Genomic and proteomic expression analysis of Leishmania promastigote and amastigote life stages: the Leishmania genome is constitutively expressed

Leishmania are protozoan parasites that cause a wide spectrum of clinical diseases in humans and are a major public health risk in several countries. Leishmania life cycle consists of an extracellular flagellated promastigote stage within the midgut of a sandfly vector, and a morphological distinct intracellular amastigote stage within macrophages of a mammalian host. This study reports the use of DNA oligonucleotide genome microarrays representing 8160 genes to analyze the mRNA expression profiles of L. major promastigotes and lesion derived amastigotes. Over 94% of the genes were expressed in both life stages. Advanced statistical analysis identified a surprisingly low degree of differential mRNA expression: 1.4% of the total genes in amastigotes and 1.5% in promastigotes. These microarray results demonstrate that the L. major genome is essentially constitutively expressed in both life stages and suggest that Leishmania is constitutively adapted for survival and replication in either the sandfly vector or macrophage host utilizing an appropriate set of genes for each vastly different environment. Quantitative proteomics, using the isotope coded affinity tag (ICAT) technology and mass spectrometry, was used to identify L. infantum promastigote and axenic amastigote differentially expressed proteins. Of the 91 distinct proteins identified, 8% were differentially expressed in the amastigote stage, 20% were differentially expressed in the promastigote stage, and the remaining 72% were considered constitutively expressed. The differential expression was validated by the identification of previously reported stage specific proteins and identified several amastigote and promastigote novel stage specific proteins.     

A Representative Study of Deaths of North Indian Migrants and Its Medical Certification Across the World

Many Indians is moving to other nations of the world in the search of employment, education or other reasons. The process of globalization along with the faster mode of traveling and communication has facilitated this movement in the hope of getting more opportunities and earning of easy money abroad, than in India. Unfortunately, sometimes they meet a tragic end and their families in India get only their dead bodies back from abroad. This study focuses on these kind of unfortunate tragic events faced by Indians in different countries and thereby raise a concern on their safety abroad and necessitate the need of relooking in to the quality of medical certification of death and medico legal investigations to find out the real reasons of deaths to avoid any kind of doubt in mind. Data was collected from medical death certificates and passports of the deceased Indians. There was a total of 711 dead bodies/human remains received in 2012 at IGI airport New Delhi. The Middle East countries together contributed a total of 398 (55.98?%) cases. The distribution as per manner of death shows that in maximum number of cases (269), the manner of death was ambiguous with unspecified aetiology. The study therefore recommends for upgradation of the level of medico legal investigations in form of 2nd autopsy in recipient country and proper medical death certification.     

Effective hand function assessment after burn injuries

This study compared two methods of hand function assessment, the Michigan Hand Outcomes Questionnaire (MHQ) and the Test d'Evaluation des Membres Supérieurs des Personnes Agées (TEMPA) in 20 patients discharged from a regional adult burn center (1995-1999). Spearman's rank correlation coefficient analysis was used to compare the MHQ and TEMPA scores, with P <.05 considered significant. The MHQ revealed that 68% of patients reported hand function deterioration, mainly with the nondominant hand (65%). Activities of daily living (76%) and work (59%) were the most affected. According to the MHQ, patient satisfaction correlated with work performance (r =.66, P =.002), aesthetics (r =.64, P =.003), pain (r =.59, P =.008), and activities of daily living (r =.54, P =.017). The MHQ indicated more hand function deterioration than the TEMPA. There was a significant correlation between the MHQ and TEMPA total scores (r =.68, P =.001). This study supports using the MHQ to determine which patients would benefit from the more resource-consuming TEMPA.     

Pharmacophore combination as a useful strategy to discover new antitubercular agents

The present study is aimed at combining two well-known pharmacophores (pyrazoline and benzoxazole nucleus) to design and synthesize a series of substituted pyrazoline-based benzoxazole derivatives. In vitro antitubercular evaluation against Mycobacterium tuberculosis H37Rv, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains showed that most of the target compounds displayed potent activity (MIC ~1.25–25 μg/mL) where few compounds were found to be better than isoniazid against MDR-TB (MIC = 3.25 μg/mL) and XDR-TB (MIC = 12.5 μg/mL). Cytotoxicity assay of these active compounds in VERO cell lines displayed good selectivity index. In order to gain insights into the plausible binding motifs, the target compounds were docked into enoyl-acyl carrier protein reductase, a molecular target of isoniazid. All the docked compounds occupied the same hydrophobic binding pocket and interacted mostly by dispersion interactions. Contribution of the three pharmacophoric fragments (pyrazoline, benzoxazole and aryl ring) toward protein–ligand binding was evaluated at semi empirical quantum mechanics level. The interaction energies suggested that most of the binding was governed by the benzoxaxole moiety followed by pyrazoline and aryl rings.     

Relationship of muscle sympathetic nerve activity to insulin sensitivity

Purpose

An association between insulin resistance and activation of the sympathetic nervous system has been reported in previous studies. However, potential interactions between insulin sensitivity and sympathetic neural mechanisms in healthy people remain poorly understood. We conducted a study to determine the relationship between sympathetic activity and insulin resistance in young, healthy humans.

Methods

Thirty-seven healthy adults (18–35 years, BMI <28 kg m^?2) were studied. Resting muscle sympathetic nerve activity (MSNA) was measured with microneurography and insulin sensitivity of glucose and free fatty acid metabolism was measured during a hyperinsulinemic-euglycemic clamp with two levels of insulin.

Results

During lower doses of insulin, we found a small association between lower insulin sensitivity and higher MSNA (P < 0.05) but age was a cofactor in this relationship. Overall, we found no difference in insulin sensitivity between groups of low and high MSNA, but when women were analyzed separately, insulin sensitivity was lower in the high MSNA group compared with the low MSNA group of women.

Conclusions

These data suggest that MSNA and insulin sensitivity are only weakly associated with young healthy individuals and that age and sex may be important modifiers of this relationship.