A computational model of the cerebrospinal fluid system incorporating lumped-parameter cranial compartment and one-dimensional distributed spinal compartment

The dynamic transmission of pressure through the cerebro-circulatory system may play a role in the genesis of pathological conditions of the brain and spinal cord. This study aims to lay down the foundations for computer modelling of the cerebrospinal (CSF) pressure dynamics in the cranio-spinal cavity as a single entity. The cerebro-vascular system was modelled as a set of resistors and capacitors. The model of the CSF space comprised a lumped cranial compartment and a distributed spinal compartment. Apart from simulating normal (baseline) conditions, the effects of jugular vein compression, and thoracic pressure elevation by coughing were investigated by applying pressure waveforms at the appropriate points in the model. The Chiari malformation was simulated by assigning high resistance to the circulation of the CSF between the cranium and the spine. The model was capable of reproducing physiologically plausible results for all forms of excitation. The spinal cavity behaved effectively as a lumped compartment, except for the cough excitation where wave-type behaviour was evident. In that case, the Chiari obstruction resulted in prolonged periodic straining of the spinal cord. This result can be of significance for understanding the mechanism of the formation of cysts in the spinal cord.     

Differential membrane redistribution of P2X receptor isoforms in response to osmotic and hyperglycemic stress in the rat lens

P2X_{1, 2, 3, 4, 6 and 7} are all expressed in a differentiation-dependent manner in the rat lens. However, in the lens outer cortex the subcellular distribution of all P2X isoforms is predominantly associated with a pool of receptors located in cytoplasmic vesicles. Here we investigate whether osmotic and hyperglycemic stress can alter the subcellular distribution of this cytoplasmic pool of P2X receptors. We show that in a discrete zone of the deeper outer cortex an isoform and stimulus-specific shift in the subcellular distribution of P2X receptors occurs from the cytoplasm to defined membrane domains. In response to hypertonic stress P2X₁ and P2X₄ isoforms became more closely associated with the broad sides of fiber cells, while under hypotonic conditions P2X₄ and P2X₆ isoforms associate with the narrow side membranes. No such changes in subcellular distribution were observed for P2X_{2,3 and 7} isoforms. Lens cultured in 50 mM glucose exhibited cell swelling in this zone but only P2X₄ associated with narrow side membranes. Our results indicate P2X receptors can be differentially recruited to specific membrane domains of lens fiber cells by osmotic and hyperglycemic stress. Furthermore they suggest the involvement of specific P2X isoforms in the regulation of fiber cell volume and the initiation of diabetic cataract.     

The Role of Human Error Analysis in Occupational and Environmental Risk Assessment: A Serbian Experience

Human error analysis is certainly a challenge today for all involved in safety and environmental risk assessment. The risk assessment process should not ignore the role of humans in accidental events and the consequences that may derive from human error. This article presents a case study of the Success Likelihood Index Method (SLIM) applied to the Electric Power Company of Serbia (EPCS), with the aim to disclose the importance of human error analysis in risk assessment. A database on work-related injuries, accidents, and critical interventions that occurred over a 10-year period in the EPCS provided the basis for this study. The research comprised analysis of 1074 workplaces, with a total of 3997 employees. A detailed analysis identified 10 typical human errors, performance shaping factors (PSFs), and estimated human error probability (HEP). Based on the obtained research results one can conclude that PSF control remains crucial for human error reduction, and thus prevention of occupational injuries and fatalities (the number of injuries decreased from 58 in 2012 to 44 in 2013, no fatalities recorded). Furthermore, the case study performed at the EPCS confirmed that the SLIM is highly applicable for quantification of human errors, comprehensive, and easy to perform.     

Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host

Dengue virus (DENV), a flavivirus of global importance, is transmitted to humans by mosquitoes. In this study, we developed in vitro and in vivo models of saliva-mediated enhancement of DENV infectivity. Serine protease activity in Aedes aegypti saliva augmented virus infectivity in vitro by proteolyzing extracellular matrix proteins, thereby increasing viral attachment to heparan sulfate proteoglycans and inducing cell migration. A serine protease inhibitor reduced saliva-mediated enhancement of DENV in vitro and in vivo, marked by a 100-fold reduction in DENV load in murine lymph nodes. A saliva-mediated infectivity enhancement screen of fractionated salivary gland extracts identified serine protease CLIPA3 as a putative cofactor, and short interfering RNA knockdown of CLIPA3 in mosquitoes demonstrated its role in influencing DENV infectivity. Molecules in mosquito saliva that facilitate viral infectivity in the vertebrate host provide novel targets that may aid in the prevention of disease.     

GWAS‐based pathway analysis differentiates between fluid and crystallized intelligence

Cognitive abilities vary among people. About 40–50% of this variability is due to general intelligence (g), which reflects the positive correlation among individuals' scores on diverse cognitive ability tests. g is positively correlated with many life outcomes, such as education, occupational status and health, motivating the investigation of its underlying biology. In psychometric research, a distinction is made between general fluid intelligence (gF) – the ability to reason in novel situations – and general crystallized intelligence (gC) – the ability to apply acquired knowledge. This distinction is supported by developmental and cognitive neuroscience studies. Classical epidemiological studies and recent genome‐wide association studies (GWASs) have established that these cognitive traits have a large genetic component. However, no robust genetic associations have been published thus far due largely to the known polygenic nature of these traits and insufficient sample sizes. Here, using two GWAS datasets, in which the polygenicity of gF and gC traits was previously confirmed, a gene‐ and pathway‐based approach was undertaken with the aim of characterizing and differentiating their genetic architecture. Pathway analysis, using genes selected on the basis of relaxed criteria, revealed notable differences between these two traits. gF appeared to be characterized by genes affecting the quantity and quality of neurons and therefore neuronal efficiency, whereas long‐term depression (LTD) seemed to underlie gC. Thus, this study supports the gF–gC distinction at the genetic level and identifies functional annotations and pathways worthy of further investigation.     

Staphylococcus stepanovicii sp. nov., a novel novobiocin-resistant oxidase-positive staphylococcal species isolated from wild small mammals

Five novobiocin-resistant and oxidase-positive staphylococcal strains were isolated from wild small mammals. Phenotypic studies and phylogenetic analysis based on 16S rRNA, rpoB and dnaJ gene sequences revealed that these strains were members of the Staphylococcus sciuri cluster group and were similar to Staphylococcus fleurettii. DNA–DNA hybridisation with closely related staphylococcal species suggested that the strains represented a novel species. The name Staphylococcus stepanovicii is proposed, and the type strain is 196^T (=PCM 2693^T =CCM 7717^T).