White matter injury restoration after stem cell administration in subcortical ischemic stroke

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Introduction]: An animal model of subcortical ischemic stroke with white matter affectation was induced in rats by injection of endothelin-1. At 24 hours, 2 × 10 6 ADMSC were administered intravenously to the treatment group. Functional evaluation, lesion size, fiber tract integrity, cell death, proliferation, white matter repair markers (Olig-2, NF, and MBP) and NogoA were all studied after sacrifice (7 days and 28 days). ADMSC migration and implantation in the brain as well as proteomics analysis and functions of the secretome were also analyzed. [Results]: Neither ADMSC migration nor implantation to the brain was observed after ADMSC administration. In contrast, ADMSC implantation was detected in peripheral organs. The treatment group showed a smaller functional deficit, smaller lesion area, less cell death, more oligodendrocyte proliferation, more white matter connectivity and higher amounts of myelin formation. The treated animals also showed higher levels of white matter-associated markers in the injured area than the control group. Proteomics analysis of the ADMSC secretome identified 2,416 proteins, not all of them previously described to be involved in brain plasticity. [Conclusions]: White matter integrity in subcortical stroke is in part restored by ADMSC treatment; this is mediated by repair molecular factors implicated in axonal sprouting, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery after stroke.This study was supported by research grants PS12/01754, PI11/00909 and INVICTUS (RD12/0014) (Spanish Neurovascular Network), SAF2010-37926, ProteoRed-PT13/0001/0017 and a Sara Borrell postdoctoral fellowship (CD12/00706, to LOO) from Research Institute Carlos III, Ministry of Science and Innovation of Spain. Furthermore, TS (CP12/03121) and FC (CP14/00154) are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III-Peer Reviewe

Aneurismal subarachnoid hemorrhage in a Chilean population, with emphasis on risk factors

<p>Abstract</p> <p>Background</p> <p>Subarachnoid Hemorrhage (SAH) is caused principally by the rupture of intracranial aneurisms. Important risk factors have been described such as age, sex, hypertension (HT) and season of the year, among others. The objective is to investigate the demographic characteristics and possible risk factors in a population of Chilean patients.</p> <p>Methods</p> <p>This retrospective study was based on the analysis of 244 clinical records of patients diagnosed with aneurismal SAH who were discharged from the Instituto de Neurocirugía ASENJO in Santiago, Chile.</p> <p>Results</p> <p>The mean age of patients was 49.85 years and the male:female ratio was 1:2.7. The signs and symptoms were not different between sexes; cephalea (85.7%) was predominant, followed by loss of consciousness, vomiting/nausea and meningeal signs. Risk factors included sex, age and HT. Concordant with other reports, the incidence of SAH was greatest in spring.</p> <p>Conclusions</p> <p>The demographic characteristics and risk factors observed in patients with aneurismal SAH treated in ASENJO were comparable to those of other populations. We were not able to conclude that tobacco and alcohol consumption were risk factors for this population.</p

State-Space Analysis of Time-Varying Higher-Order Spike Correlation for Multiple Neural Spike Train Data

Precise spike coordination between the spiking activities of multiple neurons is suggested as an indication of coordinated network activity in active cell assemblies. Spike correlation analysis aims to identify such cooperative network activity by detecting excess spike synchrony in simultaneously recorded multiple neural spike sequences. Cooperative activity is expected to organize dynamically during behavior and cognition; therefore currently available analysis techniques must be extended to enable the estimation of multiple time-varying spike interactions between neurons simultaneously. In particular, new methods must take advantage of the simultaneous observations of multiple neurons by addressing their higher-order dependencies, which cannot be revealed by pairwise analyses alone. In this paper, we develop a method for estimating time-varying spike interactions by means of a state-space analysis. Discretized parallel spike sequences are modeled as multi-variate binary processes using a log-linear model that provides a well-defined measure of higher-order spike correlation in an information geometry framework. We construct a recursive Bayesian filter/smoother for the extraction of spike interaction parameters. This method can simultaneously estimate the dynamic pairwise spike interactions of multiple single neurons, thereby extending the Ising/spin-glass model analysis of multiple neural spike train data to a nonstationary analysis. Furthermore, the method can estimate dynamic higher-order spike interactions. To validate the inclusion of the higher-order terms in the model, we construct an approximation method to assess the goodness-of-fit to spike data. In addition, we formulate a test method for the presence of higher-order spike correlation even in nonstationary spike data, e.g., data from awake behaving animals. The utility of the proposed methods is tested using simulated spike data with known underlying correlation dynamics. Finally, we apply the methods to neural spike data simultaneously recorded from the motor cortex of an awake monkey and demonstrate that the higher-order spike correlation organizes dynamically in relation to a behavioral demand

Macrophage-Derived IL1β and TNFα Regulate Arginine Metabolism in Neuroblastoma.

