Studying the effect of parallelization on the performance of Andromeda Search Engine: A search engine for peptides

Human body is made of proteins. The analysis of structure and functions of these proteins reveal important information about human body. An important technique used for protein evaluation is Mass Spectrometry. The protein data generated using mass spectrometer is analyzed for the detection of patterns in proteins. A wide variety of operations are performed on the data obtained from a mass spectrometer namely visualization, spectral deconvolution, peak alignment, normalization, pattern recognition and significance testing. There are a number of software that analyze the huge volume of data generated from a mass spectrometer. An example of such a software is MaxQuant that analyzes high resolution mass spectrometric data. A search engine called Andromeda is integrated into MaxQuant that is used for peptide identification. ^ One major drawback of the Andromeda Search Engine is its execution time. Identification of peptides involves a number of complex operations and intensive data processing. Therefore this research work focuses on implementing parallelization as a way to improve the performance of the Andromeda Search Engine. This is done by partitioning the data and distributing it across various cores and nodes. Also multiple tasks are executed concurrently on multiple nodes and cores. ^ A number of bioinformatics applications have been parallelized with significant improvement in execution time over the serial version. For this research work Task Parallel Library (TPL) and Common Library Runtime (CLR) constructs are used for parallelizing the application. The aim of this research work is to implement these techniques to parallelize the Andromeda Search Engine and gain improvement in the execution time by leveraging multi core architecture

Association of Vitamin D Deficiency and Mood Disorders: A Systematic Review

The cells of our body comprise calcitriol (1,25(OH) vitamin D2), the active form of vitamin D, an integral biological substance that has an impact on a large number of biological processes. While high prevalence of vitamin D deficiency is detected in population worldwide, the reports from sun-soaked countries like India are also alarming to note that the deficiency of vitamin D as high as 70 to 90% is observed leading to several chronic diseases in the majority of people. Deficiency of vitamin D is observed not only because of low levels of vitamin D in the diet, less exposure to sunlight, reduced cutaneous vitamin D synthesis, but also due to consumption of particular medicines, undue alcohol intake, and tobacco smoking. Vitamin D is known to affect estradiol, dopamine, and pro-inflammatory cytokine levels, besides being involved in the regulation of mechanisms pertaining to hormones like glucocorticoids. When vitamin D binds to vitamin D receptors (VDR) present in the central nervous system, it is noted to be responsible for the regulation of brain neuronal functions. Low 25-hydroxy vitamin D levels are found to have a higher incidence of various mood disorders. This review focusses on vitamin D receptors, VDR gene mutations, and pathophysiology causing vitamin D deficiency disorders

Pathophysiology of altered color perception

Human beings are able to perceive hundreds of shades of color which depends on the three types of cone system and various ratios of stimulation in response to different wavelengths. Perceptually and cognitively, men and women may experience appearance of color differently. The convention seems to be that women tend to prefer brighter and gratifying colors and men are more comfortable with stifled and soft colors. The reason may be linked to hormonal, developmental and environmental differences amongst both the sexes. The present review discusses various types of clinical and experimental studies done on alteration in color perception

Association of Pre-Pregnancy Body Mass Index and Gestational Weight Gain with Preterm Delivery in Pregnant Women

