Molecular changes in hippocampal energy metabolism in mice selectively bred for extremes in stress reactivity: Relevance of mitochondrial dysfunction for affective disorders.

Affective disorders, such as major depression, are frequently associated with metabolic disturbances involving mitochondria. Although dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is known to alter energy metabolism, the precise mechanisms linking stress and metabolic disturbances are not sufficiently understood. We used a mouse model of affective disorders to investigate the impact of a genetic predisposition for extremes in stress reactivity on behavioural and metabolic phenotypes as well as energy metabolism. Adult males of three independent mouse lines selectively bred for high, intermediate or low HPA axis reactivity were tested for exploratory and locomotor activity as well as stress-coping behaviour. Additionally, basal and stress-induced plasma corticosterone levels, body weight, food intake and body composition were measured. At the molecular level, the hippocampal transcriptome was analysed using microarray, serial analysis of gene expression and qRT-PCR. Finally, mitochondrial DNA copy number, damages and mitochondrial respiration were assessed. We found clear effects of the differential stress reactivity on the behavioural, morphometric and metabolic measures. Remarkably, the hyperactive behavioural and neuroendocrine stress-coping style of high-reactivity mice was associated with significant changes in the expression of an extended list of genes involved in energy metabolism and several mitochondrial functions. Yet, only minor changes were found in mitochondrial DNA copy number, damages and respiration. Thus, our findings support a prominent role of glucocorticoids in shaping the major endophenotypes of the stress reactivity mouse model and contribute towards understanding the important role of HPA axis dysregulation and changes in energy metabolism in the pathophysiology of affective disorders.

mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations.

Mitochondria participate in metabolism and signaling. They adapt to the requirements of various cell types. Publicly available expression data permit to study expression dynamics of genes with mitochondrial function (mito-genes) in various cell types, conditions and organisms. Yet, we lack an easy way of extracting these data for mito-genes. Here, we introduce the visual data mining platform mitoXplorer, which integrates expression and mutation data of mito-genes with a manually curated mitochondrial interactome containing ∼1200 genes grouped in 38 mitochondrial processes. User-friendly analysis and visualization tools allow to mine mitochondrial expression dynamics and mutations across various datasets from four model species including human. To test the predictive power of mitoXplorer, we quantify mito-gene expression dynamics in trisomy 21 cells, as mitochondrial defects are frequent in trisomy 21. We uncover remarkable differences in the regulation of the mitochondrial transcriptome and proteome in one of the trisomy 21 cell lines, caused by dysregulation of the mitochondrial ribosome and resulting in severe defects in oxidative phosphorylation. With the newly developed Fiji plugin mitoMorph, we identify mild changes in mitochondrial morphology in trisomy 21. Taken together, mitoXplorer (http://mitoxplorer.ibdm.univ-mrs.fr) is a user-friendly, web-based and freely accessible software, aiding experimental scientists to quantify mitochondrial expression dynamics.

First Confirmed Report of Leaf Blight on Browntop Millet Caused by Bipolaris setariae in Southern Peninsular India.

