Predictors of Postconcussion Symptomatology in a Mild Head Injury College Population.

Mild head injury is the most common form of head injury and the majority of individuals who sustain such injuries are young adults. Following mild head injury, individuals often complain of a number of physical, cognitive, and behavioral symptoms referred to as postconcussion symptoms (PCS). The most commonly reported postconcussion symptoms are headache, dizziness, decreased concentration, memory problems, irritability, fatigue, visual disturbances, sensitivity to noise, judgement problems, and anxiety. These symptoms can persist from months to years following injury and may even be permanent and cause disability (Brown, Fann, & Grant, 1994; Gouvier, Cubic, Jones, Brantley, and Cutlip, 1992). Both organic and psychological etiologies have been suggested for persistent PCS and most investigators now believe that a combination of multiple organic and psychological factors contribute to the development and continuation of these symptoms (Bohnen & Jolles, 1992). A number of neurocognitive, psychosocial, premorbid, and injury-related variables have been implicated in the development of persistent PCS including reduced information processing, increased psychological distress, external locus of control, female gender, positive premorbid history of psychological disturbance, and previous history of head injury. However, the findings among the various research studies have been conflicting. Determining the variables that influence the development of persisting PCS is important for identifying those at risk for chronic PCS following mild head injury and subsequently for tailoring preventative and palliative intervention strategies to manage PCS. Given this information, the present study attempted to identify premorbid/injury-related, neurocognitive, and psychosocial factors associated with persistent postconcussion symptomatology among mildly head-injured college students. The findings demonstrated that current psychological distress and female gender were the best predictors of PCS; high rates of PCS were associated with the presence of either of these factors. Decreased information processing and external locus of control were also related to PCS, but the relationships were weak. Prior head injury and premorbid history of psychological problems were not related to PCS. The results suggest that emotional status and gender are more important in predicting persistent PCS than neurocognitive status, psychological history, or history of previous mild head injury

Polyadenylation regulates the stability of Trypanosoma brucei mitochondrial RNAs

Polyadenylation of RNAs plays a critical role in modulating rates of RNA turnover and ultimately in controlling gene expression in all systems examined to date. In mitochondria, the precise mechanisms by which RNAs are degraded, including the role of polyadenylation, are not well understood. Our previous in organello pulse-chase experiments suggest that poly(A) tails stimulate degradation of mRNAs in the mitochondria of the protozoan parasite Trypanosoma brucei (Militello, K. T., and Read, L. K. (2000) Mol. Cell. Biol. 21, 731-742). In this report, we developed an in vitro assay to directly examine the effects of specific 3′-sequences on RNA degradation. We found that a salt-extracted mitochondrial membrane fraction preferentially degraded polyadenylated mitochondrially and non-mitochondrially encoded RNAs over their non-adenylated counterparts. A poly(A) tail as short as 5 nucleotides was sufficient to stimulate rapid degradation, although an in vivo tail length of 20 adenosines supported the most rapid decay. A poly(U) extension did not promote rapid RNA degradation, and RNA turnover was slowed by the addition of uridine residues to the poly(A) tail. To stimulate degradation, the poly(A) element must be located at the 3′ terminus of the RNA. Finally, we demonstrate that degradation of polyadenylated RNAs occurs in the 3′ to 5′ direction through the action of a hydrolytic exonuclease. These experiments demonstrate that the poly(A) tail can act as a cis-acting element to facilitate degradation of T. brucei mitochondrial mRNAs

Natively oxidized amino acid residues in the spinach cytochrome b\u3csub\u3e6\u3c/sub\u3e f complex

© 2018, Springer Science+Business Media B.V., part of Springer Nature. The cytochrome b6f complex of oxygenic photosynthesis produces substantial levels of reactive oxygen species (ROS). It has been observed that the ROS production rate by b6f is 10–20 fold higher than that observed for the analogous respiratory cytochrome bc1 complex. The types of ROS produced (O2•−, 1O2, and, possibly, H2O2) and the site(s) of ROS production within the b6f complex have been the subject of some debate. Proposed sources of ROS have included the heme bp, PQp•− (possible sources for O2•−), the Rieske iron–sulfur cluster (possible source of O2•− and/or 1O2), Chl a (possible source of 1O2), and heme cn (possible source of O2•− and/or H2O2). Our working hypothesis is that amino acid residues proximal to the ROS production sites will be more susceptible to oxidative modification than distant residues. In the current study, we have identified natively oxidized amino acid residues in the subunits of the spinach cytochrome b6f complex. The oxidized residues were identified by tandem mass spectrometry using the MassMatrix Program. Our results indicate that numerous residues, principally localized near p-side cofactors and Chl a, were oxidatively modified. We hypothesize that these sites are sources for ROS generation in the spinach cytochrome b6f complex

Application of a Novel Quantitative Tractography Based Analysis of Diffusion Tensor Imaging to Examine Fiber Bundle Length in Human Cerebral White Matter

This paper reviews basic methods and recent applications of length-based fiber bundle analysis of cerebral white matter using diffusion magnetic resonance imaging (dMRI). Diffusion weighted imaging (DWI) is a dMRI technique that uses the random motion of water to probe tissue microstructure in the brain. Diffusion tensor imaging (DTI) is an extension of DWI that measures the magnitude and direction of water diffusion in cerebral white matter, using either voxel-based scalar metrics or tractography-based analyses. More recently, quantitative tractography based on diffusion tensor imaging (qtDTI) technology has been developed to help quantify aggregate structural anatomical properties of white matter fiber bundles, including both scalar metrics of bundle diffusion and more complex morphometric properties, such as fiber bundle length (FBL). Unlike traditional scalar diffusion metrics, FBL reflects the direction and curvature of white matter pathways coursing through the brain and is sensitive to changes within the entire tractography model. In this paper, we discuss applications of this approach to date that have provided new insights into brain organization and function. We also discuss opportunities for improving the methodology through more complex anatomical models and potential areas of new application for qtDTI

