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排序方式: 共有163条查询结果,搜索用时 15 毫秒
51.
Bae GU Domené S Roessler E Schachter K Kang JS Muenke M Krauss RS 《American journal of human genetics》2011,(2):231-240
Holoprosencephaly (HPE), a common human congenital anomaly defined by a failure to delineate the midline of the forebrain and/or midface, is associated with diminished Sonic hedgehog (SHH)-pathway activity in development of these structures. SHH signaling is regulated by a network of ligand-binding factors, including the primary receptor PTCH1 and the putative coreceptors, CDON (also called CDO), BOC, and GAS1. Although binding of SHH to these receptors promotes pathway activity, it is not known whether interactions between these receptors are important. We report here identification of missense CDON mutations in human HPE. These mutations diminish CDON's ability to support SHH-dependent gene expression in cell-based signaling assays. The mutations occur outside the SHH-binding domain of CDON, and the encoded variant CDON proteins do not display defects in binding to SHH. In contrast, wild-type CDON associates with PTCH1 and GAS1, but the variants do so inefficiently, in a manner that parallels their activity in cell-based assays. Our findings argue that CDON must associate with both ligand and other hedgehog-receptor components, particularly PTCH1, for signaling to occur and that disruption of the latter interactions is a mechanism of HPE. 相似文献
52.
Manfred Georg Moertl Helmut Karl Lackner Ilona Papousek Andreas Roessler Helmut Hinghofer-Szalkay Uwe Lang Vassiliki Kolovetsiou-Kreiner Dietmar Schlembach 《PloS one》2013,8(4)
Background
The autonomic nervous system plays a central role in the functioning of systems critical for the homeostasis maintenance. However, its role in the cardiovascular adaptation to pregnancy-related demands is poorly understood. We explored the maternal cardiovascular systems throughout pregnancy to quantify pregnancy-related autonomic nervous system adaptations.Methodology
Continuous monitoring of heart rate (R-R interval; derived from the 3-lead electrocardiography), blood pressure, and thoracic impedance was carried out in thirty-six women at six time-points throughout pregnancy. In order to quantify in addition to the longitudinal effects on baseline levels throughout gestation the immediate adaptive heart rate and blood pressure changes at each time point, a simple reflex test, deep breathing, was applied. Consequently, heart rate variability and blood pressure variability in the low (LF) and high (HF) frequency range, respiration and baroreceptor sensitivity were analyzed in resting conditions and after deep breathing. The adjustment of the rhythms of the R-R interval, blood pressure and respiration partitioned for the sympathetic and the parasympathetic branch of the autonomic nervous system were quantified by the phase synchronization index γ, which has been adopted from the analysis of weakly coupled chaotic oscillators.Results
Heart rate and LF/HF ratio increased throughout pregnancy and these effects were accompanied by a continuous loss of baroreceptor sensitivity. The increases in heart rate and LF/HF ratio levels were associated with an increasing decline in the ability to flexibly respond to additional demands (i.e., diminished adaptive responses to deep breathing). The phase synchronization index γ showed that the observed effects could be explained by a decreased coupling of respiration and the cardiovascular system (HF components of heart rate and blood pressure).Conclusions/Significance
The findings suggest that during the course of pregnancy the individual systems become increasingly independent to meet the increasing demands placed on the maternal cardiovascular and respiratory system. 相似文献53.
Gérard Leboulle Claudia Niggebrügge Reinhard Roessler Adriana D. Briscoe Randolf Menzel Natalie Hempel de Ibarra 《Insect biochemistry and molecular biology》2013,43(10):959-969
Targeted knock-down is the method of choice to advance the study of sensory and brain functions in the honeybee by using molecular techniques. Here we report the results of a first attempt to interfere with the function of a visual receptor, the long-wavelength-sensitive (L-) photoreceptor. RNA interference to inhibit this receptor led to a reduction of the respective mRNA and protein. The interference effect was limited in time and space, and its induction depended on the time of the day most probably because of natural daily variations in opsin levels. The inhibition did not effectively change the physiological properties of the retina. Possible constraints and implications of this method for the study of the bee's visual system are discussed. Overall this study underpins the usefulness and feasibility of RNA interference as manipulation tool in insect brain research. 相似文献
54.
Huang P Ho SR Wang K Roessler BC Zhang F Hu Y Bowe DB Kudlow JE Paterson AJ 《American journal of physiology. Cell physiology》2011,300(3):C456-C465
The protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification plays an important role in skeletal muscle development and physiological function. In this study, bitransgenic mice were generated that overexpressed NCOAT(GK), an O-GlcNAcase-inactive spliced variant of the O-GlcNAcase gene, specifically in skeletal muscle using the muscle creatine kinase promoter. Expression of the chimeric enhanced green fluorescent protein-NCOAT(GK) transgene caused an increase of cellular O-GlcNAc levels, along with the accumulation and activation of proapoptotic factors in muscles of bitransgenic mice. The consequence of overexpressing the transgene for a 2-wk period was muscle atrophy and, in some cases, resulted in the death of male mice. Muscle atrophy is a common complication of many diseases, some of which correlate markedly with high cellular O-GlcNAc levels, such as diabetes. Our study provides direct evidence linking muscle atrophy and the disruption of O-GlcNAcase activity. 相似文献
55.
