Cullin-RING ubiquitin ligases (CRLs) are critical in ubiquitinating Myc, while COP9 signalosome (CSN) controls neddylation of Cullin in CRL. The mechanistic link between Cullin neddylation and Myc ubiquitination/degradation is unclear. Here we show that Myc is a target of the CSN subunit 6 (CSN6)-Cullin signalling axis and that CSN6 is a positive regulator of Myc.
View Article and Find Full Text PDFIn response to environmental cues, cells coordinate a balance between anabolic and catabolic pathways. In eukaryotes, growth factors promote anabolic processes and stimulate cell growth, proliferation, and survival through activation of the phosphoinositide 3-kinase (PI3K)-Akt pathway. Akt-mediated phosphorylation of glycogen synthase kinase-3β (GSK-3β) inhibits its enzymatic activity, thereby stimulating glycogen synthesis.
View Article and Find Full Text PDFThe mammalian constitutive photomorphogenesis 9 (COP9) signalosome (CSN), a protein complex involved in embryonic development, is implicated in cell cycle regulation and the DNA damage response. Its role in tumor development, however, remains unclear. Here, we have shown that the COP9 subunit 6 (CSN6) gene is amplified in human breast cancer specimens, and the CSN6 protein is upregulated in human breast and thyroid tumors.
View Article and Find Full Text PDFIn animal cells, growth factors coordinate cell proliferation and survival by regulating the phosphoinositide 3-kinase/Akt signaling pathway. Deregulation of this signaling pathway is common in a variety of human cancers. The PI3K-dependent signaling kinase complex defined as mammalian target of rapamycin complex 2 (mTORC2) functions as a regulatory Ser-473 kinase of Akt.
View Article and Find Full Text PDFObjective: To determine the extent of carnivore-transmitted parasitic zoonoses in a community in eastern Kazakhstan, a region where cystic echinococcosis (CE) re-emerged in recent years.
Methods: Cross sectional ultrasound study of 3126 human subjects to determine the extent of human cystic and alveolar echinococcosis (AE). Blood samples were taken from each subject and analysed for antibodies against Echinococcus, Toxocara and Toxoplasma spp.
In animals, liver and white adipose are the main sites for the de novo fatty acid synthesis. Deletion of fatty acid synthase or acetyl-CoA carboxylase (ACC) 1 in mice resulted in embryonic lethality, indicating that the de novo fatty acid synthesis is essential for embryonic development. To understand the importance of de novo fatty acid synthesis and the role of ACC1-produced malonyl-CoA in adult mouse tissues, we generated liver-specific ACC1 knockout (LACC1KO) mice.
View Article and Find Full Text PDFIn order to evaluate the epidemiology of parasitism in farmed ruminants in the changed agricultural context in Kazakhstan, 505 cattle, sheep and goats were surveyed for gastrointestinal parasitism using coprological examination, and a further thirty sheep and four goats using post mortem extraction of helminths. The dominant helminth genera were Marshallagia, Nematodirus and Trichostrongylus. Haemonchus was also present.
View Article and Find Full Text PDFCystic echinococcosis (CE) caused by Echinococcus granulosus has always been an endemic disease in central Asia. During the period of Soviet Administration up to 1991, human surgical incidence rates tended to be relatively low with perhaps at most 1-5 cases per 100,000 per year. Following the collapse of the Soviet Union and the emergence of the New Independent States there has been profound economic and social changes.
View Article and Find Full Text PDFMuch of Central Asia is characterized by an arid landscape. Foci of Echinococcus multilocularis have a very patchy distribution. This is due to a significant deficiency of moisture in the superficial layers of the ground and is related to the types of animal colonies.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2005
Acetyl-CoA carboxylases (ACC1 and ACC2) catalyze the carboxylation of acetyl-CoA to form malonyl-CoA, an intermediate metabolite that plays a pivotal role in the regulation of fatty acid metabolism. We previously reported that ACC2 null mice are viable, and that ACC2 plays an important role in the regulation of fatty acid oxidation through the inhibition of carnitine palmitoyltransferase I, a mitochondrial component of the fatty-acyl shuttle system. Herein, we used gene targeting to knock out the ACC1 gene.
