Host genetic regulation of immune-based and infectious diseases: Introduction to mammalian genome special issue: genetics of infectious disease

Infectious disease remains a leading cause of mortality worldwide and includes a wide range of ailments caused by a pathogen, typically a virus, bacterium, fungus or parasite, entering and living in the host body. For many decades, but particularly after the molecular biology revolution brought about by the advent of recombinant DNA techniques in the 1970s, the tenet for an infectious disease biologist was to identify genes on the microbe that might play a role in the pathogenic traits of that organism. By first cloning that gene, mutating it in a defined way, analysing the altered phenotype or function of the mutant strain then restoring the gene function to re-establish pathogenicity and satisfy Koch’s postulates, it was assumed this would lead to a complete understanding of disease. Koch’s postulates however imply that virulence traits reside solely in the microbe and are therefore independent of the host. It is now clear that this aspect of the postulate is erroneous and that indeed the susceptibility of the host is paramount and typically as important, if not more important, than the traits of the microbe in determining the outcome of infection and disease

Optimization of inhomogeneous electron correlation factors in periodic solids

A method is presented for the optimization of one-body and inhomogeneous two-body terms in correlated electronic wave functions of Jastrow-Slater type. The most general form of inhomogeneous correlation term which is compatible with crystal symmetry is used and the energy is minimized with respect to all parameters using a rapidly convergent iterative approach, based on Monte Carlo sampling of the energy and fitting energy fluctuations. The energy minimization is performed exactly within statistical sampling error for the energy derivatives and the resulting one- and two-body terms of the wave function are found to be well-determined. The largest calculations performed require the optimization of over 3000 parameters. The inhomogeneous two-electron correlation terms are calculated for diamond and rhombohedral graphite. The optimal terms in diamond are found to be approximately homogeneous and isotropic over all ranges of electron separation, but exhibit some inhomogeneity at short- and intermediate-range, whereas those in graphite are found to be homogeneous at short-range, but inhomogeneous and anisotropic at intermediate- and long-range electron separation.Comment: 23 pages, 15 figures, 1 table, REVTeX4, submitted to PR

Facial asymmetry-3D assessment of infants with cleft lip and palate

OBJECTIVES: To determine the degree of facial asymmetry in infants with unilateral cleft lip and/or palate, and quantify improvements following primary surgery, in three dimensions. DESIGN: The faces of 20 infants with unilateral clefts (10 UCL; 10 UCLP), and 20 age-matched, non-cleft controls, were captured using the C3D (TM) stereophotogrammetry system prior to primary lip/nose repair (at 3 months), at 6 months and at age 1 year. METHODS: Procrustes techniques were applied to 3D landmark configurations to its mirror image. Mean squared distances between landmarks and their antimeres were calculated and expressed as asymmetry scores for each 3D configuration. Full-face, nose and lip median scores were compared and changes with time evaluated (P < 0.01). RESULTS: There were no significant changes in asymmetry scores in the control group from 3 months to 1 year. The UCLP group was more asymmetric than the UCL group, displaying greatest improvement in nasal symmetry following primary repair. The lips continued to improve over time. The UCL group had significant nasal asymmetry, which did not appear to improve with primary surgery. CONCLUSIONS: Immediate improvement in asymmetry scores in children with UCLP is related to the production of a more symmetrical nasal form after primary surgery. In contrast, the nasal asymmetry seen in children with UCL is unchanged despite surgery. Full face asymmetry scores may mask subtle changes over time. Nasal and lip asymmetry should be considered individually

Facial characterization of infants with cleft lip and palate using a three-dimensional capture technique

Objective: To characterize the soft tissue features of infants with unilateral cleft lip (UCL) and unilateral complete cleft lip and palate (UCLP) prior to primary surgery and compare with noncleft controls. Design: Prospective controlled capture of the facial morphology of infants using a noninvasive three-dimensional stereophotogrammetry method. Participants: 23 children with presurgical cleft: 11 UCL (M = 6, F = 5); 12 UCLP (M = 9, F = 3), and 21 noncleft controls (M = 7, F = 14) were imaged at approximately 3 months of age (range 10 to 16 weeks). Main Outcome Measure: Accurate, repeatable quantification of facial soft tissues in infants with clefts prior to surgery. Results: Significant differences (p < .05) were found between the UCLP group and UCL and control groups in anatomical and soft nose width, cleft-side alar wing length, and nasal tip horizontal displacement. Both cleft groups were significantly different from controls and from each other in cleft-side nostril dimensions, alar wing angulation, columella angle, and alar base to corner of mouth dimension; alar base width; and soft tissue defect in nose and the lip and philtrum length bordering the cleft. Significant differences between clefts and controls were identified in the nostril and philtrum on the noncleft side. Conclusions: The use of children with UCL as controls for UCLP studies is inappropriate. This technique overcame the limitations of direct measurement of infant faces to aid the surgeon in the planning and subsequent re-evaluation of surgical rationale