Structural definition of a conserved neutralization epitope on HIV-1 gp120

The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 A resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.     

Short Report： Cyclic patterns of incidence rate for skin malignant melanoma： association with heliogeophysical activity

Background： Our previous studies revealed cyclicity in the incidence rate of skin malignant melanoma （SMM; ICD9, Dx： 172） in the Czech Republic （period T=7.50～7.63 years）, UK （T= 11.00 years） and Bulgaria （T= 12.20 years）. Incidences com- pared with the sunspot index Rz （lag-period dT=＋2, ＋4, ＋6, ＋ 10 or ＋ 12 years） have indicated that maximal rates are most likely to appear on descending slopes of the ;ll-year solar cycle, i.e., out of phase. We summarized and explored more deeply these cyclic variations and discussed their possible associations with heliogeophysical activity （HGA） components exhibiting similar cyclicity. Methods： Annual incidences of SMM from 5 countries （Czech Republic, UK, Bulgaria, USA and Canada） over various time spans during the years 1964-1992 were analyzed and their correlations with cyclic Rz （sunspot number） and aa （planetary geomagnetic activity） indices were summarized. Periodogram regression analysis with trigonometric approximation and phase-correlation analysis were applied. Results： Previous findings on SMM for the Czech Republic, UK and Bulgaria have been validated, and cyclic patterns have been revealed for USA （T=8.63 years, P〈0.05） and Canada （Ontario, T=9.91 years, P〈0.10）. Also, various ＇hypercycles＇ were established （T=45.5, 42.0, 48.25, 34.5 and 26.5 years, respectively） describing long-term cyclic incidence patterns. The association of SMM for USA and Canada with Rz （dT=＋6 and ＋7 years, respectively） and aa （dT=-10 and ＋9 years, respectively） was described. Possible interactions of cyclic non-photic influences （UV irradiation, Schumann resonance signal, low-frequency geomagnetic fluctuations） with brain waves absorbance, neuronal calcium dynamics, neuro-endocrine axis modulation, melatonin/serotonin disbalance and skin neuro-immunity impairment as likely causal pathways in melanoma appearance, were also discussed. Conclusion： The above findings on cyclicity and temporal assoc     

Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12

We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, approximately 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 x 10(-9) for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP.     

The SARS-CoV S glycoprotein

The severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein alone can mediate the membrane fusion required for virus entry and cell fusion. It is also a major immunogen and a target for entry inhibitors. Recent rapid advances in our knowledge of the structure and function of this protein have lead to the development of a number of candidate vaccine immunogens and SARS-CoV entry inhibitors.     

Effects of female sex hormones on polyamine-oxidizing enzyme activities and polyamine concentrations in immature rat uterus and liver

17-estradiol (E₂) and progesterone (P) treatment of immature female rats (10 g/100 g body weight) respectively resulted in 1.38-fold (p<0.02) and 1.42-fold (p<0.02) increase in the uterine polyamine oxidase activity, and 2.45-fold (p<0.001) and 1.43-fold (p<0.02) increase in the uterine diamine oxidase activity, as compared to the controls. E₂ caused a 5-fold (p<0.05) and a 1.36-fold (p<0.05) increase in putrescine and spermidine concentration respectively in rat uterus. Increases of 1.7-fold (p<0.02) and 1.6-fold (p<0.05) in putrescine and spermine concentration were determined in the P-treated uterus, as compared to the controls. The spermidine/spermine ratio, which is regarded as an index of growth rate, was higher in the E₂-treated uterus and lower in the P-treated uterus than in the control uterus. No statistically significant hormonal effects were estimated in the immature liver. The data reported suggest the possibility of an involvement of polyamine-oxidizing enzymes in the modulation of polyamine concentrations in rat uterus by the female sex hormones.     

Distribution of polyamine oxidase activity in rat tissues and subcellular fractions

The activity of polyamine oxidase (PAO) in rat tissues, and its subcellular distribution, were assayed using a simple polarographic method. The highest PAO activity was measured in the liver and the lowest in the skeletal muscle. In liver, kidney and uterus the highest specific PAO activity was found in the light mitochondrial fraction. PAO was not found in the microsomal fraction except in the kidney.     

Evolution of nanoporosity in dealloying

Dealloying is a common corrosion process during which an alloy is 'parted' by the selective dissolution of the most electrochemically active of its elements. This process results in the formation of a nanoporous sponge composed almost entirely of the more noble alloy constituents. Although considerable attention has been devoted to the morphological aspects of the dealloying process, its underlying physical mechanism has remained unclear. Here we propose a continuum model that is fully consistent with experiments and theoretical simulations of alloy dissolution, and demonstrate that nanoporosity in metals is due to an intrinsic dynamical pattern formation process. That is, pores form because the more noble atoms are chemically driven to aggregate into two-dimensional clusters by a phase separation process (spinodal decomposition) at the solid-electrolyte interface, and the surface area continuously increases owing to etching. Together, these processes evolve porosity with a characteristic length scale predicted by our continuum model. We expect that chemically tailored nanoporous gold made by dealloying Ag-Au should be suitable for sensor applications, particularly in a biomaterials context.     

Distribution of polyamine oxidase activity in rat tissues and subcellular fractions.

The activity of polyamine oxidase (PAO) in rat tissues, and its subcellular distribution, were assayed using a simple polarographic method. The highest PAO activity was measured in the liver and the lowest in the skeletal muscle. In liver, kidney and uterus the highest specific PAO activity was found in the light mitochondrial fraction. PAO was not found in the microsomal fraction except in the kidney.