The inositol pyrophosphate synthesis pathway in Trypanosoma brucei is linked to polyphosphate synthesis in acidocalcisomes

Inositol pyrophosphates are novel signaling molecules possessing high-energy pyrophosphate bonds and involved in a number of biological functions. Here, we report the correct identification and characterization of the kinases involved in the inositol pyrophosphate biosynthetic pathway in Trypanosoma brucei: inositol polyphosphate multikinase (TbIPMK), inositol pentakisphosphate 2-kinase (TbIP5K) and inositol hexakisphosphate kinase (TbIP6K). TbIP5K and TbIP6K were not identifiable by sequence alone and their activities were validated by enzymatic assays with the recombinant proteins or by their complementation of yeast mutants. We also analyzed T. brucei extracts for the presence of inositol phosphates using polyacrylamide gel electrophoresis and high-performance liquid chromatography. Interestingly, we could detect inositol phosphate (IP), inositol 4,5-bisphosphate (IP2), inositol 1,4,5-trisphosphate (IP3), and inositol hexakisphosphate (IP6) in T. brucei different stages. Bloodstream forms unable to produce inositol pyrophosphates, due to downregulation of TbIPMK expression by conditional knockout, have reduced levels of polyphosphate and altered acidocalcisomes. Our study links the inositol pyrophosphate pathway to the synthesis of polyphosphate in acidocalcisomes, and may lead to better understanding of these organisms and provide new targets for drug discovery

Influence of Ketotifen, Cromolyn Sodium, and Compound 48/80 on the survival rates after intestinal ischemia reperfusion injury in rats

<p>Abstract</p> <p>Background</p> <p>Mast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats.</p> <p>Methods</p> <p>120 healthy Sprague-Dawley rats were randomly divided into 5 groups, Sham-operated group (group S), model group (group M), group K, group C and group CP. Intestinal damage was triggered by clamping the superior mesenteric artery for 75 minutes, group K, C, and CP were treated with kotifen 1 mg·kg^-1, CS 50 mg·kg^-1, and CP 0.75 mg·kg^-1i.v. at 5 min before reperfusion and once daily for three days following reperfusion respectively. Survival rate in each group was recorded during the three days after reperfusion. All the surviving rats were killed for determining the concentration of serum glutamic-oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), the ratio of AST compare ALT(S/L), total protein(TP), albumin(ALB), globulin(GLB), the ratio of ALB compare GLB(A/G), phosphocreatine kinase(CK), lactate dehydrogenase(LDH), urea nitrogen(BUN) and creatinine(CRE) at the 3^rdday after reperfusion. And ultrastructure of IMMC, Chiu's score, lung histology, IMMC counts, the levels of TNF-α, IL-1β, IL-6 and IL-10 of the small intestine were detected at the same time.</p> <p>Results</p> <p>Intestinal ischemia-reperfusion injury reduced the survival rate. The concentrations of TP, ALB and level of IL-10 in intestine in group M decreased significantly while the concentrations of S/L, LDH and the levels of IL-6 and TNF-α in intestine increased significantly compared with group S (<it>P </it>< 0.05). Treatment with Ketotifen and CS increased the survival rate compared with group M (<it>P </it>< 0.05), attenuated the down-regulation or up-regulation of the above index (<it>P </it>< 0.05). Treatment with CP decreased the survival rate on the 3^rdday after reperfusion compared with group M(<it>P </it>< 0.05). Group K and C had better morphology in IMMC in the small intestine and in the lungs than in group M and CP, although the Chiu's score and IMMC counts remained the same in the five groups(<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>Mast cell inhibition after ischemia prior to reperfusion and following reperfusion may decrease the multi-organ injury induced by intestine ischemia reperfusion, and increase the survival rates.</p

Potential link between caffeine consumption and pediatric depression: A case-control study

<p>Abstract</p> <p>Background</p> <p>Early-onset depressive disorders can have severe consequences both from developmental and functional aspects. The etiology of depressive disorders is complex and multi-factorial, with an intricate interaction among environmental factors and genetic predisposition. While data from studies on adults suggest that caffeine is fairly safe, effects of caffeine in children, who are in period of rapid brain development, are currently unknown. Furthermore, systematic research addressing the relationship between depressive symptoms in children and caffeine consumption is lacking.</p> <p>The present study examined the effects of caffeine consumption on depressed mood in children with depression and non-depressed participants.</p> <p>Methods</p> <p>Children and adolescents (n = 51) already enrolled in an ongoing longitudinal study, aged 9-12 years, were assessed for depressive symptoms with the Children Depressive Inventory (CDI). Psychopathological symptoms were assessed with the Child Behavioral Checklist (CBCL) and eating habits were assessed with the Nutrition-Behavior Inventory (NBI) <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. The children were compared to control children without psychopathology attending public schools in a Southern Brazilian city.</p> <p>Results</p> <p>Participants with CDI scores ≥ 15 (mean = 19; S.D. = 4) also had high NBI scores (mean = 52; S.D. = 19, p < 0.001) suggestive of a relationship between depressive symptoms and environmental factors, in this case nutrition/behavior. Additional linear regression adjusted statistical analysis, considering the factors of consumption of sweets and caffeine individually, showed that caffeine, but not sweets, was associated with depressive symptoms.</p> <p>Conclusions</p> <p>These findings indicate that depressed children consume more caffeinated drinks than non-depressed children. Nonetheless while a strong association between depressive symptoms and caffeine consumption among children was found, further research should investigate whether or not this association is due to a cause and effect relationship.</p

