Metastatic sweat gland adenocarcinoma: A clinico-pathological dilemma

Background  

Sweat gland adenocarcinoma is a rare malignancy with high metastatic potential seen more commonly in later years of life. Scalp is the most common site of occurrence and it usually spreads to lymph nodes. Liver, lung and bones are the distant sites of metastasis with fatal results. The differentiation between apocrine and eccrine metastatic sweat gland carcinoma is often difficult. The criteria's are inadequate to be of any practical utility.     

TNT Biotransformation and Detoxification by a Pseudomonas Aeruginosa Strain

Successful microbial-mediated remediation requires transformationpathways that maximize metabolism and minimize the accumulation of toxic products. Pseudomonas aeruginosa strain MX, isolated from munitions-contaminated soil, degraded 100 mg TNT L^-1 in culture medium within 10 h under aerobic conditions. The major TNT products were 2-amino-4,6-dinitrotoluene (2ADNT, primarily in the supernatant) and 2,2'-azoxytoluene (2,2'AZT, primarily in the cell fraction), which accumulated as major products via the intermediate2-hydroxylamino-4,6-dinitrotoluene (2HADNT). The 2HADNT and2,2'AZT were relatively less toxic to the strain than TNT and 2ADNT. Aminodinitrotoluene (ADNT) production increased when yeast extract was added to the medium. While TNT transformation rate was not affected by pH, more HADNTs accumulated at pH 5.0 than at pH 8.0 and AZTs did not accumulate at the lower pH. The appearance of 2,6-diamino-4-nitrotoluene (2,6DANT) and 2,4-diamino-6-nitrotoluene (2,4DANT); dinitrotoluene (DNT) and nitrotoluene (NT); and 3,5-dinitroaniline (3,5DNA) indicated various routes of TNT metabolism and detoxification by P. aeruginosa strain MX.     

Comparative assessment of in situ bioremediation potential of cadmium resistant acidophilic Pseudomonas putida 62BN and alkalophilic Pseudomonas monteilli 97AN strains on soybean

A study was undertaken to examine the effects of the acidophilic strain 62BN (pH 5.5) and alkalophilic strain 97AN (pH 9.0) on remediation of cadmium and their subsequent effects on soybean (Glycine max var. PS-1347) in acidic and alkaline soils, respectively. The effect of cadmium on soybean plants was studied in acidic (pH 6.3 ± 0.2) and alkaline (8.5 ± 0.2) soil amended with 124 μM CdCl₂ concentration, respectively, and the cadmium toxicity was evident from stunted growth, poor rooting, and cadmium accumulation in each case. Furthermore, 16S ribosomal DNA (rDNA) sequencing identified 62BN as a Pseudomonas putida strain and 97AN as a Pseudomonas monteilli strain. In situ studies showed that on seed bacterization, both the P. putida 62BN strain and P. monteilli 97AN strain were able to enhance plant growth in terms of agronomical parameters, in the presence of cadmium in acidic and alkaline soils, respectively. Apart from this, strain 62BN and 97AN reduced cadmium concentration in plant and soil significantly (p < 0.05) in their respective soil types. Further comparative analysis revealed that P. putida 62BN was more effective than P. monteilli 97AN strain in remediation of cadmium. The bacterial strains offer promise as inoculants to improve the growth of plants in the presence of toxic Cd concentrations in the environment with their optimum pH.     

Synthesis,Spectral Characterization,and Pharmacological Importance of New 4H-1,4-Benzothiazines,Their Sulfone Analogues,and Ribofuranosides

The present article describes the synthesis of new 4H-1,4-benzothiazines via condensation and oxidative cyclization of substituted 2-aminobenzenethiols with compounds containing active methylene groups. It is believed that the reaction proceeds via intermediary of the enaminoketone system. The sulfone derivatives were synthesized by oxidation of 4H-1,4-benzothiazines using 30% hydrogen peroxide in glacial acetic acid. Benzothiazines were used as bases to prepare ribofuranosides by treatment with a sugar derivative (β-D-ribofuranosyl-1-acetate-2,3,5-tribenzoate). The pharmacological importance of the synthesized compounds was evaluated by their, antimicrobial properties against various bacterial strains and fungal species. The structures of the compounds have been confirmed by spectral and chemical analysis.     

High-Specificity Targeted Functional Profiling in Microbial Communities with ShortBRED

Profiling microbial community function from metagenomic sequencing data remains a computationally challenging problem. Mapping millions of DNA reads from such samples to reference protein databases requires long run-times, and short read lengths can result in spurious hits to unrelated proteins (loss of specificity). We developed ShortBRED (Short, Better Representative Extract Dataset) to address these challenges, facilitating fast, accurate functional profiling of metagenomic samples. ShortBRED consists of two components: (i) a method that reduces reference proteins of interest to short, highly representative amino acid sequences (“markers”) and (ii) a search step that maps reads to these markers to quantify the relative abundance of their associated proteins. After evaluating ShortBRED on synthetic data, we applied it to profile antibiotic resistance protein families in the gut microbiomes of individuals from the United States, China, Malawi, and Venezuela. Our results support antibiotic resistance as a core function in the human gut microbiome, with tetracycline-resistant ribosomal protection proteins and Class A beta-lactamases being the most widely distributed resistance mechanisms worldwide. ShortBRED markers are applicable to other homology-based search tasks, which we demonstrate here by identifying phylogenetic signatures of antibiotic resistance across more than 3,000 microbial isolate genomes. ShortBRED can be applied to profile a wide variety of protein families of interest; the software, source code, and documentation are available for download at http://huttenhower.sph.harvard.edu/shortbred     

A Longitudinal Study: Changes in Cortical Thickness and Surface Area during Pubertal Maturation

Sex hormones have been shown to contribute to the organization and function of the brain during puberty and adolescence. Moreover, it has been suggested that distinct hormone changes in girls versus boys may contribute to the emergence of sex differences in internalizing and externalizing behavior during adolescence. In the current longitudinal study, the influence of within-subject changes in puberty (physical and hormonal) on cortical thickness and surface area was examined across a 2-year span, while controlling for age. Greater increases in Tanner Stage predicted less superior frontal thinning and decreases in precuneus surface area in both sexes. Significant Tanner Stage and sex interactions were also seen, with less right superior temporal thinning in girls but not boys, as well as greater decreases in the right bank of the superior temporal sulcus surface area in boys compared to girls. In addition, within-subject changes in testosterone over the 2-year follow-up period were found to relate to decreases in middle superior frontal surface area in boys, but increases in surface area in girls. Lastly, larger increases in estradiol in girls predicted greater middle temporal lobe thinning. These results show that within-subject physical and hormonal markers of puberty relate to region and sex-specific changes in cortical development across adolescence.     

Comparative Genomic Analysis of Buffalo (Bubalus bubalis) NOD1 and NOD2 Receptors and Their Functional Role in In-Vitro Cellular Immune Response

Nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) are innate immune receptors that recognize bacterial cell wall components and initiate host immune response. Structure and function of NLRs have been well studied in human and mice, but little information exists on genetic composition and role of these receptors in innate immune system of water buffalo—a species known for its exceptional disease resistance. Here, a comparative study on the functional domains of NOD1 and NOD2 was performed across different species. The NOD mediated in-vitro cellular responses were studied in buffalo peripheral blood mononuclear cells, resident macrophages, mammary epithelial, and fibroblast cells. Buffalo NOD1 (buNOD1) and buNOD2 showed conserved domain architectures as found in other mammals. The domains of buNOD1 and buNOD2 showed analogy in secondary and tertiary conformations. Constitutive expressions of NODs were ubiquitous in different tissues. Following treatment with NOD agonists, peripheral lymphocytes showed an IFN-γ response along-with production of pro-inflammatory cytokines. Alveolar macrophages and mammary epithelial cells showed NOD mediated in-vitro immune response through NF-κB dependent pathway. Fibroblasts showed pro-inflammatory cytokine response following agonist treatment. Our study demonstrates that both immune and non-immune cells could generate NOD-mediated responses to pathogens though the type and magnitude of response depend on the cell types. The structural basis of ligand recognition by buffalo NODs and knowledge of immune response by different cell types could be useful for development of non-infective innate immune modulators and next generation anti-inflammatory compounds.     

Probing kinetic drug binding mechanism in voltage-gated sodium ion channel: open state versus inactive state blockers

The kinetics and nonequilibrium thermodynamics of open state and inactive state drug binding mechanisms have been studied here using different voltage protocols in sodium ion channel. We have found that for constant voltage protocol, open state block is more efficient in blocking ionic current than inactive state block. Kinetic effect comes through peak current for mexiletine as an open state blocker and in the tail part for lidocaine as an inactive state blocker. Although the inactivation of sodium channel is a free energy driven process, however, the two different kinds of drug affect the inactivation process in a different way as seen from thermodynamic analysis. In presence of open state drug block, the process initially for a long time remains entropy driven and then becomes free energy driven. However in presence of inactive state block, the process remains entirely entropy driven until the equilibrium is attained. For oscillating voltage protocol, the inactive state blocking is more efficient in damping the oscillation of ionic current. From the pulse train analysis it is found that inactive state blocking is less effective in restoring normal repolarisation and blocks peak ionic current. Pulse train protocol also shows that all the inactive states behave differently as one inactive state responds instantly to the test pulse in an opposite manner from the other two states.