Neuroblastoma is the most common childhood solid tumor, yet the prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting arginine metabolism, either by blocking cationic amino acid transporter 1 (CAT-1)-dependent arginine uptake in vitro or therapeutic depletion of arginine by pegylated recombinant arginase BCT-100, significantly delayed tumor development and prolonged murine survival. Tumor cells polarized infiltrating monocytes to an M1-macrophage phenotype, which released IL1β and TNFα in a RAC-alpha serine/threonine-protein kinase (AKT)-dependent manner. IL1β and TNFα established a feedback loop to upregulate ARG2 expression via p38 and extracellular regulated kinases 1/2 (ERK1/2) signaling in neuroblastoma and neural crest-derived cells. Proteomic analysis revealed that enrichment of IL1β and TNFα in stage IV human tumor microenvironments was associated with a worse prognosis. These data thus describe an immune-metabolic regulatory loop between tumor cells and infiltrating myeloid cells regulating ARG2, which can be clinically exploited. SIGNIFICANCE: These findings illustrate that cross-talk between myeloid cells and tumor cells creates a metabolic regulatory loop that promotes neuroblastoma progression

The Hi-GAL compact source catalogue – I. The physical properties of the clumps in the inner Galaxy (−71. ◦ 0 < ℓ < 67.◦ 0)

Hi-GAL (Herschel InfraRed Galactic Plane Survey) is a large-scale survey of the Galactic plane, performed with Herschel in five infrared continuum bands between 70 and 500 µm. We present a band-merged catalogue of spatially matched sources and their properties derived from fits to the spectral energy distributions (SEDs) and heliocentric distances, based on the photometric catalogues presented in Molinari et al., covering the portion of Galactic plane −71.◦ 0 < ℓ < 67.◦ 0. The band-merged catalogue contains 100 922 sources with a regular SED, 24 584 of which show a 70-µm counterpart and are thus considered protostellar, while the remainder are considered starless. Thanks to this huge number of sources, we are able to carry out a preliminary analysis of early stages of star formation, identifying the conditions that characterize different evolutionary phases on a statistically significant basis. We calculate surface densities to investigate the gravitational stability of clumps and their potential to form massive stars. We also explore evolutionary status metrics such as the dust temperature, luminosity and bolometric temperature, finding that these are higher in protostellar sources compared to pre-stellar ones. The surface density of sources follows an increasing trend as they evolve from pre-stellar to protostellar, but then it is found to decrease again in the majority of the most evolved clumps. Finally, we study the physical parameters of sources with respect to Galactic longitude and the association with spiral arms, finding only minor or no differences between the average evolutionary status of sources in the fourth and first Galactic quadrants, or between 'on-arm' and 'interarm' positions

Leadership = Communication? The relations of leaders' communication styles with leadership styles, knowledge sharing and leadership outcomes

Purpose: The purpose of this study was to investigate the relations between leaders' communication styles and charismatic leadership, human-oriented leadership (leader's consideration), task-oriented leadership (leader's initiating structure), and leadership outcomes. Methodology: A survey was conducted among 279 employees of a governmental organization. The following six main communication styles were operationalized: verbal aggressiveness, expressiveness, preciseness, assuredness, supportiveness, and argumentativeness. Regression analyses were employed to test three main hypotheses. Findings: In line with expectations, the study showed that charismatic and human-oriented leadership are mainly communicative, while task-oriented leadership is significantly less communicative. The communication styles were strongly and differentially related to knowledge sharing behaviors, perceived leader performance, satisfaction with the leader, and subordinate's team commitment. Multiple regression analyses showed that the leadership styles mediated the relations between the communication styles and leadership outcomes. However, leader's preciseness explained variance in perceived leader performance and satisfaction with the leader above and beyond the leadership style variables. Implications: This study offers potentially invaluable input for leadership training programs by showing the importance of leader's supportiveness, assuredness, and preciseness when communicating with subordinates. Originality/value: Although one of the core elements of leadership is interpersonal communication, this study is one of the first to use a comprehensive communication styles instrument in the study of leadership. © 2009 The Author(s)

Genomic Hypomethylation in the Human Germline Associates with Selective Structural Mutability in the Human Genome

The hotspots of structural polymorphisms and structural mutability in the human genome remain to be explained mechanistically. We examine associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination (NAHR) mediated by low-copy repeats (LCRs). Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability. Specifically, methylation deserts, the ∼1% fraction of the human genome with the lowest methylation in the germline, show a tenfold enrichment for structural rearrangements that occurred in the human genome since the branching of chimpanzee and are highly enriched for fast-evolving loci that regulate tissue-specific gene expression. Analysis of copy number variants (CNVs) from 400 human samples identified using a custom-designed array comparative genomic hybridization (aCGH) chip, combined with publicly available structural variation data, indicates that association of structural mutability with germline hypomethylation is comparable in magnitude to the association of structural mutability with LCR–mediated NAHR. Moreover, rare CNVs occurring in the genomes of individuals diagnosed with schizophrenia, bipolar disorder, and developmental delay and de novo CNVs occurring in those diagnosed with autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between the epigenome, selective mutability, evolution, and human disease

A Systematic Analysis on DNA Methylation and the Expression of Both mRNA and microRNA in Bladder Cancer

Background: DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. Methodology/Principal Findings: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to "neurogenesis" and "cell differentiation" by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. Conclusions/Significance: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research