Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita

The DKC1 gene encodes a pseudouridine synthase that modifies ribosomal RNA (rRNA). DKC1 is mutated in people with X-linked dyskeratosis congenita (X-DC), a disease characterized by bone marrow failure, skin abnormalities, and increased susceptibility to cancer. How alterations in ribosome modification might lead to cancer and other features of the disease remains unknown. Using an unbiased proteomics strategy, we discovered a specific defect in IRES (internal ribosome entry site)-dependent translation in Dkc1(m) mice and in cells from X-DC patients. This defect results in impaired translation of messenger RNAs containing IRES elements, including those encoding the tumor suppressor p27(Kip1) and the antiapoptotic factors Bcl-xL and XIAP (X-linked Inhibitor of Apoptosis Protein). Moreover, Dkc1(m) ribosomes were unable to direct translation from IRES elements present in viral messenger RNAs. These findings reveal a potential mechanism by which defective ribosome activity leads to disease and cancer.     

Comparative effects of organic and inorganic selenium on selenium transfer from sows to nursing pigs

To investigate the effects of supplemental Se on the transfer of Se to nursing pigs when sows are fed diets containing a Se level above the NRC recommendation (0.15 ppm), sows were fed diets containing no supplemental Se or supplemental (0.3 ppm) Se from sodium selenite or Se yeast. A nonSe-fortified corn-soybean meal basal diet with a high endogenous Se content served as the negative control (0.20 to 0.23 ppm Se). Fifty-two sows were fed diets from 60 d prepartum until 14 d of lactation. Six sows per treatment were bled at 60 and 30 d prepartum, at farrowing, and at 14 d postpartum to measure serum Se concentrations. Colostrum was collected within 12 h postpartum, and milk was collected at 14 d of lactation. Blood was obtained from 3 pigs each from 12 litters per treatment at birth and at weaning (d 14), and pooled serum was analyzed for Se and immunoglobulin G concentrations and glutathione peroxidase activity. Regardless of treatment, serum Se in sows declined throughout gestation and gradually increased during lactation. Sows fed Se yeast tended (P < 0.06) to have greater serum Se at farrowing than sows fed unsupplemented diets. Colostrum and milk (d 14) Se concentrations increased (P < 0.01) when sows were fed Se from yeast but not from sodium selenite. At birth, serum Se was increased (P < 0.01) for pigs whose dams were fed Se yeast compared with pigs from sows fed the basal diet. At 14 d of age, there was no difference in serum Se concentration of pigs from dams fed any of the treatments. Pig serum immunoglobulin G concentrations and glutathione peroxidase-1 activity were unaffected by dietary Se source. Supplementation of gestating and lactating sow diets with Se (0.3 ppm) from an organic or inorganic source reduced the number of stillbirths per litter. However, only pigs born to sows fed organic Se (Se yeast) had greater serum Se at birth. Organic Se increased Se concentration of colostrum and 14-d milk to a greater degree than inorganic Se.     

Comparative analysis of pathogenesis-related protein 10 (<Emphasis Type="Italic">PR10</Emphasis>) genes between fungal resistant and susceptible peppers

To elucidate the functional roles of PR10 genes from two pepper species during plant-pathogen interactions, PR10 genes were isolated from fungal-resistant (Capsicum baccatum var. PBC80) and fungal-susceptible (C. annuum var. Yeoju) pepper fruits infected with anthracnose fungus (Colletotrichum acutatum). Despite strong nucleotide sequence identity, there were significant differences in the patterns of gene expression and protein accumulation between the genes from the two host species. Induced expression of the PR10 mRNA in PBC80 (bacPR10) was highly maintained from 24 h after infection (HAI) rather than that in Yeoju (annPR10). These mRNA expression patterns were correlated with the level of respective protein that was detected as two or three bands in each species. Substantial induction of bacPR10 proteins was confirmed by 2D-gel analysis followed by immunoblotting. Immunolocalization study showed that deposition of bacPR10 was exclusively observed in the pericarp of PBC80 fruits after fungal infection, suggesting functional significance in defence. Additionally, in vitro analysis of the enzymatic properties of PR10 proteins revealed that recombinant bacPR10 had higher ribonucleolytic activity and exhibited less sensitivity to proteinase treatment than did annPR10. Taken together, these results support the idea that relative abundance and prolonged longevity of bacPR10 in PBC80 fruits may contribute to their increased resistance in response to the anthracnose fungus, as compared with Yeoju fruit.     