The perinatal mortality rate, which is one of the important adverse pregnancy outcome and includes stillbirths and infant death within first week of life is estimated to be nearly 40 deaths per 1,000 pregnancies in Gujarat. Also the infant mortality rates have been estimated to be 50 deaths before age of one year per 1,000 pregnancies. It is stated that children whose mothers are illiterate or belong to low socio-economic class have two and half times more chances to die within 1 year of their birth compared to those whose mothers have completed atleast 10 years of education or belong to high socio-economic class. There are nearly 13% of women who does not receive proper antenatal care and facility during pregnancy. In India, there are nearly half of the women (52%) who possess normal BMI range: rest are either underweight or overweight. Approximately 55% of the women of total population in India are anaemic. These maternal parameters directly affect the children causing 48% of the children to be malnourished and 43% to be underweight. Therefore, it is imperative to examine the association of pre-pregnancy Body Mass Index (BMI) as well as Gestational Weight Gain (GWG) with diverse pregnancy outcomes such as gestational diabetes, gestational hypertension and also with preterm delivery, caesarean delivery, etc. The present study was designed to investigate the prevalence, GWG, various pregnancy outcomes of underweight, overweight or obese pregnant women, and to explore the relationship between pre-pregnancy BMI as well as gestational weight gain during pregnancy and adverse pregnancy outcomes. This is a prospective, multi-centric study involving pregnant women with gestation week ≤20 weeks in Ahmedabad in Gujarat region. Our study observed that out of 226 women enrolled, 44 women (19.47%) were underweight, 137 women (60.62%) were normal, 30 women (13.27%) were overweight and 15 women (6.64%) were obese. The incidence of caesarean delivery (56.92%) was found more in nuclear family as compared to joint family (46.92%). It was found that in women taking no junk food at all, the chances of LBW were 16.39%, which was less as compared to mothers who had junk food. It was also observed that amongst women taking 1 glass milk daily (42.92%), about 55.67% of had normal type of delivery. Amongst women taking 1 fruit daily (57.52%), 53% women had normal delivery. Present study spotted decrease in risk of caesarean delivery with increase in maternal haemoglobin level from 9.0 gm/dl till 12.0 gm/dl. Average weight gain observed in underweight was 12.93 ± 1.90, in normal 12.32 ± 1.71, in overweight 10.23 ± 1.28 and in obese 9.6 ± 1.50. A negative correlation was found between GWG and pre-pregnancy BMI, i.e. as pre-pregnancy BMI increase, the GWG decrease. The incidence of pre-term delivery (9.49%) was much less in normal BMI range. The average infant birth weight observed in underweight women was 2.63 ± 0.47, in normal was 2.9 ± 0.49, in overweight was 2.92 ± 0.56 and in obese was 2.95 ± 0.86. It is observed that highest birth weight is obtained in obese women, which decreases as the maternal BMI range decreases. The incidence of LBW in normal and overweight women was 15.33 and 16.67%, which was low as compared to obese and underweight women. Our study reveals that parameters such as GWG, type of family, intake of milk, fruits and junk food, haemoglobin concentration directly affects the pregnancy outcomes such as term of delivery, type of delivery and infant birth weight

ACUTE TOXICOLOGICAL INVESTIGATION OF POLYETHYLENE GLYCOL DERIVATIZED FOURTH AND FIFTH GENERATION POLY (PROPYLENEIMINE) DENDRIMERS

Objective: The aim of the present study leads a comparative assessment of the toxicological profile of PEGylated fourth and fifth-generation poly (propylene imine) dendrimers (PPI). Methods: 4.0G and 5.0G generations of PPI dendrimer were synthesized and PEGylated with Mono polyethylene glycol 5000 (MPEG-5000). Each PEGylated 4.0G and 5.0G dendrimeric generation were administered in three different doses: 2.5 mg/kg, 25 mg/kg and 250 mg/kg (i.e., low, intermediate and high dose) to wister rats. After the dose administration, the blood and tissue samples of wister rats were collected after 24 h and 15 d after. All the collected samples were proceeded for hematological, biochemical and histopathological studies. Results: After 24 h of (250 mg/kg) dose administration PEGylated 5.0G PPI dendrimer the RBC count, hemoglobin content and WBC count were found 7.873±0.129 mill/cmm, 13.833±0.491g/dl and 9033.33±2384.906 mill/cmm, while PEGylated 4.0G PPI dendrimer indicated RBC count, hemoglobin content and WBC count 8.733±0.239 mill/cmm, 14.033±0.12 g/dl and 9666.667±2567.316 mill/cmm, in blood samples as compare to RBC count 9.346±0.037 mill/cmm, hemoglobin content 15.35±0.15 g/dl and WBC count 8500±286.675 mill/cmm of the animals of normal control group. Thus there are no remarkable changes (p>0.05) in RBC count, hemoglobin content and other hematological profile after 24 h in comparison of normal control group of animals. Similarily insignificant changes (p>0.05) in serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH) and sections of different organs indicate inoffensive nature of both generations of PEGylated 4.0G and 5.0 G PPI dendrimers. Conclusion: It can be concluded that fifth-generation PPI dendrimers are more suitable as compared to fourth generation of PPI dendrimer, while both dendrimers are not generating any severe toxicity

