Absorption of hexose and pentose sugars in vivo in perfused intestinal segments in the fowl.

1. Rates of absorption of two hexose (D-glucose and D-galactose) and two pentose (D-xylose and D-arabinose) sugars were measured by in vivo perfusion, in jejunum, ileum and (distal) caecum, in immature hens conditioned to either a standard (ST) or "high fibre" (ST + 20% grass) diet. 2. Each bird was tested in one intestinal segment with all four (U-14C-labelled, 10 mM) sugars, with either the hexoses preceding the pentoses or vice versa. 3. With all treatments, absorption rates of the hexoses were alike, as were those of the pentoses. Hexose absorption was twice as fast as pentose absorption in jejunum and ileum with both dietary pretreatments, whereas in caecum hexose and pentose rates were similarly high, except when pentose (and its associated fluid transfer) was apparently inhibited by prior hexose absorption with the ST diet. 4. With the ST diet, hexose absorption (per unit length and dry weight) was faster in caecum than in jejunum and ileum, and pentose absorption was also fastest in caecum when all pentose data from testing after hexose were excluded. 5. With the ST/grass diet, hexose absorption was faster in jejunum than in ileum and caecum when expressed per unit length, and pentose absorption was fastest in caecum on a dry weight basis. 6. Hexose absorption was faster in jejunum and slower in caecum with the ST/grass pretreatment than with ST. However, the dietary comparison was not conclusive because it involved birds form (two) different hatches (of similar age and weight) tested at different times.     

Functional TIM10 chaperone assembly is redox-regulated in vivo

The TIM10 chaperone facilitates the insertion of hydrophobic proteins at the mitochondrial inner membrane. Here we report the novel molecular mechanism of TIM10 assembly. This process crucially depends on oxidative folding in mitochondria and involves: (i) import of the subunits in a Cys-reduced and unfolded state; (ii) folding to an assembly-competent structure maintained by intramolecular disulfide bonding of their four conserved cysteines; and (iii) assembly of the oxidized zinc-devoid subunits to the functional complex. We show that intramolecular disulfide bonding occurs in vivo, whereas intermolecular disulfides observed in vitro are abortive intermediates in the assembly pathway. This novel mechanism of compartment-specific redox-regulated assembly is crucial for the formation of a functional TIM10 chaperone.     

Effects of long-term treatment with eicosapentaenoic acid on the heart subjected to ischemia/reperfusion and hypoxia/reoxygenation in rats

The effects of eicosapentaenoic acid (EPA) and long-term treatment with EPA-ethylester (EPA-E) were examined in perfused rat hearts subjected to ischemia/reperfusion and adult rat cardiomyocytes subjected to hypoxia/reoxygenation. EPA (0.1 M) improved postischmic contractile dysfunction of the ischemic/reperfused heart. EPA (10 M) attenuated hypoxia/reoxygenation-induced morphological deterioration of cardiomyocytes. The results suggest the presence of direct cardioprotective effects of EPA. Rats were orally treated for 4 weeks with 1 g/kg/day of EPA-E to elucidate ex vivo effects of EPA, and the fatty acid composition of cardiac phospholipids was determined. The percent ratio of EPA in total fatty acids of cardiac phospholipids increased whereas that of arachidonic acid decreased. The percent ratio of n-3/n-6 fatty acid did not increase. Treatment with EPA-E did not improve the post-ischemic contractile function, but attenuated the ischemia/reperfusion-induced release of prostaglandins during reperfusion. Treatment with EPA-E preserved a better morphological appearance of the cardiomyocytes subjected to hypoxia/reoxygenation. The results suggest that the mechanisms responsible for cytoprotective effects of hypoxic/reoxygeanted cardiomyocytes or inhibition of metabolic alterations of the ischemic/reperfused heart by long-term EPA-E treatment did not contribute substantially to recovery of post-ischemic contractile dysfunction. The direct in vitro effects of EPA may play a role in the protection of the heart from ischemia/reperfusion or hypoxia/reoxygenation injury.     

Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis

Background

Natural killer cells are involved in the complex mechanisms underlying autoimmune diseases but few studies have investigated their role in autoimmune hepatitis. Killer immunoglobulin-like receptors are key regulators of natural killer cell-mediated immune responses.

Methods and Findings

KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 114 patients diagnosed with type 1 autoimmune hepatitis and compared with a group of 221 healthy controls. HLA Class I and Class II antigen frequencies were compared to those of 551 healthy unrelated families representative of the Sardinian population. In our cohort, type 1 autoimmune hepatitis was strongly associated with the HLA-B18, Cw5, DR3 haplotype. The KIR2DS1 activating KIR gene and the high affinity HLA-C2 ligands were significantly higher in patients compared to controls. Patients also had a reduced frequency of HLA-Bw4 ligands for KIR3DL1 and HLA-C1 ligands for KIR2DL3. Age at onset was significantly associated with the KIR2DS1 activating gene but not with HLA-C1 or HLA-C2 ligand groups.

