, the total number of enteroendocrine cells (EEC) and EECs containing gut hormones were significantly reduced in the stomach and duodenum, compared to lean, and returned to normality post-LSG. No changes in villus height/crypt depth were observed. A significant increase in mucin 2 and SGLT1 expression was detected in the obese duodenum. Expression levels of transcription factors required for differentiation of absorptive and secretory cell lineages were altered. We propose that in obesity, there is deregulation in differentiation of intestinal epithelial cell lineages that may influence the levels of released gut hormones. Post-LSG cellular differentiation profile is restored. An understanding of molecular mechanisms controlling epithelial cell differentiation in the obese intestine assists in the development of non-invasive therapeutic strategies.
Inhibition of connexin hemichannels alleviates non-alcoholic steatohepatitis in mice
Authors: Willebrords Joost , Cogliati Bruno , Pereira Isabel Veloso Alves , da Silva Tereza Cristina , Crespo Yanguas Sara , Maes Michaël , Govoni Veronica Mollica , Lima Andressa , Felisbino Daniele Aparecida , Decrock Elke , Nogueira Marina Sayuri , de Castro Inar Alves , Leclercq Isabelle , Leybaert Luc , Rodrigues Robim Marcelino , Vinken Mathieu 
Published: August 2017

AbstractWhile gap junctions mediate intercellular communication and support liver homeostasis, connexin hemichannels are preferentially opened by pathological stimuli, including inflammation and oxidative stress. The latter are essential features of non-alcoholic steatohepatitis. In this study, it was investigated whether connexin32 and connexin43 hemichannels play a role in non-alcoholic steatohepatitis. Mice were fed a choline-deficient high-fat diet or normal diet for 8 weeks. Thereafter, TAT-Gap24 or TAT-Gap19, specific inhibitors of hemichannels composed of connexin32 and connexin43, respectively, were administered for 2 weeks. Subsequently, histopathological examination was carried out and various indicators of inflammation, liver damage and oxidative stress were tested. In addition, whole transcriptome microarray analysis of liver tissue was performed. Channel specificity of TAT-Gap24 and TAT-Gap19 was examined in vitro by fluorescence recovery after photobleaching analysis and measurement of extracellular release of adenosine triphosphate. TAT-Gap24 and TAT-Gap19 were shown to be hemichannel-specific in cultured primary hepatocytes. Diet-fed animals treated with TAT-Gap24 or TAT-Gap19 displayed decreased amounts of liver lipids and inflammatory markers, and augmented levels of superoxide dismutase, which was supported by the microarray results. These findings show the involvement of connexin32 and connexin43 hemichannels in non-alcoholic steatohepatitis and, simultaneously, suggest a role as potential drug targets in non-alcoholic steatohepatitis.