Enhanced figure of merit in two-dimensional ZrNiSn nanosheets for thermoelectric applications.

A novel two-dimensional (2D) half-HeuslerZrNiSn nanosheetfor thermoelectric applications was designed from bulk half-Heusler ZrNiSn through first-principles calculation. Investigation of bulk half-Heusler and 2D nanosheet ZrNiSn was performed with the Quantum Espresso code based on a density functional theory plane wave basis set. Electronic band structure and density of states calculations were used to study the confinement effects. On moving from bulk to 2D a change of structure is observed from face-centered cubic to trigonal due to confinement effects. The semiconducting nature of bulk ZrNiSn is undisturbed while moving to a 2D nanosheet; however, the band gap is widened from 0.46 to 1.3 eV due to the restricted motion of electrons in one direction. Compared with bulk ZrNiSn, 2D nanosheets were found to have a higher Seebeck coefficient a lower thermal conductivity and higher figure of merit, which makes 2D ZrNiSn nanosheets suitable for thermoelectric applications. Atomically thin 2D structures with a flat surface have the potential to form van der Waals heterojunctions, paving the way for device fabrication at the nanoscale level.

First-principles study on novel Fe-based quaternary Heusler alloys, with robust half-metallic, thermoelectric and optical properties.

This work aims are studying new and unique Fe-based quaternary Heusler alloys for data storage, energy conversion and optoelectronics applications. The structural, magnetic, mechanical, electrical, thermal, and optical properties of novel FeCrYZ (Y = Ti, Zr, & Hf and Z = Sn, and Sb) alloys have been theoretically explored making use of density functional theory (DFT). Except for FeCrHfSb, all the alloys are found to exhibit a stable ferromagnetic ground state during the energy minimization process, also half metallic ferromagnetism exhibiting 100% spin-polarization at the Fermi level obeying Slater-Pauling rule with total integer magnetic moments of 2.00µ B and 1.00µ B respectively. FeCrTiSn, FeCrTiSb and FeCrZrSb alloys have mechanical and dynamical stability under ambient conditions. Boltzmann transport theory was used to investigate the thermoelectric performance of the materials in the temperature range of 100-900 K. The estimated dimensionless figure of merit (ZT) for FeCrTiSb is 1.76, FeCrZrSb is 0.61, and FeCrHfSb is 0.86 at 900 K. Optical spectra reveal that absorption occurs across the visible and near UV ranges of the region. Results show that the narrow bandgap, spin polarization and high ZT value of FeCrTiSb make it a promising candidate for spintronic, thermoelectric and optoelectronic applications.

Mucormycosis and diabetes in the times of COVID-19: A Mumbai-based observational study.

Background: There is a significant increase in the number of mucormycosis cases in the setting of the coronavirus disease 2019 (COVID-19) pandemic. This study was undertaken to understand the clinical profile of such patients and the risk factors associated with increased mortality of this already deadly infection. Materials and Methods: A retrospective observational study was conducted by including microbiologically confirmed cases of mucormycosis with the background of COVID-19 infection (COVID-19-associated mucormycosis [CAM]). Data was segregated into those of survivors versus non-survivors and the two groups were analyzed for various risk factors. Early and late CAM were also compared. Results: The case fatality rate was 21.73% (5/23 patients). Case fatality in early CAM was 33.3% versus 9.1% in late CAM. Rhino-orbital-cerebral mucormycosis (P = 0.01) and cranial nerve involvement (P = 0.0482) were associated with increased mortality. Diabetes and poor glycemic control were the common factors in all patients. Early CAM patients were more likely to have orbital or cerebral involvement (P = 0.0065). Patients having chronic liver disease had a higher risk of mortality (P = 0.0395). Sequential treatment or concurrent dual drug therapy with a combination of antifungal drugs was independently associated with better survival (P = 0.0395). The average duration of treatment with amphotericin-b required for cure by survivors was 29.05 ± 17.05 days. The average duration of treatment with isavuconazole/posaconazole for survivors was 50.32 ± 25.23 days. Conclusion: Early CAM had a higher case fatality rate. Patients had better recovery rates with sequential or dual antifungal treatment. The raised incidence and mortality in the COVID-19 pandemic is probably related to the COVID-19-induced immunosuppression with associated diabetes and excessive use of steroids.

Investigating the impact of a community home-based care on mental health and anti-retroviral therapy adherence in people living with HIV in Nepal: a community intervention study.

