Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes.

Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 μg/10(6) cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 μg/10(6) cells for native drugs. High RIF and INHP levels were retained in MDM for \u3e15 d following nanoparticle loading. Rapid loss of native drugs was observed in cells and culture fluids within 24 h. Antimicrobial activities were determined against Mycobacterium smegmatis (M. smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs. Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments. These were the same compartments that contained the pathogen. Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens

Localization and Androgen Regulation of Metastasis-Associated Protein 1 in Mouse Epididymis

BACKGROUND: Metastasis-associated protein 1 (MTA1), the founding member of the MTA family of genes, can modulate transcription by influencing the status of chromatin remodeling. Despite its strong correlation with the metastatic potential of cancer cells, MTA1 can also regulate crucial cellular pathways by modifying the acetylation status. We have previously reported the presence of MTA1/MTA1 in human and mouse testes, providing the evidence for its involvement in the regulation of testicular function during murine spermatogenesis. The objective of present study was to further assess the localization of MTA1 in mouse epididymis on both transcriptional and translational level, and then to explore whether MTA1 expression is regulated by androgens and postnatal epididymal development. METHODOLOGY/PRINCIPAL FINDINGS: Mice were deprived of circulating androgen by bilaterally castration and were then supplemented with exogenous testosterone propionate for one week. MTA1 was immunolocalized in the epithelium of the entire epididymis with the maximal expression in the nuclei of principal cells and of clear cells in proximal region. Its expression decreased gradually after castration, whereas testosterone treatment could restore the expression, indicating that the expression of this gene is dependent on androgen. During postnatal development, the protein expression in the epididymis began to appear from day 7 to day 14, increased dramatically from postnatal day 28, and peaked at adulthood onwards, coinciding with both the well differentiated status of epididymis and the mature levels of circulating androgens. This region- and cell-specific pattern was also conservative in normal human epididymis. CONCLUSIONS: Our data suggest that the expression of MTA1 protein could be regulated by androgen pathway and its expression level is closely associated with the postnatal development of the epididymis, giving rise to the possibility that this gene plays a potential role in sperm maturation and fertility

Dynamics and distribution of bacterial and archaeal communities in oil-contaminated temperate coastal mudflat mesocosms

Mudflats are ecologically important habitats that are susceptible to oil pollution, but intervention is difficult in these fine-grained sediments, and so clean-up usually relies on natural attenuation. Therefore, we investigated the impact of crude oil on the bacterial, diatom and archaeal communities within the upper parts of the diatom-dominated sediment and the biofilm that detached from the surface at high tide. Biodegradation of petroleum hydrocarbons was rapid, with a 50 % decrease in concentration in the 0–2-mm section of sediment by 3 days, indicating the presence of a primed hydrocarbon-degrading community. The biggest oil-induced change was in the biofilm that detached from the sediment, with increased relative abundance of several types of diatom and of the obligately hydrocarbonoclastic Oleibacter sp., which constituted 5 % of the pyrosequences in the oiled floating biofilm on day 3 compared to 0.6 % in the non-oiled biofilm. Differences in bacterial community composition between oiled and non-oiled samples from the 0–2-mm section of sediment were only significant at days 12 to 28, and the 2–4-mm-sediment bacterial communities were not significantly affected by oil. However, specific members of the Chromatiales were detected (1 % of sequences in the 2–4-mm section) only in the oiled sediment, supporting other work that implicates them in anaerobic hydrocarbon degradation. Unlike the Bacteria, the archaeal communities were not significantly affected by oil. In fact, changes in community composition over time, perhaps caused by decreased nutrient concentration and changes in grazing pressure, overshadowed the effect of oil for both Bacteria and Archaea. Many obligate hydrocarbonoclastic and generalist oil-degrading bacteria were isolated, and there was little correspondence between the isolates and the main taxa detected by pyrosequencing of sediment-extracted DNA, except for Alcanivorax, Thalassolituus, Cycloclasticus and Roseobacter spp., which were detected by both methods

Major Role of Microbes in Carbon Fluxes during Austral Winter in the Southern Drake Passage

