Dynamics of cerebrospinal fluid levels of matrix metalloproteinases in human traumatic brain injury

Matrix metalloproteinases (MMPs) are extracellular enzymes involved in the degradation of extracellular matrix (ECM) proteins. Increased expression of MMPs have been described in traumatic brain injury (TBI) and may contribute to additional tissue injury and blood–brain barrier damage. The objectives of this study were to determine longitudinal changes in cerebrospinal fluid (CSF) concentrations of MMPs after acute TBI and in relation to clinical outcomes, with patients with idiopathic normal pressure hydrocephalus (iNPH) serving as a contrast group. The study included 33 TBI patients with ventricular CSF serially sampled, and 38 iNPH patients in the contrast group. Magnetic bead-based immunoassays were utilized to measure the concentrations of eight MMPs in ventricular human CSF. CSF concentrations of MMP-1, MMP-3 and MMP-10 were increased in TBI patients (at baseline) compared with the iNPH group (p < 0.001), while MMP-2, MMP-9 and MMP-12 did not differ between the groups. MMP-1, MMP-3 and MMP-10 concentrations decreased with time after trauma (p = 0.001–0.04). Increased concentrations of MMP-2 and MMP-10 in CSF at baseline were associated with an unfavourable TBI outcome (p = 0.002–0.02). Observed variable pattern of changes in MMP concentrations indicates that specific MMPs serve different roles in the pathophysiology following TBI, and are in turn associated with clinical outcomes

Результаты паратиреоидной аллотрансплантации

АЛЛОТРАНСПЛАНТАЦИЯГИПОПАРАТИРЕОЗИММУНОСУПРЕССИЯПАРАЩИТОВИДНЫЕ ЖЕЛЕЗЫ /хирТКАНЕВАЯ ТЕРАПИ

Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system (CNS). Small non-coding RNAs (sncRNAs) and, in particular, microRNAs (miRNAs) have frequently been associated with MS. Here, we performed a comprehensive analysis of all classes of sncRNAs in matching samples of peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells, and cell-free CSF from relapsing-remitting (RRMS, n = 12 in relapse and n = 11 in remission) patients, secondary progressive (SPMS, n = 6) MS patients, and noninflammatory and inflammatory neurological disease controls (NINDC, n = 11; INDC, n = 5). We show widespread changes in miRNAs and sncRNA-derived fragments of small nuclear, nucleolar, and transfer RNAs. In CSF cells, 133 out of 133 and 115 out of 117 differentially expressed sncRNAs were increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65 out of 67 differentially expressed PBMC sncRNAs were decreased in RRMS compared to NINDC. The striking contrast between the periphery and CNS suggests that sncRNA-mediated mechanisms, including alternative splicing, RNA degradation, and mRNA translation, regulate the transcriptome of pathogenic cells primarily in the CNS target organ.Peer reviewe

A serum protein biomarker panel improves outcome prediction in human traumatic brain injury

Brain-enriched protein biomarkers of tissue fate are being introduced clinically to aid in traumatic brain injury (TBI) management. The aim of this study was to determine how concentrations of six different protein biomarkers, measured in samples collected during the first weeks after TBI, relate to injury severity and outcome. We included neuro-critical care TBI patients that were prospectively enrolled from 2007 to 2013, all having 1 to 3 blood samples drawn during the first two weeks. The biomarkers analyzed were S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), tau and neurofilament-Light (NF-L). Glasgow Outcome Score (GOS) was assessed at 12 months. In total, 172 patients were included. All serum markers were associated with injury severity as classified on computed tomography scans at admission. Almost all biomarkers outperformed other known outcome predictors with higher levels the first five days, correlating with unfavorable outcomes, and UCH-L1 (0.260 pseduo-R2) displaying the best discrimination in univariate analyses. After adjusting for acknowledged TBI outcome predictors, GFAP and NF-L added most independent information to predict favorable/unfavorable GOS, improving the model from 0.38 to 0.51 pseudo-R2. A correlation matrix indicated substantial co-variance, with the strongest correlation between UCH-L1, GFAP and tau (r=0.827 to 0.880). Additionally, the principal component analysis exhibited clustering of UCH-L1 and tau, as well as GFAP, S100B and NSE, which was separate from NF-L. In summary, a panel of several different protein biomarkers, all associated with injury severity, with different cellular origin and temporal trajectories, improve outcome prediction models

Genomic analysis of functional haloacid-degrading gene of bacillus megaterium strain bhs1 isolated from blue lake (mavi göl, turkey)