View Article and Find Full Text PDFSaiga antelope (Saiga tatarica) graze extensively on livestock pasture, potentially enabling transmission of a wide range of parasitic helminths between saigas and domestic ruminants. Thirty-six of the 38 species of helminth that have been found in saigas in Kazakhstan in the past have been found also in domestic livestock. We examined 133 saigas culled for meat in autumn 1997, and found three species of cestode and 12 nematodes (nine in the abomasum), but no trematodes or lungworms.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2005
Acc2-/- mutant mice, when fed a high-fat/high-carbohydrate (HF/HC) diet, were protected against diet-induced obesity and diabetes. To investigate the role of acetyl-CoA carboxylase 2 (ACC2) in the regulation of energy metabolism in adipose tissues, we studied fatty acid and glucose oxidation in primary cultures of adipocytes isolated from wild-type and Acc2-/- mutant mice fed either normal chow or a HF/HC diet. When fed normal chow, oxidation of [14C]palmitate in adipocytes of Acc2-/- mutant mice was approximately 80% higher than in adipocytes of WT mice, and it remained significantly higher in the presence of insulin.
View Article and Find Full Text PDFCystic echinococcosis is a re-emerging disease in central Asia. A total of 120 soil samples taken from 30 gardens of rural homesteads in southern Kazakhstan were analyzed for the presence of taeniid eggs using a concentration technique. Of these, 21 (17.
View Article and Find Full Text PDFPolymerase chain reaction (PCR) for the identification of eggs of the tapeworm Echinococcus granulosus ("sheep strain") was evaluated with primers derived from mitochondrial sequences. Specificity of these primers was confirmed by investigating DNA of other strains of E. granulosus and of 14 helminth species which inhabit the intestines of dogs.
View Article and Find Full Text PDFCystic echinococcosis, caused by Echinococcus granulosus, is an emerging disease in many parts of the world and, in particular, in eastern Europe and the former Soviet Union. This paper examines the abundance of infection of E. granulosus in the definitive host in southern Kazakhstan.
View Article and Find Full Text PDFCystic echinococcosis, caused by Echinococcus granulosus, is an emerging disease in many parts of the world and, in particular, in eastern Europe and the former Soviet Union. This paper examines the abundance and prevalence of infection of E. granulosus in cattle and sheep in Kazakhstan.
View Article and Find Full Text PDFIn recent years there has been a substantial increase in cystic echinococcosis in Kazakhstan. There are several factors that have contributed to this change in the epidemiology of the disease. The primary reason was the degradation of traditional nomadic system of livestock breeding and closing of large collective farms.
View Article and Find Full Text PDFHuman cystic echinococcosis (CE), caused by Echinococcus granulosus, is an emerging disease in central Asia. This study examined official data on the incidence of CE between 1991 and 2000 and studied routine hospital records in the main surgical hospitals in Bishkek, Kyrgystan, between 1990 and 2000. In addition, a cross-sectional ultrasound study of a rural population was undertaken in northern Kyrgystan.
View Article and Find Full Text PDFSince independence from the Soviet Union in 1991 the annual surgical incidence of cystic echinococcosis in Kazakhstan has increased from 1.4 cases/100,000 in 1991 to 5.9 cases/100,000 in 2000.
View Article and Find Full Text PDFArglabin [1(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),11(13)-dien-6, 12-olide], a sesquiterpene gamma-lactone is isolated from Artemisia glabella, a species of wormwood endemic to the Karaganda region of Kazakstan. The compound has been modified to render it water-soluble through addition of a dimethylaminohydrochloride group to the C(13) carbohydride moiety to yield Arglabin-DMA. Arglabin-DMA is a registered antitumor substance in the Republic of Kazakstan.
View Article and Find Full Text PDFMed Parazitol (Mosk)
December 1995
A hundred and forty-six isolates of Trichinella from various regions of Eurasia have been identified by the crossbreeding method (1 male + 1 female). Three independent species of Trichinella: T. nativa, T.
View Article and Find Full Text PDFTo evaluate biological and biochemical variability in nonencapsulated Trichinella isolates, biological and allozymic studies were conducted on isolates of Trichinella collected from a raptoral bird (Aquila rapax) and a fox (Vulpes corsac) in Kazakhstan and from a dasyurid marsupial (Dasyurus maculatus) on the island of Tasmania, Australia. Allozyme profiles of bird and marsupial isolates showed close similarity with the type isolate of Trichinella pseudospiralis. The avian and fox isolates successfully interbred with the type T.
View Article and Find Full Text PDFThe formation of natural foci of trichinelliasis was shown to depend on the established biocenotic relations between carnivorous animals. A highly intensive transmission of the invasion was recorded in continental areas where predators suffer from the lack of food in winter. Identification of the isolated Trichinella samples using single-pair cross hybridization and isoenzyme identification methods showed that the parasites of predators are T.
View Article and Find Full Text PDFAccording to the received data Trichinella nelsoni and T. nativa occupied different areas. T.
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