Conclusions

The activating KIR gene KIR2DS1 resulted to have an important predictive potential for early onset of type 1 autoimmune hepatitis. Additionally, the low frequency of the KIR-ligand combinations KIR3DL1/HLA-Bw4 and KIR2DL3/HLA-C1 coupled to the high frequency of the HLA-C2 high affinity ligands for KIR2DS1 could contribute to unwanted NK cell autoreactivity in AIH-1.     

Cardiorespiratory Fitness Is Associated with Hard and Light Intensity Physical Activity but Not Time Spent Sedentary in 10–14 Year Old Schoolchildren: The HAPPY Study

Background

Sedentary behaviour is a major risk factor for developing chronic diseases and is associated with low cardiorespiratory fitness in adults. It remains unclear how sedentary behaviour and different physical activity subcomponents are related to cardiorespiratory fitness in children. The purpose of this study was to assess how sedentary behaviour and different physical activity subcomponents are associated with 10–14 year-old schoolchildren''s cardiorespiratory fitness.

Methods

135 schoolchildren (81 girls, 12±1 year) completed 7-day minute-by-minute habitual physical activity monitoring using triaxial accelerometers and undertook a maximal cardiorespiratory fitness test.

Results

After controlling for sex, age, ethnicity, socioeconomic status and total wear time, light physical activity (1.5–2.9 METs) was negatively associated (β = −.24, p<.01) and hard physical activity (≥9 METs) positively associated (β = .45, p<.001) with cardiorespiratory fitness. Vigorous and hard physical activity were associated with cardiorespiratory fitness for boys (F = 5.64, p<.01) whereas light, moderate and hard physical activity were associated with physical fitness for girls (F = 10.23, p<.001). No association was found between sedentary time and cardiorespiratory fitness (r = −.13, p>.05). Sedentary to active transitions revealed little variability between cardiorespiratory fitness tertiles.

Conclusions

Hard physical activity (≥9 METs) holds greater potential for cardiorespiratory fitness compared to physical activity of lower intensities. There was no relationship between sedentary behaviour and cardiorespiratory fitness. These findings suggest that, for children, advice should focus on higher intensity physical activity and not sedentary behaviour as a means to maintain or improve cardiorespiratory fitness. Future research should explore longitudinal relationships between hard physical activity, cardiorespiratory fitness and health parameters.     

The cucurbit downy mildew pathogen Pseudoperonospora cubensis

Pseudoperonospora cubensis[(Berkeley & M. A. Curtis) Rostovzev], the causal agent of cucurbit downy mildew, is responsible for devastating losses worldwide of cucumber, cantaloupe, pumpkin, watermelon and squash. Although downy mildew has been a major issue in Europe since the mid-1980s, in the USA, downy mildew on cucumber has been successfully controlled for many years through host resistance. However, since the 2004 growing season, host resistance has been effective no longer and, as a result, the control of downy mildew on cucurbits now requires an intensive fungicide programme. Chemical control is not always feasible because of the high costs associated with fungicides and their application. Moreover, the presence of pathogen populations resistant to commonly used fungicides limits the long-term viability of chemical control. This review summarizes the current knowledge of taxonomy, disease development, virulence, pathogenicity and control of Ps. cubensis. In addition, topics for future research that aim to develop both short- and long-term control measures of cucurbit downy mildew are discussed. TAXONOMY: Kingdom Straminipila; Phylum Oomycota; Class Oomycetes; Order Peronosporales; Family Peronosporaceae; Genus Pseudoperonospora; Species Pseudoperonospora cubensis. DISEASE SYMPTOMS: Angular chlorotic lesions bound by leaf veins on the foliage of cucumber. Symptoms vary on different cucurbit species and varieties, specifically in terms of lesion development, shape and size. Infection of cucurbits by Ps. cubensis impacts fruit yield and overall plant health. INFECTION PROCESS: Sporulation on the underside of leaves results in the production of sporangia that are dispersed by wind. On arrival on a susceptible host, sporangia germinate in free water on the leaf surface, producing biflagellate zoospores that swim to and encyst on stomata, where they form germ tubes. An appressorium is produced and forms a penetration hypha, which enters the leaf tissue through the stomata. Hyphae grow through the mesophyll and establish haustoria, specialized structures for the transfer of nutrients and signals between host and pathogen. CONTROL: Management of downy mildew in Europe requires the use of tolerant cucurbit cultivars in conjunction with fungicide applications. In the USA, an aggressive fungicide programme, with sprays every 5-7 days for cucumber and every 7-10 days for other cucurbits, has been necessary to control outbreaks and to prevent crop loss. USEFUL WEBSITES: http://www.daylab.plp.msu.edu/pseudoperonospora-cubensis/ (Day Laboratory website with research advances in downy mildew); http://veggies.msu.edu/ (Hausbeck Laboratory website with downy mildew news for growers); http://cdm.ipmpipe.org/ (Cucurbit downy mildew forecasting homepage); http://ipm.msu.edu/downymildew.htm (Downy mildew information for Michigan's vegetable growers).