Inter-individual Variability for High Fat Diet Consumption in Inbred C57BL/6 Mice

Since inbred C57BL/6 mice are known to show inter-individual phenotypic variability for some traits, we tested the hypothesis that inbred C57BL/6 mice display a different tendency to consume a high fat (HF) diet. For this purpose, we used a compilation of HF intake data from an experimental protocol in which satiated mice were exposed to a HF pellet every morning for 2-h over 4 consecutive days. We found that mice displayed a large degree of variability in HF intake. Since day 1 HF intake significantly correlated with HF intake in successive days, we applied a hierarchical clustering algorithm on HF intake measurements in days 2, 3, and 4 in order to classify mice into “low” or “high” HF intake groups. “Low” HF intake group showed a day 1 HF intake similar to that seen in mice exposed to regular chow, while “high” HF intake group showed a higher day 1 HF intake as compared to “low” HF intake group. Both groups of mice increased HF consumption over the successive days, but “high” HF intake group always displayed a higher HF consumption than the “low” HF intake group. As compared to “low” HF intake group, “high” HF intake group showed a higher number of dopamine neurons positive for c-Fos in the VTA after the last event of HF intake. Thus, inbred C57BL/6 mice show inter-individual variability for HF intake and such feature may be linked to a different response to the rewarding properties of the HF diet

Agroforestry in the European common agricultural policy

Agroforestry is a sustainable land management system that should be more strongly promoted in Europe to ensure adequate ecosystem service provision in the old continent (Decision 529/2013) through the common agricultural policy (CAP). The promotion of the woody component in Europe can be appreciated in different sections of the CAP linked to Pillar I (direct payments and Greening) and Pillar II (rural development programs). However, agroforestry is not recognised as such in the CAP, with the exception of the Measure 8.2 of Pillar II. The lack of recognition of agroforestry practices within the different sections of the CAP reduces the impact of CAP activities by overlooking the optimum combinations that would maximise the productivity of land where agroforestry could be promoted, considering both the spatial and temporal scales

Risk Factors for Death in Children with Visceral Leishmaniasis

Visceral leishmaniasis (VL) is a deadly disease caused by a protozoan called Leishmania. It is transmitted to humans from infected animals by a sandfly bite. Most people actually manage to control the infection and do not get sick, while others develop a range of symptoms. VL impairs the production of blood components and causes the immune system to malfunction, thus anemia, bleeding, and bacterial infections often complicate the disease and can lead to death. To identify risk factors for death from VL, the authors studied 546 children in a referral center in Recife, Brazil. They looked at clinical history, physical examination and full blood counts on the assumption these could be easily assessed in peripheral health facilities. They found that the presence of fast breathing, jaundice, mucosal (e.g. gum) bleeding and bacterial infections would each increase the risk of death in three to four-fold. The presence of very low counts of neutrophils and platelets would increase the risk of death in three and 12-fold respectively. This knowledge can help clinicians to anticipate the use of antibiotics or transfusion of blood products in high risk patients, who would potentially benefit from transfer to centers with advanced life support facilities

Structural diversity of biologically interesting datasets: a scaffold analysis approach

ABSTRACT:The recent public availability of the human metabolome and natural product datasets has revitalized "metabolite-likeness" and "natural product-likeness" as a drug design concept to design lead libraries targeting specific pathways. Many reports have analyzed the physicochemical property space of biologically important datasets, with only a few comprehensively characterizing the scaffold diversity in public datasets of biological interest. With large collections of high quality public data currently available, we carried out a comparative analysis of current day leads with other biologically relevant datasets.In this study, we note a two-fold enrichment of metabolite scaffolds in drug dataset (42%) as compared to currently used lead libraries (23%). We also note that only a small percentage (5%) of natural product scaffolds space is shared by the lead dataset. We have identified specific scaffolds that are present in metabolites and natural products, with close counterparts in the drugs, but are missing in the lead dataset. To determine the distribution of compounds in physicochemical property space we analyzed the molecular polar surface area, the molecular solubility, the number of rings and the number of rotatable bonds in addition to four well-known Lipinski properties. Here, we note that, with only few exceptions, most of the drugs follow Lipinski's rule. The average values of the molecular polar surface area and the molecular solubility in metabolites is the highest while the number of rings is the lowest. In addition, we note that natural products contain the maximum number of rings and the rotatable bonds than any other dataset under consideration.Currently used lead libraries make little use of the metabolites and natural products scaffold space. We believe that metabolites and natural products are recognized by at least one protein in the biosphere therefore, sampling the fragment and scaffold space of these compounds, along with the knowledge of distribution in physicochemical property space, can result in better lead libraries. Hence, we recommend the greater use of metabolites and natural products while designing lead libraries. Nevertheless, metabolites have a limited distribution in chemical space that limits the usage of metabolites in library design.14 page(s

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Prevalence of normal weight obesity and its associated cardio-metabolic risk factors - Results from the baseline data of the Kerala Diabetes Prevention Program (KDPP)

BACKGROUND: Cardiometabolic disorders are frequently observed among those who have obesity as measured by body mass index (BMI). However, there is limited data available on the cardiometabolic profile of those who are non-obese by BMI but with a high body fat percentage (BFP), a phenotype frequently observed in the Indian population. We examined the prevalence of individuals with normal weight obesity (NWO) and the cardiometabolic profile of NWO individuals at high risk for type 2 diabetes(T2D) in a south Asian population. MATERIAL AND METHODS: In the Kerala Diabetes Prevention Program, individuals aged between 30 to 60 years were screened using the Indian Diabetes Risk Score(IDRS) in 60 rural communities in the Indian state of Kerala. We used data from the baseline survey of this trial for this analysis which included 1147 eligible high diabetes risk individuals(IDRS >60). NWO was defined as BMI within the normal range and a high BFP (as per Asia-pacific ethnicity based cut-off); Non-obese (NO) as normal BMI and BFP and overtly obese (OB) as BMI ≥25 kg/m2 irrespective of the BFP. Data on demographic, clinical and biochemical characteristics were collected using standardized questionnaires and protocols. Body fat percentage was assessed using TANITA body composition analyser (model SC330), based on bioelectrical impedance. RESULTS: The mean age of participants was 47.3 ± 7.5 years and 46% were women. The proportion with NWO was 32% (n = 364; 95% CI: 29.1 to 34.5%), NO was 17% (n = 200) and OB was 51% (n = 583). Among those with NWO, 19.7% had T2D, compared to 18.7% of those who were OB (p value = 0.45) and 8% with NO (p value = 0.003). Among those with NWO, mean systolic and diastolic blood pressure were 129 ± 20; 78 ± 12 mmHg, compared to 127 ± 17; 78±11 mmHg among those with OB (p value = 0.12;0.94) and 120 ± 16; 71±10 mmHg among with NO (p value<0.001; 0.001), respectively. A similar pattern of association was observed for LDL cholesterol and triglycerides. After adjusting for other risk factors, the odds of having diabetes (OR:2.72[95% CI:1.46-5.08]) and dyslipidemia (2.37[1.55-3.64]) was significantly more in individuals with NWO as compared to non-obese individuals. CONCLUSIONS: Almost one-third of this South Asian population, at high risk for T2D, had normal weight obesity. The significantly higher cardiometabolic risk associated with increased adiposity even in lower BMI individuals has important implications for recognition in clinical practice