Molecular biology of Hendra and Nipah viruses

The structure and genetic organization of Hendra and Nipah viruses places them in the subfamily Paramyxovirinae. However, low homology with other subfamily members and several novel biological and molecular features such as genome length and F(0 )cleavage site suggest classification in a new genus within the Paramyxovirinae.     

Echocardiographic Abnormalities in Normotensive Obese Patients: Relationship with Visceral Fat

Objective: To evaluate the relationship of echocardiographic characteristics and visceral adipose tissue (VAT) distribution in normotensive obese patients. Research Methods and Procedures: Echocardiographic parameters were assessed in 28 normotensive obese patients [7 men, 21 women, mean age, 43.2 years; mean body mass index (BMI), 37.2 kg/m²; 10 with impaired glucose tolerance (IGT); 6 with type 2 diabetes] and 18 sex‐ and age‐matched healthy, normal‐weight controls (4 men, 14 women; mean age, 45.8 years; mean BMI, 22.4 kg/m²) by an M‐mode, color‐doppler videofluoroscope. VAT in the obese patients was assessed by computed tomography (at L4 level). Results: The obese patients had a significantly larger internal diastolic left ventricular (LV) diameter (p < 0.05), a thicker end‐diastolic septum (p < 0.001) and posterior wall (p < 0.001), a greater indexed (g/m^2.7) LV mass (p < 0.001), a higher atrial diastolic filling wave velocity (p < 0.001), a lower ratio between early and atrial diastolic filling wave velocities (p < 0.01), and a prolonged isovolumic relaxation time (p < 0.05). End‐diastolic septum and posterior wall thickness and the LV mass were significantly greater in patients with a VAT area >130 cm² than with <130 cm². In the multivariate regression analysis, only VAT (p < 0.0001), waist‐to‐hip ratio (p < 0.001), and sex (p < 0.001) were associated with the most important echocardiographic alterations. Discussion: The morphological and functional echocardiographic alterations usually found in normotensive obese patients closely correlate with the amount of intra‐abdominal fat deposition, even in the presence of diabetes or IGT.     

Dynamics of aboveground big woody organs in a foothill dipterocarp forest,West Sumatra,Indonesia

The dynamics of aboveground big woody organs over 10 cm diameter was studied at a mature foothill dipterocarp forest in West Sumatra. The biomass of big woody organs was estimated to be 519 m³ ha⁻¹ or 408 metric ton ha⁻¹ by means of a pipe model theory. The diameter distribution showed a convex curve and the mode was found at a diameter of about 20 cm. The standing mass of big dead woody litter on the forest floor was 116 m³ ha⁻¹, which accounted for 22% by voume or 9.5% by weight of the biomass of living organs respectively. Thedbh observation with two 1-ha plots for 4 yr and 5 yr respectively revealed that the average net production rate was 9.5 ton ha⁻¹ yr⁻¹. The death rate (7.9 ton ha⁻¹ yr⁻¹) accounted for 83% of the net production rate and was nearly equivalent to the decay rate (7.5 ha⁻¹ yr⁻¹) of dead wood on the forest floor. The balance between the death and decay rates was confirmed for each diameter class. Average turnover periods for big woody organs and dead woody litter were estimated to be 43 and 8.1 yr, respectively. Standing masses of live anddead woody materials accumulated in the study forest were approximately equal to those obtained in a mature tropical lowland rainforest, whereas the flow rates were lower, being only 70% of the corresponding values.     

Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway

Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs) in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs) with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID) "hot spot" in a light chain CDR (complementarity determining region) alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM) of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural information in combination of chain-shuffling as well as hot-spot CDR mutagenesis, can be exploited to broaden neutralization activity, to improve anti-viral nAb therapies, and directly manipulate virus evolution.