Molecular Basis of Sugar Sensing in Drosophila

In contrast to mammals, which sense sweet tasting molecules through a single, dimeric sugar taste receptor, Drosophila melanogaster use at least eight sugar gustatory receptor (Gr) proteins to recognize a range of dietary sugars. We showed that the sugar Gr genes are expressed in partially overlapping fashion in the single sweet gustatory receptor neuron (GRN) to generate at least 8 different subtypes and that sugar receptors heteromultimeric complexes. We used a combinatorial strategy to examine the composition of functional sugar receptors using an “empty neuron” system that is based on an octuple mutant fly strain lacking all eight sugar Gr genes. By expressing all 28 possible pairwise Gr gene combinations in the “empty neuron” that express the Ca^2+ sensitive GCaMP6 protein, we find that 18 of these combinations can reconstitute sugar responses to a subset of sugars. Remarkably, each of these combinations restores responses to wild type levels to at least one of the eight sugars that we tested, and some combinations restored high responses to two or three sugars. Some of these combinations were able to convey sugar responses to bitter GRNs when expressed under the control of the GAL4 driver for the bitter receptor Gr33a, indicating that bitter and sweet GRNs use the same signaling mechanism. To explore the possibility whether sugar receptor complexes are composed of more than two different subunits, we introduced triple combinations of sugar Gr genes in the “empty neuron”. For two of the four different triple combinations, response profile revealed new sugar responses not observed with any of the three respective pairwise combinations, suggesting that for at least some sugars, functional complexes are likely to contain three different Gr subunits. Taken together, our analysis reveals that sweet GRNs of wild type flies might have more than 20 different sugar receptor complexes, each tuned to subsets of sugars

Molecular Basis of Sugar Sensing in Drosophila

In contrast to mammals, which sense sweet tasting molecules through a single, dimeric sugar taste receptor, Drosophila melanogaster use at least eight sugar gustatory receptor (Gr) proteins to recognize a range of dietary sugars. We showed that the sugar Gr genes are expressed in partially overlapping fashion in the single sweet gustatory receptor neuron (GRN) to generate at least 8 different subtypes and that sugar receptors heteromultimeric complexes. We used a combinatorial strategy to examine the composition of functional sugar receptors using an “empty neuron” system that is based on an octuple mutant fly strain lacking all eight sugar Gr genes. By expressing all 28 possible pairwise Gr gene combinations in the “empty neuron” that express the Ca^2+ sensitive GCaMP6 protein, we find that 18 of these combinations can reconstitute sugar responses to a subset of sugars. Remarkably, each of these combinations restores responses to wild type levels to at least one of the eight sugars that we tested, and some combinations restored high responses to two or three sugars. Some of these combinations were able to convey sugar responses to bitter GRNs when expressed under the control of the GAL4 driver for the bitter receptor Gr33a, indicating that bitter and sweet GRNs use the same signaling mechanism. To explore the possibility whether sugar receptor complexes are composed of more than two different subunits, we introduced triple combinations of sugar Gr genes in the “empty neuron”. For two of the four different triple combinations, response profile revealed new sugar responses not observed with any of the three respective pairwise combinations, suggesting that for at least some sugars, functional complexes are likely to contain three different Gr subunits. Taken together, our analysis reveals that sweet GRNs of wild type flies might have more than 20 different sugar receptor complexes, each tuned to subsets of sugars

Breast cancer in association with thyroid disorders

BACKGROUND: The relationship between breast cancer and thyroid diseases is controversial. Discrepant results have been reported in the literature. The incidences of autoimmune and nonautoimmune thyroid diseases were investigated in patients with breast cancer and age-matched control individuals without breast or thyroid disease. METHODS: Clinical and ultrasound evaluation of thyroid gland, determination of serum thyroid hormone and antibody levels, and fine-needle aspiration of thyroid gland were performed in 150 breast cancer patients and 100 control individuals. RESULTS: The mean values for anti-thyroid peroxidase antibodies were significantly higher in breast cancer patients than in control individuals (P = 0.030). The incidences of autoimmune and nonautoimmune thyroid diseases were higher in breast cancer patients than in control individuals (38% versus 17%, P = 0.001; 26% versus 9%, P = 0.001, respectively). CONCLUSION: Our results indicate an increased prevalence of autoimmune and nonautoimmune thyroid diseases in breast cancer patients

