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Opposite effect of caveolin-1 in the metabolism of high-density and low-density lipoproteins.

Receptors of the scavenger class B family were reported to be localized in caveolae, the cell surface microdomains rich in free cholesterol and glycosphyngolipids, which are characterized by the presence of caveolin-1. Parenchymal hepatic and hepatoma HepG2 cells express very low levels of caveolin-1. In the present study, stable transformants of HepG2 cells expressing caveolin-1 were generated to address the effect of caveolin-1 on receptor activity. Compared to normal cells, these cells show higher (125)I-bovine serum albumin (BSA) uptake and cholesterol efflux, two indicators of functional caveolae. By immunoprecipitation, cell fractionation and confocal analyses, we found that caveolin-1 is well colocalized with the cluster of differentiation-36 (CD36) and the low-density lipoprotein (LDL) receptor (LDLr) but to a lesser extent with the scavenger receptor class B type I (SR-BI) in HepG2 cells expressing caveolin-1. However, caveolin-1 expression favors the dimerization of SR-BI. Two clones of cells expressing caveolin-1 were investigated for their lipoprotein metabolism activity. Compared to normal cells, these cells show a 71-144% increase in (125)I-LDL degradation. The analysis of the cholesteryl esters (CE)-selective uptake (CE association minus protein association) revealed that the expression of caveolin-1 in HepG2 cells decreases by 59%-73% LDL-CE selective uptake and increases high-density lipoprotein (HDL)-CE selective uptake by 44%-66%. We conclude that the expression of caveolin-1 in HepG2 cells moves the balance of LDL degradation/CE selective uptake towards degradation and favors HDL-CE selective uptake. Thus, in the normal hepatic parenchymal situation where caveolin-1 is poorly expressed, LDL-CE selective uptake is the preferred pathway.

Biological Transport↗

A method for detecting centres of natural selection in protein structures: potential for predicting the location of functional areas.

A simple method has been developed to detect protein microenvironments which are likely to be the focus of natural selection, and thereby important for function. It relies on distinguishing between the probability of an amino acid type arising by genetic mutation and the probability that it will be chosen by natural selection. When applied to proteins of known tertiary structure, the method revealed that major differences exist in the balance between neutral and selected change, and also that functional sites can be highlighted.

Animals↗

The link between composition and balance in masterworks vs. paintings of lower artistic quality.

In painting, composition is commonly defined as the two-dimensional arrangement of elements within the canvas. Each element is considered to have a perceptual weight. The arrangement of these weighted elements determines how balanced a painting is. It has been suggested that due to superior composition, masterworks may be more balanced than works of lower artistic quality. We tested this hypothesis by instructing our participants to rate masterworks and selections of lower artistic quality on balance. This hypothesis was not supported. Second, it has been suggested that rearranging elements within a painting may have a more detrimental effect on composition (and by extension balance) in masterworks than in selections of lower artistic quality. This view associates works of higher artistic quality with visual rightness, thereby predicting that compositional change would be more likely to cause deviations from a visually right state in masterworks. We tested this hypothesis by displacing an element within each painting to a different location, and measuring the effect on balance. In accordance with recent findings in the literature, we also took into account the severity of the compositional alterations. The results demonstrated that compositional alteration affected balance ratings equally across masterworks and selections of lower artistic quality. These results demonstrate that, although balance is a function of compositional structure, balance on its own is not sufficient to distinguish between works of varying artistic quality. To the extent that balance is considered a function of composition, the results suggest that masterworks are distinguished from works of lower artistic quality for reasons other than solely composition.

Adult↗

T cell repertoire formation displays characteristics of qualitative models of thymic selection.

The use of T cell receptor elements varies between mouse strains, reflecting a balance between positive and negative selection. The presence of H-2E biases V alpha and V beta usage through major histocompatibility class II isotype preferences of V elements, and mammary tumor virus-dependent, negative selection. Quantitative models of thymic selection predict that negative selection equates to 'excess' positive selection, whereas qualitative models suggest that positive and negative selection are opposing forces. This report attempts to distinguish between the models by assessing whether, at the level of the T cell repertoire, positive and negative selection have quantitative or qualitative characteristics. The data show that the effect of bearing V alpha and V beta regions which are both preferentially (or negatively) selected in the presence of H-2E is additive or synergistic, whilst positive stimuli counteract negative ones. The data thus provide support for qualitative models of thymic selection.

Animals↗

[Is it necessary to treat incisal protrusion in Tunisian children?].

