AbsoluRATE: An in-silico method to predict the aggregation kinetics of native proteins

Protein aggregation has two aspects, namely, mechanistic and kinetics. Understanding protein aggregation kinetics is critical for prediction of progression of diseases caused by amyloidosis, accumulation of aggregates in biotherapeutics during storage and engineering commercial nano-biomaterials. In this work, we have collected experimentally determined absolute protein aggregation rates and developed an SVM based regression model to predict absolute rates of protein and peptide aggregation near-physiological conditions. The regression model achieved a correlation coefficient of 0.72 with MAE of 0.91 (natural log of k_app, where k_app is in hour^?1) using leave-one-out cross-validation on a dataset of 82 non-redundant proteins/peptides. The model accounts for the experimental conditions (such as temperature, pH, ionic and protein concentration) and sequence-based properties. The amino acid sequence features revealed by this model as being important for aggregation kinetics, are also associated with the aggregation mechanism. In particular, inherent aggregation propensity of the protein/peptide sequence and number of aggregation prone regions (APRs) unpunctuated by the gatekeeping residues, were found to play important roles in the prediction of the absolute aggregation rates. This analysis shows that mechanism and kinetics of protein aggregation are coupled via common sequence attributes. The aggregation kinetic prediction method developed in this work is available at https://web.iitm.ac.in/bioinfo2/absolurate-pred/index.html.     

Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii

Apicomplexan parasites are causative agents of major human diseases. Calcium Dependent Protein Kinases (CDPKs) are crucial components for the intracellular development of apicomplexan parasites and are thus considered attractive drug targets. CDPK7 is an atypical member of this family, which initial characterization suggested to be critical for intracellular development of both Apicomplexa Plasmodium falciparum and Toxoplasma gondii. However, the mechanisms via which it regulates parasite replication have remained unknown. We performed quantitative phosphoproteomics of T. gondii lacking TgCDPK7 to identify its parasitic targets. Our analysis lead to the identification of several putative TgCDPK7 substrates implicated in critical processes like phospholipid (PL) synthesis and vesicular trafficking. Strikingly, phosphorylation of TgRab11a via TgCDPK7 was critical for parasite intracellular development and protein trafficking. Lipidomic analysis combined with biochemical and cellular studies confirmed that TgCDPK7 regulates phosphatidylethanolamine (PE) levels in T. gondii. These studies provide novel insights into the regulation of these processes that are critical for parasite development by TgCDPK7.     

Study on the Trace Elements in <Emphasis Type="Italic">Swertia chirayita</Emphasis> (Roxb.) H. Karsten

An attempt has been made to analyze some trace elements and electrolytes like Zn, Cu, Mn, Fe, Co, Na, K, Ca, and Li present in the Swertia chirayita roots and leaves. The concentration of Ca in all the samples was more than 1,346.0 mg/kg and the concentration of other elements was found in the order K > Ca > Fe > Na > Mn > Zn > Co > Cu > Li in different samples of S. chirayita.     

Developmental changes in the brain levels of neurotransmitters as influenced by maternal ethanol consumption in the rat.

Abstract— Effects of prolonged maternal ethanol consumption by pregnant and lactating rats were investigated on the cerebral contents of certain neurotransmitters and the activities of their enzymes in fetal and neonatal brains. Ethanol consumption by the pregnant rats resulted in a significant decrease in the fetal brain contents of acetylcholine and an increase in γ-aminobutyric acid and glutamate. The cerebral levels of 5-hydroxytryptamine (5-HT), norepinephrine of choline in the fetal brains from the ethanol group were not significantly different from those observed in the control group. With the increase in gestational age, an increase in the levels of 5-HT, norepinephrine, acetylcholine, γ-amino-butyric acid (GABA) and glutamate was observed in the fetal brains from both ethanol and control groups. The brains of neonates suckling on ethanol-fed mothers showed a significant decrease in acetylcholine levels and an increase in GABA and glutamate levels as compared to the corresponding controls. The activities of L-glutamate decarboxylase and GABA-aminotransferase in the fetal as well as neonatal brains were decreased in the ethanol-fed group as compared to the controls. A single injection of acetaldehyde resulted in a decrease in acetylcholine, GABA and glutamate levels in both neonatal and adult brains.     

Development of Satranidazole Mucoadhesive Gel for the Treatment of Periodontitis

The aim of the paper was to develop satranidazole-containing mucoadhesive gel for the treatment of periodontitis. Different mucoadhesive gels were prepared, using various gelling agents like sodium carboxymethylcellulose (SCMC), poloxamer 407, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and the mucoadhesive polymer carbopol 934P. The selected formulations (based on the mucoadhesive force) were studied for different mechanical properties, such as mucoadhesive strength, hardness, compressibility, adhesiveness, and cohesiveness through Texture Profile Analyzer. In vitro satranidazole release from the prepared formulations was also determined and compared with marketed preparation of metronidazole (Metrogyl® gel). The formulation SC30 (containing SCMC 3% w/v) showed maximum mucoadhesive strength (167.72 ± 3.76 g) and adhesiveness (−46.23 ± 0.34 N mm), with low hardness (9.81 ± 0.04 N) and compressibility (40.05 ± 0.48 N mm) and moderate cohesiveness (0.87 ± 0.01). SC30 formulation exhibited long-term release. Thus, SC30 gel was evaluated for its clinical effectiveness along with marketed metronidazole gel. At the end of the study (42 days of clinical studies), both formulations were found to significantly reduce the probing depth, plaque index, gingival index, calculus criteria, and bleeding index. However, the SC30 gel was more effective in reducing the above parameters than marketed metronidazole gel. This study confirmed the acceptability and effectiveness of satranidazole gel for treatment of periodontitis.Key words: mucoadhesive gel, periodontitis, satranidazole, texture profile analysis     

Monitoring of aquatic macroinvertebrates as bioindicator for assessing the health of wetlands: A case study in the Central Himalayas,India

The present contribution encompasses the first case study on the aquatic macroinvertebrates as bioindicators for assessing the health of Asan wetland (area 3.2 km²), located in the foothills of Central Himalayas, India. Monthly sampling from all the sampling sites in five replicates was made for a period of 12 months (July 2002–June 2003) at 9:00–11:00 h. A total of 32 species of macroinvertebrates were found with the Ephemeroptera and Gastropoda being the most abundant component of invertebrates communities. The Shannon–Wiener diversity index calculated for macroinvertebrates ranged from 3.50 to 4.61. Seasonal fluctuations in the density of macroinvertebrates revealed maximum density (451–503 ind m^?2) during winter and minimum (126–143 ind m^?2) during monsoon season. The density of macroinvertebrates was influenced by the anthropogenic disturbances and water level fluctuations causing disturbance in the littoral zone of the wetland. The statistical relationships between turbidity, transparency, dissolved oxygen and water temperature and macroinvertebrates of Asan wetland were also computed for assessing the impact of anthropogenic disturbances on macroinvertebrates.