An in vivo RNAi screen identifies evolutionary conserved Drosophila fat storage regulators

One main goal for all organisms, in order to survive under environmental changes, is to maintain energy homeostasis. Energy homeostasis depends mainly on three processes, the energy uptake, energy storage and energy consumption, respectively. An impairment of energy homeostasis or the lipid metabolism can cause body fat accumulation, which could finally lead to obesity. Since the outspread of obesity widely increased over the last years, the need to unveil new regulators of body fat storage rises. In order to identify novel body fat storage regulators, we used the fruit fly Drosophila melanogaster to do a conditional in vivo RNAi knockdown (KD) screen in the fat storage tissue of adult flies. Hereby, lethality due to developmental impairment can be excluded, which allows to screen for novel regulators in adult flies. By this approach, 6796 genes were down-regulated directly in the fat storage tissue of the fly and the body fat levels were determined. By further validations, I was able to identify 77 gene KDs, which resulted in obese or lean flies. Notably, most of the identified genes and processes are conserved up to humans. A Gene Ontology analysis of these genes revealed several processes, including store-operated calcium entry (SOCE), which was so far unrelated to body fat storage control. Interestingly, modulations of SOCE genes, which resulted in decreased intracellular Ca2+ levels (iCa2+) causes obesity in flies. Controversial, modulations that leads to increased iCa2+ resulted in lean flies. In order to reveal the role of SOCE for body fat storage control, I characterized the effects of the central component known as the Stromal interaction molecule (Stim). A Stim KD in the fat storage tissue of mature adult flies resulted in decreased iCa2+ and obese flies, which also showed an increase in fat cell mass, likely driven through hypertrophy and hyperplasia. Further characterization of these flies revealed no effects on the activity or the metabolic rate, indicating that the body fat accumulation is independent from the energy expenditure. On the other hand, Stim KD flies show hyperphagia, which is driven by up-regulation of the orexigenic short neuropeptide F (sNPF) in the central nervous system of the fly. This regulation and the enriched energy intake drives an obesogenic program in the fat storage tissue of Stim KD flies, by up-regulation of the lipogenic mdy/DmDGAT1 and down-regulation of the lipolytic bmm/DmATGL genes. These findings suggest a control of the energy storage, which is driven by SOCE via an inter-organ communication signaling pathway

MotifAdjuster: a tool for computational reassessment of transcription factor binding site annotations

MotifAdjuster helps to detect errors in binding site annotations

Salmonella enterica Modulates Its Infectivity in Response to Intestinal Stimuli

ABSTRACT En route to its intestinal target cells Salmonella enterica passes different host niches and encounters various environmental cues. These are expected to promote Salmonella in the decision of changing its extracellular life style to intracellular. We find that prior incubation of bacteria in the presence of signals which are characteristic for the small intestine affects invasion in a model system: Salmonella grown at high osmotic pressure in the presence of bile or in amino acid rich medium, infect host cells most efficiently. Hence, Salmonella enterica modulates its infectivity in response to these stimuli which consequently determines the success of infection. Our results close the current gap between signal and actual behavior and may serve as a basis for further investigations for example if Salmonella has an adaptive prediction of environmental changes

The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Trost E, Ott L, Schneider J, et al. The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence. BMC Genomics. 2010;11(1): 728

‘Speak, votives, …’. Dedicatory practice in sanctuaries of Hera

Votive offerings are the durable remains of the largely lost dialogue between worshipper and deity. Due to the scarceness of cult-specific literary evidence, they are the main source for gaining information about the reasons why they were dedicated, and they may provide insight into individual, polis and panhellenic cult aspects. The aim of this paper is to assess how much information on the different aspects can be gained from the analysis of the votive offerings. Does the presence of the same types of dedications across different sanctuaries of the same deity suggest a shared panhellenic cult aspect and, in turn, do votive types that just occur in one sanctuary suggest an individual or polis aspect? As to the evidence from selected Hera sanctuaries across the Greek world, it will be argued that panhellenic and individual aspects of the cults are difficult to trace. The analysis of the votive offerings mainly provides insight into the polis aspect, i.e. the nature of the particular cult that was shaped by the specific religious beliefs and needs of the polis to which it belonged.Les offrandes sont les vestiges durables d’un dialogue en grande partie perdu entre le dédicant et la divinité. En raison de la rareté des attestations littéraires liées aux cultes, les offrandes sont la principale source d’information sur les motifs des dédicaces et elles peuvent nous éclairer sur les aspects du culte au niveau individuel, civique et panhellénique. Le but de cet article est d’évaluer la quantité d’informations que l’on peut récolter sur ces différents aspects grâce à l’analyse des offrandes. La présence d’un même type de dédicace dans différents sanctuaires consacrés à la même divinité implique-t-elle un aspect cultuel panhellénique ? Inversement, les objets votifs rencontrés dans un seul sanctuaire suggèrent-ils un aspect individuel ou civique ? En ce qui concerne les attestations provenant des sanctuaires d’Héra dans le monde grec, on arguera qu’il est difficile d’y repérer des aspects panhelléniques ou individuels du culte. L’analyse des offrandes renseigne surtout sur l’aspect civique, c’est-à-dire la nature d’un culte précis constitué par les croyances religieuses et les besoins propres à la cité à laquelle appartenait le sanctuaire

The significance of votive offerings in selected Hera sanctuaries in the Peloponnese, Ionia and western Greece

SIGLEAvailable from British Library Document Supply Centre- DSC:DN055726 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

On the performance of pre-microRNA detection algorithms

MicroRNAs are crucial for post-transcriptional gene regulation, and their dysregulation has been associated with diseases like cancer and, therefore, their analysis has become popular. The experimental discovery of miRNAs is cumbersome and, thus, many computational tools have been proposed. Here we assess 13 ab initio pre-miRNA detection approaches using all relevant, published, and novel data sets while judging algorithm performance based on ten intrinsic performance measures. We present an extensible framework, izMiR, which allows for the unbiased comparison of existing algorithms, adding new ones, and combining multiple approaches into ensemble methods. In an exhaustive attempt, we condense the results of millions of computations and show that no method is clearly superior; however, we provide a guideline for biomedical researchers to select a tool. Finally, we demonstrate that combining all of the methods into one ensemble approach, for the first time, allows reliable purely computational pre-miRNA detection in large eukaryotic genomes.Scientific Research Council of Turkey (TUBITAK 113E326