Structure determination of an anti-HIV-1 Fab 447-52D–peptide complex from an epitaxially twinned data set

Separation of two individual lattices within an epitaxially twinned data set allowed the crystal structure of the V3-specific neutralizing antibody 447-52D in complex with a V3 peptide (UG1033) to be determined. The structure confirms that the neutralization breadth of Fab 447-52D is likely to be attributable to the extensive focus on main-chain hydrogen-bond interactions with the peptide that permit the recognition of a range of V3 sequences

Study investigating the role of skeletal muscle mass estimation in metastatic spinal cord compression

Background Age-related loss of functional muscle mass is associated with reduced functional ability and life expectancy. In disseminated cancer, age-related muscle loss may be exacerbated by cachexia and poor nutritional intake, increasing functional decline, morbidity and accelerate death. Patients with spinal metastases frequently present for decompressive surgery with decision to operate based upon functional assessment. A subjective assessment of physical performance has, however, been shown to be a poor indicator of life expectancy in these patients. We aimed to develop an objective measure based upon lean muscle mass to aid decision making, in these individuals, by investigating the association between muscle mass and 1-year survival. Methods Muscle mass was calculated as total psoas area (TPA)/ vertebral body area (VBA), by two independent blinded doctors from CT images, acquired within 7 days of spinal metastases surgery, at the mid L3 vertebral level. Outcome at 1 year following surgery was recorded from a prospectively updated metastatic spinal cord compression database. Results 86 patients were followed for 1 year, with an overall mortality of 39.5 %. Mortality rates at 1 year were significantly high among patients in the lowest quartile of muscle mass, compared with those in the highest quartile (57.1 vs 23.8 %, p = 0.02). Conclusion Death within 1 year in individuals with spinal metastases is related to lean muscle mass at presentation. Assessment of lean muscle mass may inform decision to operate in patients with spinal metastases

Autotaxin activity predicts transplant-free survival in primary sclerosing cholangitis

Autotaxin has been associated with liver disease severity and transplant-free survival. This study aimed to validate autotaxin as a biomarker in two cohorts of Norwegian large-duct PSC patients, one discovery panel (n = 165) and one validation panel (n = 87). Serum activity of autotaxin was measured in diluted sera by a fluorometric enzymatic assay. Patients reaching an end-point, liver transplantation or death, (discovery panel: n = 118 [71.5%]; validation panel: n = 35 [40.2%]), showed higher autotaxin activity compared with the other patients, P < 0.001 and P = 0.004, respectively. Kaplan-Meier survival analyses showed a strong association between increasing autotaxin activity and shorter liver transplant-free survival (discovery panel: P < 0.001, validation panel: P = 0.001). There was no relationship between autotaxin activity and the presence of inflammatory bowel disease or occurrence of hepatobiliary malignancy. In a multivariable analysis, high autotaxin activity was associated with an increased risk of liver transplantation or death (hazard ratio 2.03 (95% confidence interval 1.21–3.40), P < 0.01), independent from Mayo risk score, an in-house enhanced liver fibrosis score and interleukin-8 in serum. In conclusion, increased serum autotaxin activity is associated with reduced liver transplant-free survival independent from Mayo risk score and markers of inflammation and fibrosis