Fikir adamlarımızın pehlivanlıkları:Şair Mehmet Akif, filozof Rıza Tevfik, Edip Ercümend Ekrem ve Faik Hoca merhum

Taha Toros Arşivi, Dosya No: 98/A-Tevfik Fikret. Not: Gazetenin "Güreş Musahabeleri" köşesinde yayımlanmıştır.İstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

DIA-based systems biology approach unveils E3 ubiquitin ligase-dependent responses to a metabolic shift

The yeast Saccharomyces cerevisiae is a powerful model system for systems-wide biology screens and large-scale proteomics methods. Nearly complete proteomics coverage has been achieved owing to advances in mass spectrometry. However, it remains challenging to scale this technology for rapid and high-throughput analysis of the yeast proteome to investigate biological pathways on a global scale. Here we describe a systems biology workflow employing plate-based sample preparation and rapid, single-run, data-independent mass spectrometry analysis (DIA). Our approach is straightforward, easy to implement, and enables quantitative profiling and comparisons of hundreds of nearly complete yeast proteomes in only a few days. We evaluate its capability by characterizing changes in the yeast proteome in response to environmental perturbations, identifying distinct responses to each of them and providing a comprehensive resource of these responses. Apart from rapidly recapitulating previously observed responses, we characterized carbon source-dependent regulation of the GID E3 ligase, an important regulator of cellular metabolism during the switch between gluconeogenic and glycolytic growth conditions. This unveiled regulatory targets of the GID ligase during a metabolic switch. Our comprehensive yeast system readout pinpointed effects of a single deletion or point mutation in the GID complex on the global proteome, allowing the identification and validation of targets of the GID E3 ligase. Moreover, this approach allowed the identification of targets from multiple cellular pathways that display distinct patterns of regulation. Although developed in yeast, rapid whole-proteome–based readouts can serve as comprehensive systems-level assays in all cellular systems

Crystal structure of rac-3-hydroxy-2-(p-tolyl)-2,3,3a,4,7,7a-hexahydro-1H-4,7-methanoisoindol-1-one

In the title compound, C16H17NO2, the cyclohexene ring adopts a boat conformation, and the five-membered rings have envelope conformations with the bridging atom as the flap. Their mean planes are oriented at a dihedral angle of 86.51 (7)°. The molecular structure is stabilized by a short intramolecular C - H⋯O contact. In the crystal, molecules are linked by O - H⋯O hydrogen bonds forming chains propagating along [100]. The chains are linked by C - H⋯π interactions, forming slabs parallel to (001)

Cambios en los componentes del aceite volátil de salvia abisinia, salvia de almizcle y salvia médica [Salvia aethiopis L., Salvia sclarea L. y Salvia officinalis L. (híbrida)] que crecen en diferentes localizaciones

This study was conducted simultaneously in different locations in Çanakkale, Balıkesir and Kütahya in order to determine the effect of location on the volatile oil components, volatile oil rate and volatile oil quality of Abyssinian sage, Musk sage and Medical sage (Salvia aethiopis L., Salvia sclarea L. and Salvia officinalis L. (hybrid)) plants from the 2015 growing season. Field experiments were carried out in 3 replicates according to the randomized block design. These plants’ volatile oils were obtained by the hydrodistillation method (GC-MS/FID) and the volatile oil rates in three different locations were measured as 0.53%, 0.21%, 0.20%, respectively. The basic components of the volatile oil were determined as follows: β-caryophyllene 36.22%, 30.46%, 35.96%, α-copaene 15.06%, 16.46%, 16.58%, germacrene-D 13.23%, 20.01%, 15.20%, β-cubebene 5.62%, 7.04%, 6.93%, α–humulene 8.68%, 7.40%, 8.54%, caryophylleneoxide 7.40%, 1.82%, 3.53%. No volatile oil was acquired from Salvia sclarea L. except for the Çanakkale location which was only 0.02% and the main components in this volatile oil were measured as germacrene-D 20.78%, and phytol 17.81%. The best volatile oil contents from Abyssinian sage and Musk sage were obtained from the Çanakkale location with 0.53% and 0.02%, respectively. The rates of volatile oils from Medical sage (Salvia officinalis L. (hybrid)) were 1.00%, 1.40% and 0.96%, respectively, in the three locations. The main components in this volatile oil were measured as α-thujone 46,00%, 44.53%, 35.78%, β-thujone 5.05%, 6.31%, 8.61%, camphor 10.73%, 19.15%, 18.68%, 1.8-cineole 8.99%, 7.23%, 5.06%, viridiflorol 1.85%, 2.28%, 4.23%. The highest volatile oil rate in Medical sage was reached at the Balıkesir location at a rate of 1.40%. As a result of this study it was found that volatile oil components are comparatively richer in terpenes and the amount of volatile oil differs according to ecological factors.Este estudio se llevó a cabo simultáneamente en las ubicaciones de Çanakkale, Balikirir y Kütahya para definir el efecto de la ubicación en los componentes del aceite volátil, la cantidad de aceite y su calidad en salvia abisinia, salvia de almizcle y salvia médica [(Salvia aethiopis L., Salvia sclarea L. y Salvia officinalis L. (híbrida)] en la temporada de crecimiento 2015. Los experimentos de campo se repitieron 3 veces y de acuerdo con el diseño de bloques al azar. Los aceites volátiles de estas plantas se obtuvieron por el método de hidrodestilación (GC-MS/ FID) y las cantidades en las tres ubicaciones fueron de 0,53%, 0,21% y 0,20%. Los componentes básicos del aceite fueron: β-cariofileno 36,22%, 30,46%, 35,96%, α-copaeno 15,06%, 16,46%, 16,58%, germacreno-D 13,23%, 20,01%, 15,20%, β-cubebene 5,62%, 7,04%, 6,93%, α-humuleno 8,68%, 7,40%, 8,54% y cariofilenóxido 7,40%, 1,82%, 3,53%. No se consiguió aceite volátil de Salvia sclarea L. a excepción de la ubicación de Çanakkale que fue solo de 0,02% y los componentes principales en este aceite fueron germacrene-D 20,78%, y fitol 17,81%. El mayor contenido de aceite volátil de salvia abisinia y salvia de almizcle se obtuvo en la ubicación de Çanakkale con 0,53% y 0,02% respectivamente. Las cantidades de aceite de salvia médica (Salvia officinalis L. (híbrida) fueron de 1,00%, 1,40% y 0,96%, respectivamente, en las tres ubicaciones. Los componentes principales de estos aceites fueron: α-tujona 46,00%, 44,53%, 35,78%, β-tujona 5,05%, 6,31%, 8,61%, alcanfor 10,73%, 19,15%, 18,68%, 1,8-cineole 8,99%, 7,23%, 5,06% y viridiflorol 1,85%, 2,28%, 4,23%. La cantidad de aceite más alta de salbia médica se obtuvo en la ubicación de Balıkesir con una cantidad del 1,40%. Como resultado, se concluye que los componentes volátiles del aceite son comparativamente más ricos en terpenos y la cantidad de aceite volátil varía según los factores ecológicos

Urinary proteome profiling for stratifying patients with familial Parkinson's disease

The prevalence of Parkinson's disease (PD) is increasing but the development of novel treatment strategies and therapeutics altering the course of the disease would benefit from specific, sensitive, and non-invasive biomarkers to detect PD early. Here, we describe a scalable and sensitive mass spectrometry (MS)-based proteomic workflow for urinary proteome profiling. Our workflow enabled the reproducible quantification of more than 2,000 proteins in more than 200 urine samples using minimal volumes from two independent patient cohorts. The urinary proteome was significantly different between PD patients and healthy controls, as well as between LRRK2 G2019S carriers and non-carriers in both cohorts. Interestingly, our data revealed lysosomal dysregulation in individuals with the LRRK2 G2019S mutation. When combined with machine learning, the urinary proteome data alone were sufficient to classify mutation status and disease manifestation in mutation carriers remarkably well, identifying VGF, ENPEP, and other PD-associated proteins as the most discriminating features. Taken together, our results validate urinary proteomics as a valuable strategy for biomarker discovery and patient stratification in PD

Phosphorylation of serine-893 in CARD11 suppresses the formation and activity of the CARD11-BCL10-MALT1 complex in T and B cells

CARD 11 acts as a gatekeeper for adaptive immune responses after T cell or B cell antigen receptor (TCR/BCR) ligation on lymphocytes. PKC theta/beta-catalyzed phosphorylation of CARD11 promotes the assembly of the CARD11-BCL10-MALT1 (CBM) complex and lymphocyte activation. Here, we demonstrated that PKC theta/beta-dependent CARD11 phosphorylation also suppressed CARD11 functions in T or B cells. Through mass spectrometry-based proteomics analysis, we identified multiple constitutive and inducible CARD11 phosphorylation sites in T cells. We demonstrated that a single TCR- or BCR-inducible phosphorylation on Ser 893 in the carboxyl terminus of CARD1 1 prevented the activation of the transcription factor NF-kappa B, the kinase JNK, and the protease MALT1. Moreover, CARD11 Ser(893) phosphorylation sensitized BCR-addicted lymphoma cells to toxicity induced by Bruton's tyrosine kinase (BTK) inhibitors. Phosphorylation of Ser 893 in CARD11 by PKCO controlled the strength of CARD11 scaffolding by impairing the formation of the CBM complex. Thus, PKCO simultaneously catalyzes both stimulatory and inhibitory CARD11 phosphorylation events, which shape the strength of CARD11 signaling in lymphocytes

Theoretical study of hydrogen adsorption in Ti-decorated capped carbon nanotube

We present ab initio study using dispersion-corrected density functional theory calculations to investigate the hydrogen interaction with Ti-coated, one end closed, single-walled carbon nanotube (SWCNT). Our results demonstrate that a single Ti atom binds up to five hydrogen molecules on SWCNT cap top, whereas adsorption of four hydrogen molecules is energetically more favourable. The analyses fromadsorption energy profile, highest occupied molecular orbital–lowest unoccupied molecular orbital gap and Mulliken charge distribution show contrast in first hydrogen molecule adsorption compared with the rest of four configurations. This is clearly due to the strongly different bonding nature of first hydrogen adsorption among others, between hydrogen molecules and Ti-coated SWCNT. These results not only support our understanding of adsorption nature of hydrogen in Ti-coated SWCNTs but also suggest new directions for smart storage techniques. © 2017 Informa UK Limited, trading as Taylor & Francis Group

MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells

The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation and canonical nuclear factor kappa B (NF-kappa B) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the MALT1 C terminus after T cell activation. Phospho-specific antibodies reveal that CBM-associated MALT1 is transiently hyper-phosphorylated upon TCR/CD28 co-stimulation. We identify a dual role for CK1 alpha as a kinase that is essential for CBM signalosome assembly as well as MALT1 phosphorylation. Although MALT1 phosphorylation is largely dispensable for protease activity, it fosters canonical NF-kappa B signaling in Jurkat and murine CD4 T cells. Moreover, constitutive MALT1 phosphorylation promotes survival of activated B cell-type diffuse large B cell lymphoma (ABC-DLBCL) cells addicted to chronic BCR signaling. Thus, MALT1 phosphorylation triggers optimal NF-kappa B activation in lymphocytes and survival of lymphoma cells