Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria.

Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions.

Performance and cell toxicity studies for the use of graphene oxide-bimetallic oxide hybrids in the absorptive removal of Pb(II) from wastewater: fixed-bed column study with regeneration.

The current study involves the removal of Pb(II) ions from an aqueous solution using GO/Mn-Fe hybrids in a fixed bed column study. The capability of the hybrid in the Pb removal was examined using a continuous flow fixed bed column which revealed that the hybrid had the maximum adsorption capacity of 172.768 mg/g at a flow rate of 2 mL/min, bed height of 1 cm, and influent concentration of 200 mg/L. The breakthrough curves obtained from the experiments were examined using three different models, i.e., Bohart-Adams model, Thomas Model, and Yoon-Nelson model, wherein all the models showed high correlation coefficient values. Three consecutive adsorption-desorption cycles in the column yielded regeneration efficiencies of 91.71%, 88.31%, and 85.41%. The column life factor indicated that the fixed bed would have enough capacity to avoid a zero breakthrough time for up to 9 cycles, implying that GO/Mn-Fe could be used as a cheap and efficient adsorbent in the removal of Pb(II) from contaminated water. The adsorption mechanism was postulated based on the characterization of the spent adsorbent by FTIR and SEM. The phenomenon of the adsorption process can be described in accordance with the surface complex formation theory, which suggests that an increase in pH decreases the competition between metal ions and protons, favoring metal ion adsorption. The toxicity of the synthesized hybrid was evaluated on HeLa cells and compared to the toxicity of GO. Increasing the concentration of GO/Mn-Fe hybrid from 50 to 250 g/mL resulted in a decrease in cell viability from 91.90 to 56.52%, whereas increasing the concentration of GO resulted in a decrease in cell viability from 61.59 to 37.19%. The study clearly demonstrates the use of GO/Mn-Fe hybrid as an adsorbent for efficient sequestration of Pb(II) ions with lower environmental toxicity.

Photoinduced micropatterning on biodegradable aliphatic polyester surfaces for anchoring dual brushes and its application in bacteria and cell patterning.

In view of intrinsic challenges encountered in surface patterning on actual biomaterials such as the ones based on biodegradable polymers, we have demonstrated an innovative strategy to create micro-patterns on the surface of tartaric acid based aliphatic polyester P (poly(hexamethylene 2,3-O-isoprpylidentartarate)) without significant loss of its molecular weight. Around 10 wt% PAG (photoacid generator, 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine) was purposefully encapsulated in a polyester matrix comprising of P and PLA (polylactide) at a ratio of 5 : 95. With the help of a photomask, selective areas of the matrix were exposed to UV radiation at 395 nm for 25 min to trigger the acid release from PAG entrapped unmasked areas for generating hydroxyl functionality that was later converted to an ATRP (atom transfer radical polymerization) initiating moiety on the irradiated domain of P. In subsequent steps, spatio-selective surface modification by surface initiated ATRP was carried out to generate an alternate pattern of polyPEGMA (poly(ethylene glycol)methyl ether methacrylate) and polyDMAPS (poly(3-dimethyl-(methacryloyloxyethyl)ammonium propane sulfonate)) brushes on the matrix. The patterned surface modified with dual brushes was found to be antifouling in nature (rejection of >97% of proteins). Strikingly, an alternate pattern of live bacterial cells (E. coli and S. aureus) was evident and a relatively high population of bacteria was found on the polyPEGMA brush modified domain. However, a complete reverse pattern was visible in the case of L929 mouse fibroblast cells, i.e., cells were found to predominantly adhere to and proliferate on the zwitterionic brush modified surface. An attempt was made to discuss a plausible mechanism of selective cell adhesion on the zwitterionic brush domain. This novel strategy employed on the biodegradable polymer surface provides an easy and straightforward way to micro-pattern various cells, bacteria, etc. on biodegradable substrates which hold great potential to function as biochips, diagnostics, bacteria/cell microarrays, etc.

Cytocompatible, soft and thick brush-modified scaffolds with prolonged antibacterial effect to mitigate wound infections.

Biomedical device or implant-associated infections caused by pathogenic bacteria are a major clinical issue, and their prevention and/or treatment remains a challenging task. Infection-resistant antimicrobial coatings with impressive cytocompatibility offer a step towards addressing this problem. Herein, we report a new strategy for constructing highly antibacterial as well as cytocompatible mixed polymer brushes onto the surface of 3D printed scaffold made of biodegradable tartaric acid-based aliphatic polyester blends. The mixed brushes were nothing but a combination of poly(3-dimethyl-(methacryloyloxyethyl) ammonium propane sulfonate) (polyDMAPS) and poly((oligo ethylene glycol) methyl ether methacrylate) (polyPEGMA) with varying chain length (n) of the ethylene glycol unit (n = 1, 6, 11, and 21). Both homo and copolymeric brushes of polyDMAPS with polyPEGMA exhibited antibacterial efficacy against both Gram positive and Gram negative pathogens such as E. coli (Escherichia coli) and S. aureus (Staphylococcus aureus) because of the combined action of bacteriostatic effects originating from strongly hydrated layers present in zwitterionic (polyDMAPS) and hydrophilic (polyPEGMA) copolymer brushes. Interestingly, a mixed polymer brush comprising polyDMAPS and polyPEGMA (ethylene glycol chain unit of 21) at 50/50 ratio provided zero bacterial growth and almost 100% cytocompatibility (tested using L929 mouse fibroblast cells), making the brush-modified biodegradable substrate an excellent choice for an infection-resistant and cytocompatible surface. An attempt was made to understand their extraordinary performance with the help of contact angle, surface charge analysis and nanoindentation study, which revealed the formation of a hydrophilic, almost neutral, very soft surface (99.99% reduction in hardness and modulus) after modification with the mixed brushes. This may completely suppress bacterial adhesion. Animal studies demonstrated that these brush-modified scaffolds are biocompatible and can mitigate wound infections. Overall, this study shows that the fascinating combination of an infection-resistant and cytocompatible surface can be generated on biodegradable polymeric surfaces by modulating the surface hardness, flexibility and hydrophilicity by selecting appropriate functionality of the copolymeric brushes grafted onto them, making them ideal non-leaching, anti-infective, hemocompatible and cytocompatible coatings for biodegradable implants.

Bimetallic Fe/Al-MOF for the adsorptive removal of multiple dyes: optimization and modeling of batch and hybrid adsorbent-river sand column study and its application in textile industry wastewater.

Bimetallic metal organic framework (MOF) has garnered interest over the years with its applications in industrial wastewater treatment. In this work, Fe-Al-1,4-benzene-dicarboxylic acid (FeAl(BDC)) MOF was synthesized, and adsorptive removal of Rhodamine B dye in batch and unique hybrid FeAl (BDC)-river sand fixed-bed column was studied. The experimental data from the batch studies corroborated well with the pseudo-second-order (PSO) (R2: 0.97) and Freundlich adsorption isotherm models (R2: 0.98) and achieved a maximum adsorption capacity of 48.59 mg/g in 90 min. Furthermore, a fixed-bed column study was conducted to assess the effect of varying flow rate (2, 5, 8 mL/min), bed height (5, 9, 13 cm), and feed concentration (10, 20, 30 mg/L) on the adsorption performance of FeAl(BDC) in continuous mode of operation. A uniform mixture of river sand and FeAl(BDC) by weight ratio (9:1) was packed into the column. The sand-FeAl(BDC) fixed-bed column could achieve the maximum adsorption capacity (qexp) of 113.05 mg/g at a 5 mL/min flow rate, feed concentration of 20 mg/L, and a bed height of 13 cm. The experimental data of the column study were successfully fitted well with BDST, Thomas (qcal: 114.94 mg/g), Yoon-Nelson, and dose-response models (qcal: 113.41 mg/g) and R2: 0.97-0.99. The fitting parameter values from the BDST model raise the scope of viable upscaling of the fixed-bed column. In all, it is proposed that these river sand-FeAl(BDC)-based filters can be widely used in areas facing critical contamination and in poor communities with a high demand for water.

(3-Aminopropyl)triethoxysilane and iron rice straw biochar composites for the sorption of Cr (VI) and Zn (II) using the extract of heavy metals contaminated soil.

Heavy metals like Cr (VI), when released into the environment, pose a serious threat to animal and human health. In this study, iron and (3-Aminopropyl)triethoxysilane (APTES) biochar composites were prepared from the biochar, which was produced through the pyrolysis of rice straw at 400 and 600 °C, using the chemical processes with an aim that the doping of pristine biochar structure with the Fe and NH2 radicals would enhance the removal of Cr (VI) and Zn (II) adsorption in both aqueous solution and soil. Both biochar composites were mixed at a rate of 3% (w/w) with the mine soil for the soil incubation test, and after completion of the test, a soil fertility index (SFI) was calculated. Results showed that both iron and APTES biochar composites followed the Langmuir-Freundlich isotherm showing the maximum removal capacity of 100.59 mg/g for Cr (VI) by APTES/SiBC 600 and maximum adsorption capacity of 83.92 mg/g for Zn2+ by Fe/BC 400. The SFI of the mine-soil amended with both Fe and APTES biochar composites were 16.67 and 13.04%, respectively higher than the controlled study. The mitotic index of the A. cepa cells that grew up in the soil amended with Fe/BC and APTES/SiBC were 40.47 and 44.45%, respectively, higher than the controlled study. The results indicated that the incorporation of the Fe and APTES biochar composites in the soil effectively reduced the metal toxicity and improved the soil physicochemical properties. This study opens up the prospects of using biochar composites in contaminated soil and water treatments.

Genetically Encoded Stealth Nanoparticles of a Zwitterionic Polypeptide-Paclitaxel Conjugate Have a Wider Therapeutic Window than Abraxane in Multiple Tumor Models.

Small-molecule therapeutics demonstrate suboptimal pharmacokinetics and bioavailability due to their hydrophobicity and size. One way to overcome these limitations-and improve their efficacy-is to use "stealth" macromolecular carriers that evade uptake by the reticuloendothelial system. Although unstructured polypeptides are of increasing interest as macromolecular drug carriers, current recombinant polypeptides in the clinical pipeline typically lack stealth properties. We address this challenge by developing new unstructured polypeptides, called zwitterionic polypeptides (ZIPPs), that exhibit "stealth" behavior in vivo. We show that conjugating paclitaxel to a ZIPP imparts amphiphilicity to the polypeptide chain that is sufficient to drive its self-assembly into micelles. This in turn increases the half-life of paclitaxel by 17-fold compared to free paclitaxel, and by 1.6-fold compared to the nonstealth control, i.e., ELP-paclitaxel. Treatment of mice bearing highly aggressive prostate or colon cancer with a single dose of ZIPP-paclitaxel nanoparticles leads to near-complete eradication of the tumor, and these nanoparticles have a wider therapeutic window than Abraxane, an FDA-approved taxane nanoformulation.

Potassium-iron rice straw biochar composite for sorption of nitrate, phosphate, and ammonium ions in soil for timely and controlled release.

In this study, potassium-iron rice straw biochar composite (KRSB) was produced and compared with rice straw biochar (RSB) for the sorption of NO3-, PO43-, and NH4+ in aqueous medium and soil column. RSB was produced by pyrolyzing rice straw at 400 and 600 °C in a slow pyrolysis unit. KRSB was produced through chemical and hydrothermal treatments of rice straw biochar produced at 400 and 600 °C. Batch experiment results indicate that the KRSB showed better sorption capacity for nitrate, phosphate, and ammonium ions compared to pristine RSB. The sorption isotherms of all three nutrients (NO3-, PO43-, and NH4+) were better-explained by the Langmuir-Freundlich isotherm model. The column leaching experiment showed that the KRSB loaded soil reached maximum sorption capacity for PO43- and NO3- within six and eight days, respectively but, it showed poor sorption capacity for NH4+. The soil fertility index in the 400 and 600 KRSB amended soils were significantly increased by 50.68 and 52.85%, respectively compared to the control. Results indicated that KRSB could be utilized in the soil in two ways: first, to keep the nutrients attached to its surface and second, to release the nutrients in a phased and timely manner to increase their availability for plants.

The chaperone ERp29 is required for tunneling nanotube formation by stabilizing MSec.

Tunneling nanotubes (TNTs) are membrane conduits that mediate long-distance intercellular cross-talk in several organisms and play vital roles during development, pathogenic transmission, and cancer metastasis. However, the molecular mechanisms of TNT formation and function remain poorly understood. The protein MSec (also known as TNFα-induced protein 2 (TNFAIP2) and B94) is essential for TNT formation in multiple cell types. Here, using affinity protein purification, mass spectrometric identification, and confocal immunofluorescence microscopy assays, we found that MSec interacts with the endoplasmic reticulum (ER) chaperone ERp29. siRNA-mediated ERp29 depletion in mammalian cells significantly reduces TNT formation, whereas its overexpression induces TNT formation, but in a strictly MSec-dependent manner. ERp29 stabilized MSec protein levels, but not its mRNA levels, and the chaperone activity of ERp29 was required for maintaining MSec protein stability. Subcellular ER fractionation and subsequent limited proteolytic treatment suggested that MSec is associated with the outer surface of the ER. The ERp29-MSec interaction appeared to require the presence of other bridging protein(s), perhaps triggered by post-translational modification of ERp29. Our study implicates MSec as a target of ERp29 and reveals an indispensable role for the ER in TNT formation, suggesting new modalities for regulating TNT numbers in cells and tissues.

Characterization of the membrane-bound form of the chimeric, B/C recombinant HIV-1 Env, LT5.J4b12C.

Human immunodeficiency virus 1 (HIV-1) diversity is a significant challenge in developing a vaccine against the virus. B/C recombinants have been found in India and other places but are the predominant clade prevalent in China. HIV-1 envelopes (Envs) are the target of broadly neutralizing antibodies (bNAbs) which develop spontaneously in some HIV-1 infected patients. It has been previously reported with efficiently cleaved clade A, B and C Envs that preferential binding of Envs to bNAbs as opposed to non-NAbs, a desirable property for immunogens, is correlated with efficient cleavage of the Env precursor polypeptide into constituent subunits. These Envs are suitable for designing immunogens as soluble proteins, virus-like particles or for delivery by viral vectors/plasmid DNA. However, a B/C recombinant Env with similar properties has not been reported. Here we show that the chimeric, recombinant B/C clade Env LT5.J4b12C is efficiently cleaved on the plasma membrane and selectively binds to bNAbs.

Cardiac morbidity in an HIV-1 lipodystrophy patient cohort expressing the TNF-α-238 G/A single nucleotide gene polymorphism.

In the current study we investigated the prevalence of the TNF-α 238G/A single nucleotide polymorphism (SNP) of the TNF-α gene in the development of lipodystrophy among HIV-1 infected individuals who had been receiving antiretroviral therapy (ART) in the immunodeficiency clinics of the National AIDS Research Institute (NARI) at Pune, India. We assessed the association of this SNP with the development of lipoatrophy/dyslipidemia and insulin resistance in these patients and measured carotid intima thickening which is a surrogate marker for chronic cardiac morbidity. Our results show that the incidence of the TNF-α 238G/A SNP is ~ two fold higher in patients with lipodystrophy as compared to those without lipodystrophy. Patients with lipodystrophy demonstrated a higher likelihood of the development of metabolic syndrome as evident by increased insulin sensitivity and increased percentage (%) ß cell function. Further, a significant increase in left carotid intima thickness was observed in patients with lipodystrophy. Our study validates the association of the TNF-α 238G/A SNP allelic variant with the development of HIV- lipodystrophy via the modulation of TNF-α production, which contributes to dyslipidemia, increased lipolysis, increased insulin resistance, altered differentiation of adipocytes and increased carotid intima thickness. The contribution of genetic determinants such as the TNF-α 238G/A SNP to lipodystrophy, may provide insight into the mechanisms that underlie this disease condition and may be useful in the future for personalized therapy. Additionally, these findings will be useful in monitoring chronic cardiac morbidities among HIV infected individuals who express this SNP.

Determinants in V2C2 region of HIV-1 clade C primary envelopes conferred altered neutralization susceptibilities to IgG1b12 and PG9 monoclonal antibodies in a context-dependent manner.

In the present study by examining pseudoviruses expressing patient chimeric envelopes (Envs) made between an IgG1b12 (b12)-sensitive (2-5.J3) and a b12-resistant (4.J22) HIV-1 clade C envelope, we identified determinants in the V2C2 region that governed susceptibility to b12 monoclonal antibody, but not to other CD4 binding site antibodies. Interestingly, when the V2C2 sequence of the 2-5.J3 Env was transferred to other b12-resistant primary clade C Envs, their susceptibility to b12 varied, indicating that this effect was context dependent. In addition, we identified determinants within the V2 region in the b12-resistant envelope that significantly modulated the neutralization of Env-pseudotyped viruses to PG9/PG16 MAbs. The enhanced neutralization susceptibilities of Envs to b12 and PG9 MAbs were correlated with increased exposure of their corresponding epitopes highlighting vulnerabilities in the V2C2 region that altered Env conformation necessary for the efficient accessibility of b12 and PG9 antibodies.

The effect of trauma center care on pediatric injury mortality in California, 1999 to 2011.