Prenatal diagnosis of Neu-Laxova syndrome: a case report

BACKGROUND: Neu-Laxova syndrome is a rare congenital abnormality involving multiple systems. We report a case of Neu-Laxova syndrome (NLS) diagnosed prenatally by ultrasound examination. CASE PRESENTATION: A 29-year-old gravida 3, para 2 woman was first seen in our antenatal clinic at 38 weeks' pregnancy. Except for the consanguinity and two previous abnormal stillborn babies her medical history was unremarkable. On ultrasound examination microcephaly, flat forehead, micrognathia, intrauterine growth restriction, generalized edema of the skin, hypoplastic chest, excessive soft tissue deposition of hands and feet, joint contractures and a penis without scrotal sacs were detected. She delivered a 2000 g male fetus. He died five minutes after delivery. Postmortem examination confirmed the diagnosis of Neu-Laxova syndrome. CONCLUSION: Because of the autosomal recessive inheritance of Neu-Laxova syndrome genetic counseling and early-serial ultrasound examination should be performed at risk families. Early diagnosis of the disease may offer termination of the pregnancy as an option

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis

Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.Fil: Efe, Cumali. Harran University Hospita; TurquíaFil: Lammert, Craig. University School of Medicine Indianapolis; Estados UnidosFil: Taşçılar, Koray. Universitat Erlangen-Nuremberg; AlemaniaFil: Dhanasekaran, Renumathy. University of Stanford; Estados UnidosFil: Ebik, Berat. Gazi Yasargil Education And Research Hospital; TurquíaFil: Higuera de la Tijera, Fatima. Hospital General de México; MéxicoFil: Calışkan, Ali R.. No especifíca;Fil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Gerussi, Alessio. Università degli Studi di Milano; ItaliaFil: Massoumi, Hatef. No especifíca;Fil: Catana, Andreea M.. Harvard Medical School; Estados UnidosFil: Purnak, Tugrul. University of Texas; Estados UnidosFil: Rigamonti, Cristina. Università del Piemonte Orientale ; ItaliaFil: Aldana, Andres J. G.. Fundacion Santa Fe de Bogota; ColombiaFil: Khakoo, Nidah. Miami University; Estados UnidosFil: Nazal, Leyla. Clinica Las Condes; ChileFil: Frager, Shalom. Montefiore Medical Center; Estados UnidosFil: Demir, Nurhan. Haseki Training And Research Hospital; TurquíaFil: Irak, Kader. Kanuni Sultan Suleyman Training And Research Hospital; TurquíaFil: Melekoğlu Ellik, Zeynep. Ankara University Medical Faculty; TurquíaFil: Kacmaz, Hüseyin. Adıyaman University; TurquíaFil: Balaban, Yasemin. Hacettepe University; TurquíaFil: Atay, Kadri. No especifíca;Fil: Eren, Fatih. No especifíca;Fil: Alvares da-Silva, Mario R.. Universidade Federal do Rio Grande do Sul; BrasilFil: Cristoferi, Laura. Università degli Studi di Milano; ItaliaFil: Urzua, Álvaro. Universidad de Chile; ChileFil: Eşkazan, Tuğçe. Cerrahpaşa School of Medicine; TurquíaFil: Magro, Bianca. No especifíca;Fil: Snijders, Romee. No especifíca;Fil: Barutçu, Sezgin. No especifíca;Fil: Lytvyak, Ellina. University of Alberta; CanadáFil: Zazueta, Godolfino M.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Demirezer Bolat, Aylin. Ankara City Hospital; TurquíaFil: Aydın, Mesut. Van Yuzuncu Yil University; TurquíaFil: Amorós Martín, Alexandra Noemí. No especifíca;Fil: De Martin, Eleonora. No especifíca;Fil: Ekin, Nazım. No especifíca;Fil: Yıldırım, Sümeyra. No especifíca;Fil: Yavuz, Ahmet. No especifíca;Fil: Bıyık, Murat. Necmettin Erbakan University; TurquíaFil: Narro, Graciela C.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Bıyık, Murat. Uludag University; TurquíaFil: Kıyıcı, Murat. No especifíca;Fil: Kahramanoğlu Aksoy, Evrim. No especifíca;Fil: Vincent, Maria. No especifíca;Fil: Carr, Rotonya M.. University of Pennsylvania; Estados UnidosFil: Günşar, Fulya. No especifíca;Fil: Reyes, Eira C.. Hepatology Unit. Hospital Militar Central de México; MéxicoFil: Harputluoğlu, Murat. Inönü University School of Medicine; TurquíaFil: Aloman, Costica. Rush University Medical Center; Estados UnidosFil: Gatselis, Nikolaos K.. University Hospital Of Larissa; GreciaFil: Üstündağ, Yücel. No especifíca;Fil: Brahm, Javier. Clinica Las Condes; ChileFil: Vargas, Nataly C. E.. Hospital Nacional Almanzor Aguinaga Asenjo; PerúFil: Güzelbulut, Fatih. No especifíca;Fil: Garcia, Sandro R.. Hospital Iv Víctor Lazarte Echegaray; PerúFil: Aguirre, Jonathan. Hospital Angeles del Pedregal; MéxicoFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Ratusnu, Natalia. Hospital Regional de Ushuaia; ArgentinaFil: Hatemi, Ibrahim. No especifíca;Fil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Floreani, Annarosa. Università di Padova; ItaliaFil: Fagiuoli, Stefano. No especifíca;Fil: Silva, Marcelo. Universidad Austral; ArgentinaFil: Idilman, Ramazan. No especifíca;Fil: Satapathy, Sanjaya K.. No especifíca;Fil: Silveira, Marina. University of Yale. School of Medicine; Estados UnidosFil: Drenth, Joost P. H.. No especifíca;Fil: Dalekos, George N.. No especifíca;Fil: N.Assis, David. University of Yale. School of Medicine; Estados UnidosFil: Björnsson, Einar. No especifíca;Fil: Boyer, James L.. University of Yale. School of Medicine; Estados UnidosFil: Yoshida, Eric M.. University of British Columbia; CanadáFil: Invernizzi, Pietro. Università degli Studi di Milano; ItaliaFil: Levy, Cynthia. University of Miami; Estados UnidosFil: Montano Loza, Aldo J.. University of Alberta; CanadáFil: Schiano, Thomas D.. No especifíca;Fil: Ridruejo, Ezequiel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Wahlin, Staffan. No especifíca

