Experimental investigations of the human oesophagus: anisotropic properties of the embalmed mucosa–submucosa layer under large deformation

Mechanical characterisation of the layer-specific, viscoelastic properties of the human oesophagus is crucial in furthering the development of devices emerging in the field, such as robotic endoscopic biopsy devices, as well as in enhancing the realism, and therefore effectiveness, of surgical simulations. In this study, the viscoelastic and stress-softening behaviour of the passive human oesophagus was investigated through ex vivo cyclic mechanical tests. Due to restrictions placed on the laboratory as a result of COVID-19, only oesophagi from cadavers fixed in formalin were allowed for testing. Three oesophagi in total were separated into their two main layers and the mucosa–submucosa layer was investigated. A series of uniaxial tensile tests were conducted in the form of increasing stretch level cyclic tests at two different strain rates: 1% s\(^{-1}\) and 10% s\(^{-1}\). Rectangular samples in both the longitudinal and circumferential directions were tested to observe any anisotropy. Histological analysis was also performed through a variety of staining methods. Overall, the longitudinal direction was found to be much stiffer than the circumferential direction. Stress-softening was observed in both directions, as well as permanent set and hysteresis. Strain rate-dependent behaviour was also apparent in the two directions, with an increase in strain rate resulting in an increase in stiffness. This strain rate dependency was more pronounced in the longitudinal direction than the circumferential direction. Finally, the results were discussed in regard to the histological content of the layer, and the behaviour was modelled and validated using a visco-hyperelastic matrix-fibre model.

     

BMP-2 functions independently of SHH signaling and triggers cell condensation and apoptosis in regenerating axolotl limbs

Background  

Axolotls have the unique ability, among vertebrates, to perfectly regenerate complex body parts, such as limbs, after amputation. In addition, axolotls pattern developing and regenerating autopods from the anterior to posterior axis instead of posterior to anterior like all tetrapods studied to date. Sonic hedgehog is important in establishing this anterior-posterior axis of limbs in all tetrapods including axolotls. Interestingly, its expression is conserved (to the posterior side of limb buds and blastemas) in axolotl limbs as in other tetrapods. It has been suggested that BMP-2 may be the secondary mediator of sonic hedgehog, although there is mounting evidence to the contrary in mice. Since BMP-2 expression is on the anterior portion of developing and regenerating limbs prior to digit patterning, opposite to the expression of sonic hedgehog, we examined whether BMP-2 expression was dependent on sonic hedgehog signaling and whether it affects patterning of the autopod during regeneration.     

Leptin Levels,Leptin Receptor Gene Polymorphisms,and Energy Metabolism in Women

Objective: Resting metabolic rate (RMR) is mainly determined by fat‐free mass and additionally by age, sex, hormones, and possibly genetic differences. We evaluated whether leptin levels and polymorphisms in the leptin receptor (LEPR) gene were associated with energy expenditure phenotypes. Methods: RMR, body composition, and leptin levels were measured in 125 overweight and obese women. Three LEPR polymorphisms, Lys109Arg, Gln223Arg, and Lys656Asn, were typed on genomic DNA of another group of 192 women in whom RMR was measured. Fat, protein, and carbohydrate oxidation were calculated for 103 of these subjects. In 38 subjects, glucose‐induced thermogenesis was measured over 3 hours. Results: In the first study group, a negative correlation between RMR and leptin levels was found after controlling for fat and fat‐free mass. In multiple regression analysis, leptin contributed significantly to RMR, independent of body composition. In the second study group, RMR was not associated with LEPR polymorphisms. Differences in substrate oxidation rates were found among genotypes at the Lys656Asn site. In fasting conditions, Lys656Lys showed a trend to oxidize more carbohydrates and less fat than Asn656 carriers, a trend which became significant after the glucose load when carbohydrate oxidation rate in Lys656Lys was 15% higher than in Asn656 carriers (p = 0.04), and fat oxidation rate was 44% lower (p = 0.02). Discussion: These results suggest that DNA sequence variations in the LEPR gene could affect substrate oxidation. We hypothesize that this might be caused by differences in glucose levels, leading to differences in glucose oxidation rates.     