BACKGROUND: HIV-positive people often experience mental health disorders and engage in substance use when the disease progresses. In resource limited settings, mental health services are not integrated into HIV services. In Nepal, HIV-positive people do receive psychosocial support and other basic health care services from a community home-based care intervention; however, the effects of the intervention on health outcomes is not yet known. Therefore, we examined the impact of the intervention on mental health and antiretroviral therapy (ART) adherence. METHODS: We conducted an intervention study to identify the effects of a community home-based care intervention on mental health disorders, substance use, and non-adherence to ART among HIV-positive people in Nepal from March to August 2015. In total, 344 participated in the intervention and another 338 were in the control group. The intervention was comprised of home-based psychosocial support and peer counseling, adherence support, basic health care, and referral services. We measured the participants' depression, anxiety, stress, substance use, and non-adherence to ART. We applied a generalized estimating equation to examine the effects of intervention on health outcomes. RESULTS: The intervention had positive effects in reducing depressive symptoms [Adjusted Odds Ratio (AOR) = 0.44, p < 0.001)], anxiety (AOR = 0.54, p = 0.014), stress (ß = - 3.98, p < 0.001), substance use (AOR = 0.51, p = 0.005), and non-adherence to ART (AOR = 0.62, p = 0.025) among its participants at six-month follow-up. CONCLUSIONS: The intervention was effective in reducing mental health disorders, substance use, and non-adherence to ART among HIV-positive people. Community home-based care intervention can be applied in resource limited setting to improve the mental health of the HIV-positive people. Such intervention should be targeted to include more HIV-positive people in order to improve their ART adherence. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03505866 , Released Date: April 20, 2018.

Predicting health-related quality of life in people living with HIV in Nepal: mental health disorders and substance use determinants.

HIV-positive people often experience mental health disorders and engage in substance use. Such conditions tend to impair their health-related quality of life (QOL). Evidence, however, is limited about the influence of mental health disorders and substance use on QOL by gender. Also, little is known about the influences of anxiety and high levels of stress on QOL. We recruited 682 HIV-positive people in Nepal and measured their depression, anxiety, stress levels, substance use, and QOL. Multiple linear regressions assessed the association of mental health disorders and substance use with QOL. Presence of depressive symptoms was negatively associated with all domains of QOL including the physical (men: ß = -0.68, p = 0.037; women: ß = -1.37, p < 0.001) and the psychological (men: ß = -1.08, p < 0.001; women: ß = -1.13, p < 0.001). Those who experienced anxiety had lower scores in the physical (ß = -0.89, p = 0.027) and psychological (ß = -1.75, p = 0.018) QOL domains among men and in the spiritual QOL domain (ß = -0.061, p = 0.043) among women. High stress levels were associated with lower scores across all QOL domains including the physical (men: ß = -0.16, p < 0.001; women: ß = -0.14, p < 0.001) and the psychological (men: ß = -0.09, p < 0.001; women: ß = -0.10, p < 0.001). Substance-using men were more likely to have lower scores in physical (ß = -0.70, p = 0.039) and psychological (ß = -0.073, p = 0.002) domains. Among women, meanwhile, substance use was negatively associated with the psychological domain only (ß = -0.77, p = 0.005). In conclusion, mental health disorders and substance use had negative associations with QOL. Attention should be given to addressing the mental health care needs of HIV-positive people to improve their QOL.

Evaluation of the effect of Punica granatum juice and punicalagin on NFκB modulation in inflammatory bowel disease.

Punica granatum L. (Lythraceae) inhibits cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. No pharmacological work is reported on the effects of P. granatum juice on the cellular signaling pathways involved in initiation and progression of inflammation. The present investigation evaluates the effect of P. granatum juice (PJ) and purified punicalagin (PW) on nuclear factor kappa B (NFκB) and the signaling pathways leading to its expression in colon inflammation. Male Sprague-Dawley rats were divided into six groups: positive and negative control, vehicle (50 % ethanol), standard (5-ASA 100 mg/kg, p.o.), PJ (400 mg/kg, p.o.), PW (4 mg/kg, p.o.). Colitis was induced with 2,4-dinitrobenzene sulfonic acid and animals were euthanized on 18th day. Colon samples collected were subjected to various histological assessment (CMDI, DAI), and biochemical parameters (MPO, MDA, SOD, NO). Gene expression study was carried out using RT-PCR for cytokines (TNF-α, IL-1ß, IL-18 and NF-κß). Pretreatment with PJ and PW significantly (p < 0.05) lowered the disease extent and severity as indicated by reduction in CMDI (2 ± 0.31) and DAI (1.83(#) ± 0.22) when compared with DNBS-treated rats (3.83* ± 0.17). Gene expression studies showed decreased mRNA levels of TNF-α, IL-18, and IL-1ß in PJ and PW-treated groups. NF-κß mRNA levels were found to be reduced 84 and 64 % by PJ and PW, respectively. These results suggest that P. granatum juice is more biologically active over punicalagin alone and can be potentially used for the treatment of inflammatory bowel disease.

