Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AqpZ is a homotetramer of four water-conducting channels that facilitate rapid water movements across the plasma membrane of Escherichia coli. Here we report a 3.2 angstroms crystal structure of the tetrameric AqpZ (tAqpZ). All channel-lining residues in the four monomeric channels are found orientated in nearly identical positions with one marked exception at the narrowest channel constriction, where the side chain of a highly conserved Arg-189 adopts two distinct conformational orientations. In one of the four monomers, the guanidino group of Arg-189 points toward the periplasmic vestibule, opening up the constriction to accommodate the binding of a water molecule through a tridentate H-bond. In the other three monomers, the Arg-189 guanidino group bends over to form an H-bond with carbonyl oxygen of the Thr-183, thus occluding the channel. Therefore, the tAqpZ structure reveals two distinct Arg-189 confirmations associated with water permeation through the channel constrictions. Alternation between the two Arg-189 conformations disrupts continuous flow of water, thus regulating the open probability of the water pore. Further, the difference in Arg-189 displacements is correlated with a strong electron density found between the first transmembrane helices of two open channels, suggesting that the observed Arg-189 conformations are stabilized by asymmetrical subunit interactions in tAqpZ.
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PMID:Crystal structure of AqpZ tetramer reveals two distinct Arg-189 conformations associated with water permeation through the narrowest constriction of the water-conducting channel. 1623 19

We studied a patient with refractory focal epilepsy using continuous EEG-correlated fMRI. Seizures were characterized by head turning to the left and clonic jerking of the left arm, suggesting a right frontal epileptogenic region. Interictal EEG showed occasional runs of independent nonlateralized slow activity in the delta band with right frontocentral dominance and had no lateralizing value. Ictal scalp EEG had no lateralizing value. Ictal scalp EEG suggested right-sided central slow activity preceding some seizures. Structural 3-T MRI showed no abnormality. There was no clear epileptiform abnormality during simultaneous EEG-fMRI. We therefore modeled asymmetrical EEG delta activity at 1-3 Hz near frontocentral electrode positions. Significant blood oxygen level-dependent (BOLD) signal changes in the right superior frontal gyrus correlated with right frontal oscillations at 1-3 Hz but not at 4-7 Hz and with neither of the two frequency bands when derived from contralateral or posterior electrode positions, which served as controls. Motor fMRI activations with a finger-tapping paradigm were asymmetrical: they were more anterior for the left hand compared with the right and were near the aforementioned EEG-correlated signal changes. A right frontocentral perirolandic seizure onset was identified with a subdural grid recording, and electric stimulation of the adjacent contact produced motor responses in the left arm and after discharges. The fMRI localization of the left hand motor and the detected BOLD activation associated with modeled slow activity suggest a role for localization of the epileptogenic region with EEG-fMRI even in the absence of clear interictal discharges.
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PMID:EEG-fMRI mapping of asymmetrical delta activity in a patient with refractory epilepsy is concordant with the epileptogenic region determined by intracranial EEG. 1667 42

Endothelial dysfunction is a hallmark of cardiovascular disease, and the l-arginine:NO pathway plays a critical role in determining endothelial function. Recent studies suggest that smoking, a well-recognized risk factor for vascular disease, may interfere with l-arginine and NO metabolism; however, this remains poorly characterized. Accordingly, we performed a series of complementary in vivo and in vitro studies to elucidate the mechanism by which cigarette smoke adversely affects endothelial function. In current smokers, plasma levels of asymmetrical dimethyl-arginine (ADMA) were 80% higher (P = 0.01) than nonsmokers, whereas citrulline (17%; P < 0.05) and N-hydroxy-l-arginine (34%; P < 0.05) were significantly lower. Exposure to 10% cigarette smoke extract (CSE) significantly affected endothelial arginine metabolism with reductions in the intracellular content of citrulline (81%), N-hydroxy-l-arginine (57%), and arginine (23%), while increasing ADMA (129%). CSE significantly inhibited (38%) arginine uptake in conjunction with a 34% reduction in expression of the arginine transporter, CAT1. In conjunction with these studies, CSE significantly reduced the activity of eNOS and NO production by endothelial cells, while stimulating the production of reactive oxygen species. In conclusion, cigarette smoke adversely affects the endothelial l-arginine NO synthase pathway, resulting in reducing NO production and elevated oxidative stress. In conjunction, exposure to cigarette smoke increases ADMA concentration, the latter being a risk factor for cardiovascular disease.
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PMID:Adverse effects of cigarette smoke on NO bioavailability: role of arginine metabolism and oxidative stress. 1692 96

