269 research outputs found

    Modules in the photoreceptor RGS9-1•Gβ5L GTPase-accelerating protein complex control effector coupling, GTPase acceleration, protein folding, and stability

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    RGS (regulators of G protein signaling proteins regulate G protein signaling by accelerating GTP hydrolysis, but little is known about regulation of GTPase-accelerating protein (GAP) activities or roles of domains and subunits outside the catalytic cores. RGS9-1 is the GAP required for rapid recovery of light responses in vertebrate photoreceptors and the only mammalian RGS protein with a defined physiological function. It belongs to an RGS subfamily whose members have multiple domains, including G gamma -like domains that bind G(beta5) proteins. Members of this subfamily play important roles in neuronal signaling, Within the GAP complex organized around the RGS domain of RGS9-1, we have identified a functional role for the G gamma -like-G(beta 5L) complex in regulation of GAP activity by an effector subunit, cGMP phosphodiesterase gamma and in protein folding and stability of RGS9-1, The C-terminal domain of RGS9-1 also plays a major role in conferring effector stimulation. The sequence of the RGS domain determines whether the sign of the effector effect will be positive or negative. These roles were observed in, vitro using full-length proteins or fragments for RGS9-1, RGS7, G(beta 5S), and G(beta 5s), The dependence of RGS9-1 on Gp, co-expression for folding, stability, and function has been confirmed in vivo using transgenic Xenopus laevis, These results reveal how multiple domains and regulatory polypeptides work together to fine tune G(t alpha) inactivation

    A New College

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    House Resolution No. 28 of the 1959 Michigan legislature created a committee to study the need for a four-year state-supported college in the Grand Rapids area. The committee submitted its findings and recommendations to the 1960 Legislature in a report entitled A New College: A report to the Legislative and Citizens committees on the eight-county study of higher education needs in Allegan, Barry, Ionia, Kent, Montcalm, Muskegon, Newago and Ottawa Counties by John X. Jamrich, Director of the Survey, December 1959.https://scholarworks.gvsu.edu/reports/1004/thumbnail.jp

    Analysis of Communication System in the Freelancers Ltd. and New System Suggestion

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    Tato práce se zabývá analýzou a návrhem komunikačního informačního systému ve firmě Freelancers s.r.o. Její součástí je tedy jak zkoumání momentálního stavu systému a nalezení jeho nedostatků, tak návrh systému nového, který bude slučovat všechny funkce systému předchozího, ale eliminovat jeho chyby.This thesis is about an analysis of a communication information system in Freelancers Company. First part of it is about parsing the actual system and finding its weak spots, second is suggesting new system design, with all functions of the old system, but without its mistakes.

    Regulation of development by Rx genes

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    The paired-like homeobox-containing gene Rx has a critical role in the eye development of several vertebrate species including Xenopus, mouse, chicken, medaka, zebrafish and human. Rx is initially expressed in the anterior neural region of developing embryos, and later in the retina and ventral hypothalamus. Abnormal regulation or function of Rx results in severe abnormalities of eye formation. Overexpression of Rx in Xenopus and zebrafish embryos leads to overproliteration of retinal cells. A targeted elimination of Rx in mice results in a lack of eye formation. Mutations in Rx genes are the cause of the mouse mutation eyeless (ey1), the medaka temperature sensitive mutation eyeless (el) and the zebrafish mutation chokh. In humans, mutations in Rx lead to anophthalmia. All of these studies indicate that Rx genes are key factors in vertebrate eye formation. Because these results cannot be easily reconciled with the most popular dogmas of the field, we offer our interpretation of eye development and evolution

    Biostratigraphy and paleoecology of the upper Badenian carbonate and siliciclastic nearshore facies in the Vienna Basin (Slovakia)

