Systemic and network functions of the microtubule-associated protein tau: Implications for tau-based therapies.

Tau is a microtubule-associated neuronal protein, whose primary role was long thought to regulate axonal microtubule assembly. Tau is subject to many posttranslational modifications and can aggregate into neurofibrillary tangles, which are considered to be a hallmark of several neurodegenerative diseases collectively called "tauopathies". The most common tauopathy is Alzheimer's disease, where tau pathology correlates with sites of neurodegeneration. Tau belongs to the class of intrinsically disordered proteins, which are known to interact with many partners and are considered to be involved in various signaling, regulation and recognition processes. Thus more recent evidence indicates that tau functionally interacts with many proteins and different cellular structures, which may have an important physiological role and may be involved in neurodegenerative processes. Furthermore, tau can be released from neurons and exert functional effects on other cells. This review article weighs the evidence that tau has subtle but important systemic effects on neuronal network function by maintaining physiological neuronal transmission and synaptic plasticity, which are possibly independent from tau's microtubule modulating activities. Implications for tau-based therapeutic approaches are discussed.

Dynamics of pre-shift and post-shift lung function parameters among wood workers in Ghana.

Background: Diseases affecting the lungs and airways contribute significantly to the global burden of disease. The problem in low- and middle-income countries appears to be exacerbated by a shift in global manufacturing base to these countries and inadequate enforcement of environmental and safety standards. In Ghana, the potential adverse effects on respiratory function associated with occupational wood dust exposure have not been thoroughly investigated. Methods: Sixty-four male sawmill workers and 64 non-woodworkers participated in this study. The concentration of wood dust exposure, prevalence and likelihood of association of respiratory symptoms with wood dust exposure and changes in pulmonary function test (PFT) parameters in association with wood dust exposure were determined from dust concentration measurements, symptoms questionnaire and lung function test parameters. Results: Sawmill workers were exposed to inhalable dust concentration of 3.09 ± 0.04 mg/m3 but did not use respirators and engaged in personal grooming habits that are known to increase dust inhalation. The sawmill operators also showed higher prevalence and likelihoods of association with respiratory symptoms, a significant cross-shift decline in some PFT parameters and a shift towards a restrictive pattern of lung dysfunction by end of daily shift. The before-shift PFT parameters of woodworkers were comparable to those of non-woodworkers, indicating a lack of chronic effects of wood dust exposure. Conclusions: Wood dust exposure at the study site was associated with acute respiratory symptoms and acute changes in some PFT parameters. This calls for institution and enforcement of workplace and environmental safety policies to minimise exposure at sawmill operating sites, and ultimately, decrease the burden of respiratory diseases.

Genetics of cerebral malaria: pathogenesis, biomarkers and emerging therapeutic interventions.

BACKGROUND: Cerebral malaria (CM) is a preeminent cause of severe disease and premature deaths in Sub-Saharan Africa, where an estimated 90% of cases occur. The key features of CM are a deep, unarousable coma that persists for longer than 1 h in patients with peripheral Plasmodium falciparum and no other explanation for encephalopathy. Significant research efforts on CM in the last few decades have focused on unravelling the molecular underpinnings of the disease pathogenesis and the identification of potential targets for therapeutic or pharmacologic intervention. These efforts have been greatly aided by the generation and study of mouse models of CM, which have provided great insights into key events of CM pathogenesis, revealed an interesting interplay of host versus parasite factors that determine the progression of malaria to severe disease and exposed possible targets for therapeutic intervention in severe disease. MAIN BODY: This paper reviews our current understanding of the pathogenic and immunologic factors involved in CM. We present the current view of the roles of certain gene products e.g., the var gene, ABCA-1, ICAM-1, TNF-alpha, CD-36, PfEMP-1 and G6PD, in CM pathogenesis. We also present alterations in the blood-brain barrier as a consequence of disease proliferation as well as complicated host and parasite interactions, including the T-cell immune reaction, reduced deformation of erythrocytes and cytoadherence. We further looked at recent advances in cerebral malaria treatment interventions by emphasizing on biomarkers, new diagnostic tools and emerging therapeutic options. CONCLUSION: Finally, we discuss how the current understanding of some of these pathogenic and immunologic factors could inform the development of novel therapeutic interventions to fight CM.

Effects of in utero exposure to monosodium glutamate on locomotion, anxiety, depression, memory and KCC2 expression in offspring.

In pregnancy, there is a significant risk for developing embryos to be adversely affected by everyday chemicals such as food additives and environmental toxins. In recent times, several studies have documented the detrimental effect of exposure to such chemicals on the behaviour and neurodevelopment of the offspring. This study evaluated the influence of the food additive, monosodium glutamate (MSG), on behaviour and development in mice. Pregnant dams were exposed to MSG 2 or 4 g/kg or distilled water from gestation day 10-20. On delivery, postnatal day 1 (PN 1), 3 pups were sacrificed and whole brain samples assayed for KCC2 expression by western blot. The remaining pups were housed until PN 43 before commencing behavioural assessment. Their weights were measured at birth and at 3 days intervals until PN 42. The impact of prenatal exposure to MSG on baseline exploratory, anxiety and depression behaviours as well as spatial and working memory was assessed. In utero exposure to 4 g/kg MSG significantly reduced exploratory drive and increased depression-like behaviours but did not exert any significant impact on anxiety-like behaviours (p < 0.01). Additionally, there was a two-fold increase in KCC2 expression in both 2 and 4 g/kg MSG-exposed offspring. CONCLUSION: This study indicates that, in utero exposure to MSG increases the expression of KCC2 and causes significant effect on locomotion and depression-like behaviours but only marginally affects memory function.

Assessment of corn starch as substitute for agarose in DNA gel electrophoresis.

OBJECTIVE: The use of agarose in nucleic acid electrophoresis is the gold standard. However, agarose is very expensive and not readily available in resource limited developing countries like Ghana. Hence, finding a more affordable and readily available alternative to agarose will be a major boost to molecular research in developing countries. This study was aimed at investigating the use of corn starch as a potential substitute for agarose in DNA gel electrophoresis. RESULTS: Genomic deoxyribonucleic acid (DNA) extracted from Plasmodium falciparum and primers were obtained from the West African Centre for Cell Biology of Infectious Pathogens and amplified using polymerase chain reaction. The amplicon was run on agarose gel to ascertain the molecular weight (as a positive control). When visualized under both blue light and ultraviolet light, the DNA and ladder showed clear and clean bands with the expected molecular weight. Corn starch was then modified with sodium borate buffer, casted into a gel and used to run the same DNA sample. Our findings indicated that similar to agarose, the DNA sample and ladder migrated successfully through the modified starch gel but no bands were visible when visualized under blue and ultra-violet light.