Restriction of Food Intake by Dorsomedial Hypothalamus

Leptin deficient ob/ob mice eat voraciously and their food intake is markedly reduced by leptin treatment. Leptin acts in part by regulating the activity of AGRP neurons and POMC neurons in the arcuate nucleus and neurons in other brain regions. In these dissertation, I will describe how we identify novel neuronal populations that are regulated by leptin directly or indirectly. In order to identify novel sites of leptin action, we used phosphotrap, to molecularly profile leptin responsive neurons in the hypothalamus and brain stem. In addition to identifying several known leptin responsive populations, we found that neurons in Dorsomedial Hypothalamus (DMH) expressing GSBS are activated in ob/ob mice and suppressed by leptin treatment. Because ob mice are hyperphagic, we hypothesized that GSBS neurons would activate food intake. However excitation of GSBS neurons decreased food intake and body weight in ob/ob mice while chemogenetic inhibition of GSBS neurons increased food intake and body weight. The DMH regulates Food Anticipatory Activity (FAA) and in a scheduled feeding protocol that elicits increased consumption, mice also ate more when GSBS neurons were inhibited and less when they were activated without altering food anticipatory activity, body temperature and oxygen consumption. GSBS neurons do not express the leptin receptor suggesting that GSBS neurons in the DMH play a key role to restrict excessive food intake when consumption is increased and that leptin suppresses their activity indirectly by reducing food intake. These findings reveal that neural pathways activated by acute increases of food intake can restrain food intake independent of metabolic state. This finding has potential implications for an understanding of binge eating and other nutritional disorders

CLP1 Founder Mutation Links tRNA Splicing and Maturation to Cerebellar Development and Neurodegeneration

SummaryNeurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans

The role of cytokeratin 19 levels in the determination of endometriosis stages.

Objective/Aim Endometrisosis, one of the most common gynecological disease, is characterized by the presence of endometriotic tissue outside of uterine cavity. The development and the validation of a simple blood biomarker specific and sensitive for endometriosis may facilitate the rapid and the accurate diagnosis of the disease and thus early treatment. Cytokeratin expression changes during epithelial differentiation and this expression is important for the modulation and the control of cell cycle regulation, tumor cell motility and apoptosis. Cytokeratin 19 (CK-19) is expressed in most simple epithelial cells and their malignant counterparts. The aim of this study is to investigate serum CK-19 expression levels in patients with endometriosis and to determine the diagnostic role of CK-19 levels in differentiating various stage of endometriosis. Methods Ctytokeratin-19 expression and level were studied in 70 endometriosis patients and 50 volunteers by ELISA and RT-PCR. ROC analysis was performed by comparing all stages with each other and with the control group. Results The CK-19 levels were significantly higher in the endometriosis groups than that of the control group by ELISA and RT-PCR. A significant (p < .05) difference was observed in endometriosis patients according to the stages. Conclusion Based on our data, it suggests that Cytokeratin-19 may have a potential role in the development of endometriosis

Role of Preoperative Embolization in Surgical Treatment of the Carotid Body Paragangliomas

In this study, we aimed to show the benefits of preoperative embolization on surgery of carotid body tumors

Comparison Of Wire-Guided Localization And Radio-Guided Occult Lesion Localization In Preoperative Localization Of Nonpalpable Breast Lesions

Background/aim: Breast lesions that are not palpable on physical examination but considered suspicious for malignancy on mammography or ultrasonography should be marked before surgery. Wire-guided localization (WGL) is the most frequently used method for preoperative marking of nonpalpable breast lesions (NPBLs). An alternative is marking by a radioactive agent (radio-guided occult lesion localization; ROLL). The present study aimed to compare WGL and ROLL for preoperative marking. Materials and methods: The study included 25 patients marked by ROLL and 11 patients marked by WGL. The groups were compared in terms of patient and lesion characteristics, method-related characteristics, hospital stay duration, complications, cosmetic outcomes, and rate of correct marking. Results: Suspicious lesions were marked with a success rate of 95.6% by ROLL and 100% by WGL. Complications and pain sensation rates were found significantly lower in the ROLL group compared to WGL. Although ROLL was considered more advantageous in terms of hospital stay duration, positive surgical margins, cosmetic outcomes, and excision duration, the differences between the groups were not statistically significant. Conclusion: ROLL, which is a simple, comfortable, and reliable method, could be used as an alternative to the WGL in preoperative marking of NPBLs.WoSScopu