Blue-light-induced phototropism in higher plants is regulated by phototropin, which is a photoreceptor kinase that contains a flavin mononucleotide (FMN). Recently, it was found that this kinase is inhibited by the binding of the LOV2 (light-oxygen-voltage2) domain in the dark but that its activity is increased in the light by the release of the LOV2 domain. Phototropin-associated proteins have been identified, although the proteins that are phosphorylated by phototropin are still unknown. The asymmetrical auxin distribution caused by unilateral irradiation suggests that differential growth is induced by a difference in auxin-regulated gene expression between the shaded and illuminated sides of plant organs. Transcription-related factors, such as NPH4/ARF7, MSG2/IAA19 and SCF(TIR1), play key roles in this process.
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PMID:Phototropin and light-signaling in phototropism. 1687 Apr 91

We recently experienced a case with asymmetrical cortical abnormality on MRI with focal status epilepticus following severe hypoglycemia. The cerebral blood flow and metabolisms for oxygen and glucose were determined using positron emission tomography (PET) during focal status epilepticus following severe hypoglycemia and at the follow-up period. Prolonged seizure activity produced profound glucose hypermetabolism and mild hyperemia in the region of the presumed cortical focus of epilepsy and in structures anatomically remote from the focus, corresponding to the areas of abnormal signal intensity on the MRI. The patient remained comatose and exhibited a diffuse hypoperfusion/hypometabolism and symmetrical brain atrophy on the follow-up PET and MRI, respectively. Cytotoxic brain edema due to profound glucose metabolism without compensatory increase of the blood flow during status epilepticus may account for the brain abnormality observed on the early MRI. Simultaneous examination of the cerebral blood flow and metabolism using PET can provide useful information about the pathology in patients with status epilepticus.
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PMID:Magnetic resonance imaging and positron emission tomography findings in status epilepticus following severe hypoglycemia. 1687 11

A three-dimensional anionic framework built up from [ZnO4] tetrahedra and planar [BO3] groups, stabilized by H atoms, has been found for hydrogen zinc oxide borate, H[Zn6O2(BO3)3]. Boron and one of the borate O atoms are on 18e (2) positions. Triple units of [ZnO4] tetrahedra sharing a common oxygen vertex on a 12c (3) site and strong asymmetrical linear hydrogen bonds with the H atom [on a 12c (3) position] disordered over a twofold axis are specific structural features of this zincoborate. There is evidence that the reported Zn4O(BO3)2 [Harrison, Gier & Stuky (1993). Angew. Chem. Int. Ed. Engl. 32, 724-726] corresponds to this structure.
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PMID:Proton-stabilized three-dimensional anionic framework in H[Zn6O2(BO3)3]. 1714 84

In the presence of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) damage, many DNA polymerases exhibit a dual coding potential which facilitates efficient incorporation of matched dCTP or mismatched dATP. This also holds true for the insertion of 8-oxodGTP opposite template bases dC and dA. Employing single-turnover kinetic methods, we examined human DNA polymerase beta and its novel X-family homolog, human DNA polymerase lambda, to determine which nucleotide and template base was preferred when encountering 8-oxodG and 8-oxodGTP, respectively. While DNA polymerase beta preferentially incorporated dCTP over dATP, DNA polymerase lambda did not modulate a preference for either dCTP or dATP when opposite 8-oxodG in single-nucleotide gapped DNA, as incorporation proceeded with essentially equal efficiency and probability. Moreover, DNA polymerase lambda is more efficient than DNA polymerase beta to fill this oxidized single-nucleotide gap. Insertion of 8-oxodGTP by both DNA polymerases lambda and beta occurred predominantly against template dA, thereby reiterating how the asymmetrical design of the polymerase active site differentially accommodated the anti and syn conformations of 8-oxodG and 8-oxodGTP. Although the electronegative oxygen at the C8 position of 8-oxodG may induce DNA structural perturbations, human DNA ligase I was found to effectively ligate the incorporated 8-oxodGMP to a downstream strand, which sealed the nicked DNA. Consequently, the erroneous nucleotide incorporations catalyzed by DNA polymerases lambda and beta as well as the subsequent ligation catalyzed by a DNA ligase during base excision repair are a threat to genomic integrity.
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PMID:Single-turnover kinetic analysis of the mutagenic potential of 8-oxo-7,8-dihydro-2'-deoxyguanosine during gap-filling synthesis catalyzed by human DNA polymerases lambda and beta. 1732 45

