Identification of New Genes Involved in Human Adipogenesis and Fat Storage

Since the worldwide increase in obesity represents a growing challenge for health care systems, new approaches are needed to effectively treat obesity and its associated diseases. One prerequisite for advances in this field is the identification of genes involved in adipogenesis and/or lipid storage. To provide a systematic analysis of genes that regulate adipose tissue biology and to establish a target-oriented compound screening, we performed a high throughput siRNA screen with primary (pre)adipocytes, using a druggable siRNA library targeting 7,784 human genes. The primary screen showed that 459 genes affected adipogenesis and/or lipid accumulation after knock-down. Out of these hits, 333 could be validated in a secondary screen using independent siRNAs and 110 genes were further regulated on the gene expression level during adipogenesis. Assuming that these genes are involved in neutral lipid storage and/or adipocyte differentiation, we performed InCell-Western analysis for the most striking hits to distinguish between the two phenotypes. Beside well known regulators of adipogenesis and neutral lipid storage (i.e. PPARγ, RXR, Perilipin A) the screening revealed a large number of genes which have not been previously described in the context of fatty tissue biology such as axonemal dyneins. Five out of ten axonemal dyneins were identified in our screen and quantitative RT-PCR-analysis revealed that these genes are expressed in preadipocytes and/or maturing adipocytes. Finally, to show that the genes identified in our screen are per se druggable we performed a proof of principle experiment using an antagonist for HTR2B. The results showed a very similar phenotype compared to knock-down experiments proofing the “druggability”. Thus, we identified new adipogenesis-associated genes and those involved in neutral lipid storage. Moreover, by using a druggable siRNA library the screen data provides a very attractive starting point to identify anti-obesity compounds targeting the adipose tissue

Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes

Word Sense Discrimination: A Gangplank Algorithm

L\u2019obiettivo di questo articolo \ue8 descrivere un approccio di clustering non supervisionato e basato su grafi per individuare e discriminare i differenti sensi che un termine pu\uf2 assumere all\u2019interno di un testo. Partendo da un grafo di cooccorrenze, vi definiamo una distanza fra nodi e applichiamo un algoritmo basato sulle \u201cpasserelle\u201d, cio\ue8 archi che separano regioni dense (\u201cisole\u201d) all\u2019interno del grafo. Discutiamo i risultati ottenuti su un insieme di dati composto da tweet.In this paper we present an unsupervised, graph-based approach for Word Sense Discrimination. Given a set of text sentences, a word co-occurrence graph is derived and a distance based on Jaccard index is defined on it; subsequently, the new distance is used to cluster the neighbour nodes of ambiguous terms using the concept of \u201cgangplanks\u201d as edges that separate denser regions (\u201cislands\u201d) in the graph. The proposed approach has been evaluated on a real data set, showing promising performance in Word Sense Discrimination

NP06/ENUBET Annual Report for the SPSC (2021)

We present the progress of NP06/ENUBET for the SPSC annual report 202

NP06/ENUBET annual report 2022 for the SPSC

This documents contain an executive summary of the progress of the project NP06/ENUBET in the last year for the SPSC referees' committee