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

The genetic history of the Southern Arc: a bridge between West Asia and Europe

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra–West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe

Sulfuric acid leaching of Turkish chromite concentrate

In this work a high grade chromite concentrate obtained from Pinarbasi-Kayseri district of Turkey was reacted with a solution of sulfuric acid and perchloric acid. The effect of sulfuric acid concentration, temperature, duration, and perchloric acid addition on leach recovery was studied. At the end of leach reaction chromium appeared in the solution as Cr3+ and it did not change to environmentally hazardous Cr6+. The final product in the solution was chromium(III) sulfate obtained with about 83% maximum recovery, under the optimum leaching conditions of 175 degreesC, 2 h, 70% H2SO4 and 1/2 perchloric acid/chromite ratio

Desulphurization characteristics of ladle furnace slags of a low sulphur steel

In steelmaking, one of the most important parameters for desulphurization is the oxygen potential of the system which can be expressed either by oxygen activity of the steel or by FetO activity of the slag. Removal of sulphur from the steel is enhanced when FetO activity of the slag and thus oxygen activity of the steel decreases. In this paper, ladle furnace slags of a low S steel quality currently produced in Eregli Iron and Steel Works Company (ERDEMIR), Turkey, were studied. Activity coefficients of FetO, gamma(FetO) were calculated with the relation obtained from the literature. The relation between %Decrease a(FetO) and %DeS (measured) was studied. The percentage of sulphur removal was also investigated using the data of the oxygen activity of liquid steel

Fiber optic sensors using novel substrates for hydrogen sulfide determination by solid surface fluorescence

Two different fiber optic sensors were developed for the determination of hydrogen sulfide at ppb concentration levels; a probe-type fiber optic sensor coated with polyethylene oxide containing 0.5 M CdCl2 and a fiber optic sensor utilizing 0.5 M CdCl2-pretreated filter paper as solid substrate. In the first type, CdCl2–polyethyleneoxide (PEO) mixture was coated onto the tip of a fiber optic probe and the probe was exposed to H2S. The methodology is based on the measurement of CdS fluorescence on the surface. Detection limit (3s) of the PEO-coated fiber optic system was 36.0 ppb for H2S and precision at the 0.552 ppm level was 29% R.S.D. For the fiber optic system utilizing CdCl2-pretreated filter paper, two different configurations were devised and evaluated; a bifurcated fiber optic sensor and a single fiber optic sensor. Similar figures were obtained with these two systems; the detection limit (3s) was 4.0 ppb for the bifurcated fiber optic sensor and 4.3 ppb for the single fiber optic sensor, and both sensors had linear responses in the range 0.032–1.0 ppm. Their precisions at 0.299 ppm level were also very similar, 10 and 11% R.S.D., respectively, for the bifurcated and single fiber systems. In addition to the fiber optic sensors developed, various surfactants (sodiumdodecylsulfate (SDS), Aerosol OT, Aerosol A102, Aerosol 501), some cellulosic substances (sodium carboxymethylcellulose (CMC), ethylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, α-cellulose) and several water-soluble polymers (polyacrylicacid polyethleneoxide (PEO), polyvinylalcohol (PVA)) were dissolved in proper solvents and after mixing with 0.5 M CdCl2, were spread over glass slides. These novel solid substrates were exposed to H2S and fluorescence signal on the surfaces of the glass slides was measured with a luminescence spectrometer. The new substrates were shown to be good alternatives to filter paper for the determination of H2S by room temperature solid surface fluorescence spectrometry