Views and opinion on BDNF as a target for diabetic cognitive dysfunction

Type 2 diabetes mellitus (T2DM) is a known cause of cognitive dysfunction and involves increased risk of dementia. Brain-derived neurotrophic factor (BDNF) is a member of neurotrophic family of nerve growth factors, a key protein in promoting memory, growth and survival of neurons. BDNF is recognized as a metabotrophic factor, a molecule that is involved in Alzheimer’s disease (AD) as well as in other neurological disorders. It provides cellular and local regulatory mechanisms for mediating synaptic plasticity. Impaired BDNF signaling can compromise many aspects of brain functions. Studies investigating the relationship between diabetes and BDNF in adults demonstrate that BDNF levels are decreased in T2DM and are regulated in response to plasma levels of glucose. BDNF could serve as biomarker in predicting the development of obesity and T2DM. Thirty-two cavities were predicted to locate the active sites of BDNF for the ligands to bind. The shape of the site was identified by extracting the cavity volume surfaces enclosing regions with highest probability. Different ligands can be chosen for interaction of active sites of BDNF and can be targeted for drug discovery. This review focuses on computational exploitation selectively to deliver BDNF as a drug to appropriate hypothalamic neurons, which can serve as a novel approach in diabetic encephalopathy treatment.     

Anatomical study of the skull of amphisbaenian Diplometopon zarudnyi (Squamata,Amphisbaenia)

This study investigates the amphisbaenian species skull which includes cranium, lower jaw and hyoid apparatus. The medial dorsal bones comprise the premaxilla, nasal, frontal and parietal. The premaxilla carries a large medial tooth and two lateral ones. The nasals are paired bones and separated by longitudinal suture. Bones of circumorbital series are frontal, orbitosphenoid and maxilla. The occipital ring consists of basioccipital, supraoccipital and exooccipital. Supraoccipital and basioccipital are single bones while the exo-occipitals are paired. The bones of the palate comprise premaxilla, maxilla, septomaxilla, palatine, pterygoid, ectopterygoid, basisphenoid, parasphenoid, orbitosphenoid and laterosphenoid. Prevomer and pterygoid teeth are absent. Palatine represent by two separate bones. The temporal bones are clearly visible. The lower jaw consists of the dentary, articular, coronoid, supra-angular, angular and splenial. The hyoid apparatus is represented by a Y-shaped structure. The mandible is long and is suspended from the braincase via relatively short quadrate. There is an extensive contact between the long angular and the large triangular coronoid. Thus inter-mandibular joint is bridged completely by the angular and consequently, the lower jaws are relatively rigid and kinetic. The maxillae are suspended from the braincase largely by ligaments and muscles rather than through bony articulation. In conclusion, the skull shape affects feeding strategy in Diplometopon zarudnyi. The prey is ingested and transported via a rapid maxillary raking mechanism.     

Synaptic Efficacy as a Function of Ionotropic Receptor Distribution: A Computational Study

Glutamatergic synapses are the most prevalent functional elements of information processing in the brain. Changes in pre-synaptic activity and in the function of various post-synaptic elements contribute to generate a large variety of synaptic responses. Previous studies have explored postsynaptic factors responsible for regulating synaptic strength variations, but have given far less importance to synaptic geometry, and more specifically to the subcellular distribution of ionotropic receptors. We analyzed the functional effects resulting from changing the subsynaptic localization of ionotropic receptors by using a hippocampal synaptic computational framework. The present study was performed using the EONS (Elementary Objects of the Nervous System) synaptic modeling platform, which was specifically developed to explore the roles of subsynaptic elements as well as their interactions, and that of synaptic geometry. More specifically, we determined the effects of changing the localization of ionotropic receptors relative to the presynaptic glutamate release site, on synaptic efficacy and its variations following single pulse and paired-pulse stimulation protocols. The results indicate that changes in synaptic geometry do have consequences on synaptic efficacy and its dynamics.     

Effect of Sulfuric Acid on Swelling Behavior of an Expansive Soil

Soil often becomes contaminated with a variety of chemicals due to leakage of under/aboveground chemical storage tanks, improper discharge of waste, or improper design of waste containment facilities. Contaminated soil water can influence the soil's behavior seriously. Mineralogical alterations play a vital role in such circumstances. This paper describes the impact of varying concentrations of sulfuric acid solutions on the swell behavior of expansive soil containing predominantly montmorillonite. Using the conventional oedometer tests, the swell behavior of soil compacted with water inundated with acid solutions was studied. The soil swell, which is about 2% in water, increases to about 9% with 1N and to 50% with 4N acid solutions. The induced swell in acid solutions is attributable to mineralogical changes. The formation of new minerals and their associated fabric changes are investigated by scanning electron microscopy, X-ray diffraction, and energy dispersive analysis of X-ray on soil samples treated with sulfuric acid. While minerals like gypsum and kornelite are formed in the presence of 1N sulfuric acid, aluminite and chloritoid are formed in the presence of 4N sulfuric acid. These types of alterations are known to occur in iron sulfate minerals and are also found on Mars. The mechanism of mineralogical alterations is presented.     

