Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties

<p>Abstract</p> <p>Background</p> <p>The V3 loop of the glycoprotein gp120 of HIV-1 plays an important role in viral entry into cells by utilizing as coreceptor CCR5 or CXCR4, and is implicated in the phenotypic tropisms of HIV viruses. It has been hypothesized that the interaction between the V3 loop and CCR5 or CXCR4 is mediated by electrostatics. We have performed hierarchical clustering analysis of the spatial distributions of electrostatic potentials and charges of V3 loop structures containing consensus sequences of HIV-1 subtypes.</p> <p>Results</p> <p>Although the majority of consensus sequences have a net charge of +3, the spatial distribution of their electrostatic potentials and charges may be a discriminating factor for binding and infectivity. This is demonstrated by the formation of several small subclusters, within major clusters, which indicates common origin but distinct spatial details of electrostatic properties. Some of this information may be present, in a coarse manner, in clustering of sequences, but the spatial details are largely lost. We show the effect of ionic strength on clustering of electrostatic potentials, information that is not present in clustering of charges or sequences. We also make correlations between clustering of electrostatic potentials and net charge, coreceptor selectivity, global prevalence, and geographic distribution. Finally, we interpret coreceptor selectivity based on the N⁶X⁷T⁸|S⁸X⁹sequence glycosylation motif, the specific positive charge location according to the 11/24/25 rule, and the overall charge and electrostatic potential distribution.</p> <p>Conclusions</p> <p>We propose that in addition to the sequence and the net charge of the V3 loop of each subtype, the spatial distributions of electrostatic potentials and charges may also be important factors for receptor recognition and binding and subsequent viral entry into cells. This implies that the overall electrostatic potential is responsible for long-range recognition of the V3 loop with coreceptors CCR5/CXCR4, whereas the charge distribution contributes to the specific short-range interactions responsible for the formation of the bound complex. We also propose a scheme for coreceptor selectivity based on the sequence glycosylation motif, the 11/24/25 rule, and net charge.</p

Near Constant Loss in Glassy and Crystalline LiAlSi2O6 from Conductivity Relaxation Measurements

Polycrystalline and glassy LiAlSi2O6 are studied by dielectric relaxation measurements for the purpose of characterizing the nearly frequency independent contribution to the dielectric loss (near constant loss), which is commonly found in glassy ionic conductors independent of the chemical and physical structures. The data show the near constant loss is present in both the polycrystalline and glassy states of LiAlSi2O6. Further, its magnitude and temperature dependence is comparable in both forms of the same substance. The implications of these findings on the mechanism that gives rise to the near constant loss are discussed

Ingested Fish Bone: An Unusual Mechanism of Duodenal Perforation and Pancreatic Trauma

Ingestion of gastrointestinal foreign bodies represents a challenging clinical scenario. Increased morbidity is the price for the delayed diagnosis of complications and timely treatment. We present a case of 57-year-old female patient which was admitted in the emergency room department complaining of a mid-epigastric pain over the last twenty-four hours. Based on the patient's history, physical examination and elevated serum amylase levels, a false diagnosis of pancreatitis, was initially adopted. However, a CT scan confirmed the presence of a radiopaque foreign body in the pancreatic head and the presence of air bubbles outside the intestinal lumen. The patient was unaware of the ingestion of the foreign body. At laparotomy, after an oblique duodenotomy, a fish bone pinned in the pancreatic head after the penetration of the medial aspect of the second portion of the duodenal wall was identified and successfully removed. The patient had an uneventful postoperative recovery. Wide variation in clinical presentation characterizes the complicated fish bone ingestions. The strategically located site of penetration in the visceral wall is responsible for the often extraordinary gastrointestinal tract injury patterns. Increased level of suspicion is of paramount importance for the timely diagnosis and treatment

Molecular size determination of a membrane protein in surfactants by light scattering

AbstractThe molecular size of an outer surface protein from the photosynthetic bacterium Chlorobium tepidum was studied by dynamic light scattering (DLS) and HPLC gel filtration. For that purpose, the membrane protein was isolated and studied in four different nonionic surfactants, namely t-octylphenoxypolyethenoxyethanol (Triton X-100), (methyl-6-O-(N)-heptyl-carbamoyl)-α-d-glucopyranoside (Hecameg), dodecyl-β-d-maltoside (DDM) and n-octyl-oligo-oxyethylene (Octyl-POE). The protein was isolated by solubilization of the membranes with Triton X-100. The final purification step was a gel filtration, which was also used for surfactant exchange. Light scattering reveals the simultaneous presence of particles of different sizes in the 3–6 and 20–110 nm range, respectively. The smaller size is related to the hydrodynamic radius of the individual protein/surfactant complexes, whereas the larger size is associated with the presence of complex aggregates

Antibiotics in Raw Meat Samples: Estimation of Dietary Exposure and Risk Assessment

The extensive use of antibiotics in livestock farming poses increased concerns for human health as residues of these substances are present in edible tissues. The aim of this study was the determination of the levels of four groups of antibiotics (sulfonamides&mdash;SAs, tetracyclines&mdash;TCs, streptomycines&mdash;STr and quinolones&mdash;QNLs) in meat samples (muscles, livers and kidneys from beef, chicken and pork) and the estimation of the dietary exposure to antibiotics from meat consumption and the potential hazard for human health. Fifty-four samples of raw meat were randomly collected in 2018 from the Cretan market, Greece and analyzed both with an enzyme-linked immunosorbent assay (ELISA) and liquid chromatography&ndash;mass spectrometry (LC&ndash;MS). According to the results derived from the ELISA method, only 2% of the meat samples were free from antibiotics, 2% were detected with 4 antibiotics and the great majority of the samples (87%) were detected with 2 to 3 antibiotics. SAs presented the highest detection frequencies for all samples whereas TCs were not detected in any bovine sample. The highest median concentration was detected for STr in bovine muscles (182.10 &mu;g/kg) followed by QNLs (93.36 &mu;g/kg) in pork kidneys whereas the chicken samples had higher burdens of QNLs compared to the other meat samples. LC&ndash;MS analysis showed that oxytetracycline (OTC) was the most common antibiotic in all samples. The highest median concentration of all antibiotics was detected for doxycycline (DOX) (181.73 &mu;g/kg in pork kidney) followed by OTC in bovine liver (74.46 &mu;g/kg). Risk characterization was applied for each of the two methods; The hazard quotients (HQ) did not exceed 0.059 for the ELISA method and 0.113 for the LC&ndash;MS method for any group of antibiotics, whereas the total hazard indexes (HI) were 0.078 and 0.021, respectively. The results showed the presence of different groups of antibiotics in meat from the Cretan market and that the health risk to antibiotics is low. A risk assessment analysis conducted for meat consumption and corrected for the aggregated exposure revealed no risk for the consumers

Open Access

critically ill patient: a case repor