Fucoidan regulate blood glucose homeostasis in C57BL/KSJ m+/+db and C57BL/KSJ db/db mice

Type 2 diabetes mellitus is a multisystem disease that is characterized by hyperglycemia and is associated with the dysfunction and failure of various organs. The control of postprandial hyperglycemia is important in the prevention and intervention of type 2 diabetes. Fucoidan has several biological activities in vitro and in vivo. However, the effect of fucoidan on hyperglycemia in non-diabetic and diabetic mice has not been investigated. This study was undertaken to study the effects of different molecular weight forms (5 kilodalton (k), 5-30 k and crude) of fucoidan on oral glucose tolerance tests in non-diabetic mice and on food intake, weight gain, fasting blood glucose and blood biochemistry of db/db mice. Treatment with 200 mg/mL 5 k, 5-30 k and crude fucoidan substantially prevented hyperglycemia according to oral glucose tolerance tests in non-diabetic mice. In addition, fucoidan fractions significantly reduced blood glucose levels in diabetic mice.     

Effect of Adding Different Dietary Fiber Sources on Farinographic Parameters of Wheat Flour

Breadmaking is a complex process that involves a series of parameters that must be controlled. Rheological measurements are often used to predict the behavior of wheat dough during processing and the quality of the final product. There are many different dietary fiber sources that can be used to enhance the nutritional quality of bread. However, they will affect processing and final product quality. Response surface methodology (RSM) was employed to study the effects of adding different dietary fiber sources (wheat bran, resistant starch, and locust bean gum) on farinographic parameters of wheat flour. The experiments were conducted according to a 2³ central composite rotational design (CCRD). With the experimental results or responses (farinographic parameters), the effect of each variable was calculated and the interactions between them were determined. Models that explain the effects of the different fiber sources on water absorption, arrival time, dough development time, and mixing tolerance index of wheat flour were established. The fiber sources interacted for some of the parameters analyzed, demonstrating that if two or more sources of dietary fiber are present in the mix, they might act different to what would be expected of the sum of them. It was also noticed that for most parameters, wheat bran and locust bean gum had a greater influence on farinographic parameters than resistant starch. The simultaneous presence of the three fibers, within the ranges studied, contributed to an increase in water absorption, arrival time, and mixing tolerance index, and to a reduction in departure time and dough stability.     

Distribution and characterization of class 1 integrons in Salmonella enterica serotype Gallinarum biotype Gallinarum

Fowl typhoid caused by Salmonella enterica subsp. enterica serotype Gallinarum biotype Gallinarum is the most important chicken disease in Korea. Due to appearance of new or multiple antibiotics resistances in the recently isolated strains, it was difficult to control the disease using antibiotics in our country. Therefore, the prevalence and genetic contents of class 1 integrons in biotype Gallinarum isolated between 1992 and 2001 were investigated by PCR and direct sequencing, respectively. Out of 90 strains, 35 (39%) carried class 1 integrons. The 1.0, 1.6 and 2.0kbp amplicons were amplified in 32 strains (36%), 2 strains (2%) and 1 strain (1%), respectively. The 1.0, 1.6 and 2.0 kbp amplicons contained one (aadA1a), two (aadB-aadA1b) and three cassettes (dhfrXII-orfF-aadA2), respectively, providing resistances against aminoglycosides (aadA1a, aadA1b, aadB, and aadA2) and trimethoprim (dhfrXII). The integron-carrying strains of biotype Gallinarum appeared in 1996 and acquired additional cassettes in 2000. Although the resistances to ampicillin, tetracycline and chloramphenicol are unrelated to class 1 integrons, relatively high prevalence of integron in biotype Gallinarum may be a dormant threat to the chemotherapy of the disease in the near future because of potency to acquire additional antibiotics resistances.     

Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1

The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1α activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1α. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1α expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1α was important for MSC survival under hypoxic conditions.     

Comparison of techniques for transdiaphragmatic thoracic drainage after diaphragmatic defect closure in dogs: a cadaveric study

Four thoracic evacuation techniques for pneumothorax elimination after diaphragmatic defect closure were compared in 40 canine cadavers. After creating a defect in the left side of the diaphragm, thoracic drainage was performed by thoracostomy tube insertion through the defect and a small (DD-SP) or large (DD-LP) puncture created in the caudal mediastinum, or through both the diaphragmatic defect and intact contralateral diaphragm with a small (DI-SP) or large (DI-LP) puncture in made in the caudal mediastinum. Differences in intrapleural pressure (IPP) between the right and left hemithoraxes after air evacuation along with differences in IPP before making a defect and after air evacuation in each hemithorax were calculated. A difference (p ≤ 0.0011) in IPP between the left and right hemithoraxes after air evacuation as well as before making a defect and after air evacuation in the right hemithorax was detected for the DD-SP group. No significant differences (p ≥ 0.0835) were observed for the DI-LP, DD-LP, or DI-SP groups. Creation of a large mediastinal puncture or thoracic evacuation through both a diaphragmatic defect and intact contralateral diaphragm can facilitate proper pneumothorax elimination bilaterally after diaphragmatic defect closure in dogs with a small puncture in the caudal mediastinum.