Region selectivity

SJ Cho, A Tropsha. Cross-validated R2-guided region selection for comparative molecular held analysis A simple method to achieve consistent results. J Med Chem 38 1060-1066, 1995. 

T Kimura, K Hasegawa, K Funatsu. GA strategy for variable selection m QSAR studies GA-based region selection for CoMFA modeling. J Chem Inf Comput Sci 38 276-282, 1998. 

Figure 17.2 An example of prediction of the conformations of three CDR regions of a monoclonal antibody (top row) compared with the unrefined x-ray structure (bottom row). LI and L2 are CDR regions of the light chain, and HI is from the heavy chain. The amino acid sequences of the loop regions were modeled by comparison with the sequences of loop regions selected from a database of known antibody structures. The three-dimensional structure of two of the loop regions, LI and L2, were in good agreement with the preliminary x-ray structure, whereas HI was not. However, during later refinement of the x-ray structure errors were found in the conformations of HI, and in the refined x-ray structure this loop was found to agree with the predicted conformations. In fact, all six loop conformations were correctly predicted in this case. (From C. Chothia et al.. Science 233 755-758, 1986.)...

The variable selection methods have been also adopted for region selection in the area of 3D QSAR. For example, GOLPE [31] was developed with chemometric principles and q2-GRS [32] was developed based on independent CoMFA analyses of small areas of near-molecular space to address the issue of optimal region selection in CoMFA analysis. Both of these methods have been shown to improve the QSAR models compared to original CoMFA technique. 

QTLs were also detected in tomato introgression lines (domestic tomatoes with single, defined chromosome regions selected from the progeny of a cross with a wild, non-pigmented variety) that correspond to candidate loci for which genes and mutants have been previously characterized. Detected QTLs included the r locus Psy), the Del locus (LcyE), and the B locus. Similar to the tissue-specific expression of maize Yl, the B locus codes a fruit-specific lycopene cyclase associated with higher levels of P-carotene. ... 

In situ perfusion studies assess absorption as lumenal clearance or membrane permeability and provide for isolation of solute transport at the level of the intestinal tissue. Controlled input of drug concentration, perfusion pH, osmolality, composition, and flow rate combined with intestinal region selection allow for separation of aqueous resistance and water transport effects on solute tissue permeation. This system provides for solute sampling from GI lumenal and plasma (mesenteric and systemic) compartments. A sensitive assay can separate metabolic from transport contributions. 

Langlais, P. J., McRee, R. C., Nalwalk, J. A. and Hough, L. B. Depletion of brain histamine produces regionally selective protection against thiamine deficiency-induced lesions in the rat. Metab. Brain Dis. 17 199-210, 2002. 

De Waele, J. P., Audet, R. M., Leong, D. K. and Butterworth, R. F. Portacaval anastomosis induces region-selective alterations of the endogenous opioid system in the rat brain. Hepatology 24 895-901,1996. 

Perhaps the most successful application of Fukui function and local softness is in the elucidation of the region-selective behavior of different types of pericyclic reactions including the 1,3-dipolar cycloadditions (13DC), Diels-Alder reactions, etc. These reactions can be represented as shown in Scheme 12.4. Considering the concerted approach of the two reactants A and B, there are two possible modes of addition as shown in Pathway-I and Pathway-II. 

The difference between palladium andrhodium catalyses regarding region-selectivity is also noteworthy. The palladium complex provided Markovnikov... 

Many DA receptor antagonists (neuroleptics) for treating psychoses (for example, schizophrenia) have become efficient medicines. However, most of them induce severe extrapyramidal side-effects (EPS) akin to parkinsonian symptoms and also, more seriously, they induce tardive dyskinesias (TD). There is a need for improvements in the neuroleptics in the clinic. The substituted benzamides are D2 antagonists, some of which display a high degree of limbic selectivity. Such a regional selectivity has been suggested to be beneficial from the side-effects point of view [11,12]. 

In addition to their presence, the position of functional groups in a molecule can determine its smell. This is known as regional selectivity. ... 

Figure 3.23. Near-infrared reflectance spectra with second-derivative preprocessing before (a) and after (b) region selection. 

Stressful stimuli of many types produce marked increases in brain noradrenergic function. Stress produces regional selective increases in NE turnover in the locus coeruleus (LC), limbic regions (hypothalamus, hippocampus, and amygdala), and cerebral cortex. These changes can be elicited with immobilization stress, foot-shock stress, tail-pinch stress, and conditioned fear. Exposure to stressors from which the animal cannot escape results in behavioral deficits termed learned helplessness. The learned helplessness state is associated with depletion of NE, probably reflecting the point where synthesis cannot keep up with demand. These studies have been reviewed elsewhere in detail (Bremner et al. 1996a,b). 

The first neurochemical evidence of a disturbed serotonin function in cognition came from the changes in serotonin and/or 5-hydroxyindoleacetic acid (5-HIAA) levels in a number of forebrain nuclei, the temporal and cingulate cortex, hippocampus, and other areas of the brain taken at autopsy from patients with senile dementia of the Alzheimer s type (Adolfsson et al. 1978 Arai et al. 1984 D. M. Bowen et al. 1979, 1983 A. J. Cross et al. 1983 Winblad et al. 1982). The depletions are regionally selective reductions in se-... 

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