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Ovary-selective genes I: the generation and characterization of an ovary-selective complementary deoxyribonucleic acid library.

The importance of several ovary-selective/specific genes, i.e. genes preferentially or exclusively expressed in the ovary, has been established. Indeed, null mutant female mice for the c-mos, growth and differentiation factor-9, alpha-inhibin, and zona pellucida-3 genes proved sterile. A loss of function mutation of the human FSH receptor gene established its critical role in ovarian function. These data support the hypothesis that genes expressed selectively or specifically in the ovary are probably essential for the normal functioning of this organ system. We have used the differential screening technique suppression subtractive hybridization to systematically isolate and clone genes that are expressed in an ovary-selective/specific manner. The resultant target complementary DNA (cDNA) library has been exhaustively screened to a point at which additional sequencing was increasingly unlikely (< or = 4%) to yield additional previously unencountered cDNAs. In toto, 844 clones were sequenced and analyzed for homology to known genes using the Basic Local Alignment Tool (BLAST). Of those, 342 were determined to be independent (nonredundant). One hundred and fifty-nine independent clones proved identical to previously characterized genes, whereas an additional 100 independent clones proved significantly homologous (but not identical) to previously characterized genes. Yet 83 other independent clones did not display significant homology to previously characterized genes now listed in the publicly accessible nonredundant databases. As such, these latter genes were deemed novel. Of these 83 novel genes, a total of 36 displayed ovary-specific/selective expression, as determined by probing mouse multitissue Northern blots with 32P-labeled/PCR-amplified cDNA inserts. Under these circumstances, the false positive rate was minimal, as only one novel clone was expressed at a higher level in nonovarian tissues relative to ovary. Of the 36 ovary-specific/ selective novel genes, 22 proved subject to hormonal regulation during a simulated estrous cycle. In this communication we focus on 2 such novel ovary-specific/hormonally-dependent genes, the full-length sequences of which were isolated using rapid amplification of 3'-cDNA ends technology. Taken together, the present study accomplished systematic identification of those genes that are restricted in their expression to the ovary. These ovary-selective genes may have significant implications for the understanding of ovarian function in molecular terms and for the development of innovative strategies for the promotion of fertility or its control.

17-Hydroxysteroid Dehydrogenases↗

Selective loss of KGDHC-enriched neurons in Alzheimer temporal cortex: does mitochondrial variation contribute to selective vulnerability?

THE RESEARCH OBJECTIVE: of this study was to test whether variation in mitochondrial composition is associated with "selective vulnerability" in Alzheimer brain. The term "selective vulnerability" refers to the loss of relatively vulnerable brain cells and the sparing of relatively resistant brain cells in disorders in which a genetic defect or environmental agent acts on both types of cells. The mechanisms underlying selective vulnerability are largely unknown, but mitochondria may be involved; the composition of mitochondria varies among different types of neurons, and mitochondria have an important role in cell death. Alzheimer's Disease (AD) is one of a number of neurodegenerative disorders in which both selective vulnerability and abnormalities of mitochondria occur. METHODS: We examined by immunohistochemistry the cellular distribution of a mitochondrial constituent (the alpha-ketoglutarate dehydrogenase complex, KGDHC) known to be deficient in AD, in relation to the known selective vulnerability of neurons in areas 21 and 22 of the temporal lobe in this neurodegenerative disorder. RESULTS: In normal human brain, cortical layers III and V contain neurons intensely immunoreactive for KGDHC, compared to other cells in these areas. The KGDHC-enriched cells are lost in AD (p < 0.001). In layer III, the loss of KGDHC-enriched cells is proportional to total loss of neurons, as determined by immunoreactivity to neuron specific enolase (NSE). In layer V, a higher proportion of the KGDHC-enriched neurons are lost than of other (NSE positive) neurons (p < 0.001). SIGNIFICANCE: Variations in mitochondrial composition may be one of the factors determining which cells die first when different types of cells are exposed to the same stress.

Aged↗

Use of ion-selective electrodes for blood-electrolyte analysis. Recommendations for nomenclature, definitions and conventions. International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Scientific Division Working Group on Selective Electrodes.

This paper will familiarize the reader with the terms used to describe the behavior of ion-selective electrodes, particularly in relation to their use in clinical chemistry for determination of blood electrolyte cations. It serves as an introduction to a series of papers dealing with important cations in blood, namely calcium, sodium, and potassium. The detailed relationships between the ion activity determined by means of ion-selective electrode potentiometry in undiluted specimens, and the total substance concentration measured by flame atomic-emission spectrometry are described by flow chart and equations. Adoption of a convention for reporting results is recommended. The Working Group on Selective Electrodes has taken into account recent revisions of IUPAC recommendations on nomenclature and selectivity coefficient determinations for ion-selective electrodes, and benefited from the experience of a member of the WG, who was also involved in the IUPAC discussions. Nomenclature for determined quantities follows previous IUPAC/IFCC joint recommendations.

Electrodes↗

The influence of sustained selective attention on stimulus selectivity in macaque visual area MT.

Remarkable alterations of perception during long-lasting attentional processes have been described in several recent studies. Although these findings have gained much interest, almost nothing is known about the modulation of neuronal responses during sustained attention. Therefore, we investigated the effect of prolonged selective attention on neuronal feature selectivity. Awake macaque monkeys were trained to perform a motion-tracking task that required attending one of two simultaneously presented moving bars for up to 15 sec. Extracellular recordings were obtained from neurons in macaque motion-sensitive middle temporal visual area (MT/V5). Under conditions of attention, we found high and constant direction selectivity over time. This was expressed by a strong and persistent response contrast between presentations of preferred and nonpreferred stimuli in successive motion cycles. With attention directed to another moving bar, neuronal responses to the behaviorally irrelevant stimulus became continuously less specific for the direction of motion. In particular, increasingly higher firing rates for motion in null direction caused a strong reduction of direction selectivity, which further increased with enhanced proximity between target and distracter bar. A passive condition experiment revealed that this reduction occurred only when motion remained the behaviorally relevant feature but disappeared when attention was withdrawn from this feature domain. Thus, sustained attention seems to stabilize direction selectivity of neurons in area MT against a time and competition-dependent degradation, whereas nonattended objects suffer from a reduced neuronal representation.

Animals↗

Resistance to Acarapis woodi by honey bees (Hymenoptera: Apidae): divergent selection and evaluation of selection progress.

Two generations of honey bees, Apis mellifera L., selected for resistance to tracheal mites, Acarapis woodi (Rennie), were produced from a foundation stock. The mite resistant lines had significantly low mite abundances and prevalences in each selected generation. The high mite-resistant lines of the first selected generation showed resistance equal to that of bees that had undergone natural selection from tracheal mite infestations for 3 yr in New York. Additionally, the high mite-resistant lines of the second selected generation and Buckfast bees had significantly lower mite abundances and prevalences than honey bees from control colonies which had never been exposed to tracheal mite infestation in Ontario. These results corroborate studies that have shown that honey bees possess genetic components for tracheal mite resistance that can be readily enhanced in a breeding program. The two methods used for evaluating relative resistance of honey bees to tracheal mites, a short-term bioassay and evaluation in field colonies, were positively correlated (rs = 0.64, P < 0.001).

Animals↗

Parameters selection in gene selection using Gaussian kernel support vector machines by genetic algorithm.

In microarray-based cancer classification, gene selection is an important issue owing to the large number of variables and small number of samples as well as its non-linearity. It is difficult to get satisfying results by using conventional linear statistical methods. Recursive feature elimination based on support vector machine (SVM RFE) is an effective algorithm for gene selection and cancer classification, which are integrated into a consistent framework. In this paper, we propose a new method to select parameters of the aforementioned algorithm implemented with Gaussian kernel SVMs as better alternatives to the common practice of selecting the apparently best parameters by using a genetic algorithm to search for a couple of optimal parameter. Fast implementation issues for this method are also discussed for pragmatic reasons. The proposed method was tested on two representative hereditary breast cancer and acute leukaemia datasets. The experimental results indicate that the proposed method performs well in selecting genes and achieves high classification accuracies with these genes.

