Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity

The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb). Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/ or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and Cterminal segments of gp120 and the disulfide-bonded region (DSR) of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn136 in V1 (T138N mutation) inconjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N139INN sequence, which ablates the overlapping Asn141-Asn142-Ser-Ser potential N-linked glycosylation sequons inV1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu593, Trp596 and Lys601. The 136 and/or 142glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan shield in a setting of NAb selection

Relationship between CANLPH score and in-hospital mortality in patients undergoing coronary artery bypass grafting

Aim: To evaluate the CANLPH score in in-hospital mortality after coronary artery bypass grafting. Materials &amp; methods: The 999 patients were included in this retrospective cohort study. Neutrophil/lymphocyte ratio, C-reactive protein/albumin ratio and platelet/hemoglobin ratio were determined and the CANLPH score was calculated as the sum score of 0 or 1 by the cutoff in each ratio. Results: Twenty-five patients who reached the primary end point were defined as the mortality group and the remaining as the nonmortality group. The CANLPH score was noninferior to the European System for Cardiac Operative Risk Evaluation II in receiver-operating characteristic curve analysis with difference between AUC: 0.0162, standard error (SE): 0.0394, z statistics: 0.682 and p = 0.494. Conclusion: The CANLPH score may be more appropriate in assessing the risk of in-hospital mortality after coronary artery bypass grafting. </jats:p

Interactive Education System for Medicine and Engineering Using Three Dimensional Virtual Environments

Three dimensional modeling and simulation software are becoming more widespread in many fields with the emphasis on engineering, military and medical applications. The main important features of these applications are fast prototyping, simulation of scientific and engineering problems under different conditions and interactive user interface. Therefore, an opportunity for a fast visual education course and understanding the physical and mathematical reasons lying under the problems is presented to engineers, military and scientific researches in the respective fields. The main requirements of these applications are high performance computer systems and user interfaces that feature an easier interaction. The fast developing computer architecture maintains the necessary architecture and enables the applications to improve. Considering above and the expectations of Dokuz Eylul University Faculty of Medicine, the development of a virtual environment software that will model the predefined medical processes with user interaction has been aimed In this paper, the 1. section is reserved for basic concepts and field applications. The hardware and software infrastructure and algorithm development process we used are presented in the 2. section. The 3. section presents the completed stages and first results of our application. The final, section which is the 4. section is reserved for the conclusion and future work

Radiotherapy with or without temozolomide in elderly glioblastoma patients: Treatment results and prognostic factors.

WOS: 000208852003043

Prevalence and genotyping of hepatitis C virus RNA in Turkish patients with chronic non-A, non-B liver disease

The clinical features of hepatitis C virus (HCV) infection and the distribution of HCV genotypes in 86 patients with chronic non-A, non-B (NANB) liver disease were examined in this study. The HCV infection was diagnosed using anti-HCV testing, and by the detection of HCV RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). HCV genotypes were determined in 27 of HCV RNA positive patients by restriction fragment length polymorphism (RFLP) analysis of PCR products. HCV RNA was detected in the serum of 62 out of 86 (72.1%) patients on PCR while 68 out of 81 (84%) patients were positive for anti-HCV. PCR and anti-HCV results were concordant in 60 out of 81 (74.1%) patients. Patients with HCV RNA in serum were indistinguishable from those without HCV RNA in serum apart from serum ALT and total bilirubin levels (P<0.05). The most common genotype was HCV 1b (81.5 %). Other genotypes detected were 1a (14.8 %) and 4 (3.7 %). HCV infection is the major cause of chronic non-A, non-B (NANB) liver disease and HCV 1b is the predominant genotype