Validated high-performance thin-layer chromatographic (HPTLC) method for simultaneous determination of nadifloxacin, mometasone furoate, and miconazole nitrate cream using fractional factorial design.

A high-performance thin-layer chromatographic method for simultaneous determination of nadifloxacin, mometasone furoate, and miconazole nitrate was developed and validated as per International Conference on Harmonization guidelines. High-performance thin-layer chromatographic separation was performed on aluminum plates precoated with silica gel 60F254 and methanol:ethyl acetate:toluene: acetonitrile:3M ammonium formate in water (1:2.5:6.0:0.3:0.2, % v/v) as optimized mobile phase at detection wavelength of 224 nm. The retardation factor (Rf) values for nadifloxacin, mometasone furoate, and miconazole nitrate were 0.23, 0.70, and 0.59, respectively. Percent recoveries in terms of accuracy for the marketed formulation were found to be 98.35-99.76%, 99.36-99.65%, and 99.16-100.25% for nadifloxacin, mometasone furoate, and miconazole nitrate, respectively. The pooled percent relative standard deviation for repeatability and intermediate precision studies was found to be < 2% for three target analytes. The effect of four independent variables, methanol content in total mobile phase, wavelength, chamber saturation time, and solvent front, was evaluated by fractional factorial design for robustness testing. Amongst all four factors, volume of methanol in mobile phase appeared to have a possibly significant effect on retention factor of miconazole nitrate compared with the other two drugs nadifloxacin and mometasone furoate, and therefore it was important to be carefully controlled. In summary, a novel, simple, accurate, reproducible, and robust high-performance thin-layer chromatographic method was developed, which would be of use in quality control of these cream formulations.

Validated HPTLC Method for Quantification of Luteolin and Apigenin in Premna mucronata Roxb., Verbenaceae.

A simple, rapid, and precise high-performance thin-layer chromatographic method was developed for quantitative estimation of luteolin and apigenin in Premna mucronata Roxb., family Verbenaceae. Separation was performed on silica gel 60 F254 HPTLC plates using toluene : ethyl acetate : formic acid (6 : 4 : 0.3) as mobile phase for elution of markers from extract. The determination was carried out in fluorescence mode using densitometric absorbance-reflection mode at 366 nm for both luteolin and apigenin. The methanolic extract of Premna mucronata was found to contain 10.2 mg/g % luteolin and 0.165 mg/g % of apigenin. The method was validated in terms of linearity, LOD and LOQ, accuracy, precision, and specificity. The calibration curve was found to be linear between 200 and 1000 ng/band for luteolin and 50 and 250 ng/band for apigenin. For luteolin and apigenin, the limit of detection was found to be 42.6 ng/band and 7.97 ng/band while the limit of quantitation was found to be 129.08 ng/band and 24.155 ng/band, respectively. This developed validated method is capable of quantifying and resolving luteolin and apigenin and can be applicable for routine analysis of extract and plant as a whole.

Central Composite Design for Validation of HPTLC Method for Simultaneous Estimation of Olmesartan Medoxomil, Amlodipine Besylate and Hydrochlorothiazide in Tablets.