Laser Raman scattering data for nitrogen, oxygen, and water vapor have been obtained from hydrogen-air and hydrogen-oxygen flames. The resulting ground-state and upper-state vibrational bands exhibit strong asymmetrical broadening. Experimental spectral profiles have been fitted theoretically to give a new measurement technique for the determination of rotational and vibrational excitation temperatures.
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PMID:Raman scattering from flames. 1779 91

The evolution of habitual bipedalism is still a fundamental yet unsolved question for paleoanthropologists, and carrying is popular as an explanation for both the early adoption of upright walking and as a positive selection pressure once a terrestrial lifestyle had been adopted. However, to support or reject any hypothesis that suggests carrying efficiency was an important selective pressure, we need quantitative data on the costs of different forms of carrying behavior, especially infant-carrying since reduction in the grasping capabilities of the foot would have prevented infants from clinging on for long durations. In this study, we tested the hypothesis that the mode of load carriage influences the energetic cost of locomotion. Oxygen consumption was measured in seven female participants walking at a constant speed while carrying four different 10-kg loads (a weighted vest, 5-kg dumbbells carried in each hand, a mannequin infant carried on one hip, and a 10-kg dumbbell carried in a single hand). Oxygen consumption was also measured during unloaded standing and unloaded walking. The results show that the weighted vest requires the least amount of energy of the four types of carrying and that, for this condition, humans are as efficient as mammals in general. The balanced load was carried with approximately the predicted energy cost. However, the asymmetrical conditions were considerably less efficient, indicating that, unless infant-carrying was the adaptive response to a strong environmental selection pressure, this behavior is unlikely to have been the precursor to the evolution of bipedalism.
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PMID:The energetic costs of load-carrying and the evolution of bipedalism. 1802 69

Telmisartan, in addition to blocking angiotensin (Ang) II type 1 receptor (AT(1)R), activates peroxisome proliferator activated receptor gamma (PPARgamma) signaling that interferes with nitric oxide (NO) system. Because aging of endothelial cells (ECs) is hallmarked by a reduction in NO synthesis, we hypothesized that telmisartan increases NO formation by regulated asymmetrical dimethylarginine (ADMA)-dimethylarginine dimethylaminohydrolase (DDAH)-system through blocking AT(1)R and activating PPARgamma signaling. To test this hypothesis, ECs were cultured with telmisartan, eprosartan, Ang II, and GW9662 (PPARgamma antagonist) until the twelfth passage. During the process of aging, PPARgamma protein expression decreased significantly, whereas the expression of AT(1)R increased. Telmisartan reversed these effects and dose-dependently decreased reactive oxygen species and 8-iso-prostaglandin (PG) F(2alpha) formation. This effect was associated with an upregulated activity and protein expression of DDAH, accompanied by a decrease in ADMA concentration, an increase in NO metabolites, and delayed senescence. Blockade of PPARgamma signaling by GW9662 or PPARgamma small-interference RNA prevented the effect of telmisartan on ADMA-DDAH-NO system. Coincubation with Ang II did not affect the effect of telmisartan-delayed senescence, whereas Ang II itself accelerated endothelial aging. Moreover, AT(1)R blocker eprosartan that did not influence PPARgamma protein expression had no effect on ADMA system and senescence. We have demonstrated that telmisartan mainly by activating PPARgamma signaling can alter the catabolism and release of ADMA as an important cardiovascular risk factor. We therefore propose that telmisartan translationally and posttranslationally upregulated DDAH expression via activation of PPARgamma signaling, causing ADMA to diminish and increase NO synthesis sufficient to delay senescence.
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PMID:Effect of telmisartan on nitric oxide--asymmetrical dimethylarginine system: role of angiotensin II type 1 receptor gamma and peroxisome proliferator activated receptor gamma signaling during endothelial aging. 1825 Mar 62


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