Atomic contributions to the optical rotation angle as a quantitative probe of molecular chirality

Chiral molecules are characterized by a specific rotation angle, the angle through which plane-polarized light is rotated on passing through an enantiomerically enriched solution. Recent developments in methodology allow computation of both the sign and the magnitude of these rotation angles. However, a general strategy for assigning the individual contributions that atoms and functional groups make to the optical rotation angle and, more generally, to the molecular chirality has remained elusive. Here, a method to determine the atomic contributions to the optical rotation angle is reported. This approach links chemical structure with optical rotation angle and provides a quantitative measure of molecular asymmetry propagation from a center, axis, or plane of chirality.     

应用LSI9q34探针及ES/DCDF探针检测慢性粒细胞白血病患者der(9)缺失的研究

目的 研究慢性粒细胞性白血病(CML)患者衍生9号染色体[der(9)]部分序列缺失情况,探讨LSI 9q34探针在检测der(9)缺失中的联合应用价值.方法 对52例CML患者采用不加任何刺激剂的骨髓进行24 h短期培养法制备染色体,吉姆萨显带进行核型分析.应用ES/DCDF探针及LSI 9q34探针对骨髓间期细胞进行荧光原位杂交,并检测der(9)部分序列缺失.结果 52例中经ES/DCDF探针检测全部为ber-abl融合基因阳性,其中12例患者伴有der(9)部分缺失,占23.0%,经LSI 9q34探针检测有11例患者伴有der(9)部分缺失.结论 LSI9q34探针在判断CML患者是否伴有der(9)缺失方面有较好的特异性.伴有缺失的患者疾病进展较快,预后较差,甲磺酸依马替尼治疗不能完全逆转其负性作用,建议所有bcr-abl融合基因阳性的CML患者均应行 LSI 9q34探针检测,以指导临床治疗.     

Spin-lattice relaxation in ammonium compounds with a complex molecular dynamics

Expressions are derived for the initial relaxation rate 1/T1 of protons and deuterons of nontunnelling NH4 and ND4 groups reorienting about various symmetry axes in solids. The reorientation rates are modified by a trigonal, tetragonal or monoclinic distortion of the predominantly cubic hindering potential. When the rates differ sufficiently from each other, two T1 minima are observed with a characteristic ratio. Experiments were performed in NH4VO3, (NH4)2S2O8, (NH4)2PtCl4, and their deuterated modifications, which all exhibit two T1 minima. In NH4VO3 and ND4VO3 the relaxation and spectral data agree rather well with the model of trigonal distortion. Also (NH4)2S2O8 has a preferred threefold axis but there, the large tunnel splitting of protons has to be taken into account before an agreement is reached. All the purely reorientational models fail with (NH4)2PtCl4, where, instead, the ammonium groups are proposed to be ordered into domains at low temperatures. The groups inside the domains and boundary regions give rise to the high- and low-temperature T1 minima, respectively. The boundaries are also believed to give rise to the narrow component in the deuteron spectrum at low temperatures. Evidence for a proton tunnelling frequency of 32 MHz is found in (NH4)2PtCl4.     

Cholecystokinin-B/gastrin receptor: a novel molecular probe for human small cell lung cancer

The brain-gut hormones, gastrin and cholecystokinin, have a trophic effect on the gastrointestinal mucosa in vivo and promote the growth of several neoplastic cell lines. In this study, cholecystokinin-B/gastrin receptor has been demonstrated to provide a novel molecular marker for the diagnosis of small cell lung cancer by using biopsy specimens. Physiological expression of the receptor mRNA is detectable in particular areas of the human brain, stomach, and pancreas but not in the lung. The receptor mRNA was detected selectively in all small cell lung cancer (10 cases) with a RT-PCR assay. By contrast, it was detectable in only 1 of 13 squamous cell carcinomas or 21 adenocarcinomas of the lung. Thus, the cholecystokinin-B/gastrin receptor could be an attractive therapeutic target for small cell lung cancer.     

Interaction of human SRY protein with DNA: a molecular dynamics study

Molecular dynamics simulations have been conducted to study the interaction of human sex-determining region Y (hSRY) protein with DNA. For this purpose, simulations of the hSRY high mobility group (HMG) domain (hSRY-HMG) with and without its DNA target site, a DNA octamer, and the DNA octamer alone have been carried out, employing the NMR solution structure of hSRY-HMG-DNA complex as a starting model. Analyses of the simulation results demonstrated that the interaction between hSRY and DNA was hydrophobic, just a few hydrogen bonds and only one water molecule as hydrogen-bonding bridge were observed at the protein-DNA interface. These two hydrophobic cores in the hSRY-HMG domain were the physical basis of hSRY-HMG-DNA specific interaction. They not only maintained the stability of the complex, but also primarily caused the DNA deformation. The salt bridges formed between the positive-charged residues of hSRY and phosphate groups of DNA made the phosphate electroneutral, which was advantageous for the deformation of DNA and the formation of a stable complex. We predicted the structure of hSRY-HMG domain in the free state and found that both hSRY and DNA changed their conformations to achieve greater complementarity of geometries and properties during the binding process; that is, the protein increased the angle between its long and short arms to accommodate the DNA, and the DNA became bent severely to adapt to the protein, although the conformational change of DNA was more severe than that of the hSRY-HMG domain. The sequence specificity and the role of residue Met9 are also discussed.     

Results with a cementless alumina-coated cup with dual mobility. A twelve-year follow-up study

Two groups of 12 young bulls, as similar as possible with respect to age and weight, were fed a basic diet of hay and concentrates ad libitum for 170 days. The concentrate fed to one of the groups was supplemented with 0.20 mg of organic chromium per kg DM from a fodder yeast product so that the concentration of chromium in the total dry matter of their diet was 0.90 mg/kg, compared with 0.72 mg/kg in the diet of the control group. No significant differences were observed between the two groups of animals in terms of either their daily weight gain or any of the parameters of carcass quality examined. It is therefore concluded that in Sweden there is no reason to add chromium routinely to the diet of intensively fed, growing bulls.     

Evidence for a striatal NMDA receptor modulation of nigral glutamate release. A dual probe microdialysis study in the awake freely moving rat

Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was approximately 9% greater (P < 0.05) than that of the contralateral TA muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles (P < 0.05). As a result of these coordinated changes, the DNA-to-protein ratio of the hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.     

Interactional and intrapsychic dynamics in a family with a borderline patient.

Proposes an integration of intrapsychic with interpersonal theory in explaining borderline behavior in the family. It is asserted that borderline patients use the primitive ego defenses of projective identification, splitting, and idealization to resolve their intrapsychic problems through interpersonal means. Behaviors or symptoms resulting from the employment of these defenses can be observed in family interactions. References to those behavior manifestations are presented from the family therapy literature, and the case of a family is used to illustrate family and intrapsychic dynamics. It is hypothesized that family therapy is a useful alternative for treating the borderline patient because the family is the primary structure in which borderline behavior is encouraged and maintained. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of substrate uridyl 3',5'-adenosine with ribonuclease A: a molecular dynamics study

A wealth of information available from x-ray crystallographic structures of enzyme-ligand complexes makes it possible to study interactions at the molecular level. However, further investigation is needed when i) the binding of the natural substrate must be characterized, because ligands in the stable enzyme-ligand complexes are generally inhibitors or the analogs of substrate and transition state, and when ii) ligand binding is in part poorly characterized. We have investigated these aspects in the binding of substrate uridyl 3',5'-adenosine (UpA) to ribonuclease A (RNase A). Based on the systematically docked RNase A-UpA complex resulting from our previous study, we have undertaken a molecular dynamics simulation of the complex with solvent molecules. The molecular dynamics trajectories of this complex are analyzed to provide structural explanations for varied experimental observations on the ligand binding at the B2 subsite of ribonuclease A. The present study suggests that B2 subsite stabilization can be effected by different active site groups, depending on the substrate conformation. Thus when adenosine ribose pucker is O4'-endo, Gln69 and Glu111 form hydrogen-bonding contacts with adenine base, and when it is C2'-endo, Asn71 is the only amino acid residue in direct contact with this base. The latter observation is in support of previous mutagenesis and kinetics studies. Possible roles for the solvent molecules in the binding subsites are described. Furthermore, the substrate conformation is also examined along the simulation pathway to see if any conformer has the properties of a transition state. This study has also helped us to recognize that small but concerted changes in the conformation of the substrate can result in substrate geometry favorable for 2',3' cyclization. The identified geometry is suitable for intraligand proton transfer between 2'-hydroxyl and phosphate oxygen atom. The possibility of intraligand proton transfer as suggested previously and the mode of transfer before the formation of cyclic intermediate during transphosphorylation are discussed.     

Functional neuroanatomy of the nigrostriatal and striatonigral pathways as studied with dual probe microdialysis in the awake rat--I. Effects of perfusion with tetrodotoxin and low-calcium medium

Family studies using thresholds showed that PROP (6-n-propylthiouracil) tasting is produced by a dominant allele, T. Nontasters have two recessive alleles and tasters have one or two dominant alleles. The bitterness of suprathreshold PROP and anatomical criteria subdivide tasters into medium and supertasters. Supertasters may be TT tasters, but this has yet to be demonstrated. Supertasters preceive the greatest bitterness and sweetness from many stimuli as well as the greatest oral burn from alcohol and capsaicin. Women are more likely than men to be supertasters. Otitis media and head trauma can alter taste and thus PROP classifications, complicating studies on PROP genetics. Some subjects with a history of otitis media show taste reductions, but others show enhanced tastes and appear to have more taste buds per fungiform papilla. Subjects with head trauma show reduced tastes on some oral loci, but there is evidence that severe reductions on the front of the tongue ameliorate reductions at the circumvallate papillae on the back of the tongue by a release of inhibition mechanism.     

CAMDAS: an automated conformational analysis system using molecular dynamics. Conformational Analyzer with Molecular Dynamics And Sampling

In order to investigate the relationship among virulent and avirulent Bacteroides fragilis strains, SDS-PAGE of whole-cell proteins (WP) and periplasmic proteins (PP) were used to establish a protein profile of strains isolated from human infections, fecal flora and environmental water. Despite different sources of the strains, no significant differences were observed as determined by the WP SDS-PAGE analysis. In contrast, the proteins obtained from the bacterial periplasm showed differences in the electrophoretic protein profile. Two distinct PP profile patterns were obtained. Pattern A included 6 out of the 8 virulent strains and pattern B, 6 out of 8 avirulent strains. Interestingly, an environmental strain that was capable of inducing abscesses in mice, had a PP profile highly similar to that of the virulent strains from human infections. These data indicate that PP from B. fragilis may be useful to characterize differences among virulent and avirulent strains. Moreover, strains isolated from environmental water may also be a source of exogenous infections by B. fragilis.     

Trends in the residential (inpatient) treatment of individuals with a dual diagnosis.

Clinical trends are discussed with respect to the inpatient treatment of individuals with dual diagnosis. Identified operant trends include the increased attention on functionally derived treatments and treatments designed for infrequent behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physical status as a moderator of depressive symptoms among older adults with dual sensory loss.

Objective: This study evaluated the ability of three measures of physical status—physical activity, physical condition, and body mass index (BMI)—to moderate the relationship between dual sensory loss (DSL) and depressive symptoms in older adults. Method: Nationally representative longitudinal data were used to develop multilevel models predicting depressive symptoms among two groups of older adults, 1380 who developed DSL during the study and 1308 without sensory loss. Results: All three measures were associated with depressive symptoms for persons who had or would develop a DSL: participation in physical activity and being in better physical condition were associated with lower levels of depressive symptoms, while lower BMI levels were associated with higher levels of depressive symptoms. All moderator variables had a larger effect for persons with DSL as compared to persons without sensory loss. Implications: The implication of these findings is that participation in a regular program of physical activity may provide multiple benefits to older persons with DSL. Families and health care providers can offer support for being physically active by ensuring the person has the best possible correction for the sensory losses, providing encouragement, and/or providing physical assistance with exercise. (PsycINFO Database Record (c) 2011 APA, all rights reserved)