High performance thin layer chromatographic method for simultaneous estimation of olmesartan medoxomil, amlodipine besylate and hydrochlorothiazide was developed and validated as per ICH guidelines. Moreover, robustness testing was performed applying a central composite design with k factor having 2(k) factorial runs, 2k axial experiments and two center points. High performance thin layer chromatographic separation was performed on aluminium plates precoated with silica gel 60F254 and toluene:chloroform:methanol:acetonitrile:formic acid (2:7:1.8:0.8:0.2% v/v) as optimized mobile phase. The detection wavelength for simultaneous estimation of three drugs was 232nm. The Rf values for olmesartan medoxomil, amlodipine besylate and hydrochlorthiazide were 0.78, 0.20 and 0.45, respectively. Percent recoveries in terms of accuracy for the marketed formulation was found to be 101.3-104.4, 100.7-104 and 101.5-103.9 for, olmesartan medoxomil, amlodipine besylate and hydrochlorthiazide, respectively. The pooled %relative standard deviation values for repeatability studies and intermediate precision studies was found to be less than 2% for olmesartan medoxomil, amlodipine besylate and hydrochlorthiazide, respectively. All the three factors evaluated in the robustness testing by central composite design were found to have an insignificant effect on the retention factor. However, methanol content in total mobile phase as a factor appeared to have significant effect on robustness, compared to band size and developing distance and hence it is important to be carefully controlled. In summary, a novel, simple, accurate and reproducible high performance thin layer chromatographic method was developed, which would be of use in quality control of these tablets.

Cleaning validation: quantitative estimation of atorvastatin in production area.

Carefully designed cleaning validation and its evaluation can ensure that residues of active pharmaceutical ingredient will not carry over and cross-contaminate the subsequent product. UV spectrophotometric and total organic carbon-solid sample module (TOC-SSM) method was developed and validated for the verification and determination of atorvastatin residues in the production area and to confirm the efficiency of the cleaning procedure as per ICH guideline. Atorvastatin was selected on the basis of a worst-case rating approach. It exhibited good linearity in the range of 5 to 25 µg/mL for UV spectrophotometric and 7300 to 83800 µg for the TOC-SSM method. The limit of detection was 0.419 µg/mL and 4.19 µg in the UV spectrophotometric and TOC-SSM methods, respectively. The limit of quantitation was 1.267 µg/mL and 12.69 µg in UV spectrophotometric and TOC-SSM methods, respectively. Percentage recovery from spiked stainless steel plates was found to be 95.37% and 92.82% in UV spectrophotometric and TOC-SSM methods, respectively. The calculated limit of acceptance per swab for atorvastatin (35.65 µg/swab) was not exceeded during three consecutive batches of production after cleaning procedure. Both proposed methods are suitable for quantitative determination of atorvastatin on manufacturing equipment surfaces well below the limit of contamination. The ease of sample preparation permits fast and efficient application of the proposed methods in quantitation of atorvastatin residue with precision and accuracy. Above all, the methodology is of low cost, and is a simple and less time-consuming alternative to confirm the efficiency of the cleaning procedure in pharmaceutical industries. LAY ABSTRACT: Carefully designed cleaning validation and its evaluation can ensure that residues of active pharmaceutical ingredient will not carry over and cross-contaminate the subsequent product. Atorvastatin was identified as a potential candidate among existing drug substances in production areas based on a worst-case rating approach. Atorvastatin residues were detected and quantified below acceptance limits after cleaning of production equipment using two proposed methods, namely, the UV spectrophotometric and total organic carbon-solid sample module (TOC-SSM) methods. The ease of sample preparation permits fast and efficient application of the proposed methods in quantitation of atorvastatin residue in production equipment area to confirm the efficiency of the cleaning procedure in pharmaceutical industries. Above all, the methodology is of low cost, and is a simple and less time-consuming alternative for cleaning validation.

4-[(E)-(Hy-droxy-imino)-meth-yl]-N,N-di-methyl-anilinium chloride.

In the title compound, C(9)H(13)N(2)O(+)·Cl(-), the cation, apart from the methyl groups, is almost planar, with a maximum deviation of 0.040 (1) Å; the methyl C atoms deviate by 0.389 (2) and -1.247 (1) Å, from the mean plane. In the crystal, cations and anions associate through C-H⋯Cl hydrogen bonds, forming a helical arrangement. In addition, inter-molecular O-H⋯Cl, N-H⋯Cl and C-H⋯N inter-actions are observed.

Resorcinol ninhydrin complex: 1,5,9-trihy-droxy-8-oxatetra-cyclo-[7.7.0.0(2,7).0(10,15)]hexa-deca-2,4,6,10(15),11,13-hexaen-16-one.

In the title compound, C(15)H(10)O(5), the cyclo-penta-none (r.m.s. deviation = 0.049 Å) and oxolane (r.m.s. deviation = 0.048 Å) rings make a dihedral angle of 67.91 (4)°. An intra-molecular O-H⋯O hydrogen bond is observed. In the crystal, mol-ecules associate via O-H⋯O hydrogen bonds, forming a three-dimensional network.

Validated HPTLC method for quantitative determination of gallic acid in stem bark of Myrica esculenta Buch.-Ham. ex D. Don, myricaceae.

A simple, rapid, and precise HPTLC method was developed for quantitative estimation of gallic acid in stem bark of Myrica esculenta, family Myricaceae. Separation was performed on silica gel 60F254 HPTLC plates using toluene-ethyl acetate-formic acid-methanol (3 + 3 + 0.6 + 0.4, v/v/v/v) mobile phase for separation of the extracted components. The determination was carried out in the UV densitometric absorbance-reflection mode at 280 nm. The amount of gallic acid in free and combined form in the stem bark powder was found to be 0.276 and 0.541%, respectively, on a dry weight basis. The method was validated in terms of linearity, accuracy, precision, and specificity according to International Conference on Harmonization guidelines. Gallic acid response was found to be linear over a broad concentration range of 0.4-2.0 microg/band. LOD and LOQ were 0.103 and 0.312 microg/spot, respectively. The developed method is capable of quantifying amounts of gallic acid in stem bark powder of M. esculenta.

Evaluation of bronchodilator and anti-anaphylactic activity of Myrica sapida.

BACKGROUND: Asthma is a chronic inflammatory disorder of the airways. The available treatment options have major limitations owing to low efficacy, associated adverse events and compliance issues. Therefore, the health burden of bronchial asthma is increasing globally at an alarming rate, providing a strong impetus for the development of new therapeutics. Myrica sapida is known traditionally in Ayurveda to possess anti-asthmatic activity. Hence, the present investigation was undertaken to evaluate the bronchodilator and anti-anaphylactic activity of the stem bark of Myrica sapida. METHODS: Experimental models studied were acetylcholine induced bronchospasm in guinea pigs, egg albumin induced anaphylaxis in guinea pigs, in vitro studies on tracheal strip of egg albumin sensitized guinea pigs. RESULTS: Treatment with ethanolic extract of M. sapida, 75 mg/kg, orally resulted in significant protection against acetylcholine aerosol induced bronchospasm and allergen induced anaphylaxis in guinea pigs. Ethanolic extract of M. sapida (75 mg/kg, p.o.) prevented the potentiation of responses and also produced a decrease in pD2 value of histamine and acetylcholine in guinea pig tracheal strip. CONCLUSION: These results suggest that M. sapida possesses bronchodilator activity, has potent inhibitory effect on immediate hyper-sensitivity reactions and decreases bronchial hyper-responsiveness.

Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole.

Individual variation in drug metabolism is a major cause of unpredictable side effects during therapy. Drug metabolism is controlled by a class of orphan nuclear receptors (NRs), which regulate expression of genes such as CYP (cytochrome)3A4 and MDR-1 (multi-drug resistance-1), that are involved in this process. We have found that xenobiotic-mediated induction of CYP3A4 and MDR-1 gene transcription was inhibited by ketoconazole, a commonly used antifungal drug. Ketoconazole mediated its effect by inhibiting the activation of NRs, human pregnenolone X receptor and constitutive androstene receptor, involved in regulation of CYP3A4 and MDR-1. The effect of ketoconazole was specific to the group of NRs that control xenobiotic metabolism. Ketoconazole disrupted the interaction of the xenobiotic receptor PXR with the co-activator steroid receptor co-activator-1. Ketoconazole treatment resulted in delayed metabolism of tribromoethanol anesthetic in mice, which was correlated to the inhibition of PXR activation and downmodulation of cyp3a11 and mdr-1 genes and proteins. These studies demonstrate for the first time that ketoconazole represses the coordinated activation of genes involved in drug metabolism, by blocking activation of a specific subset of NRs. Our results suggest that ketoconazole can be used as a pan-antagonist of NRs involved in xenobiotic metabolism in vivo, which may lead to novel strategies that improve drug effect and tolerance.

Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors.

