Functional Evolution of Duplicated Odorant-Binding Protein Genes, Obp57d and Obp57e, in Drosophila

Odorant-binding proteins (OBPs) are extracellular proteins found in insect chemosensilla, where they participate in the sensing of odors, tastes, and pheromones. Although a large number of OBP genes have been identified in insect genomes, their molecular functions and biological roles have been clarified in limited cases. Two OBP genes, Obp57d and Obp57e, were involved in the evolution of host-plant preference in Drosophila sechellia. Comparative analyses of the Obp57d/e genomic sequences from 27 closely related species suggested that the two genes arose by tandem gene duplication and functionally diverged from each other. In this study, the functional evolution of Obp57d and Obp57e was examined by in vitro binding assays using recombinant proteins synthesized in a bacterial system. Compared to the ancestral Dpse\OBP57de, Dmel\OBP57d was more specialized to tridecanoic acid while Dmel\OBP57e was generalized regarding their binding affinity, suggesting that the two OBP genes underwent subfunctionalization and neofunctionalization. A behavioral analysis using knockout flies supported that the biological role is different between OBP57d and OBP57e in vivo. Site-directed mutagenesis of the evolutionarily conserved amino acids revealed that these residues play an important role in protein folding. These findings provide a clue to understanding how the repertoire of OBP genes is maintained in a genome under natural selection

Using an oblique incident laser beam to measure the optical properties of stomach mucosa/submucosa tissue

<p>Abstract</p> <p>Background</p> <p>The purpose of the study is to determine the optical properties and their differences for normal human stomach mucosa/submucosa tissue in the cardiac orifice <it>in vitro </it>at 635, 730, 808, 890 and 980 nm wavelengths of laser.</p> <p>Methods</p> <p>The measurements were performed using a CCD detector, and the optical properties were assessed from the measurements using the spatially resolved reflectance, and nonlinear fitting of diffusion equation.</p> <p>Results</p> <p>The results of measurement showed that the absorption coefficients, the reduced scattering coefficients, the optical penetration depths, the diffusion coefficients, the diffuse reflectance and the shifts of diffuse reflectance of tissue samples at five different wavelengths vary with a change of wavelength. The maximum absorption coefficient for tissue samples is 0.265 mm^-1at 980 nm, and the minimum absorption coefficient is 0.0332 mm^-1at 730 nm, and the maximum difference in the absorption coefficients is 698% between 730 and 980 nm, and the minimum difference is 1.61% between 635 and 808 nm. The maximum reduced scattering coefficient for tissue samples is 1.19 mm^-1at 635 nm, and the minimum reduced scattering coefficient is 0.521 mm^-1at 980 nm, and the maximum difference in the reduced scattering coefficients is 128% between 635 and 980 nm, and the minimum difference is 1.15% between 890 and 980 nm. The maximum optical penetration depth for tissue samples is 3.57 mm at 808 nm, and the minimum optical penetration depth is 1.43 mm at 980 nm. The maximum diffusion constant for tissue samples is 0.608 mm at 890 nm, and the minimum diffusion constant is 0.278 mm at 635 nm. The maximum diffuse reflectance is 3.57 mm^-1at 808 nm, and the minimum diffuse reflectance is 1.43 mm^-1at 980 nm. The maximum shift Δx of diffuse reflectance is 1.11 mm^-1at 890 nm, and the minimum shift Δx of diffuse reflectance is 0.507 mm^-1at 635 nm.</p> <p>Conclusion</p> <p>The absorption coefficients, the reduced scattering coefficients, the optical penetration depths, the diffusion coefficients, the diffuse reflectance and the shifts of diffuse reflectance of tissue samples at 635, 730, 808, 890 and 980 nm wavelengths vary with a change of wavelength. There were significant differences in the optical properties for tissue samples at five different wavelengths (<it>P </it>< 0.01).</p

SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer

<p>Abstract</p> <p>Background</p> <p>Association between rectal or colon cancer risk and serine hydroxymethyltransferase 1 (<it>SHMT1</it>) C1420T or methylenetetrahydrofolate reductase (<it>MTHFR</it>) C677T polymorphisms was assessed. The serum total homocysteine (HCY), marker of folate metabolism was also investigated.</p> <p>Methods</p> <p>The <it>SHMT1 </it>and <it>MTHFR </it>genotypes were determined by real-time PCR and PCR-RFLP, respectively in 476 patients with rectal, 479 patients with colon cancer and in 461 and 478, respective controls matched for age and sex. Homocysteine levels were determined by HPLC kit. The association between polymorphisms and cancer risk was evaluated by logistic regression analysis adjusted for age, sex and body mass index. The population stratification bias was also estimated.</p> <p>Results</p> <p>There was no association of genotypes or diplotypes with colon cancer. The rectal cancer risk was significantly lower for <it>SHMT1 </it>TT (OR = 0.57, 95% confidence interval (CI) 0.36-0.89) and higher for <it>MTHFR </it>CT genotypes (OR = 1.4, 95%CI 1.06-1.84). A gene-dosage effect was observed for <it>SHMT1 </it>with progressively decreasing risk with increasing number of T allele (p = 0.014). The stratified analysis according to age and sex revealed that the association is mainly present in the younger (< 60 years) or male subgroup. As expected from genotype analysis, the <it>SHMT1 </it>T allele/<it>MTHFR </it>CC diplotype was associated with reduced rectal cancer risk (OR 0.56, 95%CI 0.42-0.77 vs all other diplotypes together). The above results are unlikely to suffer from population stratification bias. In controls HCY was influenced by <it>SHMT1 </it>polymorphism, while in patients it was affected only by Dukes' stage. In patients with Dukes' stage C or D HCY can be considered as a tumor marker only in case of <it>SHMT1 </it>1420CC genotypes.</p> <p>Conclusions</p> <p>A protective effect of <it>SHMT1 </it>1420T allele or <it>SHMT1 </it>1420 T allele/<it>MTHFR </it>677 CC diplotype against rectal but not colon cancer risk was demonstrated. The presence of <it>SHMT1 </it>1420 T allele significantly increases the HCY levels in controls but not in patients. Homocysteine could be considered as a tumor marker in <it>SHMT1 </it>1420 wild-type (CC) CRC patients in Dukes' stage C and D. Further studies need to clarify why <it>SHMT1 </it>and <it>MTHFR </it>polymorphisms are associated only with rectal and not colon cancer risk.</p

A randomized, controlled trial of 3.0 mg of liraglutide in weight management

BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P&lt;0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P&lt;0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P&lt;0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)

Author Correction: The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The following authors were omitted from the original version of this Data Descriptor: Markus Reichstein and Nicolas Vuichard. Both contributed to the code development and N. Vuichard contributed to the processing of the ERA-Interim data downscaling. Furthermore, the contribution of the co-author Frank Tiedemann was re-evaluated relative to the colleague Corinna Rebmann, both working at the same sites, and based on this re-evaluation a substitution in the co-author list is implemented (with Rebmann replacing Tiedemann). Finally, two affiliations were listed incorrectly and are corrected here (entries 190 and 193). The author list and affiliations have been amended to address these omissions in both the HTML and PDF versions

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data.

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible

Thaw pond dynamics and carbon emissions in a Siberian lowland tundra landscape

status: publishe

Effect of artesunate-mefloquine fixed-dose combination in malaria transmission in amazon basin communities

Abstract\ud \ud Background\ud Studies in South-East Asia have suggested that early diagnosis and treatment with artesunate (AS) and mefloquine (MQ) combination therapy may reduce the transmission of Plasmodium falciparum malaria and the progression of MQ resistance.\ud \ud \ud Methods\ud The effectiveness of a fixed-dose combination of AS and MQ (ASMQ) in reducing malaria transmission was tested in isolated communities of the Juruá valley in the Amazon region.\ud Priority municipalities within the Brazilian Legal Amazon area were selected according to pre-specified criteria. Routine national malaria control programmatic procedures were followed. Existing health structures were reinforced and health care workers were trained to treat with ASMQ all confirmed falciparum malaria cases that match inclusion criteria. A local pharmacovigilance structure was implemented. Incidence of malaria and hospitalizations were recorded two years before, during, and after the fixed-dose ASMQ intervention. In total, between July 2006 and December 2008, 23,845 patients received ASMQ. Two statistical modelling approaches were applied to monthly time series of P. falciparum malaria incidence rates, P. falciparum/Plasmodium vivax infection ratio, and malaria hospital admissions rates. All the time series ranged from January 2004 to December 2008, whilst the intervention period span from July 2006 to December 2008.\ud \ud \ud Results\ud The ASMQ intervention had a highly significant impact on the mean level of each time series, adjusted for trend and season, of 0.34 (95%CI 0.20 – 0.58) for the P. falciparum malaria incidence rates, 0.67 (95%CI 0.50 – 0.89) for the P. falciparum/P. vivax infection ratio, and 0.53 (95%CI 0.41 – 0.69) for the hospital admission rates. There was also a significant change in the seasonal (or monthly) pattern of the time series before and after intervention, with the elimination of the malaria seasonal peak in the rainy months of the years following the introduction of ASMQ. No serious adverse events relating to the use of fixed-dose ASMQ were reported.\ud \ud \ud Conclusions\ud In the remote region of the Juruá valley, the early detection of malaria by health care workers and treatment with fixed-dose ASMQ was feasible and efficacious, and significantly reduced the incidence and morbidity of P. falciparum malaria.CNPq (process #309156/2007-6