The influence of cultural factors on the demography and pattern of gene flow from the Makiritare to the Yanomama Indians

A single village of Yanomama Indians was found to have frequencies of Di^a of 0.06 and of Ap^a of 0.08, in contrast to 40 other villages whereDi^a was absent and Ap^a quite rare. The source of these genes was identified as a village of Makiritare Indians, but the two allele frequencies were approximately the same or even higher in the Yanomama than in the Makiritare village. Demographic, social and cultural parameters affecting marriage and reproduction in the two tribes explain this. Genealogical relationships and informants' accounts collected in the field, when viewed against the traditional marriage practices, reproductive advantages of headmen, and differential treatment of captured women, indicate that the mating and reproduction parameters inherent in tribal social organization of this kind constitute an essential part of the explanation of the genetic findings. It is argued that mating systems of this sort are such that the probability of a new gene introduced by a captive surviving in the recipient population is a function of the sex of the initial carrier. The implications for tribalization and potentially radical changes in allele frequencies are briefly explored by considering aspects of settlement pattern and population fissioning known to characterize the tribes in question. Finally, it is shown that genetic sampling from a single location can and does result in unrepresentative allele frequencies when this single sample is taken to characterize the tribe as a whole.     

The Human Obesity Gene Map: The 1998 Update

PÉRUSSE, LOUIS, YVON C. CHAGNON, JOHN WEISNAGEL, AND CLAUDE BOUCHARD. The human obesity gene map: the 1998 update. Obes Res. 1999;7:111–129. An update of the human obesity gene map incorporating published results up to the end of October 1998 is presented. Evidence from the human obesity cases caused by single gene mutations; other Mendelian disorders exhibiting obesity as a clinical feature; quantitative trait loci uncovered in human genome-wide scans and in crossbreeding experiments with mouse, rat, and pig models; association and case-control studies with candidate genes; and linkage studies with genes and other markers is reviewed. The most noticeable changes from the 1997 update is the number of obesity cases due to single gene mutations that increased from three cases due to mutations in two genes to 25 cases due to 12 mutations in seven genes. A look at the obesity gene map depicted in Figure 1 reveals that putative loci affecting obesity-related phenotypes are found on all but chromosome Y of the human chromosomes. Some chromosomes show at least three putative loci related to obesity on both arms (1, 2, 3, 6, 7, 8, 9, 11, 17, 19, 20, and X) and several on one chromosome arm only (4q, 5q, 10q, 12q, 13q, 15q, 16p, and 22q). The number of genes and other markers that have been associated or linked with human obesity phenotypes is increasing very rapidly and now approaches 27.     

Familial Resemblance for Plasma Leptin: Sample Homogeneity across Adiposity and Ethnic Groups

Objective: Previous studies show a wide range in the percentage of variance in leptin levels attributable to genetic factors. These studies differ markedly with respect to ethnicity, study design, and statistical methodology. Therefore, the purpose of this study was to investigate heterogeneity hypotheses across ethnic groups and by adiposity level, using the same statistical methods. Research Methods and Procedures: Samples included black vs. white (HERITAGE Family Study) and random vs. obese (Québec Family Study) individuals from 432 families (1432 individuals). Heritability for leptin, alternatively adjusted for age and sex and then for age, sex, and adiposity was estimated with the use of familial correlations. Heterogeneity in the magnitude of the familial resemblance between samples and the effect of adjusting for adiposity was explored. Results: Heritability did not vary across samples stratified by adiposity level or ethnic group or across adjustment schemes. Maximal heritability, the percentage of additive phenotypic variability due to all familial sources, was 32%. Discussion: Whereas leptin and adiposity were highly correlated within individuals, removing the effects of adiposity did not significantly alter the magnitude of the familial component for leptin. Moreover, this effect did not vary as a function of ethnicity (black vs. white) or adiposity level. Thus, no evidence for heterogeneity was detected. However, a comparison among previous studies raises questions concerning possible genetic heterogeneity in other ethnic groups in which complex interactions among leptin, adiposity, and diabetes status may be important.     

Use of an organic buffer (hepes) in human lymphocytoid cell line cultures

Summary N-2-Hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) added to bicarbonate buffer in cell culture medium was found to promote continuous logarithmic growth of human lymphocytoid cell lines. Consistent high yields of viable cells were obtained in the combined buffer system. Storage of lymphocytoid cells in the combined buffer system at room temperature allowed successful reinitiation of growth of the cultures.