Ablation of NG2 Proteoglycan Leads to Deficits in Brown Fat Function and to Adult Onset Obesity

Obesity is a major health problem worldwide. We are studying the causes and effects of obesity in C57Bl/6 mice following genetic ablation of NG2, a chondroitin sulfate proteoglycan widely expressed in progenitor cells and also in adipocytes. Although global NG2 ablation delays early postnatal adipogenesis in mouse skin, adult NG2 null mice are paradoxically heavier than wild-type mice, exhibiting larger white fat deposits. This adult onset obesity is not due to NG2-dependent effects on CNS function, since specific ablation of NG2 in oligodendrocyte progenitors yields the opposite phenotype; i.e. abnormally lean mice. Metabolic analysis reveals that, while activity and food intake are unchanged in global NG2 null mice, O2 consumption and CO2 production are decreased, suggesting a decrease in energy expenditure. Since brown fat plays important roles in regulating energy expenditure, we have investigated brown fat function via cold challenge and high fat diet feeding, both of which induce the adaptive thermogenesis that normally occurs in brown fat. In both tests, body temperatures in NG2 null mice are reduced compared to wild-type mice, indicating a deficit in brown fat function in the absence of NG2. In addition, adipogenesis in NG2 null brown pre-adipocytes is dramatically impaired compared to wild-type counterparts. Moreover, mRNA levels for PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor γ coactivator (PGC)1-α, proteins important for brown adipocyte differentiation, are decreased in NG2 null brown fat deposits in vivo and NG2 null brown pre-adipocytes in vitro. Altogether, these results indicate that brown fat dysfunction in NG2 null mice results from deficits in the recruitment and/or development of brown pre-adipocytes. As a consequence, obesity in NG2 null mice may occur due to disruptions in brown fat-dependent energy homeostasis, with resulting effects on lipid storage in white adipocytes

A cross-lingual adaptation approach for rapid development of speech recognizers for learning disabled users

Building a voice-operated system for learning disabled users is a difficult task that requires a considerable amount of time and effort. Due to the wide spectrum of disabilities and their different related phonopathies, most approaches available are targeted to a specific pathology. This may improve their accuracy for some users, but makes them unsuitable for others. In this paper, we present a cross-lingual approach to adapt a general-purpose modular speech recognizer for learning disabled people. The main advantage of this approach is that it allows rapid and cost-effective development by taking the already built speech recognition engine and its modules, and utilizing existing resources for standard speech in different languages for the recognition of the users’ atypical voices. Although the recognizers built with the proposed technique obtain lower accuracy rates than those trained for specific pathologies, they can be used by a wide population and developed more rapidly, which makes it possible to design various types of speech-based applications accessible to learning disabled users.This research was supported by the project ‘Favoreciendo la vida autónoma de discapacitados intelectuales con problemas de comunicación oral mediante interfaces personalizados de reconocimiento automático del habla’, financed by the Centre of Initiatives for Development Cooperation (Centro de Iniciativas de Cooperación al Desarrollo, CICODE), University of Granada, Spain. This research was supported by the Student Grant Scheme 2014 (SGS) at the Technical University of Liberec

PDGF-B-driven gliomagenesis can occur in the absence of the proteoglycan NG2

<p>Abstract</p> <p>Background</p> <p>In the last years, the transmembrane proteoglycan NG2 has gained interest as a therapeutic target for the treatment of diverse tumor types, including gliomas, because increases of its expression correlate with dismal prognosis. NG2 has been shown to function as a co-receptor for PDGF ligands whose aberrant expression is common in gliomas. We have recently generated a glioma model based on the overexpression of PDGF-B in neural progenitors and here we investigated the possible relevance of NG2 during PDGF-driven gliomagenesis.</p> <p>Methods</p> <p>The survival curves of NG2-KO mice overexpressing PDGF-B were compared to controls by using a Log-rank test. The characteristics of tumors induced in NG2-KO were compared to those of tumors induced in wild type mice by immunostaining for different cell lineage markers and by transplantation assays in adult mice.</p> <p>Results</p> <p>We showed that the lack of NG2 does not appreciably affect any of the characterized steps of PDGF-driven brain tumorigenesis, such as oligodendrocyte progenitor cells (OPC) induction, the recruitment of bystander OPCs and the progression to full malignancy, which take place as in wild type animals.</p> <p>Conclusions</p> <p>Our analysis, using both NG2-KO mice and a miRNA based silencing approach, clearly demonstrates that NG2 is not required for PDGF-B to efficiently induce and maintain gliomas from neural progenitors. On the basis of the data obtained, we therefore suggest that the role of NG2 as a target molecule for glioma treatment should be carefully reconsidered.</p

Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms

Leukodystrophies are genetically determined disorders characterized by the selective involvement of the central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies are degenerative in nature, but some only impair white matter function. The clinical course is mostly progressive, but may also be static or even improving with time. Progressive leukodystrophies are often fatal, and no curative treatment is known. The last decade has witnessed a tremendous increase in the number of defined leukodystrophies also owing to a diagnostic approach combining magnetic resonance imaging pattern recognition and next generation sequencing. Knowledge on white matter physiology and pathology has also dramatically built up. This led to the recognition that only few leukodystrophies are due to mutations in myelin- or oligodendrocyte-specific genes, and many are rather caused by defects in other white matter structural components, including astrocytes, microglia, axons and blood vessels. We here propose a novel classification of leukodystrophies that takes into account the primary involvement of any white matter component. Categories in this classification are the myelin disorders due to a primary defect in oligodendrocytes or myelin (hypomyelinating and demyelinating leukodystrophies, leukodystrophies with myelin vacuolization); astrocytopathies; leuko-axonopathies; microgliopathies; and leuko-vasculopathies. Following this classification, we illustrate the neuropathology and disease mechanisms of some leukodystrophies taken as example for each category. Some leukodystrophies fall into more than one category. Given the complex molecular and cellular interplay underlying white matter pathology, recognition of the cellular pathology behind a disease becomes crucial in addressing possible treatment strategies

