Developmental Dyslexia: Evidence for a Subgroup with a Reversal of Cerebral Asymmetry

The Computerized Brain Tomograms of 24 Patients with Developmental Dyslexia Were Analyzed for Cerebral Asymmetry. Ten Patients Showed a Reversal of the Pattern of Asymmetry Regularly Observed in Normal Right-Handed Individuals So that the Right Parietooccipital Region Was Wider Than the Left. the Ten Dyslexic Patients with This Reversal of Cerebral Asymmetry Had a Lower Mean Verbal IQ Than the Other 14 Dyslexic Patients in This Study. the Reversal of Cerebral Asymmetry that Occurred in Ten of the Dyslexic Patients May Result in Language Lateralization to a Cerebral Hemisphere that is Structurally Less Suited to Support Language Function and Thus Act as a Risk Factor for the Development of Reading Disability. © 1978, American Medical Association. All Rights Reserved

Vasodilator Phosphostimulated Protein (VASP) Protects Endothelial Barrier Function During Hypoxia

The endothelial barrier controls the passage of solutes from the vascular space. This is achieved through active reorganization of the actin cytoskeleton. A central cytoskeletal protein involved into this is vasodilator-stimulated phosphoprotein (VASP). However, the functional role of endothelial VASP during hypoxia has not been thoroughly elucidated. We determined endothelial VASP expression through real-time PCR (Rt-PCR), immunhistochemistry, and Western blot analysis during hypoxia. VASP promoter studies were performed using a PGL3 firefly luciferase containing plasmid. Following approval by the local authorities, VASP−/− mice and littermate controls were subjected to normobaric hypoxia (8% O2, 92% N2) after intravenous injection of Evans blue dye. In in vitro studies, we found significant VASP repression in human microvascular and human umbilical vein endothelial cells through Rt-PCR, immunhistochemistry, and Western blot analysis. The VASP promoter construct demonstrated significant repression in response to hypoxia, which was abolished when the binding of hypoxia-inducible factor 1 alpha was excluded. Exposure of wild-type (WT) and VASP−/− animals to normobaric hypoxia for 4 h resulted in an increase in Evans blue tissue extravasation that was significantly increased in VASP−/− animals compared to WT controls. In summary, we demonstrate here that endothelial VASP holds significant importance for endothelial barrier properties during hypoxia

Lessons learned from monitoring of turbidity currents and guidance for future platform designs

Turbidity currents transport globally significant volumes of sediment and organic carbon into the deep-sea and pose a hazard to critical infrastructure. Despite advances in technology, their powerful nature often damages expensive instruments placed in their path. These challenges mean that turbidity currents have only been measured in a few locations worldwide, in relatively shallow water depths (≪2 km). Here, we share lessons from recent field deployments about how to design the platforms on which instruments are deployed. First, we show how monitoring platforms have been affected by turbidity currents including instability, displacement, tumbling and damage. Second, we relate these issues to specifics of the platform design, such as exposure of large surface area instruments within a flow and inadequate anchoring or seafloor support. Third, we provide recommended improvements to improve design by simplifying mooring configurations, minimising surface area, and enhancing seafloor stability. Finally we highlight novel multi-point moorings that avoid interaction between the instruments and the flow, and flow-resilient seafloor platforms with innovative engineering design features, such as ejectable feet and ballast. Our experience will provide guidance for future deployments, so that more detailed insights can be provided into turbidity current behaviour, and in a wider range of settings

The Incidence of Adjacent Segment Degeneration after Cervical Disc Arthroplasty (CDA): A Meta Analysis of Randomized Controlled Trials

Cervical disc arthroplasty is being used as an alternative degenerative disc disease treatment with fusion of the cervical spine in order to preserve motion. However, whether replacement arthoplasty in the spine achieves its primary patient centered objective of lowering the frequency of adjacent segment degeneration is not verified yet.We conducted a meta-analysis according to the guidelines of the Cochrane Collaboration using databases including PubMed, Cochrane Central Register of Controlled Trials and Embase. The inclusion criteria were: 1) Randomized, controlled study of degenerative disc disease of the cervical spine involving single segment or double segments using Cervical disc arthroplasty (CDA) with anterior cervical discectomy and fusion (ACDF) as controls; 2) A minimum of two-year follow-up using imaging and clinical analyses; 3) Definite diagnostic evidences for "adjacent segment degeneration" and "adjacent segment disease"; 4) At least a minimum of 30 patients per population. Two authors independently selected trials; assessed methodological quality, extracted data and the results were pooled.No study has specifically compared the results of adjacent segment degenerative; Two papers describing 140 patients with 162 symptomatic cervical segment disorders and compared the rate of postoperative adjacent segment disease development between CDA and ACDF treatments, three publications describing the rate of adjacent-segment surgery including 1273 patients with symptomatic cervical segments. The result of the meta-analysis indicates that there were fewer the rate of adjacent segment disease and the rate for adjacent-segment surgery comparing CDA with ACDF, but the difference was not statistically significant.Based on available evidence, it cannot be concluded, that CDA can significantly reduce the postoperative rate of the adjacent segment degenerative and adjacent segment disease. However, due to some limitations, the results of this meta-analysis should be cautiously accepted, and further studies are needed