Carbon cycling in Southern Ocean is a major issue in climate change, hence the need to understand the role of biota in the regulation of carbon fixation and cycling. Southern Ocean is a heterogeneous system, characterized by a strong seasonality, due to long dark winter. Yet, currently little is known about biogeochemical dynamics during this season, particularly in the deeper part of the ocean. We studied bacterial communities and processes in summer and winter cruises in the southern Drake Passage. Here we show that in winter, when the primary production is greatly reduced, Bacteria and Archaea become the major producers of biogenic particles, at the expense of dissolved organic carbon drawdown. Heterotrophic production and chemoautotrophic CO2 fixation rates were substantial, also in deep water, and bacterial populations were controlled by protists and viruses. A dynamic food web is also consistent with the observed temporal and spatial variations in archaeal and bacterial communities that might exploit various niches. Thus, Southern Ocean microbial loop may substantially maintain a wintertime food web and system respiration at the expense of summer produced DOC as well as regenerate nutrients and iron. Our findings have important implications for Southern Ocean ecosystem functioning and carbon cycle and its manipulation by iron enrichment to achieve net sequestration of atmospheric CO2

Bacillus indicus sp. nov., an arsenic-resistant bacterium isolated from an aquifer in West Bengal, India

Strain Sd/3T (=MTCC 4374T=DSM 15820T), an arsenic-resistant bacterium, was isolated from a sand sample obtained from an arsenic-contaminated aquifer in Chakdah district in West Bengal, India (23° 3' N 88° 35' E). The bacterium was Gram-positive, rod-shaped, non-motile, endospore-forming and yellowish-orange pigmented. It possessed all the characteristics that conform to the genus Bacillus, such as it had A4β murein type (L-orn-D-Asp) peptidoglycan variant, MK-7 as the major menaquinone and iso-C15:0 and anteiso-C15:0 as the major fatty acids. Based on its chemotaxonomic and phylogenetic characteristics, strain Sd/3T was identified as a species of the genus Bacillus. It exhibited maximum similarity (95%) at the 16S rRNA gene level with Bacillus cohnii; however, DNA-DNA similarity with B. cohnii was 60·7%. Strain Sd/3T also exhibited a number of phenotypic differences from B. cohnii (DSM 6307T). These data suggest that Sd/3T represents a novel species of the genus Bacillus. The name Bacillus indicus sp. nov. is proposed

Leifsonia pindariensis sp. nov., isolated from the Pindari glacier of the Indian Himalayas, and emended description of the genus Leifsonia

Strain PON10<SUP>T</SUP> is a yellow-pigmented, Gram-positive, aerobic, motile, rod-shaped bacterium isolated from the Pindari glacier of the Indian Himalayas. The cell-wall peptidoglycan contained dl-diaminobutyric acid as the diamino acid. The predominant fatty acids were anteiso-C<SUB>15:0</SUB>, anteiso-C<SUB>17:0</SUB> and iso-C<SUB>16:0</SUB> and the major isoprenoid quinones were MK-10 and MK-11. Based on the above characteristics, strain PON10<SUP>T</SUP> was assigned to the genus Leifsonia. blast sequence similarity results indicated that Leifsonia ginsengi and Leifsonia poae were the nearest relatives, with 16S rRNA gene sequence similarity of 97.0 and 96.8% to the respective type strains. A difference of 3% in the 16S rRNA gene sequence indicated that PON10<SUP>T</SUP> represents a novel species of the genus Leifsonia, and therefore DNA-DNA hybridization was not done. In addition, PON10<SUP>T</SUP> showed a number of differences from Leifsonia ginsengi and Leifsonia poae with respect to phenotypic and chemotaxonomic characteristics. Thus, based on the differences it exhibited from Leifsonia ginsengi and Leifsonia poae, strain PON10<SUP>T</SUP> was identified as representing a novel species named Leifsonia pindariensis sp. nov. The type strain is PON10<SUP>T</SUP> (=LMG 24222<SUP>T</SUP> =MTCC9128<SUP>T</SUP>). An emended description of the genus Leifsonia is also presented

