ChAT (choline acetyltransferase) is found in cholinergic neurons where its function is to catalyze the reaction between acetyl-CoA and choline to form the neurotransmitter ACh. The density of ...cholinergic neurons and levels of ChAT gene expression have been studied extensively in Alzheimer’s Disease (AD). ChAT is encoded by one gene, however through the use of differential splicing and utilization of alternative promoters, multiple transcripts of the protein exist. My studies focus on the proteins transcribed from the M-type mRNA, which yield the common 69-kDa ChAT protein, as well as a primate specific 82-kDa ChAT protein. The two proteins differ by a 118 amino acids amino-terminal extension. Studies previously conducted in this laboratory found that the 82-kDa ChAT contained a nuclear localization signal (NLS) that targeted the protein into the nucleus of cells. Analysis of the primary amino acid sequence of ChAT indicates additional putative nuclear transport domains. In addition to the unknown functional significance of nuclear ChAT, the endogenous expression of 82-kDa ChAT has yet to be shown. Our results highlight novel functional transport domains within the human 69-kDa and 82-kDa ChAT enzymes by employing confocal microscopy. Furthermore, using immunohistochemical techniques, we demonstrate for the first time, the endogenous nuclear expression of 82-kDa ChAT in human neural tissue of neurologically normal and Clinical Dementia Rated (CDR) cases. Moreover, combining functional genomics technology with cell biology, we illustrate that in addition to synthesizing the neurotransmitter ACh, ChAT is involved in the negative regulation of toxic Aβ peptide production. Taken together, these studies further our knowledge of the ChAT isoforms, their cellular localization, their endogenous expression, as well as their direct influence on Aβ peptide production. This research can have implications in diseases such as AD, where the toxic effects of Aβ peptides target cholinergic neurons. These studies were designed to broaden our understanding of the cellular mechanisms governing ChAT isoforms in the presynaptic cholinergic environment. The information collected enhances our understanding of ACh biosynthesis as well as the regulation, modulation, and cell signaling events involving ChAT in the physiological state. Keywords. choline acetyltransferase, cholinergic, nuclear localization signal, nuclear export signal, subcellular distribution, nucleocytoplasmic shuttling protein, nuclear transport, Alzheimer disease, mild-cognitive impairment, immunohistochemistry, amyloid processing, secretases, microarray, Amyloid Processing Protein.
To estimate the incidence, short-term outcome, and spatial distribution of stroke patients and to evaluate the completeness of case ascertainment in Ludhiana.
This population-based prospective cohort ...study was conducted in Ludhiana, Punjab, Northwest India. All first-ever stroke patients (≥18 years) were included between March 2010 and March 2013 using WHO Stepwise Approach Surveillance methodology from the city. Stroke patient data were obtained from hospitals, scan centers, and general practitioners, and details of deaths from the Municipal Corporation.
Out of 7,199 stroke patients recruited, 3,441 were included in final analysis. The mean age was 59 ± 15 years. The annual incidence rate was 140/100,000 (95% confidence interval CI 133-147) and age-adjusted incidence rate was 130/100,000 (95% CI 123-137). The annual incidence rate for stroke in the young (18-49 years) was 46/100,000 (95% CI 41-51). The case fatality at 28 days was 22%. Patients above 60 years of age (p = 0.03) and patients who were managed in public hospitals had poor survival (p = 0.01). Hot spots for cumulative incidence were seen in central and southern parts of the city, and hot spots for poor outcome were seen in the outskirts of the city.
The incidence rates are similar to other studies from India. Stroke patient survival is poor in public hospitals. The finding of spatial analysis is of public health significance for stroke prevention and strengthening of stroke services.
Prediction of local scale frost events can be helpful for farmers to minimize crop loss due to frost damage. This study aims to detect a temporal trend in the occurrence of frost events and develop ...frost prediction models using multivariate statistical techniques like logistic regression, artificial neural network model, and thumb rules for two diverse locations of India (Palampur and Ludhiana). In these statistical models, eight daily meteorological parameters viz., maximum temperature (Tmax), minimum temperature (Tmin), wind speed, precipitation, sunshine duration, cumulative pan evaporation, morning relative humidity (RH1), and afternoon relative humidity (RH2) 1 to 5 days preceding the frost events for the period of 2004–2016 and 1982–2013 at Palampur and Ludhiana, respectively were used. Principal Component Analysis was performed to select the weather parameter that has maximum effect on the occurrence of frost event. Ten different skill scores like accuracy, bias, and probability of false detection were used to evaluate the accuracy of frost prediction models. The Mann–Kendall trend test showed a significant increasing annual trend in the number of frost events at Ludhiana, with a remarkable increase in December. The results also showed that lower afternoon relative humidity 1-day preceding the frost event at Palampur and calm wind and lower evaporation 1-day preceding at Ludhiana augmented the occurrence of frost events. Among the techniques for developing frost prediction models, the logistic regression model performed better over artificial neural network and thumb rule-based models. The logistic regression model performed better for the plain region (Ludhiana) than for the hilly area (Palampur). The developed models are most suitable for predicting the radiation frost.