Browntop millet (Brachiaria ramosa (L.) Stapf), which is native to the United States, was recently introduced into India as one of the small millet crop. In September 2018, leaf blight symptoms were observed on cv. Dundu Korale on the adaxial side of the leaves in a field at Bangalore, India (13.0784oN, 77.5793oE). Initial lesions were brown with small yellow halo that ranged from 1 to 5 mm and eventually enlarged exhibiting light brown centers. Afterwards, spots coalesced and leaves were blighted. About 75% of the plants were infected in the field of 0.5 ha. Samples of symptomatic and asymptomatic leaves were collected, and nine isolates were recovered from culture on potato dextrose agar (PDA). Single conidial isolation was performed. Colonies were grey to olive green with regular margins at 7 days when cultured on PDA at 27 ± 1oC and 16 h light and 8 h dark cycles. Conidiophores were single or in clusters from 4.92 to 6.04 µm in width. Conidia were fusoid, cylindrical to slightly curved ranging from 38.50 to 130 µm in length and from 8.30 to 17 µm in width, with 4 to 10 distosepta (n =100). Hilum was flat to inconspicuous or slightly protruded. Based on the morphology, the pathogen was identified as a Bipolaris species according to the genus standard descriptions of Helminthosporium (Alcorn 1988). Misra and Prakash (1972) reported that Helminthosporium setariae causing leaf spot on browntop millet in India, but they did not provide any morphological or molecular evidence of identification. For molecular identification, the genomic DNA of isolate BTMH3 was extracted and the internal transcribed spacer region (ITS) and glyceraldehyde-3-phosphate dehydrogenase gene (GPD) were amplified using the pairs of primers ITS1/ITS4 (White et al. 1990) and GPD1/GPD2 (Berbee et al. 1999), respectively. BLAST analysis of ITS (MT750301; 562 matching base pairs) and GPD (MT896702; 562 matching base pairs) sequences showed 99.82% of identity with sequences of Bipolaris setariae (Sawada) Shoemaker type strain CBS 141.31 (ITS: EF452444 and GPD: EF513206). Pathogenicity was proved by spraying 10 healthy 20-day-old browntop millet plants with conidial suspension (106 conidia/ml). Control plants were sprayed with distilled water. Plants were covered with transparent polythene bags in a greenhouse at 28 ± 2oC and high relative humidity of 90%. Symptoms were observed at five days post inoculation. The pathogen was re-isolated from infected areas using the same protocol as before, whereas the control plants were symptomless. The re-isolated pathogen was confirmed as B. setariae based on morphological characters and PCR assay. To the best of our knowledge, this is the first report of leaf blight on browntop millet caused by B. setariae in the southern peninsular region of India. Disease specimen was deposited in Herbarium Cryptogamae Indiae Orientalis (HCIO), New Delhi, India with accession number 52209. Grain yield losses caused by leaf blight on browntop millet remain to be determined, however our findings indicate that cultivar cv. Dundu Korale is susceptible to B. setariae.

Phenotypic and Genotypic screening of fifty-two rice (Oryza sativa L.) genotypes for desirable cultivars against blast disease.

Magnaporthe oryzae, the rice blast fungus, is one of the most dangerous rice pathogens, causing considerable crop losses around the world. In order to explore the rice blast-resistant sources, initially performed a large-scale screening of 277 rice accessions. In parallel with field evaluations, fifty-two rice accessions were genotyped for 25 major blast resistance genes utilizing functional/gene-based markers based on their reactivity against rice blast disease. According to the phenotypic examination, 29 (58%) and 22 (42%) entries were found to be highly resistant, 18 (36%) and 29 (57%) showed moderate resistance, and 05 (6%) and 01 (1%), respectively, were highly susceptible to leaf and neck blast. The genetic frequency of 25 major blast resistance genes ranged from 32 to 60%, with two genotypes having a maximum of 16 R-genes each. The 52 rice accessions were divided into two groups based on cluster and population structure analysis. The highly resistant and moderately resistant accessions are divided into different groups using the principal coordinate analysis. According to the analysis of molecular variance, the maximum diversity was found within the population, while the minimum diversity was found between the populations. Two markers (RM5647 and K39512), which correspond to the blast-resistant genes Pi36 and Pik, respectively, showed a significant association to the neck blast disease, whereas three markers (Pi2-i, Pita3, and k2167), which correspond to the blast-resistant genes Pi2, Pita/Pita2, and Pikm, respectively, showed a significant association to the leaf blast disease. The associated R-genes might be utilized in rice breeding programmes through marker-assisted breeding, and the identified resistant rice accessions could be used as prospective donors for the production of new resistant varieties in India and around the world.

Tools for visualization and analysis of molecular networks, pathways, and -omics data.

Biological pathways have become the standard way to represent the coordinated reactions and actions of a series of molecules in a cell. A series of interconnected pathways is referred to as a biological network, which denotes a more holistic view on the entanglement of cellular reactions. Biological pathways and networks are not only an appropriate approach to visualize molecular reactions. They have also become one leading method in -omics data analysis and visualization. Here, we review a set of pathway and network visualization and analysis methods and take a look at potential future developments in the field.

Genome expansion and gene loss in powdery mildew fungi reveal tradeoffs in extreme parasitism.

Powdery mildews are phytopathogens whose growth and reproduction are entirely dependent on living plant cells. The molecular basis of this life-style, obligate biotrophy, remains unknown. We present the genome analysis of barley powdery mildew, Blumeria graminis f.sp. hordei (Blumeria), as well as a comparison with the analysis of two powdery mildews pathogenic on dicotyledonous plants. These genomes display massive retrotransposon proliferation, genome-size expansion, and gene losses. The missing genes encode enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, probably reflecting their redundancy in an exclusively biotrophic life-style. Among the 248 candidate effectors of pathogenesis identified in the Blumeria genome, very few (less than 10) define a core set conserved in all three mildews, suggesting that most effectors represent species-specific adaptations.