Nef Decreases HIV-1 Sensitivity to Neutralizing Antibodies that Target the Membrane-proximal External Region of TMgp41

Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs) that target the membrane proximal external region (MPER) of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly discovered activity for Nef has important implications for anti-HIV-1 immunity and AIDS pathogenesis

The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults

Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing a variety of chronic diarrheal diseases. In addition to current pharmacological therapies, there is growing interest in alternative products such as mucoprotectants, which form a mucoadhesive film over the epithelium to reduce and protect against the development of altered intestinal permeability, dysbiosis, and mucosal micro-inflammation. This manuscript focuses on chronic diarrhea in adults, and we will review recent evidence on the ability of these natural compounds to improve symptoms associated with chronic diarrhea and to exert protective effects for the intestinal barrier

HIV Replication Enhances Production of Free Fatty Acids, Low Density Lipoproteins and Many Key Proteins Involved in Lipid Metabolism: A Proteomics Study

BACKGROUND: HIV-infected patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia. Although progression of these disorders has been associated with the use of various protease inhibitors and other antiretroviral drugs, HIV-infected individuals who have not received these treatments also develop lipid abnormalities albeit to a lesser extent. How HIV alters lipid metabolism in an infected cell and what molecular changes are affected through protein interaction pathways are not well-understood. RESULTS: Since many genetic, epigenetic, dietary and other factors influence lipid metabolism in vivo, we have chosen to study genome-wide changes in the proteomes of a human T-cell line before and after HIV infection in order to circumvent computational problems associated with multiple variables. Four separate experiments were conducted including one that compared 14 different time points over a period of >3 months. By subtractive analyses of protein profiles overtime, several hundred differentially expressed proteins were identified in HIV-infected cells by mass spectrometry and each protein was scrutinized for its biological functions by using various bioinformatics programs. Herein, we report 18 HIV-modulated proteins and their interaction pathways that enhance fatty acid synthesis, increase low density lipoproteins (triglycerides), dysregulate lipid transport, oxidize lipids, and alter cellular lipid metabolism. CONCLUSIONS: We conclude that HIV replication alone (i.e. without any influence of antiviral drugs, or other human genetic factors), can induce novel cellular enzymes and proteins that are significantly associated with biologically relevant processes involved in lipid synthesis, transport and metabolism (p = <0.0002-0.01). Translational and clinical studies on the newly discovered proteins may now shed light on how some of these proteins may be useful for early diagnosis of individuals who might be at high risk for developing lipid-related disorders. The target proteins could then be used for future studies in the development of inhibitors for preventing lipid-metabolic anomalies. This is the first direct evidence that HIV-modulates production of proteins that are significantly involved in disrupting the normal lipid-metabolic pathways

Sliding behavior of droplet on a hydrophobic surface with hydrophilic cavities: A simulation study

This paper presents a detailed computational fluid dynamics simulation study on water droplet mobility and cavity fillings resulting from a sliding droplet on a titled surface or substrate with round shaped cavities in a serial arrangement. The effects of different hydrophobicity (or contact angle) values for cavity and non-cavity surfaces, cavity depths, cavity spacings, plate tilting angles, and initial droplet volumes on its mobility were investigated. The findings are reported in terms of the total number of filled cavities, its duration, and the average volume of droplet per cavity. This study can be useful for the design and development of the passive microfluidics related devices and applications

Adsorption of chromium (VI) on functionalized and non-functionalized carbon nanotubes

We did a comparative study on the adsorption capacity of Cr (VI) between functionalized carbon nanotubes (CNTs) and non-functionalized CNTs. The statistical analysis reveals that the optimum conditions for the highest removal of Cr (VI) are at pH 9, with dosage 0.1 gram, agitation speed and time of 120 rpm and 120 minutes, respectively. For the initial concentration of 1.0 mg/l, the removal efficiency of Cr (VI) using functionalized CNTs was 87.6% and 83% of non-functionalized CNTs. The maximum adsorption capacities of functionalized and non-functionalized CNTs were 2.517 and 2.49 mg/g, respectively. Langmuir and Freundlich models were adopted to study the adsorption isotherm, which provided a K L and K F value of 1.217 L/mg and 18.14 mg1−n L n /g functionalized CNT, while 2.365 L/mg and 2.307 mg1−n L n /g for non-functionalized CNTs. This result proves that functionalized CNTs are a better adsorbent with a higher adsorption capacity compared with the non-functionalized CNTs

Synthesis and Structural Properties of Niobium Pentoxide Powders: A Comparative Study of the Growth Process

Powders Nb2 O5 were prepared by two different synthesis method, Sol-Gel and polymeric precursors (Pechini). In the Pechini method before adding the citric acid in the process, four different solutions were used to get the samples. For Sol-gel method, two different processes were also used in obtaining powders. The precursor was completely solubilized in ethanol and then hydrolyzed with ammonia and water. The calcination of the samples was between 500 and 750°C. The resulting powders were characterized by Scanning Electron Microscopy (SEM), Brunauer, Emmett and Teller (BET) surface area measurements, UV-visible and Raman spectroscopy. The formation of T&#8722;Nb2 O5 orthorhombic took place upon calcination at 7500C. Crystallite sizes were determined using the Scherrer method which resulted in an uniformed size of about 25 &#8722; 65nm. Ultraviolet-Visible diffuse reflectance spectroscopy indicated a variation in the optical band gap values (3.32-3.40 eV) in crystal growth process. The Raman vibrational modes indicate the presence of the orthorhombic phase of the material