It is thought that incisor protrusion could be ethnic-related because Tunisians, as Africans, might reflect the genetic influence of the incisal protrusion of their darker skinned neighbors. We first compiled local standards by determining the normal incisor positions of children of the Sfax region with balanced facial patterns. We selected 95 teenagers from 5 different high schools in Sfax (average age: 16 years 9 months), all having a normal dentition and a balanced facial pattern. This first study showed that upper and lower incisors were protruded 3 mm beyond American standards. Second, we studied incisor stability after four-first bicuspid extraction treatment. We selected 26 patients all having Class I molar relationships and upper and lower incisor protrusion. We compared x-ray incisor measurements of 3 radiographs: before treatment, after treatment and 2 or 3 years post-treatment. This study shows that incisor relapse ranges between 20 and 30%.

Adolescent↗

[Boron balance in agroecosystem on brown-red soil of south Hubei Province].

Five sequential cropping systems including rape/soybean-rice, wheat/watermelon-rice, rape/corn-soybean, wheat-sesame and soybean-sesame, were selected study the boron balance in agroecosystem on brown-red soil of south Hubei Province. The results show that the main output of boron was runoff and leaching, which accounted for 48-53% and 41% of the total respectively, while the output by products accounted for 3.4-10.1%. The main inputs were from rainfall, irrigation, fertilization seeds and seedlings, and natural return.

Boron↗

Prenatal finding of a fetus with mosaicism for two balanced de novo chromosome rearrangements.

Karyotyping of a fetus with mild cerebral ventriculomegaly detected with ultrasound at 23 weeks revealed two apparently balanced structural rearrangements in mosaic form. Using conventional cytogenetics and FISH, the chromosomal constitution was identified as 46,XX,t(3;10)(p13;q21.1),inv(6)(p23q12)/46,XX. A 46,XX chromosome constitution was predominantly present in the skin whereas in the fetal blood the cell line with two balanced chromosome rearrangements was selectively retained. To the best of our knowledge this is the first prenatal case of mosaicism for two de novo balanced structural chromosome rearrangements to be reported.

Adult↗

BalanceReTrainer: a new standing-balance training apparatus and methods applied to a chronic hemiparetic subject with a neglect syndrome.

In this paper we present a mechanical apparatus and methods named BalanceReTrainer for standing-balance training in neurologically impaired individuals. BalanceReTrainer provides an impaired individual with a fall-safe balancing environment, where the balancing efforts of a standing individual are augmented by stabilizing forces acting at the level of pelvis in the sagittal and frontal planes of motion, assisting the balancing activity ankle and hip muscles and at the level of shanks, assisting the knee extensor muscles. A range of different levels of supporting forces is generated by passive, compliant means. Additionally, movement in the sagittal and frontal planes, acquired by transducers is fed to an electronic interface which transforms the current inclinations into a computer mouse signals, which are interfaced to a personal computer (PC) where balance training and evaluation program is running. The level of stiffness support and level of difficulty of computer task can be selected according to current balancing abilities of the impaired individual. We further present results of a case study where an ambulatory chronic hemiparetic subject with neglect syndrome received ten days of balance training on BalanceReTrainer. Biomechanical evaluation of weight-shifting activity before and after treatment shows a substantial functional improvement.

Adult↗

Immunomodulation and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis.

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that primarily affects children. Topical corticosteroids have been the mainstay of treatment since the late 1950s. While providing excellent short-term efficacy, topical corticosteroid usage is limited by potential adverse effects, including impairment of the function and viability of Langerhans cells/dendritic cells. The recently introduced topical calcineurin inhibitors pimecrolimus cream 1% (Elidel) and tacrolimus ointment 0.03 and 0.1% (Protopic) exhibit a more selective mechanism of action and do not affect Langerhans cells/dendritic cells. For the immune system of young children 'learning' to mount a balanced Th1/Th2 response, this selective effect has particular benefits. In clinical experience, topical calcineurin inhibitors have been shown to be a safe and effective alternative to topical corticosteroids in almost 7 million patients (>5 million on pimecrolimus; >1.7 million on tacrolimus). Topical pimecrolimus is primarily used in children with mild and moderate AD, whereas tacrolimus is used preferentially in more severe cases. None of the topical calcineurin inhibitors have been associated with systemic immunosuppression-related malignancies known to occur following long-term sustained systemic immunosuppression with oral immunosuppressants (e.g., tacrolimus, cyclosporine A, and corticosteroids) in transplant patients. Preclinical and clinical data suggest a greater skin selectivity and larger safety margin for topical pimecrolimus.

Administration, Topical↗

Selecting "significant" differentially expressed genes from the combined perspective of the null and the alternative.

In the search for genes associated with disease, statistical analysis yields a key towards reproducible results. To avoid a plethora of type I errors, classical gene selection procedures strike a balance between magnitude and precision of observed effects in terms of p-values. Protecting false discovery rates recovers some power but still ranks genes according to classical p-values. In contrast, we propose a selection procedure driven by the concern to detect well-specified important alternatives. By summarizing evidence from the perspective of both the null and such an alternative hypothesis, genes line up in a substantially different order with different genes yielding powerful signals. A cutoff point for a measure of relative evidence which balances the standard p-value, p0, with its counterpart, p1, derived from the perspective of the target alternative, determines our gene selection. We find the cutoff point that maximizes an expected specific gain. This yields an optimal decision which exploits gene-specific variances and thus involves different type I and type II errors across genes. We show the dramatic impact of this alternative perspective on the detection of differentially expressed genes in hereditary breast cancer. Our analysis does not rely on parametric assumptions on the data.

Biometry↗

[The influence of anthocyanins from Aronia melanocarpa on selected parameters of oxidative stress and microelements contents in men with hypercholesterolemia].

THE AIM OF THE STUDY: Our investigations was to estimate the influence of Aronia anthocyanins (Aronox by Agropharm) on selected parameters of oxidative and antioxidative balance as well as on the concentration of selected metals in red blood cells in men with hipercholesterolaemia. MATERIAL AND METHODS: 16 men aged 27 +/- 6.4 years old with blood cholesterol concentration on the level of 205-250 mg/dl took 240 mg of anthocyanins a day for 30 days. Before and after the period of anthocyanins administration a blood sample was taken and following parameters were estimated: lead, aluminium, cooper and zinc concentration in erythrocytes with the method of atomic emission spectrometry with induced coupling plasma (AES-ICP), concentration of substances reacting with thiobarbituric acid (TBARS) and superoxide dismutase, glutathione peroxidase and catalase activities in hemolysate. CONCLUSION: 30 days long administration of 240 mg of anthocyanins a day, caused a substantial increase of glutathione peroxidase and catalase activities. The lead, aluminium and cooper concentration was decreased while zinc concentration in red blood cells was increased.

Adult↗

Checks and balancers: balancer chromosomes to facilitate genome annotation.

Phenotype-driven mutagenesis screens are used to discover gene function in model organisms. Mutations that are induced by chemical mutagens can occur anywhere in the genome. However, the use of a balancer chromosome (where a phenotypically marked segment of a chromosome is inverted) in a mutagenesis screen enables mutations to be mapped in a defined region of the genome and maintained stably in a heterozygous state. Mouse balancer chromosomes can be engineered using Cre-loxP technology in selected regions of the genome. Balancer mutagenesis screens will provide a systematic functional analysis of the genes on mouse chromosomes, and consequently, will facilitate a functional annotation of the mammalian genome sequence.

Animals↗

Microstimulation of the dorsolateral prefrontal cortex biases saccade target selection.

A long-standing issue concerning the executive function of the primate dorsolateral prefrontal cortex is how the activity of prefrontal neurons is linked to behavioral response selection. To establish a functional relationship between prefrontal memory fields and saccade target selection, we trained three macaque monkeys to make saccades to the remembered location of a visual cue in a delayed spatial match-to-sample saccade task. We electrically stimulated sites in the prefrontal cortex with subthreshold currents during the delay epoch while monkeys performed this task. Our results show that the artificially injected signal interacts with the neural activity responsible for target selection, biasing saccade choices either towards the receptive/movement field (RF/MF) or away from the RF/MF, depending on the stimulation site. These findings might reflect a functional link between prefrontal signals responsible for the selection bias by modulating the balance between excitation and inhibition in the competitive interactions underlying behavioral selection.

Animals↗

Computer support for interpreting family histories of breast and ovarian cancer in primary care: comparative study with simulated cases.

