Systems genetics of susceptibility to obesity-induced diabetes in mice.

Inbred strains of mice are strikingly different in susceptibility to obesity-driven diabetes. For instance, deficiency in leptin receptor (db/db) leads to hyperphagia and obesity in both C57BL/6 and DBA/2 mice, but only on the DBA/2 background do the mice develop beta-cell loss leading to severe diabetes, while C57BL/6 mice are relatively resistant. To further investigate the genetic factors predisposing to diabetes, we have studied leptin receptor-deficient offspring of an F2 cross between C57BL/6J (db/+) males and DBA/2J females. The results show that the genetics of diabetes susceptibility are enormously complex and a number of quantitative trait loci (QTL) contributing to diabetes-related traits were identified, notably on chromosomes 4, 6, 7, 9, 10, 11, 12, and 19. The Chr. 4 locus is likely due to a disruption of the Zfp69 gene in C57BL/6J mice. To identify candidate genes and to model coexpression networks, we performed global expression array analysis in livers of the F2 mice. Expression QTL (eQTL) were identified and used to prioritize candidate genes at clinical trait QTL. In several cases, clusters of eQTLs colocalized with clinical trait QTLs, suggesting a common genetic basis. We constructed coexpression networks for both 5 and 12 wk old mice and identified several modules significantly associated with clinical traits. One module in 12 wk old mice was associated with several measures of hepatic fat content as well as with other lipid- and diabetes-related traits. These results add to the understanding of the complex genetic interactions contributing to obesity-induced diabetes.

Heridas por proyectil de arma de fuego. Atipicidad en orificios de entrada y el fenómeno de ''cola de cometa": Reporte de caso / Gunshot wounds. Atypicality in entry holes and the "comet tail" phenomenon: Case report

El análisis de los orificios de entrada por proyectil de arma de fuego en una autopsia médico legal representa un importante papel en la determinación de la forma y causa de muerte en casos relacionados con armas de fuego. Su valoración puede proporcionar información valiosa sobre las características del arma utilizada, la distancia entre el arma de fuego y la víctima, entre otros factores que contribuyen a la investigación. El fenómeno de ''cola de cometa" observado en ciertos orificios de entrada es poco frecuente y conocido. Por lo anterior, el objetivo de este artículo es investigar las características y mecanismos de producción de los orificios de entrada con este fenómeno, proporcionando información sobre su formación, las posibles implicaciones y consideraciones médico legales a tomar en cuenta para su diagnóstico de esta causa de muerte. Se presenta un reporte de caso que destaca la descripción del fenómeno de ''cola de cometa" en una investigación forense de la vida real, proporcionando información valiosa sobre su utilidad y potencial para mejorar la precisión del análisis de heridas de bala. Se realizó revisión de artículos científicos, sobre orificios de entrada en heridas por proyectil de arma de fuego con el fenómeno de ''cola de cometa".

The analysis of firearm projectile entry holes in a medicolegal autopsy plays an important role in determining the manner and cause of death in cases involving firearms. The assessment can provide valuable information about the characteristics of the weapon used, the distance between the firearm and the victim, among other factors that contribute to the investigation. The ''comet tail" phenomenon observed in certain entry holes is rare and well known. Therefore, the objective of this article is to investigate the characteristics and mechanisms of production of the entrance orifices with this phenomenon, providing information about their formation, the possible implications, and medical-legal considerations to be taken into account for the diagnosis of this cause of death. A case report is presented highlighting the description of the ''comet tail" phenomenon in a real-life forensic investigation, providing valuable insight into its utility and potential to improve the accuracy of gunshot wound analysis. A review of scientific articles was carried out on entry holes in gunshot wounds with the "comet tail" phenomenon.

Dose-response impact of various tocotrienols on serum lipid parameters in 5-week-old female chickens.

The cholesterol-suppressive action of the tocotrienol-rich-fraction (TRF) of palm oil may be due to the effect of its constituent tocotrienols on beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase activity. The tocotrienols, modulate HMG-CoA reductase activity via a post-transcriptional mechanism. As a consequence small doses (5-200 ppm) of TRF-supplemented diets fed to experimental animals lower serum cholesterol levels. These findings led us to evaluate the safety and efficacy of large supplements of TRF and its constituents. Diets supplemented with 50, 100, 250, 500, 1000, or 2000 ppm of TRF, alpha-tocopherol, alpha-tocotrienol, gamma-tocotrienol, or 6-tocotrienol were fed to chickens for 4 wk. There were no differences between groups or within groups in weight gain, or in feed consumption at the termination of the feeding period. Supplemental TRF produced a dose-response (50-2000 ppm) lowering of serum total and LDL cholesterol levels of 22% and 52% (P < 0.05), respectively, compared with the control group. alpha-Tocopherol did not affect total or LDL-cholesterol levels. Supplemental alpha-tocotrienol within the 50-500 ppm range produced a dose-response lowering of total (17%) and LDL (33%) cholesterol levels. The more potent gamma and delta isomers yielded dose-response (50-2,000 ppm) reductions of serum total (32%) and LDL (66%) cholesterol levels. HDL cholesterol levels were minimally impacted by the tocotrienols; as a result, the HDL/LDL cholesterol ratios were markedly improved (123-150%) by the supplements. Serum triglyceride levels were significantly lower in sera of pullets receiving the higher supplements. The safe dose of various tocotrienols for human consumption might be 200-1000 mg/d based on this study.

A genome-wide set of congenic mouse strains derived from CAST/Ei on a C57BL/6 background.

We previously reported the construction of two sets of heterozygous congenic strains spanning the mouse genome. For both sets, C57BL/6J was employed as the background strain while DNA from either DBA/2 or CAST/Ei was introgressed to form the congenic region. We have subsequently bred most of these strains to produce homozygous breeding stocks. Here, we report the characterization of the strain set based on CAST/Ei. CAST/Ei is the most genetically distant strain within the Mus mus species and many trait variations relevant to common diseases have been identified in CAST/Ei mice. Despite breeding difficulties for some congenic regions, presumably due to incompatible allelic variations between CAST/Ei and C57BL/6, the resulting congenic strains cover about 80% of the autosomal chromosomes and will be useful as a resource for the further analysis of quantitative trait loci between the strains.