Molecular biodiversity of cassava begomoviruses in Tanzania: evolution of cassava geminiviruses in Africa and evidence for East Africa being a center of diversity of cassava geminiviruses

Cassava is infected by numerous geminiviruses in Africa and India that cause devastating losses to poor farmers. We here describe the molecular diversity of seven representative cassava mosaic geminiviruses (CMGs) infecting cassava from multiple locations in Tanzania. We report for the first time the presence of two isolates in East Africa: (EACMCV-[TZ1] and EACMCV-[TZ7]) of the species East African cassava mosaic Cameroon virus, originally described in West Africa. The complete nucleotide sequence of EACMCV-[TZ1] DNA-A and DNA-B components shared a high overall sequence identity to EACMCV-[CM] components (92% and 84%). The EACMCV-[TZ1] and -[TZ7] genomic components have recombinations in the same genome regions reported in EACMCV-[CM], but they also have additional recombinations in both components. Evidence from sequence analysis suggests that the two strains have the same ancient origin and are not recent introductions. EACMCV-[TZ1] occurred widely in the southern part of the country. Four other CMG isolates were identified: two were close to the EACMV-Kenya strain (named EACMV-[KE/TZT] and EACMV-[KE/TZM] with 96% sequence identity); one isolate, TZ10, had 98% homology to EACMV-UG2Svr and was named EACMV-UG2 [TZ10]; and finally one isolate was 95% identical to EACMV-[TZ] and named EACMV-[TZ/YV]. One isolate of African cassava mosaic virus with 97% sequence identity with other isolates of ACMV was named ACMV-[TZ]. It represents the first ACMV isolate from Tanzania to be sequenced. The molecular variability of CMGs was also evaluated using partial B component nucleotide sequences of 13 EACMV isolates from Tanzania. Using the sequences of all CMGs currently available, we have shown the presence of a number of putative recombination fragments that are more prominent in all components of EACMV than in ACMV. This new knowledge about the molecular CMG diversity in East Africa, and in Tanzania in particular, has led us to hypothesize about the probable importance of this part of Africa as a source of diversity and evolutionary change both during the early stages of the relationship between CMGs and cassava and in more recent times. The existence of multiple CMG isolates with high DNA genome diversity in Tanzania and the molecular forces behind this diversity pose a threat to cassava production throughout the African continent.     

Olfactory receptor genes cooperate with protocadherin genes in human extreme obesity

Worldwide, the incidence of obesity has increased dramatically over the past decades. More knowledge about the complex etiology of obesity is needed in order to find additional approaches for treatment and prevention. Investigating the exome sequencing data of 30 extremely obese subjects (BMI 45–65 kg/m²) shows that predicted damaging missense variants in olfactory receptor genes on chromosome 1q and rare predicted damaging variants in the protocadherin (PCDH) beta-cluster genes on chromosome 5q31, reported in our previous work, co-localize in subjects with extreme obesity. This implies a synergistic effect between genetic variation in these gene clusters in the predisposition to extreme obesity. Evidence for a general involvement of the olfactory transduction pathway on itself could not be found. Bioinformatic analysis indicates a specific involvement of the PCDH beta-cluster genes in controlling tissue development. Further mechanistic insight needs to await the identification of the ligands of the 1q olfactory receptors. Eventually, this may provide the possibility to manipulate food flavor in a way to reduce the risk of overeating and of extreme obesity in genetically predisposed subjects.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-015-0465-3) contains supplementary material, which is available to authorized users.     

Adaptation of acidogenic sludge to increasing glycerol concentrations for biohydrogen production

Hydrogen is a promising alternative as an energetic carrier and its production by dark fermentation from wastewater has been recently proposed, with special attention to crude glycerol as potential substrate. In this study, two different feeding strategies were evaluated for replacing the glucose substrate by glycerol substrate: a one-step strategy (glucose was replaced abruptly by glycerol) and a step-by-step strategy (progressive decrease of glucose concentration and increase of glycerol concentration from 0 to 5 g L^?1), in a continuous stirred tank reactor (12 h of hydraulic retention time (HRT), pH 5.5, 35 °C). While the one-step strategy led to biomass washout and unsuccessful H₂ production, the step-by-step strategy was efficient for biomass adaptation, reaching acceptable hydrogen yields (0.4?±?0.1 mol_H2?mol^?1 _{glycerol consumed}) around 33 % of the theoretical yield independently of the glycerol concentration. Microbial community structure was investigated by single-strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) fingerprinting techniques, targeting either the total community (16S ribosomal RNA (rRNA) gene) or the functional Clostridium population involved in H₂ production (hydA gene), as well as by 454 pyrosequencing of the total community. Multivariate analysis of fingerprinting and pyrosequencing results revealed the influence of the feeding strategy on the bacterial community structure and suggested the progressive structural adaptation of the community to increasing glycerol concentrations, through the emergence and selection of specific species, highly correlated to environmental parameters. Particularly, this work highlighted an interesting shift of dominant community members (putatively responsible of hydrogen production in the continuous stirred tank reactor (CSTR)) according to the gradient of glycerol proportion in the feed, from the family Veillonellaceae to the genera Prevotella and Clostridium sp., putatively responsible of hydrogen production in the CSTR.     