BACKGROUND: Trauma centers (TCs) have been shown to decrease mortality in adults, but this has not been demonstrated at a population level in all children. We hypothesized that seriously injured children would have increased survival in a TC versus nontrauma center (nTC), but there would be no increased benefit from pediatric-designated versus adult TC care. METHODS: This was a retrospective study of the unmasked California Office of Statewide Health and Planning Department patient discharge database (1999-2011). DRG International Classification of Diseases-9th Rev. (ICD-9) diagnostic codes indicating trauma were identified for children (0-18 years), and injury severity was calculated from ICD-9 codes using validated algorithms. To adjust for hospital case mix, we selected patients with ICD-9 codes that were capable of causing death and which appeared at both TCs and nTCs. Instrumental variable (IV) analysis using differential distance between the child's residence to a TC and to the nearest hospital was applied to further adjust for unobservable differences in TC and nTC populations. Instrumental variable regression models analyzed the association between mortality and TC versus nTC care as well as for pediatric versus adult TC designations, adjusting for demographic and clinical variables. RESULTS: Unadjusted mortality for the entire population of children with nontrivial trauma (n = 445,236) was 1.2%. In the final study population (n = 77,874), mortality was 5.3%, 3.8% in nTCs and 6.1% in TCs. IV regression analysis demonstrated a 0.79 percentage point (95% confidence interval, -0.80 to -0.30; p = 0.044) decrease in mortality for children cared for in TC versus nTC. No decrease in mortality was demonstrated for children cared for in pediatric versus adult TCs. CONCLUSION: Our IV TC outcome models use improved injury severity and case mix adjustment to demonstrate decreased mortality for seriously injured California children treated in TCs. These results can be used to take evidence-based steps to decrease disparities in pediatric access to, and subsequent outcomes for, trauma care. LEVEL OF EVIDENCE: Therapeutic/care management, level III.

Use of first line antiretroviral therapy from a free ART programme clinic in Pune, India - a preliminary report.

BACKGROUND & OBJECTIVES: The treatment outcomes under national antiretroviral therapy (ART) programme are being evaluated in some ART centres in the country. We carried out this study to analyze the impact of first line antiretroviral therapy in HIV infected patients attending a free ART roll out national programme clinic in Pune, India. METHODS: Antiretroviral naive HIV infected patients attending the clinic between December 2005 and April 2008 and followed up till March 31, 2011 were included in the analysis. The enrolment and follow up of these patients were done as per the national guidelines. Viral load estimations were done in a subset of patients. results: One hundred and forty two patients with median CD4 count of 109 cells/µl (IQR: 60-160) were initiated on treatment. The median follow up was 44 months (IQR: 37-53.3 months). Survival analysis showed that the probability of being alive at the end of 5 years was 85 per cent. Overall increase in the median CD4 count was statistically significant (P<0.001). It was significant in patients with >95 per cent adherence (P<0.001). In 14 per cent patients, the absolute CD4 count did not increase by 100 or more cells/µl at the end of 12 months. Viral load estimation in a subset of 68 patients showed undetectable levels in 61 (89.7%) patients after a median duration of 46 months (IQR: 38.3-54.8). INTERPRETATION & CONCLUSIONS: The first line treatment was effective in patients attending the programme clinic. The adherence level influenced immunological and virological outcomes of patients.

Unique C2V3 sequence in HIV-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization.

Broadly neutralizing antibodies to HIV-1 usually develops in chronic infections. Here, we examined the basis of enhanced sensitivity of an env clone amplified from cross neutralizing plasma of an antiretroviral naïve chronically infected Indian patient (ID50 >600-fold higher compared to other autologous env clones). The enhanced autologous neutralization of pseudotyped viruses expressing the sensitive envelope (Env) was associated with increased sensitivity to reagents and monoclonal antibodies targeting distinct sites in Env. Chimeric viruses constructed by swapping fragments of sensitive Env into resistant Env backbone revealed that the presence of unique residues within C2V3 region of gp120 governed increased neutralization. The enhanced virus neutralization was also associated with low CD4 dependence as well as increased binding of Env trimers to IgG1b12 and CD4-IgG2 and was independent of gp120 shedding. Our data highlighted vulnerabilities in the Env obtained from cross neutralizing plasma associated with the exposure of discontinuous neutralizing epitopes and enhanced autologous neutralization. Such information may aid in Env-based vaccine immunogen design.

Association of enhanced HIV-1 neutralization by a single Y681H substitution in gp41 with increased gp120-CD4 interaction and macrophage infectivity.