Związki organiczne pochodzenia naturalnego w osadach z oczyszczalni ścieków

Organic compounds of natural origin were analyzed in three types of sludge produced by waste water treatment plant – limed sludge with 12 % of CaO, limed sludge with 6% of CaO and sludge without processing. Analysis was performed by pyrolytic gas chromatography with mass spectrometry detection (Py-GC/MS). The main component pf natural origin in waste-water treatment sludge were determined. They comprise compounds form the following groups: fatty acids and their methylesters, steroids, substances derived from polysaccharides, substances derived from lignin, compounds with nitrogen (both heterocyclic and aliphatic), substances with so called non-specific origin (toluene, styrene, acetic acid, methylphenols and phenols). Interpretation was attempted for identification of organic compounds sources as well as determination of humification and mineralization degree. The ratio benzene/toluene was used as the criterion for humification in waste-water treatment sludge. Benzene is derived from degradation of condensed aromatic structure, toluene is derived from both condensed aromatic structures and pseudostable organic matter. The ratio furfural/pyrolle was used of expression of mineralization degree of organic matter. Furfural is a product of labile organic matter (saccharides) while pyrolle originates from stable organic matter (humified components containing nitrogen). Compared with non-limed sludges, limed sludges have higher rate of decomposition of organic matter as well as subsequent mineralization. Limed sludges accumulate more compounds derived from lignine which is caused by more intensive decomposition of polysaccharides. From the point of view of utilization in agriculture, limed sludge is the most suitable sludge produced by waste-water treatment.Przeanalizowano związki organiczne pochodzenia naturalnego w trzech typach osadów wytwarzanych przez oczyszczalnie ścieków - szlam wapnowany zawierający 12% CaO, szlam wapnowany z 6% CaO i osady nieprzetworzone. Analizę przeprowadzono za pomocą pirolitycznej chromatografii gazowej ze spektrometrią masową (Py-GC / MS). Określono główne składniki pochodzenia naturalnego w osadach z oczyszczalni ścieków. Stanowią one związki z następujących grup: kwasy tłuszczowe oraz ich estry metylowe, steroidy, substancje pochodzących z polisacharydów, substancje pochodzące z ligniny, związki z azotem (zarówno heterocyklicze i alifatyczne), substancje o tzw. niespecyficznym pochodzeniu (toluen, styren, kwas octowy, metylofenole i fenole). Przedstawiono próbę identyfikacji źródeł związków organicznych, a także określenia stopnia humifikacji i mineralizacji. Stosunek benzenu do toluenu stosuje się w osadach z oczyszczalni ścieków jako kryterium humifikacji. Benzen jest pochodną z degradacji skondensowanej struktury aromatycznej, toluen pochodzi zarówno ze skondensowanych struktur aromatycznych jak i z pseudostabilnej materii organicznej. Stosunek furfural/pyrol użyto w celu ekspresji stopnia mineralizacji materii organicznej. Furfural jest produktem nietrwałej substancji organicznej (sacharydy), a pyrol pochodzi ze stabilnej materii organicznej (nawilżonych składników zawierających azot). W porównaniu z niewapnowanymi osadami, osady wapnowane mają wyższy wskaźnik rozkładu materii organicznej, jak i późniejszej mineralizacji. Wapnowane osady gromadzą więcej związków pochodzących z ligniny co jest spowodowane bardziej intensywnym rozkładem polisacharydów. Z punktu widzenia wykorzystania w rolnictwie, szlam wapnowany jest najbardziej odpowiednim osadem wytwarzanym przez oczyszczalnie ścieków

Cost-Efficient Development of Acoustic Models for Speech Recognition of Related Languages

When adapting an existing speech recognition system to a new language, major development costs are associated with the creation of an appropriate acoustic model (AM). For its training, a certain amount of recorded and annotated speech is required. In this paper, we show that not only the annotation process, but also the process of speech acquisition can be automated to minimize the need of human and expert work. We demonstrate the proposed methodology on Croatian language, for which the target AM has been built via cross-lingual adaptation of a Czech AM in 2 ways: a) using commercially available GlobalPhone database, and b) by automatic speech data mining from HRT radio archive. The latter approach is cost-free, yet it yields comparable or better results in LVCSR experiments conducted on 3 Croatian test sets

Language Issue in Erkin Azam's Publicity

The article analyzes Erkin Azam's thoughts and opinions on language in journalism. Questions such as the status of the Uzbek language, how it was used before now and the state of the language after independence were sought

Modified constitutive equations for nonirradiated Zr1Nb alloy

28.00; Translated from Czech. (Kovove Mater. 1990 v. 28(2) p. 152-164)Available from British Library Document Supply Centre- DSC:9023.19(VR-Trans--4672)T / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo