NTRODUCTION. The adenosine receptor is a member of the rhodopsin-like family of G protein-coupled receptors (GPCRs). In human, there are 4 subtypes of adenosine receptors: X0, X0X, X0X, and A3. Among them, the A2B subtype is implied in atherosclerosis of smooth muscle cells, in mast cell activation in asthma, resulting in bronchoconstriction, in intestinal (dys)function, and in dilation of certain vascular beds (Feoktistov et al., 1998; Xxxxxxx and Xxxxxxxxx, 1998; Xxxxxxx, 2005; Xxxx et al., 2005). Despite extensive efforts, structural information on GPCRs is still scarce. To date, two crystal structures are available, that of the inactive state of bovine rhodopsin (Xxxxxxxxxx et al., 2000) and, very recently, of the human β2 adrenergic receptor (Xxxxxxxx et al., 2007; Xxxxxxxxx et al., 2007; Xxxxxxxxx et al., 2007). Until now the structure of bovine rhodopsin has been used as a template to build homology models for GPCRs (Xxxxxxxx et al., 2003; Xxxx et al., 2006; Xxxxxxx and Xxxx, 2006; Xxxxx et al., 2006). The availability of the β2-adrenergic receptor structure enabled us to build and compare two homology models of the human adenosine A2B receptors. Rhodopsin-like GPCRs (class A GPCRs) share a large number of conserved sequence patterns. For example, the most conserved residues in each transmembrane (TM) helix are: N1.50, D2.50, R3.50, W4.50, P5.50, P6.50, and P7.50, following the numbering scheme introduced by Xxxxxxxxxxx and Xxxxxxxxx (1995). These patterns are easily identified and used for multiple sequence alignment of rhodopsin-like GPCRs to allow sequence comparison and model building (Xxxxxxxxxx et al., 2003). Highly conserved patterns imply an important structural and/or functional role. Several conserved patterns have been identified among class A GPCRs: a disulfide bridge formed by the two Cys residues located in extracellular loop 2 (IL2) and at the beginning of TM3 (Xxxx et al., 2005); salt bridges between TM3 and TM6 or TM1 and TM7 (Xxx et al., 1997; Xxxxxxxxxxx et al., 2001); the DRY/ERY motif at the end of TM3 (Alewijnse et al., 2000); CWxP in TM 6 (Xxx et al., 2002; Xxxxxxxx et al., 2004); and an extended motif consisting of the NPxxY motif in TM 7 with the F in TM8 5 or 6 amino acids downstream of the NPxxY motif (Xxxxxxxx et al., 2001; Xxxxxx et al., 2005; Xxxxxxxxxx, et al., 2003) This NPxxY motif is highly conserved and is part of the NxxxNPxxY motif. In our previous study (Xxxxxxx et al., 2004a), we applied random mutagenesis followed by funct...
NTRODUCTION. Many studies have noted a higher prevalence of psychiatric morbidity in patients with epilepsy compared with normal controls -9 Reviews of the relevant literature suggest that mood and anxiety disorders are the most frequently diagnosed psy- chiatric disorders in patients with epilepsy 0-13. Also, an increased prevalence of per- sonality (disorder) traits or disorders is frequently found in these patients 4-16 Traditionally, temporal lobe epilepsy (TLE) is considered to present a relatively specific risk factor, notably for affective disorders, because of the major involvement of the limbic system in both seizure generation in TLE and in the regulation of af- fect and mood. Numerous studies have reported an increased rate of psychiatric disturbances in patients with TLE, compared to patients with other types of epilepsy 1,2,5,14,17-26. Other studies, however, failed to document such an association between TLE and psychiatric symptoms 6,9,27-4 . The laterality of the seizure focus has also been considered as a potential risk factor for psychiatric illness in epilepsy. Some authors emphasize the role of the right hemisphere 42,43, which is suggested to have more extensive limbic connections than the left hemisphere, whereas the majority of the studies implicate the left hemisphere 5,26,44-48, or find no effect of lateralization at all 32,35,37,38,49-54. Although there is support for the association between epilepsy and psychiatric disorders, the empirical evidence for a specific association between the localisation and lateralization of the epileptogenic zone in partial epilepsy and psy- chiatric morbidity remains equivocal. Both, methodological and theoretical factors appear to account for these discrep- ant findings. For psychiatric assessment, a variety of diagnostic instruments is used, ranging from predominantly subjective self-reporting questionnaires to objective and reliable diagnostic tests. Some authors use cut-off scores to classify the sub- jects, whereas others use mean scores. Psychiatric findings from these studies are thus difficult to compare. The same can be said for the selection of patients with epilepsy who were investi- gated, and the control subjects. Several studies fail to define clear diagnostic xxxxx- ria for epilepsy and/or psychiatric disorders and their selection criteria, and precise definitions of epilepsy subgroups are often unclear or not provided for at all. Early studies on the prevalence of psychiatric syndromes in epilep...
NTRODUCTION. The District shall comply with the following travel and per diem reimbursement requirements, as well as all other reimbursement requirements set forth in general or special law and specifically Section 112.061 Florida Statute, as may be amended:
NTRODUCTION. 1.1 Parties This Settlement Agreement is entered by and between Center for Advanced Public Awareness, Inc. CAPA ) and Ground Up International Ground Up ), with CAPA and Ground Up CAPA is a California nonprofit corporation dedicated to protecting the environment, improving human health, and promoting environmentally sound practices. Ground Up supplied the footwear (flip-flops) referenced in this Settlement Agreement to Wal-Mart Stores, Inc. ( Wal-Mart ), the entity named in CAPA September 17, 2017, 60-Day Notice of Violation. As the manufacturer of the products covered by this Settlement Agreement, Ground Up is stepping in to resolve the alleged violations at issue. General Allegations
NTRODUCTION. 63.1 Upon implementation of LNP, both Parties agree to conform and provide such LNP pursuant to FCC regulations and compliance with the Industry Forum. To the extent consistent with the FCC and Industry rules as amended from time to time, the requirements for LNP shall include the following:
