Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

The impact of the global economic crisis on working capital of real sector in Turkey

Objective of this study is to reveal the impact of the recent global economic crisis, triggered in 2007 and unveiled in 2008, on the working capital of real sector in Turkey. Since it is obvious that ratios would help in such an analysis, we have analyzed the current assets and liabilities related ratios, based on financial statements of Turkish real sector firms, quoted in the Istanbul Stock Exchange (ISE). Pre-crisis era has been compared with the crisis era, while the degrees of the affection of the real sector current assets and current liabilities have been tested through hypotheses, and two-tail-significance test has been conducted. The results of this study draw conclusions from an empirical investigation showing that the 45 ISE companies, chosen among others, have been affected on a limited basis

The Efficiency Analysis of Non-life Insurance Companies Active in Turkey

This paper evaluates the technical effi ciencies of non-life insurance companies, which are active in Turkey in 2007, using Data Envelopment Analysis (DEA). DEA, which is a nonparametric method, facilitates to examine different input-output components. DEA is a management evaluation tool that assists in identifying the most efficient and ineffi cient decision making units (DMUs) in the best practice frontier. In this study, as inputs of 23 non-life insurance companies, the number of agents, the number of brokers, fi xed assets, shareholders’ equity and as outputs the investment incomes, premiums received are used. Empirical results of BCC and CCR models, which are DEA models, show that the most efficient insurance company is RAY

Establishing a Network among Entrepreneurs, Angle Investors and Venture Capital Firms, Structure and Importance of This Network

SMEs that operate in information technology (IT) sector need venture capital besides conventional financial techniques (capital, loans, etc.). Venture capitalists can be categorized into two groups as personal and institutional venture capitalists. Those who are individual venture capitalists are called angel investors. Institutional ones are called venture capital firms. When we look at the world, we come across to networks that gather angel investors and venture capital firms with entrepreneurs. Development of IT sector, which is very important in the development of our country, is closely related with the establishment of similar networks. In this study, in-depth interviews are conducted with the managers and/or owners of thirty SMEs in Erciyes Technopark. This descriptive research determines how these networks can be established the role of technoparks in these networks, contribution of angle investors and venture capital firms to this type of network, and shows how entrepreneurs perceive these types of networks. Establishing a network is expected to provide cooperative behaviors, innovation and information flows. Corporations, technoparks and universities are considered to act as an intermediary in a virtual environment in order to establish this type of network.Venture capital; Angle investors; Network; New economy; Technoparks

A new architecture selection strategy in solving seasonal autoregressive time series by artificial neural networks

The only suggestions given in the literature for determining the archi- tecture of neural networks are based on observations, and a simulation study to determine the architecture has not yet been reported. Based on the results of the simulation study described in this paper, a new architecture selection strategy is proposed and shown to work well. It is noted that although in some studies the period of a seasonal time series has been taken as the number of inputs of the neural network model, it is found in this study that the period of a seasonal time series is not a parameter in determining the number of inputs

Acoustic evidence of shallow gas accumulations and active pockmarks in the Izmir Gulf, Aegean sea

Based on high-resolution Chirp seismic, multibeam bathymetry and side scan sonar data collected in the Izmir Gulf, Aegean Sea in 2008 and 2010, gas-related structures have been identified, which can be classified into three categories: (1) shallow gas accumulations and gas chimneys, (2) mud diapirs, and (3) active and inactive pockmarks. On the Chirp profiles, shallow gas accumulations were observed along the northern coastline of the outer Izmir Gulf at 3-20 m below the seabed. They appear as acoustic turbidity zones and are interpreted as biogenic gas accumulations produced in organic-rich highstand fan sediments from the Gediz River. The diapiric structures are interpreted as shale or mud diapirs formed under lateral compression due to regional counter-clockwise rotation of Anatolian microplate. Furthermore, the sedimentary structure at the flanks suggests a continuous upward movement of the diapirs. Several pockmarks exist close to fault traces to the east of Hekim Island; most of them were associated with acoustic plumes indicating active degassing during the survey period in 2008. Another Chirp survey was carried out just over these plumes in 2010 to demonstrate if the gas seeps were still active. The surveys indicate that the gas seep is an ongoing process in the gulf. Based on the Chirp data, we proposed that the pockmark formation in the area can be explained by protracted seep model, whereby sediment erosion and re distribution along pockmark walls result from ongoing (or long lasting) seepage of fluids over long periods of time. The existence of inactive pockmarks in the vicinity, however, implies that gas seepage may eventually cease or that it is periodic. Most of the active pockmarks are located over the fault planes, likely indicating that the gas seepage is controlled by active faulting. (C) 2011 Elsevier Ltd. All rights reserved

Real-life risk factors of inadequate procedure prior to colonoscopy in a Turkish population

Colonoscopy is one of the main diagnostic tools for symptoms related to the colon and colorectal cancer screening programs. Inadequate cleansing of colonoscopy leads to misdiagnosis of adenomas. It is recommended to re-evaluate ine&#64256;ective colonoscopy. It is of utmost importance to predict whether the bowel is clean or not because the procedure is expensive, invasive and time- consuming. This study aimed to identify the risk factors of inadequate bowel preparation. The consecutive two hundred and &#64257;fty-three patients who were referred for colonoscopy were enrolled into the study. The demographic and clinical data were obtained using a questionnaire. Only 79.1% of colonoscopy were assessed as adequate. In the univariate analysis; adherence to protocol, older age, consuming high-&#64257;ber diet in last two days, number of days of low residue diet, consumed all laxative, consumed 1.5 L water after laxative usage, regular diet for dinner before the day of colonoscopy, amount of water consumed before the day of colonoscopy, amount of water consumed in the morning of the day of colonoscopy, fasting status in the morning of the CD, and were found signi&#64257;cantly relevant for adequate bowel preparation. Older age, number of days of low residue diet, consuming high-&#64257;ber diet in last two days, regular diet for the dinner before the day of colonoscopy, not Consumed all laxatives were independent risk factors for inadequate colonoscopy. These factors are reversible risk factors except older age. Increasing the adherence to the protocol with education seems to improve the bowel preparation quality. [Med-Science 2022; 11(1.000): 36-40