Paul G. Roessler 《Journal of phycology》1987,23(3):494-498
UDPglucose pyrophosphorylase activity was detected in cell-free extracts of the diatom Cyclotella cryptica TI3L Reimann, Lewin and Guillard. When assayed in the direction of UDPglucose formation, the enzyme had maximal activity at pH 7.8 and was stimulated by Mg2+and Mn2+ions. 3-Phosphoglycerate and inorganic phosphate had little effect on enzymatic activity, and the enzyme was relatively insensitive to feedback inhibition from UDPglucose (K, > I millimolar). A glucan was formed from UDP-[14C]glucose in cell-free extracts of C. cryptica. This glucan had a median molecular weight of 4600 (as determined by gel filtration chromatograbhy) and could be hydrolyzed by laminarinase. Partial acid hydrolysis of the glucan resulted in the formation of glucose and laminaribiose. but not cellobiose. These results suggest that the synthesis of chrysolaminarin (the major storage carbohydrate of diatoms) occurs via the activity of UDPglucose pyrophosphorylase. followed by glucosyl transfer from UDPglucose to the growing β-(1–3)-linked glucan. 相似文献
56.
57.
Haditsch B Roessler A Hinghofer-Szalkay HG 《Physiological research / Academia Scientiarum Bohemoslovaca》2007,56(6):779-787
Previous investigations revealed that most of the fluid regulating hormones showed no consistent relationship to the hypoxic diuretic response (HDR). In this study we examined if adrenomedullin (AM), a hypoxia-mediated diuretic/natriuretic peptide is connected to HDR. Thirty-three persons were examined at low altitude (LA), on the third exposure day at 3440 m (medium altitude, MA) and on the fourteenth day at 5050 m (high altitude, HA). Nocturnal diuresis rose from 460 ml [interquartile range 302 ml] at LA to 560 [660] ml at MA to 1015 [750] ml at HA (p<0.005). Sodium excretion was similar at LA and MA (41.8 [27.0] vs. 41.4 [28.4] mM) and increased to 80.2 [29.1] mM at HA (p<0.005). Urinary AM excretion was 7.9 [3.9] at LA, 7.5 [5.7] pM at MA, and increased to 10.5 [5.1] pM (p<0.05) at HA. Urinary AM excretion was correlated to diuresis (r=0.72, p<0.005) and sodium excretion (r=0.57, p<0.005). Plasma AM concentration rose from 16.4 [3.1] to 18.8 [4.9] pM/l at MA (p<0.005) and to 18.3 [4.3] pM/l at HA (p<0.005). Plasma AM concentration and urinary AM excretion were not correlated, neither were plasma AM concentration and diuresis or natriuresis. Our data suggest the involvement of increased renal AM production in the pathophysiology of high altitude fluid and sodium loss. 相似文献
58.
Kyria Boundy-Mills Matthias Hess A. Rick Bennett Matthew Ryan Seogchan Kang David Nobles Jonathan A. Eisen Patrik Inderbitzin Irnayuli R. Sitepu Tamas Torok Daniel R. Brown Juliana Cho John E. Wertz Supratim Mukherjee Sherry L. Cady Kevin McCluskey 《Applied and environmental microbiology》2015,81(17):5671-5674
The mission of the United States Culture Collection Network (USCCN; http://usccn.org) is “to facilitate the safe and responsible utilization of microbial resources for research, education, industry, medicine, and agriculture for the betterment of human kind.” Microbial culture collections are a key component of life science research, biotechnology, and emerging global biobased economies. Representatives and users of several microbial culture collections from the United States and Europe gathered at the University of California, Davis, to discuss how collections of microorganisms can better serve users and stakeholders and to showcase existing resources available in public culture collections. 相似文献
59.
Shipeng Wei Bryan C. Roessler Sylvain Chauvet Jingyu Guo John L. Hartman IV Kevin L. Kirk 《The Journal of biological chemistry》2014,289(29):19942-19957
ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares gating principles with conventional ligand-gated ion channels, but the allosteric network that couples ATP binding at its nucleotide binding domains (NBDs) with conformational changes in its transmembrane helices (TMs) is poorly defined. It is also unclear whether the mechanisms that govern CFTR gating are conserved with the thermodynamically distinct MRPs. Here we report a new class of gain of function (GOF) mutation of a conserved proline at the base of the pore-lining TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and activation by the weak agonist, 5′-adenylyl-β,γ-imidodiphosphate (AMP-PNP). TM6 proline mutations exhibited additive GOF effects when combined with a previously reported GOF mutation located in an outer collar of TMs that surrounds the pore-lining TMs. Each TM substitution allosterically rescued the ATP sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP binding. Both classes of GOF mutations also rescued defective drug export by a yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the conserved TM6 proline helps set the energy barrier to both CFTR channel opening and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar allosteric mechanisms for coupling conformational changes in their translocation pathways to ATP binding at their NBDs. 相似文献
60.
Parkin A Bowman L Roessler MM Davies RA Palmer T Armstrong FA Sargent F 《FEBS letters》2012,586(5):536-544
Salmonella enterica serovar Typhimurium is a Gram negative bacterial pathogen and a common cause of food-borne illness. Molecular hydrogen has been shown to be a key respiratory electron donor during infection and H(2) oxidation can be catalysed by three genetically-distinct [NiFe] hydrogenases. Of these, hydrogenases-1 (Hyd-1) and Hyd-2 have well-characterised homologues in Escherichia coli. The third, designated Hyd-5 here, is peculiar to Salmonella and is expressed under aerobic conditions. In this work, Salmonella was genetically modified to enable the isolation and characterisation of Hyd-5. Electrochemical analysis established that Hyd-5 is a H(2)-oxidising enzyme that functions in very low levels of H(2) and sustains this activity in high levels of O(2). In addition, electron paramagnetic resonance spectroscopy of the Hyd-5 isoenzyme reveals a complex paramagnetic FeS signal at high potentials which is comparable to that observed for other O(2)-tolerant respiratory [NiFe] hydrogenases. Taken altogether, Hyd-5 can be classified as an O(2)-tolerant hydrogenase that confers upon Salmonella the ability to use H(2) as an electron donor in aerobic respiration. 相似文献