OBJECTIVES: To evaluate the potential effect of computer support on general practitioners' management of familial breast and ovarian cancer, and to compare the effectiveness of two different types of computer program. DESIGN: Crossover experiment with balanced block design. PARTICIPANTS: Of a random sample of 100 general practitioners from Buckinghamshire who were invited, 41 agreed to participate. From these, 36 were selected for a fully balanced study. INTERVENTIONS: Doctors managed 18 simulated cases: 6 with computerised decision support system Risk Assessment in Genetics (RAGs), 6 with Cyrillic (an established pedigree drawing program designed for clinical geneticists), and 6 with pen and paper. MAIN OUTCOME MEASURES: Number of appropriate management decisions made (maximum 6), mean time taken to reach a decision, number of pedigrees accurately drawn (maximum 6). Secondary measures were method of support preferred for particular aspects of managing family histories of cancer; importance of specific information on cancer genetics that might be provided by an "ideal computer program." RESULTS: RAGs resulted in significantly more appropriate management decisions (median 6) than either Cyrillic (median 3) or pen and paper (median 3); median difference between RAGs and Cyrillic 2.5 (95% confidence interval 2.0 to 3.0; P<0.0001). RAGs also resulted in significantly more accurate pedigrees (median 5) than both Cyrillic (median 3.5) and pen and paper (median 2); median difference between RAGs and Cyrillic 1.5 (1.0 to 2.0; P<0.0001). The time taken to use RAGs (median 178 seconds) was 51 seconds longer per case (95% confidence interval 36 to 65; P<0.0001) than pen and paper (median 124 seconds) but was less than Cyrillic (median 203 seconds; difference 23. (5 to 43; P=0.02)). 33 doctors (92% (78% to 98%)) preferred using RAGs overall. The most important elements of an "ideal computer program" for genetic advice in primary care were referral advice, the capacity to create pedigrees, and provision of evidence and explanations to support advice. CONCLUSIONS: RAGs could enable general practitioners to be more effective gatekeepers to genetics services, empowering them to reassure the majority of patients with a family history of breast and ovarian cancer who are not at increased genetic risk.

Breast Neoplasms↗

Effects of hypocaloric dextrose and amino acids on body composition and nitrogen balance in rats.

Studies were conducted to compare the effects of isocaloric intake of glucose, amino acids, and combinations of these nutrients on nitrogen balance, body composition, and selected metabolic parameters of adult rats. Diets were administered either orally or intravenously at 20% (semi-starvation) of the daily caloric requirement. Although nitrogen balance was improved when all calories were supplied as amino acids when compared to glucose alone, one-half the amino acids could be replaced with glucose without sacrificing nitrogen balance. Animals from the semi-starvation treatment showed similar weight and body composition changes, there was no apparent difference whether the diets were administered orally or intravenously. These results indicate that replacement of at least one-half the calories of an all amino acid hypocaloric diet with glucose does not adversely affect body composition weight change or nitrogen balance, but may reduce blood urea nitrogen, ketosis, and cost of nutritional support.

Amino Acids↗

A multi-purpose rehabilitation frame: a novel apparatus for balance training during standing of neurologically impaired individuals.

We present a novel mechanical apparatus, named Multi-purpose Rehabilitation Frame (MRF), and methods for balance training during standing of neurologically impaired individuals. The device has two degrees of freedom (DOF), which allow for constrained movement of both lower limbs and pelvis in the sagittal and frontal planes. The MRF aims at improving balancing in impaired individuals by providing a stiffness support and action of perturbations, which facilitate development of alternative balancing strategies. The level of stiffness support and strength of perturbations, which are generated by means of two hydraulic servo-controlled actuators, can be selected according to current balancing abilities of an impaired individual. We further present preliminary results of nine days of balance training in two paraplegic and two incomplete tetraplegic subjects standing in the MRF. All subjects improved their balancing abilities as measured from the level of needed supporting stiffness provided by the MRF.

Adult↗

Cytogenetic instability with balanced chromosome changes in an SV40 transformed human uroepithelial cell line.

Cytogenetic analysis at the 15th, 34th, 50th, and 56th passages of an SV40 immortalized human uroepithelial cell line (SV-HUC-1) showed continuous chromosome change and marker formation. Throughout these passages the transformed cells maintained their epithelial morphology, were SV40 T antigen positive, did not shed infectious SV40 virus, and were repeatedly found to be nontumorigenic when innoculated into athymic nude mice. Each of the passages studied was characterized by extensive karyotypic changes due to formation, rearrangement, and disappearance of different markers. A marker involving chromosome 1 was stable at three of the passages studied, whereas markers involving the X chromosome changed at each passage studied. Because of the incorporation of several chromosomes or chromosome arms into markers, the karyotype was genetically balanced in the first passage studied, with no net loss or gain of chromosomal material despite a modal number of 44. In subsequent passages, despite continued instability and generation of new markers, there was a slight but additive loss of genomic balance which increased with time in culture. Since continued karyotypic rearrangements did not lead to tumorigenic conversion, it is probable that genetic instability coupled with selection for the most balanced genome may be important for the immortalization of this cell line.

Cell Line, Transformed↗

A selective biomimetic tweezer for noradrenaline.

The new highly preorganized tweezer molecule 1 binds noradrenaline in polar solvents with unprecedented specificity. It uses a biomimetic recognition pattern and rejects almost all other neurotransmitters. LB experiments on a film balance reflect the same selectivity if 1 is incorporated into a stearic acid monolayer.

Alkynes↗