Advances in Pest Control: The Role of <i>Bacillus thuringiensis</i>

302-321Bacillus thuringiensis (Bt), a popularly known biopesticide, has widest scope in skirmishing diverse species of insects. Numerous reports have appeared on the ecology and distribution of Bt around the world. Characterizing Bt strains based on cry gene contents envisages more on its application potential. In the recent past, organizing the cry gene nomenclature based on protein/nucleotide sequence has overcome many ambiguities that persisted for long. This initiative of the decade has paved way to face the challenges of new additions in cry genes and assigning its phylogenetic position. In vitro evidences on insect mortality are most often not reproducible under field conditions. Therefore, numerous formulations have been developed by various entrepreneurs to combat insect pest menace. In malevolence of all advantages, development of resistance is the greatest threat to Bt indnstry and environmentalists as well. Though several alternative methods are practiced, it needs enormous effort to really understand the mode of development of resistance and to combat it accordingly. In agrarian and health sector, development of transgenic organisms is the recent trendsetter deserving attention. However, there is a cause for concern in advocating transgenics since the long-term effects of transgenics on the living organisms is not well understood. After weighing the advantages and &nbsp;disadvantages of application of Bt in the environment, it could be concluded that Bt definitely offers best scope in being biodegradable, non-toxic, target specific and most importantly renewable compared to chemical insecticides for the control of insect-pests

Effect of fiber layer formation on mechanical and wear properties of natural fiber filled epoxy hybrid composites

Natural fiber-reinforced polymer matrix composites are gathering significance in future trend applications such as automotive, aerospace, sport, and other engineering applications due to their superior enhanced mechanical, wear, and thermal properties. Compared to synthetic fiber, natural fiber is low adhesive and flexural strength properties. The research aims to synthesize the epoxy hybrid composites by utilizing the silane (pH = 4) treated Kenaf (KF) and sisal fiber (SF) as layering by uni, bi, and multi-unidirectional via hand layup techniques. Thirteen composite samples have been prepared by three-layer formation adopted with different weight ratios of E/KF/SF such as 100E/0KF/0SF, 70E/30KF/0SF, 70E/0KF/30SF, 70E/20KF/10SF, and 70E/10KF/20SF respectively. The effect of layer formation on the tensile, flexural, and impact strength of composites is studied by ASTM D638, D790, and D256 standards. The unidirectional fiber layer formed (sample 5) 70E/10KF/20SF composite is found maximum tensile and flexural strength of 57.9 ± 1.2 MPa and 78.65 ± 1.8 MPa. This composite is subjected to wear studies by pin-on-disc wear apparatus configured with a hardened grey cast-iron plate under an applied load of 10, 20, 30, and 40 N at different sliding velocities of 0.1, 0.3, 0.5, and 0.7 m/s. The wear rate of the sample progressively increases with increasing load and sliding speed of the composite. The minimum wear rate of 0.012 mg/min (sample 4) is found on 7.6 N frictional force at 0.1 m/s sliding speed. Moreover, sample 4 at a high velocity of 0.7 m/s with a low load (10 N) shows a wear rate of 0.034 mg/min. The wear-worn surface is examined and found adhesive and abrasive wear on a high frictional force of 18.54 N at 0.7 m/s. The enhanced mechanical and wear behavior of sample 5 is recommended for automotive seat frame applications

Reclassification of Amycolatopsis mediterranei DSM 46095 as Amycolatopsis rifamycinica sp. nov.

Previous experiments have suggested that the rifamycin-producing strain DSM 46095 might not belong to Amycolatopsis mediterranei. Analysis of its 16S rRNA gene sequence and construction of a phylogenetic tree showed most similarity to Amycolatopsis kentuckyensis NRRL B-24129T, Amycolatopsis lexingtonensis NRRL B-24129T and Amycolatopsis pretoriensis NRRL B-24133T, but the strain was probably not a member of any of these species. Results from DNA-DNA hybridization experiments and comparison of DNA profiling patterns using pulsed-field gel electrophoresis also supported the assignment of strain DSM 46095 to a novel species. Analyses of phospholipids, fatty acid methyl esters and physiological characteristics also showed that the differences between different isolates of A. mediterranei and A. mediterranei DSM 46095 were as large as those between Amycolatopsis species. Strain DSM 46095 represents a novel species of the genus Amycolatopsis for which the name Amycolatopsis rifamycinica sp. nov. is proposed, with the type strain NT 19T (=DSM 46095T=ATCC 27643T)