Pear cv. ‘Patharnakh’ is the most promising cultivar of pear grown in the subtropics of northwestern India. The fruit is generally harvested from July to the first week of August and is largely ...transported to far-off markets within the country. A study was therefore undertaken to assess the effect of harvest dates on the storage life of pear fruit. The fruits were harvested at four different times (2nd, 3rd, and 4th week of July and 1st week of August) and stored for 70 days to evaluate the physical and chemical changes that occurred during storage. During storage, fruits harvested in the 2nd week of July consistently exhibited the higher fruit firmness, titratable acidity, total antioxidant activity (TAA) and total phenolics content (TPC) than the late harvested fruits. In contrast, delayed harvested fruits recorded higher spoilage percentage, total soluble solids (TSS) and total sugars. Moreover, fruits harvested in the 3rd week of July had minimum weight loss and the highest sensory quality until 70th day of storage. The fruit harvested at the later harvesting stage recorded higher activities of fruit softening enzymes activity like pectin methylesterase (PME), polygalacturonase (PG) and cellulase enzymes as compared to fruit harvested at an earlier stage. Thus, the results revealed that fruits harvested during the 3rd week of July retained better quality and enhanced the storage life of ‘Patharnakh’ pear fruit stored at low temperature.
Nutrient balance is the key component to increase crop yields. Excess and imbalanced use of nutrients has caused nutrient mining from the soil and deteriorated crop productivity and ultimately soil ...health. Replenishment of these nutrients has a direct impact on soil health and crop productivity. Based on this fact, the present research was conducted to determine the effects of long-term integrated use of organic and inorganic fertilizers on soil nutrient status and yield (grain and straw) in rice. Different combinations of inorganic nitrogen (N) and organic sources (sewage sludge and compost) were applied to the soil. Data revealed that application of mineral NPK in combination with 50% N through compost significantly increased the organic matter content (0.36%), available phosphorus (16.50 kg/ha) and available potassium content (239.80 kg/ha) in soil. The maximum available N (225.12 kg/ha) was found by the substitution of 50% N through sewage sludge. This improvement in soil nutrient status through combined use of organic and inorganic fertilizers produced significant increase in grain and straw yield as compared to inorganic fertilizers alone. Maximum grain (6.96 t/ha) and straw (8.56 t/ha) yields were found in treatment having substitution of 50% N (recommended) through compost @10t/ha. Also, a significant positive correlation was found between soil nutrients and straw and grain yield in rice. Thus the study demonstrated that substitution of 50% inorganic N through compost will be a good alternative for improving soil fertility.
ABSTRACT
Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity ...are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregation prone regions as well as T- and B-cell immune epitopes from protein sequence and structure have become available recently. Here, we describe a potential coupling between aggregation and immunogenicity: T-cell and B-cell immune epitopes in therapeutic proteins may contain aggregation-prone regions. The details of biological mechanisms behind this observation remain to be understood. However, our observation opens up an exciting potential for rational design of de-immunized novel, as well as follow on biotherapeutics with reduced aggregation propensity.
Cystic ehinococcosis (CE) caused by Echinococcus granulosus remains a neglected zoonotic disease despite its considerable human and animal health concerns. This is the first systematic analysis of ...the livestock and human related economic losses due to cystic echinococcosis in India.
Data about human cases were obtained from a tertiary hospital. Human hydatidosis cases with and without surgical interventions were extrapolated to be 5647 and 17075 per year assuming a total human population of 1210193422 in India. Data about prevalence of hydatid cysts in important food producing animals were obtained from previously published abattoir based epidemiological surveys that reported a prevalence of 5.39% in cattle, 4.36% in buffaloes, 3.09% in pigs, 2.23% in sheep and 0.41% in goats. Animal population data were sourced from the latest census conducted by the Department of Animal Husbandry, Dairying and Fisheries, India. Other input parameters were obtained from published scientific literature. Probability distributions were included for many input values to account for variability and uncertainty. Sensitivity analyses were conducted to evaluate the effect of important parameters on the estimated economic losses.
The analysis revealed a total annual median loss of Rs. 11.47 billion (approx. US $ 212.35 million). Cattle and buffalo industry accounted for most of the losses: 93.05% and 88.88% of the animal and total losses, respectively. Human hydatidosis related losses were estimated to be Rs. 472.72 million (approx. US $ 8.75 million) but are likely to be an under-estimate due to under-reporting of the disease in the country. The human losses more than quadrupled to Rs. 1953 million i.e. approx. US $ 36.17 million, when the prevalence of human undiagnosed cases was increased to 0.2% in the sensitivity analyses. The social loss and psychological distress were not taken into account for calculating human loss. The results highlight an urgent need for a science based policy to control and manage the disease in the country.
