Attenuated associations between increasing bmi and unfavorable lipid profiles in chinese buddhist vegetarians. Asia

Obesity is related to hyperlipidemia and risk of cardiovascular disease. Health benefits of vegetarian diets have well-documented in the Western countries where both obesity and hyperlipidemia were prevalent. We studied the association between BMI and various lipid/lipoprotein measures, as well as between BMI and predicted coronary heart disease probability in lean, low risk populations in Southern China. The study included 170 Buddhist monks (vegetarians) and 126 omnivore men. Interaction between BMI and vegetarian status was tested in the multivariable regression analysis adjusting for age, education, smoking, alcohol drinking, and physical activity. Compared with omnivores, vegetarians had significantly lower mean BMI, blood pressures, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol to high density lipoprotein ratio, triglycerides, apolipoprotein B and A-I, as well as lower predicted probability of coronary heart disease. Higher BMI was associated with unfavorable lipid/lipoprotein profile and predicted probability of coronary heart disease in both vegetarians and omnivores. However, the associations were significantly diminished in Buddhist vegetarians. Conclusions: Vegetarian diets not only lower BMI, but also attenuate the BMI-related increases of atherogenic lipid/lipoprotein and the probability of coronary heart disease

In vitro template-change PCR to create single crossover libraries: a case study with B. thuringiensis Cry2A toxins

During evolution the creation of single crossover chimeras between duplicated paralogous genes is a known process for increasing diversity. Comparing the properties of homologously recombined chimeras with one or two crossovers is also an efficient strategy for analyzing relationships between sequence variation and function. However, no well-developed in vitro method has been established to create single-crossover libraries. Here we present an in vitro template-change polymerase change reaction that has been developed to enable the production of such libraries. We applied the method to two closely related toxin genes from B. thuringiensis and created chimeras with differing properties that can help us understand how these toxins are able to differentiate between insect species

Identification of vertebra-like elements and their possible differentiation from sclerotomes in the hagfish

The hagfish, a group of extant jawless fish, are known to lack true vertebrae and, for this reason, have often been excluded from the group Vertebrata. However, it has yet to be conclusively shown whether hagfish lack all vertebra-like structures, and whether their somites follow developmental processes and patterning distinct from those in lampreys and gnathostomes. Here we report the presence of vertebra-like cartilages in the in-shore hagfish, Eptatretus burgeri. These elements arise as small nodules occupying anatomical positions comparable to those of gnathostome vertebrae. Examination of hagfish embryos suggests that the ventromedial portion of a somite transforms into mesenchymal cells that express cognates of Pax1/9 and Twist, strikingly similar to the pattern of sclerotome development in gnathostomes. We conclude that the vertebra-like elements in the hagfish are homologous to gnathostome vertebrae, implying that this animal underwent secondary reduction of vertebrae in most of the trunk

Regionalization by fuzzy expert system based approach optimized by genetic algorithm.

In recent years soft computing methods are being increasingly used to model complex hydrologic processes. These methods can simulate the real life processes without prior knowledge of the exact relationship between their components. The principal aim of this paper is perform hydrological regionalization based on soft computing concepts in the southern strip of the Caspian Sea basin, north of Iran. The basin with an area of 42,400 sq. km has been affected by severe floods in recent years that caused damages to human life and properties. Although some 61 hydrometric stations and 31 weather stations with 44 years of observed data (1961–2005) are operated in the study area, previous flood studies in this region have been hampered by insufficient and/or reliable observed rainfall-runoff records. In order to investigate the homogeneity (h) of catchments and overcome incompatibility that may occur on boundaries of cluster groups, a fuzzy expert system (FES) approach is used which incorporates physical and climatic characteristics, as well as flood seasonality and geographic location. Genetic algorithm (GA) was employed to adjust parameters of FES and optimize the system. In order to achieve the objective, a MATLAB programming code was developed which considers the heterogeneity criteria of less than 1 (H < 1) as the satisfying criteria. The adopted approach was found superior to the conventional hydrologic regionalization methods in the region because it employs greater number of homogeneity parameters and produces lower values of heterogeneity criteria

Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China

BACKGROUND: While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6-62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5 x 10(9) cells/L vs 93.0 x 10(9) cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003). CONCLUSIONS/SIGNIFICANCE: The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases

Batch effect confounding leads to strong bias in performance estimates obtained by cross-validation.

BACKGROUND: With the large amount of biological data that is currently publicly available, many investigators combine multiple data sets to increase the sample size and potentially also the power of their analyses. However, technical differences ("batch effects") as well as differences in sample composition between the data sets may significantly affect the ability to draw generalizable conclusions from such studies. FOCUS: The current study focuses on the construction of classifiers, and the use of cross-validation to estimate their performance. In particular, we investigate the impact of batch effects and differences in sample composition between batches on the accuracy of the classification performance estimate obtained via cross-validation. The focus on estimation bias is a main difference compared to previous studies, which have mostly focused on the predictive performance and how it relates to the presence of batch effects. DATA: We work on simulated data sets. To have realistic intensity distributions, we use real gene expression data as the basis for our simulation. Random samples from this expression matrix are selected and assigned to group 1 (e.g., 'control') or group 2 (e.g., 'treated'). We introduce batch effects and select some features to be differentially expressed between the two groups. We consider several scenarios for our study, most importantly different levels of confounding between groups and batch effects. METHODS: We focus on well-known classifiers: logistic regression, Support Vector Machines (SVM), k-nearest neighbors (kNN) and Random Forests (RF). Feature selection is performed with the Wilcoxon test or the lasso. Parameter tuning and feature selection, as well as the estimation of the prediction performance of each classifier, is performed within a nested cross-validation scheme. The estimated classification performance is then compared to what is obtained when applying the classifier to independent data

Uncoupling Protein-4 (UCP4) Increases ATP Supply by Interacting with Mitochondrial Complex II in Neuroblastoma Cells

Mitochondrial uncoupling protein-4 (UCP4) protects against Complex I deficiency as induced by 1-methyl-4-phenylpyridinium (MPP+), but how UCP4 affects mitochondrial function is unclear. Here we investigated how UCP4 affects mitochondrial bioenergetics in SH-SY5Y cells. Cells stably overexpressing UCP4 exhibited higher oxygen consumption (10.1%, p<0.01), with 20% greater proton leak than vector controls (p<0.01). Increased ATP supply was observed in UCP4-overexpressing cells compared to controls (p<0.05). Although state 4 and state 3 respiration rates of UCP4-overexpressing and control cells were similar, Complex II activity in UCP4-overexpressing cells was 30% higher (p<0.05), associated with protein binding between UCP4 and Complex II, but not that of either Complex I or IV. Mitochondrial ADP consumption by succinate-induced respiration was 26% higher in UCP4-overexpressing cells, with 20% higher ADP:O ratio (p<0.05). ADP/ATP exchange rate was not altered by UCP4 overexpression, as shown by unchanged mitochondrial ADP uptake activity. UCP4 overexpression retained normal mitochondrial morphology in situ, with similar mitochondrial membrane potential compared to controls. Our findings elucidate how UCP4 overexpression increases ATP synthesis by specifically interacting with Complex II. This highlights a unique role of UCP4 as a potential regulatory target to modulate mitochondrial Complex II and ATP output in preserving existing neurons against energy crisis

Tumor response to radiotherapy is dependent on genotype-associated mechanisms in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>We have previously shown that in vitro radiosensitivity of human tumor cells segregate non-randomly into a limited number of groups. Each group associates with a specific genotype. However we have also shown that abrogation of a single gene (p21) in a human tumor cell unexpectedly sensitized xenograft tumors comprised of these cells to radiotherapy while not affecting in vitro cellular radiosensitivity. Therefore in vitro assays alone cannot predict tumor response to radiotherapy.</p> <p>In the current work, we measure in vitro radiosensitivity and in vivo response of their xenograft tumors in a series of human tumor lines that represent the range of radiosensitivity observed in human tumor cells. We also measure response of their xenograft tumors to different radiotherapy protocols. We reduce these data into a simple analytical structure that defines the relationship between tumor response and total dose based on two coefficients that are specific to tumor cell genotype, fraction size and total dose.</p> <p>Methods</p> <p>We assayed in vitro survival patterns in eight tumor cell lines that vary in cellular radiosensitivity and genotype. We also measured response of their xenograft tumors to four radiotherapy protocols: 8 × 2 Gy; 2 × 5Gy, 1 × 7.5 Gy and 1 × 15 Gy. We analyze these data to derive coefficients that describe both in vitro and in vivo responses.</p> <p>Results</p> <p>Response of xenografts comprised of human tumor cells to different radiotherapy protocols can be reduced to only two coefficients that represent 1) total cells killed as measured in vitro 2) additional response in vivo not predicted by cell killing. These coefficients segregate with specific genotypes including those most frequently observed in human tumors in the clinic. Coefficients that describe in vitro and in vivo mechanisms can predict tumor response to any radiation protocol based on tumor cell genotype, fraction-size and total dose.</p> <p>Conclusions</p> <p>We establish an analytical structure that predicts tumor response to radiotherapy based on coefficients that represent in vitro and in vivo responses. Both coefficients are dependent on tumor cell genotype and fraction-size. We identify a novel previously unreported mechanism that sensitizes tumors in vivo; this sensitization varies with tumor cell genotype and fraction size.</p