GENERATION DEPENDENT TARGETING POTENTIAL OF DONEPEZIL LOADED POLY (PROPYLENEIMINE) DENDRIMER THROUGH GOAT NASAL MUCOSA

Objective: In the domain of nano drug delivery, dendrimers are the most explored bioactive polymeric carrier system. The present work was aimed to study the diffusion potential of different generations of Poly (propyleneimine) (PPI) dendrimers on goat nasal mucosa in an ex vivo study and synthesize a stable dendrimer for olfactory drug delivery.Methods: The generations (3.0G, 4.0G, and 5.0G) of PPI dendrimer were synthesized, and PEGylated by MPEG 5000 and then loaded with donepezil. A comparative study was carried out among all generations in term of their drug loading capacity, stability, sustained release behaviour as well as for targeting efficacy. An ex-vivo study was carried out on Franz Diffusion Cell with goat nasal mucosa.Results: The developed G3, G4, and G5 dendrimerformulations had entrapment efficiency of 24.33±0.56%, 40.12±0.62%, and 60.4±0.6%, respectively. The nasal diffusion study revealed that 5.0G PPI dendrimer increased diffusion of donepezil up to 47% as compared to the pure solution of donepezil while 10% improvement in diffusion was seen as compared to 4.0 G PPI dendrimer. Thus obtained results claimed that the drug loading as well as targeting potential of PPI dendrimers increased with the increase in the number of generation. The investigation outcome indicated promising results of 5.0G PPI dendrimer over the 3.0G and 4.0G PPI dendrimer generations for their drug loading capacity, stability, and sustained release action.Conclusion: The 5.0G PPI dendrimer proved its superior candidature over the other lower generations of PPI dendrimers for drug delivery and drug targeting

Whole Cell Cross-Linking to Discover Host–Microbe Protein Cognate Receptor/Ligand Pairs

Bacterial surface ligands mediate interactions with the host cell during association that determines the specific outcome for the host–microbe association. The association begins with receptors on the host cell binding ligands on the microbial cell to form a partnership that initiates responses in both cells. Methods to determine the specific cognate partnerships are lacking. Determining these molecular interactions between the host and microbial surfaces are difficult, yet crucial in defining biologically important events that are triggered during association of the microbiome, and critical in defining the initiating signal from the host membrane that results in pathology or commensal association. In this study, we designed an approach to discover cognate host–microbe receptor/ligand pairs using a covalent cross-linking strategy with whole cells. Protein/protein cross-linking occurred when the interacting molecules were within 9–12 Å, allowing for identification of specific pairs of proteins from the host and microbe that define the molecular interaction during association. To validate the method three different bacteria with three previously known protein/protein partnerships were examined. The exact interactions were confirmed and led to discovery of additional partnerships that were not recognized as cognate partners, but were previously reported to be involved in bacterial interactions. Additionally, three unknown receptor/ligand partners were discovered and validated with in vitro infection assays by blocking the putative host receptor and deleting the bacterial ligand. Subsequently, Salmonella enterica sv. Typhimurium was cross-linked to differentiated colonic epithelial cells (caco-2) to discover four previously unknown host receptors bound to three previously undefined host ligands for Salmonella. This approach resulted in a priori discovery of previously unknown and biologically important molecules for host/microbe association that were casually reported to mediate bacterial invasion. The whole cell cross-linking approach promises to enable discovery of possible targets to modulate interaction of the microbiome with the host that are important in infection and commensalism, both of with initiate a host response

A rare case of retroperitoneal leiomyosarcoma

Leiomyosarcoma, a rare malignancy of smooth muscle may arise from the retroperitoneum. They often reach a large size before diagnosis is made. Patient presents with vague symptoms, as such retroperitoneal malignancies are related to displacement of organs and obstructive phenomenon. The present paper is one of the very few case reports of retroperitoneal leiomyosarcoma which illustrates the presenting symptoms, gross and microscopic findings, treatment modalities and prognostic indicators of a 70 years old male seen at Government medical college, New Civil Hospital, Surat

Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling.

Complex glycans cover the gut epithelial surface to protect the cell from the environment. Invasive pathogens must breach the glycan layer before initiating infection. While glycan degradation is crucial for infection, this process is inadequately understood. Salmonella contains 47 glycosyl hydrolases (GHs) that may degrade the glycan. We hypothesized that keystone genes from the entire GH complement of Salmonella are required to degrade glycans to change infection. This study determined that GHs recognize the terminal monosaccharides (N-acetylneuraminic acid (Neu5Ac), galactose, mannose, and fucose) and significantly (p < 0.05) alter infection. During infection, Salmonella used its two GHs sialidase nanH and amylase malS for internalization by targeting different glycan structures. The host glycans were altered during Salmonella association via the induction of N-glycan biosynthesis pathways leading to modification of host glycans by increasing fucosylation and mannose content, while decreasing sialylation. Gene expression analysis indicated that the host cell responded by regulating more than 50 genes resulting in remodeled glycans in response to Salmonella treatment. This study established the glycan structures on colonic epithelial cells, determined that Salmonella required two keystone GHs for internalization, and left remodeled host glycans as a result of infection. These data indicate that microbial GHs are undiscovered virulence factors