Lack of Evidence for the Role of Human Adenovirus‐36 in Obesity in a European Cohort

Adenovirus infection has been shown to increase adiposity in chickens, mice, and nonhuman primates. Adenovirus type 36 (Ad‐36) DNA was detected in adipose tissues in these animal trials. In the United States, Ad‐36 significantly correlates with obesity as illustrated by an Ad‐36 seroprevalence of 30% in obese individuals and 11% in nonobese individuals. We investigated the possibility of a similar correlation of Ad‐36 in Dutch and Belgian persons. In total, 509 serum samples were analyzed for Ad‐36 antibodies using a serum neutralization assay. In addition, PCR was used to detect adenoviral DNA in visceral adipose tissue of 31 severely obese surgical patients. Our results indicated an overall Ad‐36 seroprevalence of 5.5% increasing with age. BMI of Ad‐36 seropositive humans was not significantly different from seronegative humans. No adenoviral DNA could be found using PCR on visceral adipose tissue. In conclusion, this first Ad‐36 study in the Netherlands and in Belgium indicates that Ad‐36 does not play a role as a direct cause of BMI increase and obesity in humans in Western Europe.     

Delayed blockade of the kinin B1 receptor reduces renal inflammation and fibrosis in obstructive nephropathy

Renal fibrosis is the common histological feature of advanced glomerular and tubulointerstitial disease leading to end-stage renal disease (ESRD). However, specific antifibrotic therapies to slow down the evolution to ESRD are still absent. Because persistent inflammation is a key event in the development of fibrosis, we hypothesized that the proinflammatory kinin B1 receptor (B1R) could be such a new target. Here we show that, in the unilateral ureteral obstruction model of renal fibrosis, the B1R is overexpressed and that delayed treatment with an orally active nonpeptide B1R antagonist blocks macrophage infiltration, leading to a reversal of the level of renal fibrosis. In vivo bone marrow transplantation studies as well as in vitro studies on renal cells show that part of this antifibrotic mechanism of B1R blockade involves a direct effect on resident renal cells by inhibiting chemokine CCL2 and CCL7 expression. These findings suggest that blocking the B1R is a promising antifibrotic therapy.     

Whole genome sequencing of a natural recombinant Toxoplasma gondii strain reveals chromosome sorting and local allelic variants

Background  

Toxoplasma gondii is a zoonotic parasite of global importance. In common with many protozoan parasites it has the capacity for sexual recombination, but current evidence suggests this is rarely employed. The global population structure is dominated by a small number of clonal genotypes, which exhibit biallelic variation and limited intralineage divergence. Little is known of the genotypes present in Africa despite the importance of AIDS-associated toxoplasmosis.     

High frequency of rare variants with a moderate-to-high predicted biological effect in protocadherin genes of extremely obese

Relatively rare variants with a moderate-to-high biological effect may contribute to the genetic predisposition of common disorders. To investigate this for obesity, we performed exome sequencing for 30 young (mean age: 29.7 years) extremely obese Caucasian subjects (mean body mass index: 51.1 kg/m²; m/f = 11/29). Rare variants with a moderate-to-high predicted biological effect were assembled and subjected to functional clustering analysis. It showed that the 55 clustered protocadherin genes on chromosome 5q31 have a significantly (P = 0.002) higher frequency of rare variants than a set of 325 reference genes. Since the protocadherin genes are expressed in the hypothalamus, we tested another 167 genes related to the function of the hypothalamus, but in those genes, the frequency of rare variants was not different from that of the reference genes. To verify the relation of variation in the protocadherin genes with extreme obesity, we analyzed data from more than 4,000 European Americans present on the Exome Variant Server, representing a sample of the general population. The significant enrichment of rare variants in the protocadherin genes was only observed with the group of extremely obese individuals but not in the “general population”, indicating an association between rare variants in the protocadherin cluster genes and extreme obesity.