Topological organization of whole-brain white matter in HIV infection

Infection with human immunodeficiency virus (HIV) is associated with neuroimaging alterations. However, little is known about the topological organization of whole-brain networks and the corresponding association with cognition. As such, we examined structural whole-brain white matter connectivity patterns and cognitive performance in 29 HIV+ young adults (mean age = 25.9) with limited or no HIV treatment history. HIV+ participants and demographically similar HIV− controls (n = 16) residing in South Africa underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural network models were constructed using diffusion MRI-based multifiber tractography and T(1)-weighted MRI-based regional gray matter segmentation. Global network measures included whole-brain structural integration, connection strength, and structural segregation. Cognition was measured using a neuropsychological global deficit score (GDS) as well as individual cognitive domains. Results revealed that HIV+ participants exhibited significant disruptions to whole-brain networks, characterized by weaker structural integration (characteristic path length and efficiency), connection strength, and structural segregation (clustering coefficient) than HIV− controls (p < 0.05). GDSs and performance on learning/recall tasks were negatively correlated with the clustering coefficient (p < 0.05) in HIV+ participants. Results from this study indicate disruption to brain network integrity in treatment-limited HIV+ young adults with corresponding abnormalities in cognitive performance

Estimating survival in patients with gastrointestinal cancers and brain metastases: An update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA).

BackgroundPatients with gastrointestinal cancers and brain metastases (BM) represent a unique and heterogeneous population. Our group previously published the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with GI cancers (GI-GPA) (1985-2007, n = 209). The purpose of this study is to update the GI-GPA based on a larger contemporary database.MethodsAn IRB-approved consortium database analysis was performed using a multi-institutional (18), multi-national (3) cohort of 792 patients with gastrointestinal (GI) cancers, with newly-diagnosed BM diagnosed between 1/1/2006 and 12/31/2017. Survival was measured from date of first treatment for BM. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. These factors were incorporated into the updated GI-GPA.ResultsMedian survival (MS) varied widely by primary site and other prognostic factors. Four significant factors (KPS, age, extracranial metastases and number of BM) were used to formulate the updated GI-GPA. Overall MS for this cohort remains poor; 8 months. MS by GPA was 3, 7, 11 and 17 months for GPA 0-1, 1.5-2, 2.5-3.0 and 3.5-4.0, respectively. &gt;30% present in the worst prognostic group (GI-GPA of ≤1.0).ConclusionsBrain metastases are not uncommon in GI cancer patients and MS varies widely among them. This updated GI-GPA index improves our ability to estimate survival for these patients and will be useful for therapy selection, end-of-life decision-making and stratification for future clinical trials. A user-friendly, free, on-line app to calculate the GPA score and estimate survival for an individual patient is available at brainmetgpa.com

Tissue Transglutaminase Is a Negative Regulator of Monomeric Lacritin Bioactivity

PURPOSE. Molar accounting of bioactive fluids can expose new regulatory mechanisms in the growing proteomic focus on epithelial biology. Essential for the viability of the surface epithelium of the eye and for normal vision is the thin, but protein-rich, tear film in which the small tear glycoprotein lacritin appears to play a prominent prosecretory, cytoprotective, and mitogenic role. Although optimal bioactive levels in cell culture are 1 to 10 nM over a biphasic dose optimum, ELISA suggests a sustained tear lacritin concentration in the midmicromolar range in healthy adults. Here we identify a reconciling mechanism. METHODS. Monoclonal anti-lacritin 1F5 antibody was generated, and applied together with a new anti-C-terminal polyclonal antibody to tear and tissue Western blotting. In vitro tissue transglutaminase (Tgm2) cross-linking was monitored and characterized by mass spectrometry. RESULTS. Blotting for lacritin in human tears or saliva surprisingly detected immunoreactive material with a higher molecular weight and prominence equal or exceeding the~23 to 25 kDa band of monomeric glycosylated lacritin. Exogenous Tgm2 initiated lacritin cross-linking within 1 minute and was complete by 90 minutes-even with as little as 0.1 nM lacritin, and involved the donors lysine 82 and 85 and the acceptor glutamine 106 in the syndecan-1 binding domain. Lacritin spiked into lacritin-depleted tears formed multimers, in keeping with~0.6 lM TGM2 in tears. Cross-linking was absent when Tgm2 was inactive, and cross-linked lacritin, unlike recombinant monomer, bound syndecan-1 poorly. Enhanced TGM2 expression correlates with reduced cell viability, caspase activation, TNF receptor clustering, 7 and mitochondrial dysfunction 8 associated with hyperosmolar stress in dry eye. 14 Could TGM2 in tears regulate ocular surface biology? Lacritin is a 12.3 kDa tear prosecretory mitogen 15 with glutamine and lysine residues suitable for TGM2 catalyzed cross-linking. Lacritin promotes corneal epithelial cell survival (Zimmerman K, et al. IOVS 2012;53:ARVO E-Abstract 4231) and proliferation