Despite the high mutation rate of HIV-1, the amino acid sequences of the membrane-spanning domain (MSD) of HIV-1 gp41 are well conserved. Arginine residues are rarely found in single membrane-spanning domains, yet an arginine residue, R(696) (the numbering is based on that of HXB2), is highly conserved in HIV-1 gp41. To examine the role of R(696), it was mutated to K, A, I, L, D, E, N, and Q. Most of these substitutions did not affect the expression, processing or surface distribution of the envelope protein (Env). However, a syncytia formation assay showed that the substitution of R(696) with amino acid residues other than K, a naturally observed mutation in the gp41 MSD, decreased fusion activity. Substitution with hydrophobic amino acid residues (A, I, and L) resulted in a modest decrease, while substitution with D or E, potentially negatively-charged residues, almost abolished the syncytia formation. All the fusion-defective mutants showed slower kinetics with the cell-based dual split protein (DSP) assay that scores the degree of membrane fusion based on pore formation between fusing cells. Interestingly, the D and E substitutions did show some fusion activity in the DSP assays, suggesting that proteins containing D or E substitutions retained some fusion pore-forming capability. However, nascent pores failed to develop, due probably to impaired activity in the pore enlargement process. Our data show the importance of this conserved arginine residue for efficient membrane fusion.
Amino Acid Substitution ; Animals ; Arginine ; chemistry ; metabolism ; Cell Line ; Cercopithecus aethiops ; HIV Envelope Protein gp41 ; chemistry ; metabolism ; HIV-1 ; metabolism ; Humans ; Kinetics ; Membrane Fusion ; physiology ; Mutation ; Protein Structure, Tertiary

Purpose: This study was performed to determine the prognostic value of lymphocyte-to-CRP ratio after curative resection for hepatocellular carcinoma. Methods: Between July 2010 and October 2021, 173 consecutive patients (144 male, 29 female) who underwent surgical resection for pathologically confirmed hepatocellular carcinoma were included in this retrospective study. Cox regression analysis was used to evaluate the relationship between clinicopathological characteristics and recurrence-free survival (RFS) and overall survival (OS). A P-value of <0.05 was considered statistically significant. Results: The patients (mean age, 71 years) were stratified into high (≥9,500, n = 108) and low (<9,500, n = 65) lymphocyteto-CRP ratio groups. The low lymphocyte-to-CRP ratio group had significantly worse RFS and OS. Low lymphocyte-toCRP ratio (hazard ratio [HR], 1.865; 95% confidence interval [CI], 1.176–2.960; P = 0.008), multiple tumors (HR, 3.333; 95% CI, 2.042–5.343; P < 0.001), and microvascular invasion (HR, 1.934; 95% CI, 1.178–3.184; P = 0.009) were independently associated with RFS, whereas low albumin-to-globulin ratio (HR, 2.270; 95% CI, 1.074–4.868; P = 0.032), α-FP of ≥25 ng/mL (HR, 2.187; 95% CI, 1.115–4.259; P = 0.023), and poor tumor differentiation (HR, 2.781; 95% CI, 1.041–6.692; P = 0.042) were independently associated with OS. Lymphocyte-to-CRP ratio had a higher area under the curve (0.635) than other inflammation-based markers (0.51–0.63). Conclusion Lymphocyte-to-CRP ratio is superior to other inflammation-based markers as a predictor of RFS in patients with surgically resected hepatocellular carcinoma.

BACKGROUND: Oral health is thought to be associated with diet quality, and socioeconomic status (SES) affects both oral health and diet. The aim of this study was to investigate the association between the number of teeth and dietary intake as well as nutritional biomarker, considering the subjects' SES. METHODS: We conducted a cross-sectional analysis of data from 2049 individuals aged ≥ 50 years from the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 2010. The number of remaining teeth was categorized into age-specific quartiles (Q1 to Q4). We assessed the adjusted means and 95% confidence intervals for dietary variables by the number of teeth using analysis of covariance. Stratified analyses by SES were also conducted. RESULTS: The intake of grain products was 31 g higher, and those of vegetables and meat were 30 g and 8 g lower, respectively, in Q1 (fewer teeth) than in Q4 (more teeth). Carbohydrate intake was higher whereas protein, minerals (potassium, magnesium, and zinc), vitamins (vitamins A, E, B, B, β-carotene, and folic acid), and dietary fiber intakes were lower among individuals with fewer teeth. Adjusted mean serum albumin levels were low in Q1. The associations between the number of teeth and dietary intake were more evident in individuals with a low SES. CONCLUSIONS Having few remaining teeth was associated with a low nutrient intake and low serum albumin levels in middle-aged and older Japanese adults, and these associations were more evident in individuals with low SES.
Aged ; Aged, 80 and over ; Carbohydrates ; Cross-Sectional Studies ; Diet ; Energy Intake ; physiology ; Female ; Humans ; Japan ; Male ; Middle Aged ; Nutrients ; Nutrition Surveys ; Nutritional Status ; Serum Albumin ; analysis ; Socioeconomic Factors ; Tooth ; Vegetables