Purpose: Bacillus megaterium strain BHS1, isolated from an alkaline water sample taken from Mavi Golu (Blue Lake, Turkey), can grow on minimal medium containing 2,2-dichloropropionic acid. We characterized this bacterium at the genomic level. Methods: The HiSeq platform was used to carry out genome sequencing, de novo assembly, and scaffolding with strain BHS1. Next, genome data were analyzed to demarcate DNA regions containing protein-coding genes and determine the function of certain BHS1 genes. Finally, results from a colorimetric chloride ion-release assay demonstrated that strain BHS1 produces dehalogenase. Results: De novo assembly of the BHS1 genomic sequence revealed a genome size of similar to 5.37 Mb with an average G+C content of 38%. The predicted nuclear genome harbors 5509 protein-coding genes, 1353 tRNA genes, 67 rRNA genes, and 6 non-coding (mRNA) genes. Genomic mapping of strain BHS1 revealed its amenability to synthesize two families of dehalogenases (Cof-type haloacid dehalogenase IIB family hydrolase and haloacid dehalogenase type II), suggesting that these enzymes can participate in the catabolism of halogenated organic acids. The mapping identified seven Na+/H+ antiporter subunits that are vital for adaptation of the bacterium to an alkaline environment. Apart from a pairwise analysis to the well-established L-2-haloacid dehalogenases, whole-cell analysis strongly suggested that the haloacid dehalogenase type II might act stereospecifically on L-2-chloropropionic acid, D,L-2-chloropropionic acid, and 2,2-dichloropropionic acid. Whole-cell studies confirmed the utilization of these three substrates and the gene's role in dehalogenation. Conclusions: To our knowledge, this is the first report of the full genome sequence for strain BHS1, which enabled the characterization of selected genes having specific metabolic activities and their roles in the biodegradation of halogenated compounds

Научно-исследовательская, культурно-массовая, физкультурно-спортивная и общественная деятельность студентов как факторы успешности их учебно-познавательного процесса

Материалы IV Респ. науч.-метод. конф., посвящ. 120-летию со дня рождения П. О. Сухого, Гомель, 29–30 окт. 2015 г

Memory B cells activate brain-homing, autoreactive CD4(+) T cells in multiple sclerosis

Multiple sclerosis is an autoimmune disease that is caused by the interplay of genetic, particularly the HLA-DR15 haplotype, and environmental risk factors. How these etiologic factors contribute to generating an autoreactive CD4+ T cell repertoire is not clear. Here, we demonstrate that self-reactivity, defined as “autoproliferation” of peripheral Th1 cells, is elevated in patients carrying the HLA-DR15 haplotype. Autoproliferation is mediated by memory B cells in a HLA-DR-dependent manner. Depletion of B cells in vitro and therapeutically in vivo by anti-CD20 effectively reduces T cell autoproliferation. T cell receptor deep sequencing showed that in vitro autoproliferating T cells are enriched for brain-homing T cells. Using an unbiased epitope discovery approach, we identified RASGRP2 as target autoantigen that is expressed in the brain and B cells. These findings will be instrumental to address important questions regarding pathogenic B-T cell interactions in multiple sclerosis and possibly also to develop novel therapies

The humanistic roots of Islamic administration and leadership for education : philosophical foundations for cross-cultural and transcultural teaching

For a number of decades, a humanistic approach has been a minor but persistent one in the Western field of administrative and leadership studies, and only recently has been broadening to include other humanist traditions (Dierksmeier et al., 2011) and has yet to be fully explored in educational administration and its pedagogy and curriculum although some foundational work has been done (e.g., Samier, 2005). The focus in this chapter is on the Islamic humanist tradition as it relates to the teaching of educational administration and leadership in a Muslim context, with implications for cross-cultural and transcultural use. The second purpose of the chapter is to show the correspondences that exist between the Islamic and Western humanist traditions in terms of human values, knowledge and educational ideal, which in this chapter are argued to be close to the Western Idealist tradition and the German Bildung conception of education as well as the strong interpretive and hermeneutic foundations that originated in the Islamic tradition and which influenced the foundations of many relevant European schools of thought, particularly in the Enlightenment.The initial section of the chapter is a comparative examination of the central principles of the Islamic humanist tradition from the classical through to contemporary times with the Western humanist tradition as they relate to conceptions of the good, ethics, the construction of meaning and a set of higher order values predicated upon human dignity, integrity, empathy, well-being, and the public good (Goodman, 2003) covering a number of important scholars like Al Farabi, al Isfanhani, and Edward Said (e.g., Kraemer, 1986). In both, professions are viewed as meaningful work that allow for large measures of decision making, and are grounded in human qualities and needs including autonomy, freedom and emancipation balanced with responsibilities, obligations and duties to society. These are compared with the corresponding principles of knowledge in Western humanism which includes a strong constructivist view of reality (Makdisi, 1990). Secondly, the chapter examines the principles of good or ideal leadership and administration that humanism aims at in its preparation of officials, including those in the educational sector in both the classical Islamic tradition (Hassi, 2012) and Western approaches to humanistic administration and leadership (Czarniawska-Joerges & Guillet de Monthoux, 1994; Gagliardi & Czarniawska, 2006; Leoussi, 2000). The third section focusses on close correspondences that exist between the Islamic (Afsaruddin, 2016; al-Attas, 1980; Yasin & Jani, 2013) and Western (Aloni, 2007; Veugelers, 2011) humanist education traditions in terms of educational ideal as well as the kind of teaching practices that distinguish these traditions (Daiber, 2013; Dossett, 2014) as they apply to educational administration and leadership (Greenfield & Ribbins, 1993). The chapter concludes with a discussion of how the Islamic humanist tradition can contribute to cross-cultural and transcultural graduate teaching in international educational administration (Khan & Amann, 2013)

Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin