Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase inhibitors

Recently, there is considerable interest in the field of anti-HIV therapy to identify and develop chromatin-modifying histone deacetylase (HDAC) inhibitors that can effectively reactivate latent HIV in patients. The hope is that this would help eliminate cells harboring latent HIV and achieve an eventual cure of the virus. However, how effectively these drugs can stimulate latent HIVs in quiescent primary CD4 T cells, despite their relevant potencies demonstrated in cell line models of HIV latency, is not clear. Here, we show that the HDAC inhibitors valproic acid (VPA) and trichostatin A (TSA) are unable to reactivate HIV in latently infected primary CD4 T cells generated in the H80 co-culture system. This raises a concern that the drugs inhibiting HDAC function alone might not be sufficient for stimulating latent HIV in resting CD4 T cells in patients and not achieve any anticipated reduction in the pool of latent reservoirs

Robust water repellent ZnO nanorod array by Swift Heavy Ion Irradiation: Effect of Electronic Excitation Induced Local Chemical State Modification

Tailoring the surface properties by varying the chemistry and roughness could be of interest for self-cleaning applications. We demonstrate the transformation of hydrophobic ZnO Nano rod (NR) array into superhydrophobic nature by changing the local chemical state and without altering the surface roughness by swift heavy ion (SHI) irradiation. The aligned ZnO NR arrays were irradiated using 150 MeV Ag ions with different fluences from 5E10 to 3E12 ions/cm2. The observed static water contact angles of ZnO NRs samples were 103° ± 3°, 152° ± 4°,161° ± 3°, 164° ± 2°, 167° ± 2°,154 ± 3° and 151° ± 2° for the pristine, ion fluencies of 1E11, 3E11, 5E11, 7E11, 1E12 and 3E12 ions cm−2, respectively. The change in local surface chemistry via formation of surface oxygen related defects due to electronic excitations induced by ion irradiation determine the water dewetting properties. It is found that surface oxygen related defects could be tuned by varying the fluence of the SHIs. Durability tests show that the SHI induced surface oxygen-deficient ZnO NRs have the stable superhydrophobic behavior for more than a year

Enzymatic hydrolysis of sorghum straw using native cellulase produced by T. reesei NCIM 992 under solid state fermentation using rice straw

Cellulose is a major constituent of renewable lignocellulosic waste available in large quantities and is considered the most important reservoir of carbon for the production of glucose, for alternative fuel and as a chemical feedstock. Over the past decade, the emphasis has been on the enzymatic hydrolysis of cellulose to glucose and the efficiency of which depends on source of cellulosic substrate, its composition, structure, pretreatment process, and reactor design. In the present study, efforts were made to produce cellulase enzyme using rice straw. The produced enzyme was used for the hydrolysis of selected lignocellulosic substrate, i.e., sorghum straw. When rice straw was used as a substrate for cellulase production under solid state fermentation, the highest enzyme activity obtained was 30.7 FPU/gds, using T. reesei NCIM 992. 25 FPU/g of cellulase was added to differently treated (native, alkali treated, alkali treated followed by 3% acid treated and alkali treated followed by 3 and 5% acid treated) sorghum straw and hydrolysis was carried out at 50 °C for 60 h. 42.5% hydrolysis was obtained after 36 h of incubation. Optimization of enzyme loading, substrate concentration, temperature, time and buffer yielded a maximum of 546.00 ± 0.55 mg/g sugars (54.60 ± 0.44 g/l) with an improved hydrolysis efficiency of 70 ± 0.45%. The enzymatic hydrolyzate can be used for fermentation of ethanol by yeasts

Optimization of xylanase production by filamentous fungi in solid state fermentation and scale-up to horizontal tube bioreactor

Five microorganisms, namely Aspergillus niger CECT 2700, A. niger CECT 2915, A. niger CECT 2088, Aspergillus terreus CECT 2808, and Rhizopus stolonifer CECT 2344, were grown on corncob to produce cell wall polysaccharide-degrading enzymes, mainly xylanases, by solid-state fermentation (SSF). A. niger CECT 2700 produced the highest amount of xylanases of 504±7 U/g dry corncob (dcc) after 3 days of fermentation. The optimization of the culture broth (5.0 g/L NaNO3, 1.3 g/L (NH4)2SO4, 4.5 g/L KH2PO4, and 3 g/L yeast extract) and operational conditions (5 g of bed loading, using an initial substrate to moistening medium of 1:3.6 (w/v)) allowed increasing the predicted maximal xylanase activity up to 2,452.7 U/g dcc. However, different pretreatments of materials, including destarching, autoclaving, microwave, and alkaline treatments, were detrimental. Finally, the process was successfully established in a laboratory-scale horizontal tube biore- actor, achieving the highest xylanase activity (2,926 U/g dcc) at a flow rate of 0.2 L/min. The result showed an overall 5.8-fold increase in xylanase activity after optimization of culture media, operational conditions, and scale-up.We are grateful to the Spanish Ministry of Science and Innovation for the financial support of this work (project CTQ2011-28967), which has partial financial support from the FEDER funds of the European Union; to the Leonardo da Vinci Programme for founding the stay of Felisbela Oliveira in Vigo University; to MAEC-AECID (Spanish Government) for the financial support for Perez-Bibbins, B. and to Spanish Ministry of Education, Culture and Sports for Perez-Rodriguez's FPU; and to Solla E. and Mendez J. (CACTI-University of Vigo) for their excellent technical assistance in microscopy