Tristetraprolin Mediates Radiation-Induced TNF-α Production in Lung Macrophages

The efficacy of radiation therapy for lung cancer is limited by radiation-induced lung toxicity (RILT). Although tumor necrosis factor-alpha (TNF-α) signaling plays a critical role in RILT, the molecular regulators of radiation-induced TNF-α production remain unknown. We investigated the role of a major TNF-α regulator, Tristetraprolin (TTP), in radiation-induced TNF-α production by macrophages. For in vitro studies we irradiated (4 Gy) either a mouse lung macrophage cell line, MH-S or macrophages isolated from TTP knockout mice, and studied the effects of radiation on TTP and TNF-α levels. To study the in vivo relevance, mouse lungs were irradiated with a single dose (15 Gy) and assessed at varying times for TTP alterations. Irradiation of MH-S cells caused TTP to undergo an inhibitory phosphorylation at Ser-178 and proteasome-mediated degradation, which resulted in increased TNF-α mRNA stabilization and secretion. Similarly, MH-S cells treated with TTP siRNA or macrophages isolated from ttp (−/−) mice had higher basal levels of TNF-α, which was increased minimally after irradiation. Conversely, cells overexpressing TTP mutants defective in undergoing phosphorylation released significantly lower levels of TNF-α. Inhibition of p38, a known kinase for TTP, by either siRNA or a small molecule inhibitor abrogated radiation-induced TNF-α release by MH-S cells. Lung irradiation induced TTP^Ser178 phosphorylation and protein degradation and a simultaneous increase in TNF-α production in C57BL/6 mice starting 24 h post-radiation. In conclusion, irradiation of lung macrophages causes TTP inactivation via p38-mediated phosphorylation and proteasome-mediated degradation, leading to TNF-α production. These findings suggest that agents capable of blocking TTP phosphorylation or stabilizing TTP after irradiation could decrease RILT.     

Antimicrobial and immunomodulating activities of hesperidin and ellagic acid against diarrheic Aeromonas hydrophila in a murine model

Aims

The present study is designed to evaluate the in vitro and in vivo bactericidal and immunomodulating activities of hesperidin (HES) and ellagic acid (EA) against Aeromonas hydrophila. A hydrophila, an uncommon human pathogen, can cause invasive infections in immunocompromised individuals and common clinical presentations in acute gastrointestinal illness, soft-tissue infections and sepsis. The antimicrobial activities of medicinal plants against A. hydrophila have received only cursory attention.

Methods

We examined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values in vitro. Moreover, the effects of HES and EA against bacterial colonization were studied in vivo. Also, humoral immune response was tested against A. hydrophila-LPS or A. hydrophila-ECP antigen preparations and the intestinal histopathological alterations were studied.

Results

Data revealed that the treatments with HES and EA each had antimicrobial activities against A. hydrophila. Both HES and EA treatments significantly increased anti-LPS IgM levels and reduced anti-LPS and anti-ECP IgA levels to their normal values in comparison to the infected group, which recorded significantly elevated levels two week post-infection. In conclusion, the present data suggest that HES and EA have antimicrobial and immunomodulating activities against murine A. hydrophila infections.

Significant

These data warrant clinical studies to delineate HES and EA roles in human infectious diseases.     

Monitoring of co-infection virus and virus-like naturally in sweet pepper plant

Eight sweet pepper plant samples showing viral and viral like symptoms were collected from open field and used for detecting viral infections through biological, serological and biochemical methods. DAS-ELISA, DBIA and TPIA have relative effectiveness for detecting parenchymal viruses (CMV, TMV and PVY) and vascular virus (TYLCV), and the DAS-ELISA and TPIA are found more efficient (87.5%) than DBIA (78.1%). The examined leaf samples were found co-infected with different mixed types of viruses including (CMV, TMV, PVY and TYLCV), (CMV, PVY and TYLCV), (TMV, PVY and TYLCV) and (TMV and TYLCV) that enhanced different degrees of severe external symptoms. There are 2 out of 8 samples infected with Phytoplasma sp. by Diene’s stain and PCR using generated 16S rDNA gene primer with expected amplicon size of 680?bp. The co-infections with various viruses and phytoplasma has 12.5% frequency that reduced the levels of protein content, peroxidase and polyphenol oxidase activity quantitatively and qualitatively in 2 samples in comparison with other mixed categories. The sweet pepper plant can be considered as a reservoir for parenchymal and vascular viruses and Phytoplasma sp. due to the synergistic and antagonistic effects causing unusual and unpredictable biological and epidemiological, viral and viral-like via host biochemical effects.     

Export of dissolved iron from river catchments in northeast Japan

Landscape and Ecological Engineering - This study investigated the export of dissolved iron (DFe) from river catchments with emphasis on land use and land cover (LULC). The DFe concentrations were...