Deficiency of Vasodilator-Stimulated Phosphoprotein (VASP) Increases Blood-Brain-Barrier Damage and Edema Formation after Ischemic Stroke in Mice

Background: Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification. Methodology/Principal Findings: Focal cerebral ischemia was induced in Vasp2/2 mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan’s Blue tracer was applied to visualize the extent of blood-brainbarrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p,0.05) and edema volumes (1.7 mm360.5 mm3 versus 0.8 mm360.4 mm3; p,0.0001) were significantly enhanced in Vasp2/2 mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm3617.3 mm3 versus 39.3 mm3610.7 mm3, respectively; p,0.01) and a non significant trend (p.0.05) towards worse neurological outcomes. Conclusion: Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage

A meta-analysis of the investment-uncertainty relationship

In this article we use meta-analysis to investigate the investment-uncertainty relationship. We focus on the direction and statistical significance of empirical estimates. Specifically, we estimate an ordered probit model and transform the estimated coefficients into marginal effects to reflect the changes in the probability of finding a significantly negative estimate, an insignificant estimate, or a significantly positive estimate. Exploratory data analysis shows that there is little empirical evidence for a positive relationship. The regression results suggest that the source of uncertainty, the level of data aggregation, the underlying model specification, and differences between short- and long-run effects are important sources of variation in study outcomes. These findings are, by and large, robust to the introduction of a trend variable to capture publication trends in the literature. The probability of finding a significantly negative relationship is higher in more recently published studies. JEL Classification: D21, D80, E22 1

Oxygen-Independent Stabilization of Hypoxia Inducible Factor (HIF)-1 during RSV Infection

BACKGROUND: Hypoxia-inducible factor 1 (HIF)-1alpha is a transcription factor that functions as master regulator of mammalian oxygen homeostasis. In addition, recent studies identified a role for HIF-1alpha as transcriptional regulator during inflammation or infection. Based on studies showing that respiratory syncytial virus (RSV) is among the most potent biological stimuli to induce an inflammatory milieu, we hypothesized a role of HIF-1alpha as transcriptional regulator during infections with RSV. METHODOLOGY, PRINCIPAL FINDINGS: We gained first insight from immunohistocemical studies of RSV-infected human pulmonary epithelia that were stained for HIF-1alpha. These studies revealed that RSV-positive cells also stained for HIF-1alpha, suggesting concomitant HIF-activation during RSV infection. Similarly, Western blot analysis confirmed an approximately 8-fold increase in HIF-1alpha protein 24 h after RSV infection. In contrast, HIF-1alpha activation was abolished utilizing UV-treated RSV. Moreover, HIF-alpha-regulated genes (VEGF, CD73, FN-1, COX-2) were induced with RSV infection of wild-type cells. In contrast, HIF-1alpha dependent gene induction was abolished in pulmonary epithelia following siRNA mediated repression of HIF-1alpha. Measurements of the partial pressure of oxygen in the supernatants of RSV infected epithelia or controls revealed no differences in oxygen content, suggesting that HIF-1alpha activation is not caused by RSV associated hypoxia. Finally, studies of RSV pneumonitis in mice confirmed HIF-alpha-activation in a murine in vivo model. CONCLUSIONS/SIGNIFICANCE: Taking together, these studies suggest hypoxia-independent activation of HIF-1alpha during infection with RSV in vitro and in vivo

Mechanical Properties of Plant Underground Storage Organs and Implications for Dietary Models of Early Hominins

The diet of early human ancestors has received renewed theoretical interest since the discovery of elevated d13C values in the enamel of Australopithecus africanus and Paranthropus robustus. As a result, the hominin diet is hypothesized to have included C4 grass or the tissues of animals which themselves consumed C4 grass. On mechanical grounds, such a diet is incompatible with the dental morphology and dental microwear of early hominins. Most inferences, particularly for Paranthropus, favor a diet of hard or mechanically resistant foods. This discrepancy has invigorated the longstanding hypothesis that hominins consumed plant underground storage organs (USOs). Plant USOs are attractive candidate foods because many bulbous grasses and cormous sedges use C4 photosynthesis. Yet mechanical data for USOs—or any putative hominin food—are scarcely known. To fill this empirical void we measured the mechanical properties of USOs from 98 plant species from across sub-Saharan Africa. We found that rhizomes were the most resistant to deformation and fracture, followed by tubers, corms, and bulbs. An important result of this study is that corms exhibited low toughness values (mean = 265.0 J m-2) and relatively high Young’s modulus values (mean = 4.9 MPa). This combination of properties fits many descriptions of the hominin diet as consisting of hard-brittle objects. When compared to corms, bulbs are tougher (mean = 325.0 J m-2) and less stiff (mean = 2.5 MPa). Again, this combination of traits resembles dietary inferences, especially for Australopithecus, which is predicted to have consumed soft-tough foods. Lastly, we observed the roasting behavior of Hadza hunter-gatherers and measured the effects of roasting on the toughness on undomesticated tubers. Our results support assumptions that roasting lessens the work of mastication, and, by inference, the cost of digestion. Together these findings provide the first mechanical basis for discussing the adaptive advantages of roasting tubers and the plausibility of USOs in the diet of early hominins