HIV-1 variants that show unusual sensitivity to autologous antibodies due to presence of critical neutralization signatures would likely contribute towards rational envelope based HIV-1 vaccine design. In the present study, we found that presence of a naturally occurring H681 in gp41 membrane proximal external region (MPER) of a clade C envelope (Env) obtained from a recently infected Indian patient conferred increased sensitivity to autologous and heterologous plasma antibodies. Furthermore, Env-pseudotyped viruses expressing H681 showed increased sensitivity to soluble CD4, b12 and 4E10 monoclonal antibodies both in related and unrelated Envs and was corroborated with increased Env susceptibility and binding to cellular CD4 as well as with prolonged exposure of MPER epitopes. The increased gp120-CD4 interaction was further associated with relative exposure of CD4-induced epitopes and macrophage infectivity. In summary, our data indicate that Y681H substitution exposes neutralizing epitopes in CD4bs and MPER towards comprehensive interference in HIV-1 entry.

Short communication: evidence of HIV type 1 clade C env clones containing low V3 loop charge obtained from an AIDS patient in India that uses CXCR6 and CCR8 for entry in addition to CCR5.

Abstract HIV-1 clade C is the major subtype circulating in India and preferentially uses CCR5 during the entire disease course. We have recently shown that env clones from an Indian patient; NARI-VB105 uses multiple coreceptors for entry and was presented with an unusual V3 loop sequence giving rise to high net V3 loop positive charges. Here we show that env clones belonging to subtype C obtained from an AIDS patient, NARI-VB52, use CXCR6 and CCR8 in addition to CCR5 for entry. However, unlike the NARI-105 patient, the env clones contained a low V3 loop net charge of +3 with a conserved GPGQ motif typical of CCR5 using subtype C strains, indicating that residues outside the V3 loop contributed to extended coreceptor use in this particular patient.

Evolutionary constraints acting on DDX3X protein potentially interferes with Rev-mediated nuclear export of HIV-1 RNA.

Differential host-pathogen interactions direct viral replication in infected cells. In HIV-1 infected cells, nuclear export of viral RNA transcripts into cellular cytoplasm is governed by interaction of HIV-1 Rev, Exportin-1 (CRM-1) and DDX3X. Knock down of DDX3X has been shown to drastically impair HIV replication. Here we show that evolutionary forces are responsible for demarking previously unidentified critical functionally important residues on the surface of DDX3X. Using computational approaches, we show that these functional residues, depending on their location, are capable of regulating ATPase and RNA helicase functions of DDX3X. The potential of these residues in designing better blockers against HIV-1 replication was also assessed. Also, using stepwise docking simulations, we could identify DDX3X-CRM-1 interface and its critical functional residues. Our data would help explain the role of DDX3X in HIV-1 Rev function with potential to design new intervention strategies against HIV-1 replication.

Changes in U.S. hospitalization and mortality rates following smoking bans.

U.S. state and local governments have increasingly adopted restrictions on smoking in public places. This paper analyzes nationally representative databases, including the Nationwide Inpatient Sample, to compare short-term changes in mortality and hospitalization rates in smoking-restricted regions with control regions. In contrast with smaller regional studies, we find that smoking bans are not associated with statistically significant short-term declines in mortality or hospital admissions for myocardial infarction or other diseases. An analysis simulating smaller studies using subsamples reveals that large short-term increases in myocardial infarction incidence following a smoking ban are as common as the large decreases reported in the published literature.

Iron oxide nanoparticle-assisted arsenic removal from aqueous system.

Iron oxide nanoparticles (IONPs) can play a significant role in the cycling of heavy metals. Arsenite [As(III)] is highly toxic, mobile, and predominant species in arsenic-contaminated groundwater. IONPs have been synthesized and tested for the removal of As(III) from arsenic contaminated water. In this work, we synthesized IONPs, as a finely divided loose nanopowder, using a chemical method involving a dispersion of the metal cations (Fe3+) through polymer molecules of polyvinyl alcohol (PVA) in an aqueous medium. X-ray diffraction (XRD) analysis confirmed the formation of a single phase rhombohedral crystal structure of R3c space group. Transmission electron microscopic images corroborate the result of IONPs of 45 nm average size and the rhombohedral shape. Selective experiments, conducted with an initial concentration of 0.25 ppm of As(III), have demonstrated the maximum As(III) adsorption capacity (96%) in 2.0 gL(- 1) IONPs in water at pH 4.5-7.5. At room temperature, the adsorption isotherm studies have revealed a better correlation with the Langmuir isotherm than the Freundlich isotherm. Characteristic surface hydrolysis of IONPs as = Fe-OH species has been studied in terms of the vibration bands. The results reveal that the removal of the As(III) species from water is associated with the As(III) adsorption onto the IONPs followed by a surface hydrolysis of the iron species.