Installation of the METU Defocusing Beamline to Perform Space Radiation Tests

METU Defocusing Beamline (DBL) is being installed at TAEA SANAEM Proton Accelerator Facility [1] for radiation tests of electronic devices to be used in satellites and spacecrafts which are exposed to a high radiation dose in space or at the Hi-Lumi LHC [2]. 15 - 30 MeV protons from the accelerator are spread out over an area of 15.40 X 21.55 cm to provide large irradiation in accordance to ESA/ESCC No. 25100 standard with METU-DBL. A wide selectable flux menu ranging from 10(5) - 10(10) p/cm(2)/s will be available to users starting in summer 2019. The final design has been updated with the experience gained from the pre-test setup installation [3] and the ensuing irradiation campaign with different users [4]. In this paper, magnetic measurement results of a custom design quadrupole magnet, as well as updates to the mechanical, robotic and control subsystems are presented

Metu-Defocusing Beamline : A 15-30 Mev Proton Irradiation Facility and Beam Measurement System

Middle East Technical University – Defocusing Beam Line (METU-DBL) project is an irradiation facility providing 15 MeV to 30 MeV kinetic energy protons for testing various high radiation level applications, ranging from Hi-Lumi LHC upgrade, space electronic components to nuclear material research. The project located inside the premises of the TAEA (Turkish Atomic Energy Agency) SANAEM (Saraykoy Nuclear Education and Research Center) close to Ankara, provides users a wide selectable flux menu (105–1010 p/cm2/s). The facility is now being commissioned and the facility will be providing a large test area (20 cm x 15 cm) for material, detector and electronics tests. The proton beam is monitored along the beamline using aluminum oxide screens and the flux and uniformity is measured using three detectors attached to the robotic system for cross- checks. A fiber scintillator detector scans the large irradiation area while small area diamond detector and Timepix3 detector are used for spot checks for calibration. Several samples can be radiated simultaneously inside the irradiation area and the robotic system provides 5 separate holders for samples which can be moved in or out, providing users flexibility for the desired fluence. This talk will first introduce METU- DBL as a radiation test facility, then discuss the radiation monitoring of the beam area and the radiation room, while highlighting how this facility can be used for future testing of materials for radiation tolerance

Metu-Defocusing Beamline : A 15-30 Mev Proton Irradiation Facility and Beam Measurement System

Middle East Technical University – Defocusing Beam Line (METU-DBL) project is an irradiation facility providing 15 MeV to 30 MeV kinetic energy protons for testing various high radiation level applications, ranging from Hi-Lumi LHC upgrade, space electronic components to nuclear material research. The project located inside the premises of the TAEA (Turkish Atomic Energy Agency) SANAEM (Saraykoy Nuclear Education and Research Center) close to Ankara, provides users a wide selectable flux menu (105–1010 p/cm2/s). The facility is now being commissioned and the facility will be providing a large test area (20 cm x 15 cm) for material, detector and electronics tests. The proton beam is monitored along the beamline using aluminum oxide screens and the flux and uniformity is measured using three detectors attached to the robotic system for cross- checks. A fiber scintillator detector scans the large irradiation area while small area diamond detector and Timepix3 detector are used for spot checks for calibration. Several samples can be radiated simultaneously inside the irradiation area and the robotic system provides 5 separate holders for samples which can be moved in or out, providing users flexibility for the desired fluence. This talk will first introduce METU- DBL as a radiation test facility, then discuss the radiation monitoring of the beam area and the radiation room, while highlighting how this facility can be used for future testing of materials for radiation tolerance

NGLY1 mutation causes neuromotor impairment, intellectual disability, and neuropathy

N-glycanase 1 (NGLY1) is a conserved enzyme that is responsible for the deglycosylation of misfolded N-glycosylated proteins in the cytoplasm prior to their proteasome-mediated degradation. Disruption of this degradation process has been associated with various neurologic diseases including amyotrophic lateral sclerosis and Parkinson's disease. Here, we describe two siblings with neuromotor impairment, apparent intellectual disability, corneal opacities, and neuropathy who were found to possess a novel homozygous frame-shift mutation due to a 4 base pair deletion in NGLY1 (c.1533_1536delTCAA. p.Asn511LysfsX51). We hypothesize that this mutation likely limits the capability of neuronal cells to respond to stress due to accumulation of misfolded proteins, thereby impairing their survival and resulting in progressive loss of neurological function. (C) 2014 Elsevier Masson SAS. All rights reserved