Abrasion resistance and compressive strength of unprocessed rice husk ash concrete

This paper investigates the effects of adding natural rice husk ash collected from uncontrolled burning and without previous grinding (NRHA) as cement replacement in concrete. To obtain an adequate particle size, NRHA was mixed with coarse aggregate for a convenient period of time before adding the other components. Compressive strength, water absorption, porosity, and abrasion resistance expressed as weight loss were examined. Test results show that decreasing the particle size through mixing with coarse aggregate improved the compressive strength, reduced the permeability, and increased the abrasion resistance of concrete. By mixing NRHA with aggregate for 8 min, abrasion resistance improved by 10.35 and 23.62% over the control concrete at 28 and 91 days, respectively. Incorporating NRHA in concrete by grinding with coarse aggregate during the mixing process could be suitable for making normal-strength concrete and for applications where abrasion resistance is an important parameter. In addition, using NRHA as a partial replacement cement contributes to the reduction of CO2 emissions due to the production of cement

Development of microsatellite markers for identifying Brazilian Coffea arabica varieties

Microsatellite markers, also known as SSRs (Simple Sequence Repeats), have proved to be excellent tools for identifying variety and determining genetic relationships. A set of 127 SSR markers was used to analyze genetic similarity in twenty five Coffea arabica varieties. These were composed of nineteen commercially important Brazilians and six interspecific hybrids of Coffea arabica, Coffea canephora and Coffealiberica. The set used comprised 52 newly developed SSR markers derived from microsatellite enriched libraries, 56 designed on the basis of coffee SSR sequences available from public databases, 6 already published, and 13 universal chloroplast microsatellite markers. Only 22 were polymorphic, these detecting 2-7 alleles per marker, an average of 2.5. Based on the banding patterns generated by polymorphic SSR loci, the set of twenty-five coffee varieties were clustered into two main groups, one composed of only Brazilian varieties, and the other of interspecific hybrids, with a few Brazilians. Color mutants could not be separated. Clustering was in accordance with material genealogy thereby revealing high similarity

Anthropomorphic Measurements That Include Central Fat Distribution Are More Closely Related with Key Risk Factors than BMI in CKD Stage 3

Background: Body Mass Index (BMI) as a marker of obesity is an established risk factor for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, BMI can overestimate obesity. Anthropomorphic measurements that include central fat deposition are emerging as a more important risk factor. We studied BMI, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and conicity index (CI) in a cohort of patients with CKD stage 3 and compared the associations with other known risk factors for CKD progression and CVD. Methods: 1740 patients with CKD stage 3 were recruited from primary care for the Renal Risk in Derby study. Each participant underwent clinical assessment, including anthropomorphic measurements and pulse wave velocity (PWV), as well as urine and serum biochemistry tests. Results: The mean age of the cohort was 72.969 years with 60 % females. The mean eGFR was 52.5610.4 ml/min/1.73 m 2 and 16.9 % of the cohort had diabetes. With the cohort divided into normal and increased risk of morbidity and mortality using each anthropomorphic measurement, those measurements that included increased central fat distribution were significantly associated with more risk factors for CKD progression and CVD than increased BMI. Univariable analysis demonstrated central fat distribution was correlated with more risk factors than BMI. Subgroup analyses using recognised BMI cut-offs to define obesity and quartiles of WHR and CI demonstrated that increasing central fat distribution wa

Patterns and Perceptions of Climate Change in a Biodiversity Conservation Hotspot

Quantifying local people's perceptions to climate change, and their assessments of which changes matter, is fundamental to addressing the dual challenge of land conservation and poverty alleviation in densely populated tropical regions To develop appropriate policies and responses, it will be important not only to anticipate the nature of expected changes, but also how they are perceived, interpreted and adapted to by local residents. The Albertine Rift region in East Africa is one of the world's most threatened biodiversity hotspots due to dense smallholder agriculture, high levels of land and resource pressures, and habitat loss and conversion. Results of three separate household surveys conducted in the vicinity of Kibale National Park during the late 2000s indicate that farmers are concerned with variable precipitation. Many survey respondents reported that conditions are drier and rainfall timing is becoming less predictable. Analysis of daily rainfall data for the climate normal period 1981 to 2010 indicates that total rainfall both within and across seasons has not changed significantly, although the timing and transitions of seasons has been highly variable. Results of rainfall data analysis also indicate significant changes in the intra-seasonal rainfall distribution, including longer dry periods within rainy seasons, which may contribute to the perceived decrease in rainfall and can compromise food security. Our results highlight the need for fine-scale climate information to assist agro-ecological communities in developing effective adaptive management

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer