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Regulatory T cells (T.sub.reg cells), a distinct subset of CD4.sup.+ T cells, are necessary for the maintenance of immune self-tolerance and homeostasis.sup.1,2. Recent studies have demonstrated that T.sub.reg cells exhibit a unique metabolic profile, characterized by an increase in mitochondrial metabolism relative to other CD4.sup.+ effector subsets.sup.3,4. Furthermore, the T.sub.reg cell lineage-defining transcription factor, Foxp3, has been shown to promote respiration.sup.5,6; however, it remains unknown whether the mitochondrial respiratory chain is required for the T cell-suppression capacity, stability and survival of T.sub.reg cells. Here we report that T.sub.reg cell-specific ablation of mitochondrial respiratory chain complex III in mice results in the development of fatal inflammatory disease early in life, without affecting T.sub.reg cell number. Mice that lack mitochondrial complex III specifically in T.sub.reg cells displayed a loss of T cell-suppression capacity without altering T.sub.reg cell proliferation and survival. T.sub.reg cells deficient in complex III showed decreased expression of genes associated with T.sub.reg function, whereas Foxp3 expression remained stable. Loss of complex III in T.sub.reg cells increased DNA methylation as well as the metabolites 2-hydroxyglutarate (2-HG) and succinate that inhibit the ten-eleven translocation (TET) family of DNA demethylases.sup.7. Thus, T.sub.reg cells require mitochondrial complex III to maintain immune regulatory gene expression and suppressive function.Specific ablation of mitochondrial complex III subunits in T.sub.reg cells in mice results in inflammatory disease, altered T.sub.reg gene expression and defective T.sub.reg function, indicating a key functional role for mitochondrial complex III in T.sub.reg cells., Author(s): Samuel E. Weinberg [sup.1] , Benjamin D. Singer [sup.1] [sup.2] , Elizabeth M. Steinert [sup.1] , Carlos A. Martinez [sup.2] , Manan M. Mehta [sup.1] , Inmaculada Martínez-Reyes [sup.1] [...]

Combining crown rust resistance (CRR) genes is an objective of many oat (A vena sativa L.) breeding programs. Genetic suppressors of CRR have been reported, but the genetic nature of such suppressors has not been investigated. An excess of susceptible seedlings in segregating progeny, of crosses involving genotypes with Pc-38 and Pc-62 suggested the Pc-38 parent may have a factor that inhibits the expression of Pc-62. Our objectives were to (i) examine a putative genetic interaction between oat CRR gene Pc-62 and a dominant suppressor, (ii) utilize chromosome interchange stocks to define genetically the location of the suppressor, (iii) evaluate the effect of gene dosage combinations on the resistance-suppression relationship, and (iv) examine alternative explanations of distorted segregation (genetic background and differential gamete transmission). The use of duplication-deficiency (Dp-Df) genotypes placed a putative suppressor on an interchanged chromosome segment that contains Pc-38. Resistance conferred by, Pc-62 was suppressed in [F.sub.1] trisomic CRR locus combinations (1 Pc-62:2 Pc-38) in comparison to the expression of resistance in [F.sub.1] seedlings hemizygous for Pc-62. The Pc-38 segment contributed by two independently derived cultivars; produced equivalent suppression in [F.sub.1] combinations with Pc-62. The presence of Pc38 in an interchanged position in the cultivar Dumont allowed production of mono- and diallelic combinations of resistance genes and evaluation of mono-, di-, and trisomic segregation of the CRR locus. Diallelic trisomic segregation for the CRR locus indicated that an increasing dosage of Pc-62, relative to the suppressor and Pc-38, decreased the degree of suppression. Male transmission of Dp-Df gametes was not reduced relative to the frequency of gametes with a complete chromosome complement., Genetic and cytogenetic analysis of oat hybrids indicate chromosome interchange differences are present among oat cultivars (Leach, 1989; Singh and Kolb, 1991) and the wild hexaploid species A. sterilis L. [...]

The yeast non-mendelian factor [[psi.sup.+]] has been suggested to be a self-modified protein analogous to mammalian prions. Here it is reported that an intermediate amount of the chaperone protein Hsp104 was required for the propagation of the [osi] factor. Overproduction or inactivation of Hsp104 caused the loss of [[psi.sup.+]]. These results suggest that chaperone proteins play a role in prion-like phenomena, and that a certain level of chaperone expression can cure cells of prions without affecting viability. This may lead to antiprion treatments that involve the alteration of chaperone amounts or activity., Certain mammalian neurodegenerative diseases, such as sheep scrapie, human Creutzfeldt-Jacob disease, and bovine spongiform encephalopathy, are widely believed to be caused by proteins in an unusual protease-resistant conformation, called prions [...]

Mutatations of the gene encoding p53, a 53-kilodalton cellular protein, are found frequently in human tumor cells, suggesting a crucial role for this gene in human oncogenesis. To model the [...]

Association of Human Papillomavirus Types 16 and 18 E6 Proteins with p53 THE HUMAN PAPILLOMAVIRUSES (HPVs) that infect the anogenital area can be separated on the basis of their clinical [...]

Identification of a Chromosome 18q Gene That Is Altered in Colorectal Cancers CURRENT THEORIES ON THE ORIGIN OF HUMAN CANCER suggest that it arises, at least in part, from the [...]

The activation of the tumor suppressor protein p53 can lead to cell cycle arrest or to apoptosis. Attardi et al. used subtractive hybridization to identify a gene involved specifically in [...]

Transgenic plants that overproduce useful products project an appealing image: Grains with increased protein content, fruits and vegetables with enhanced nutritional value...flowers with deeper colors. But in trying to create [...]

Identifying Tumor Suppressor Genes in Human Colorectal Cancer APPROXIMATELY A DECADE AGO, THE MOLECULAR GENETIC era of human cancer was ushered in with the discovery of 'dominantly acting' activated cellular [...]