A Normalization Model of Attentional Modulation of Single Unit Responses

Although many studies have shown that attention to a stimulus can enhance the responses of individual cortical sensory neurons, little is known about how attention accomplishes this change in response. Here, we propose that attention-based changes in neuronal responses depend on the same response normalization mechanism that adjusts sensory responses whenever multiple stimuli are present. We have implemented a model of attention that assumes that attention works only through this normalization mechanism, and show that it can replicate key effects of attention. The model successfully explains how attention changes the gain of responses to individual stimuli and also why modulation by attention is more robust and not a simple gain change when multiple stimuli are present inside a neuron's receptive field. Additionally, the model accounts well for physiological data that measure separately attentional modulation and sensory normalization of the responses of individual neurons in area MT in visual cortex. The proposal that attention works through a normalization mechanism sheds new light a broad range of observations on how attention alters the representation of sensory information in cerebral cortex

Regulation of miR-146a by RelA/NFkB and p53 in STHdhQ111/HdhQ111 Cells, a Cell Model of Huntington's Disease

Huntington's disease (HD) is caused by the expansion of N-terminal polymorphic poly Q stretch of the protein huntingtin (HTT). Deregulated microRNAs and loss of function of transcription factors recruited to mutant HTT aggregates could cause characteristic transcriptional deregulation associated with HD. We observed earlier that expressions of miR-125b, miR-146a and miR-150 are decreased in STHdhQ111/HdhQ111 cells, a model for HD in comparison to those of wild type STHdhQ7/HdhQ7 cells. In the present manuscript, we show by luciferase reporter assays and real time PCR that decreased miR-146a expression in STHdhQ111/HdhQ111 cells is due to decreased expression and activity of p65 subunit of NFkB (RelA/NFkB). By reporter luciferase assay, RT-PCR and western blot analysis, we also show that both miR-150 and miR-125b target p53. This partially explains the up regulation of p53 observed in HD. Elevated p53 interacts with RelA/NFkB, reduces its expression and activity and decreases the expression of miR-146a, while knocking down p53 increases RelA/NFkB and miR-146a expressions. We also demonstrate that expression of p53 is increased and levels of RelA/NFkB, miR-146a, miR-150 and miR-125b are decreased in striatum of R6/2 mice, a mouse model of HD and in cell models of HD. In a cell model, this effect could be reversed by exogenous expression of chaperone like proteins HYPK and Hsp70. We conclude that (i) miR-125b and miR-150 target p53, which in turn regulates RelA/NFkB and miR-146a expressions; (ii) reduced miR-125b and miR-150 expressions, increased p53 level and decreased RelA/NFkB and miR-146a expressions originate from mutant HTT (iii) p53 directly or indirectly regulates the expression of miR-146a. Our observation of interplay between transcription factors and miRNAs using HD cell model provides an important platform upon which further work is to be done to establish if such regulation plays any role in HD pathogenesis

Evaluation of Leishmania donovani Protein Disulfide Isomerase as a Potential Immunogenic Protein/Vaccine Candidate against Visceral Leishmaniasis

In Leishmania species, Protein disulfide isomerase (PDI) - a redox chaperone, is reported to be involved in its virulence and survival. This protein has also been identified, through proteomics, as a Th1 stimulatory protein in the soluble lysate of a clinical isolate of Leishmania donovani (LdPDI). In the present study, the molecular characterization of LdPDI was carried out and the immunogenicity of recombinant LdPDI (rLdPDI) was assessed by lymphocyte proliferation assay (LTT), nitric oxide (NO) production, estimation of Th1 cytokines (IFN-γ and IL-12) as well as IL-10 in PBMCs of cured/endemic/infected Leishmania patients and cured L. donovani infected hamsters. A significantly higher proliferative response against rLdPDI as well as elevated levels of IFN-γ and IL-12 were observed. The level of IL-10 was found to be highly down regulated in response to rLdPDI. A significant increase in the level of NO production in stimulated hamster macrophages as well as IgG2 antibody and a low level of IgG1 in cured patient's serum was observed. Higher level of IgG2 antibody indicated its Th1 stimulatory potential. The efficacy of pcDNA-LdPDI construct was further evaluated for its prophylactic potential. Vaccination with this construct conferred remarkably good prophylactic efficacy (∼90%) and generated a robust cellular immune response with significant increases in the levels of iNOS transcript as well as TNF-α, IFN-γ and IL-12 cytokines. This was further supported by the high level of IgG2 antibody in vaccinated animals. The in vitro as well as in vivo results thus indicate that LdPDI may be exploited as a potential vaccine candidate against visceral Leishmaniasis (VL)