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    This study provides a comprehensive examination of algal bioherm structures, including reefs and carpets that contain nannoplankton and foraminifera, originating from the upper Badenian (middle Miocene) strata of the Vienna Basin in the Central Paratethys. These lithofacies primarily consist of the carbonate red algal genus Lithothamnion. Through an integrated approach that combines calcareous nannoplankton, foraminifera, sedimentology, and palynology, the study explores the Serravallian (upper Badenian) sediments from the Vienna Basin. The biostratigraphic age, consistent with the NN6 and CPN9 zones, is further corroborated by 87Sr/86Sr dating. This research highlights the importance of taphonomic processes and paleoecological proxies in small-scale characterization and detecting short-term shifts within paleoenvironmental conditions. These unique bioherm structures enable a novel description of a limestone formation within the Vienna Basin (Sandberg Formation), which seems pervasive across the Central Paratethys region. The findings uphold the hypothesis of a profound connection between the Mediterranean and Central Paratethys via the Trans-Tethyan Trench Corridor, bolstered by upwelling conditions observed in the eastern perimeter of the Vienna Basin. Two main inhibitory mechanisms for carbonate growth in the Upper Badenian within the Central Paratethys area are confirmed: the first is a substantial siliciclastic influx from the Alps and Carpathians, supported by the ongoing rifting of the Vienna and Danube Basins; the second is the propagation of evaporites in the Transcarpathian and Transylvanian Basins leading to precipitation, which disrupts carbonate growth. This investigation underlines the intertwined relationship between regional geodynamics and carbonate sedimentation processes during the Miocene.Web of Science701art. no.

    Paleoecological evaluation of the fossiliferous layers of Upper Badenian at the Dubová site (northwestern part of the Danube basin)

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    Miocénne sedimenty na úpätí Malých Karpát bývajú častokrát veľmi bohaté na fosílie,napriek tomu dočasné odkryvy často nebývajú zdokumentované. V práci predstavujemevýsledky získané zo záchranných prác z už nejestvujúceho odkryvu jz. od obce Dubová,ktorý vznikol vďaka stavebnej činnosti. Veľmi podrobne sme zdokumentovali faunu a flórumarginálnych morských sedimentov vrchného bádenu (spodný seraval) nanoplanktónovejzóny NN6 a ekobiozóny Ammonia beccarii, ktorá je laterálnym ekvivalentom zónybulimino/bolivínovej. Na základe diverzifikovanej asociácie vápnitého nanoplanktónu,dierkavcov, koralov, mäkkýšov a machoviek interpretujeme zmeny paleoprostredia počassedimentácie. Aj v krátkom časovom úseku, ktorý reprezentoval profil s hrúbkou 2,5 m, smeodhalili rôzne typy paleoekologického prostredia, ktoré boli ovplyvnené zmenami salinity,prínosom živín a dynamikou vodného prostredia. V celom profile predpokladáme veľmiplytkovodné prostredie, maximálne do 40 m, striedanie epizód s nízkym obsahom kyslíka(prevaha zástupcov rodu Ammonia), ktoré vznikali pravdepodobne v závislosti od energieprostredia. Salinita sa počas sedimentácie menila postupne od morskej, dokumentovanejschránkami dierkavcov (Elphidium, Borelis) a machoviek Cupuladria a Reusirella, pohyposalínnu dokumentovanú mäkkýšmi rodov Vitta a Pustulosia smerom do nadložia.Vodný stĺpec dokumentuje príbrežné prostredie vonkajšieho šelfu, vysoká abundancia redepozitovvápnitého nanoplanktónu kriedového a paleogénneho veku umožňuje uvažovaťo riečnych prínosoch paleo-Váhu.The Miocene sediments at the foothills of the Malé Karpaty Mts. are often rich in fossils,temporary outcrops are often not documented yet. This work presents findings froma construction pit southwest of the Dubová village, excavated during the constructionactivities. We have documented the fauna and flora of the marginal marine sediments ofthe Upper Badenian (Lower Serravallian) within the NN6 Zone and the Ammonia beccariieco-biozone, which is the lateral equivalent of the Bulimina–Bolivina Zone. We interpretpaleoenvironmental changes during sedimentation based on the diverse association ofcalcareous nannoplankton, foraminifera, corals, molluscs, and bryozoans. In a relativelyshort period, represented by a 2.5-meter-thick profile, we identified various types of paleoecologicalenvironments influenced by changes in salinity, nutrient input, and aquaticdynamics. The entire profile suggests a very shallow water environment, maximum up to40 m, alternating episodes with low oxygen content (predominance of the Ammonia genus),likely influenced by the environment‘s energy. During sedimentation, the salinity graduallytransitioned from marine, indicated by foraminifera (Elphidium, Borelis) and bryozoansCupuladria and Reussirella, to hyposaline, marked by the presence of molluscs Vitta andPustulosia towards the overlying bed. The water column documents a coastal environmentof the outer shelf, and the high abundance of reworked calcareous nannoplankton of theCretaceous and Paleogene suggests contributions from the paleo-Váh River

    Evolution of the lower Badenian depositional system in the East Slovakian Basin: Implications for reservoir rock potential

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    The Transcarpathian Basin, consisting of the Predov and Trebisov sub-basins, is situated at the border of the Western and Eastern Carpathians. Hydrocarbon exploration in this basin has been ongoing for more than 60 years and reserves of economic importance are located in the E to NE part of the basin. The Trebisov sub-basin was analysed to characterize and predict lower Badenian (Langhian) reservoir rocks. To achieve this aim, new sedimentary facies, seismic facies, petrographic and paleontological analyses were performed, combined with original total porosity and permeability measurements. Based on the planktic foraminifera and calcareous nannoplankton zonation, the lower Badenian sequence in the Trebisov sub-basin was divided into a lower and an upper interval. The presence of very well sorted sandstone layers, glauconite grains, albitization, selective alteration of tuffs into zeolites as well as the fossil assemblages reinforce the volcanic influenced marine environments. Documented sedimentary structures indicate subaqueous density flows preceded by the newly observed fluvial and deltaic facies. The total sandstone porosity measurements indicate a gradual porosity decrease with depth marked by a value of 13.21 % at the surface decreasing down to 6.41 % at similar to 3 km below the surface. These numbers correspond to reservoirs with low to reduced porosity. Diagenetic products such as illite, chlorite and feldspar cement together with compaction effects, and variations in the crystallinity in siliceous cement led to the modification of initial porosity. The potential lower Badenian reservoir sandstones are frequently deformed by strike-slip faults responsible for the large pull-apart basin complex (seen as horsetail structures on reflection seismic sections) forming various fault-bounded structural traps. The lower Badenian sandstones present at the top of two anti-clinal structures in the central part of the basin, display very strong reflection amplitudes on newly merged 3D reflection seismic data underlining the additional exploration potential in the basin.Web of Science73435231

    Mutant Neurogenin-3 in congenital malabsorptive diarrhea

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    Background: Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine. The NEUROG3 gene (NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells. Methods: We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3. We then tested the ability of the observed mutations to alter NEUROG3 function, using in vitro and in vivo assays. Results: The patients had few intestinal enteroendocrine cells positive for chromogranin A, but they had normal numbers of Paneth\u27s, goblet, and absorptive cells. We identified two homozygous mutations in NEUROG3, both of which rendered the NEUROG3 protein unable to activate NEUROD1, a downstream target of NEUROG3, and compromised the ability of NEUROG3 to bind to an E-box element in the NEUROD1 promoter. The injection of wild-type but not mutant NEUROG3 messenger RNA into xenopus embryos induced NEUROD1 expression. Conclusions: A newly discovered disorder characterized by malabsorptive diarrhea and a lack of intestinal enteroendocrine cells is caused by loss-of-function mutations in NEUROG3. Copyright © 2006 Massachusetts Medical Society

    Polytene chromosome squash methods for studying transcription and epigenetic chromatin modification in Drosophila using antibodies

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    The giant polytene chromosomes from Drosophila third instar larval salivary glands provide an important model system for studying the architectural changes in chromatin morphology associated with the process of transcription initiation and elongation. Especially, analysis of the heat shock response has proved useful in correlating chromatin structure remodeling with transcriptional activity. An important tool for such studies is the labeling of polytene chromosome squash preparations with antibodies to the enzymes, transcription factors, or histone modifications of interest. However, in any immunohistochemical experiment there will be advantages and disadvantages to different methods of fixation and sample preparation, the relative merits of which must be balanced. Here we provide detailed protocols for polytene chromosome squash preparation and discuss their relative pros and cons in terms of suitability for reliable antibody labeling and preservation of high resolution chromatin structure
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