Rhabdoid tumors (RTs) are aggressive and currently incurable pediatric malignancies. INI1/hSNF5 is a tumor suppressor biallelically inactivated in RTs. Our previous studies have indicated that cyclin D1 is a key downstream target of INI1/hSNF5 and genesis and/or survival of RTs in vivo is critically dependent on the presence of cyclin D1. In this report, we have tested the hypothesis that therapeutic targeting of cyclin D1 is an effective means of treating RTs. We found that RNA interference of cyclin D1 in rhabdoid cells was sufficient to induce G1 arrest and apoptosis. Furthermore, we found that pharmacological intervention with low micromolar concentrations of N-(4-hydroxyphenyl)retinamide (4-HPR), which downmodulates cyclin D1, induced G1 arrest and apoptosis in rhabdoid cell lines. 4-HPR in combination with 4-hydroxy-tamoxifen (4OH-Tam), synergistically inhibited survival as well as anchorage-dependent and -independent growth of rhabdoid cells and caused synergistic induction of cell cycle arrest and apoptosis. 4-HPR and tamoxifen exhibited synergistic growth inhibition of RTs in xenograft models in vivo. The effects of combination of drugs were correlated to the depletion of cyclin D1 levels both in in vitro and in vivo tumor models. These results demonstrate that 4-HPR and tamoxifen are effective chemotherapeutic agents for RTs. We propose that downmodulation of cyclin D1 is a novel and effective therapeutic strategy for RTs.

Effect of hydrocarbons and other parameters on hydrocarbon-utilizing Pichia angusta MTCC-225.

Pichia angusta MTCC-225, a catalase-positive yeast that utilizes methanol and lighter hydrocarbons, is the subject of this investigation. An orthogonal experimental design L16 was used to investigate the effects of methanol, a gas mixture, zero air, temperature, agitation, and salts solution on hydrocarbon utilizing P. angusta. QUALITEK-4 Software was used for automatic design and analysis of the experimental results. Among the various parameters tested, agitation contributed the highest influence (56.5%). Zero air, methanol concentration, and gas mixture showed a moderate influence on the growth of P. angusta. Methanol concentration and gas mixture showed a 10.91 and 10.12% influence, respectively, on yeast growth. Zero air played an important role, with a 15.19% influence on the utilization of hydrocarbon.

Homodimerization of human bilirubin-uridine-diphosphoglucuronate glucuronosyltransferase-1 (UGT1A1) and its functional implications.

Genetic lesions of bilirubin-uridine-diphosphoglucuronate glucuronosyltransferase-1 (UGT1A1) completely or partially abolish hepatic bilirubin glucuronidation, causing Crigler-Najjar syndrome type 1 or 2, respectively. Clinical observations indicate that some mutant forms of human UGT1A1 (hUGT1A1) may be dominant-negative, suggesting their interaction with the wild-type enzyme. To evaluate intermolecular interaction of hUGT1A1, Gunn rat fibroblasts were stably transduced with hUGT1A1 cDNA. Gel permeation chromatography of solubilized microsomes suggested dimerization of hUGT1A1 in solution. Nearest-neighbor cross-linking analysis indicated that, within microsomal membranes, hUGT1A1 dimerized more efficiently at pH 7.4 than at pH 9. Two-hybrid analysis in yeast and mammalian systems demonstrated positive interaction of hUGT1A1 with itself, but not with another UGT isoform, human UGT1A6, which differs only in the N-terminal domain. Dimerization was abolished by deletion of the membrane-embedded helix from the N-terminal domain of hUGT1A1, but not by substitution of several individual amino acid residues or partial deletion of the C-terminal domain. A C127Y substitution abolished UGT1A1 activity, but not its dimerization. Coexpression of mutagenized and wild-type hUGT1A1 in COS-7 cells showed that the mutant form markedly suppressed the catalytic activity of wild-type hUGT1A1. Homodimerization of hUGT1A1 may explain the dominant-negative effect of some mutant forms of the enzyme.

Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1.

Integase interactor 1 (INI1), also known as hSNF5, is a protein that interacts with HIV-1 integrase. We report here that a cytoplasmically localized fragment of INI1 (S6; aa183-294) containing the minimal integrase-interaction domain potently inhibits HIV-1 particle production and replication. Mutations in S6 or integrase that disrupt integrase-INI1 interaction abrogated the inhibitory effect. An integrase-deficient HIV-1 transcomplemented with integrase fused to Vpr was not affected by S6. INI1 was specifically incorporated into virions and was required for efficient HIV-1 particle production. These results indicate that INI1 is required for late events in the viral life cycle, and that ectopic expression of S6 inhibits HIV-1 replication in a transdominant manner via its specific interaction with integrase within the context of Gag-Pol, providing a novel strategy to control HIV-1 replication.