Algorithms↗

Malignant arrhythmias in acute myocardial infarction. Relationship to serum potassium and effect of selective and non-selective beta-blockade.

The risk of malignant arrhythmias during myocardial infarction is greatly increased in patients with diuretic-induced hypokalaemia. In our study an increased risk was seen also in hypokalaemic patients not treated with diuretics. This indicates that hypokalaemia as such could trigger malignant arrhythmias. The frequency of hypokalaemia was much higher (22.5%) in diuretic-treated infarct patients than in those not treated with diuretics (12.9%). Thus, hypokalaemia should be avoided in diuretic-treated patients with increased risk of myocardial infarction. The incidence of malignant arrhythmias in hypokalaemic patients was 13.2% in those treated with non-selective beta-blockers on admission versus 26.1% in those treated with selective beta-blockers; corresponding figures in infarctions with serum potassium concentrations above 3.6 mmol/L were 9.4% and 10.4%, respectively. Non-selective beta-blockers reduced the frequency of malignant arrhythmias in hypokalaemic infarctions. This was in contrast to selective beta-blockers, which had no favourable effect on the frequency of malignant arrhythmias in hypokalaemic infarctions. Non-selective beta-blockers did not completely counteract the hypokalaemia. Still, the risk of malignant arrhythmias decreased. Thus, our study indicates that apart from hypokalaemia, some additional mechanism specifically linked to adrenaline stimulation in important for the development of malignant arrhythmias in acute myocardial infarction.

Adrenergic beta-Antagonists↗

Characteristics of Line 1 Hereford females resulting from selection by independent culling levels for below-average birth weight and high yearling weight or by mass selection for high yearling weight.

Simultaneous selection for low birth weight and high yearling weight has been advocated to improve efficiency of beef production. Two sublines of Line 1 Hereford cattle were established by selection either for below-average birth weight and high yearling weight (YB) or for high yearling weight alone (YW). Direct effects on birth weight and yearling weight diverged between sublines with approximately four generations of selection. The objective of this study was to estimate genetic trends for traits of the cows. A three-parameter growth curve [Wt = A(1 - b0e(-kt))] was fitted to age (t, d)-weight (W, kg) data for cows surviving past 4.5 yr of age (n = 738). The resulting parameter estimates were analyzed simultaneously with birth weight and yearling weight using multiple-trait restricted maximum likelihood methods. To estimate maternal additive effects on calf gain from birth to weaning (MILK) the two-trait model previously used to analyze birth weight and yearling weight was transformed to the equivalent three-trait model with birth weight, gain from birth to weaning, and gain from weaning to yearling as dependent variables. Heritability estimates were 0.32, 0.27, 0.10, and 0.20 for A, b0, k, and MILK, respectively. Genetic correlations with direct effects on birth weight were 0.34, -0.11, and 0.55 and with direct effects on yearling weight were 0.65, -0.17, and 0.11 for A, b0, and k, respectively. Genetic trends for YB and YW, respectively, were as follows: A (kg/generation), 8.0+/-0.2 and 10.1+/-0.2; b0 (x 1,000), -1.34+/-0.07 and -1.16+/-0.07; k (x 1,000), -14.3+/-0.1 and 4.3+/-0.1; and MILK (kg), 1.25+/-0.05 and 1.89+/-0.05. Beef cows resulting from simultaneous selection for below-average birth weight and increased yearling weight had different growth curves and reduced genetic trend in maternal gain from birth to weaning relative to cows resulting from selection for increased yearling weight.

Animal Husbandry↗

Grazing selectivity and in vivo digestibility of switchgrass strains selected for differing digestibility.

Animal selectivity and digestibility differences among switchgrass strains selected for different in vitro dry matter digestibilities (IVDMD) were measured in a grazing trial with esophageally fistulated steers and a sheep digestion trial. Extrusa selected by esophageally fistulated steers grazing high-IVDMD (Trailblazer), Pathfinder and low-IVDMD strains of switchgrass were compared, as were top and whole plant hand-clipped samples from each strain. Trailblazer extrusa had higher (P less than .1) in vitro organic matter disappearance (IVOMD) and lower (P less than .1) NDF and ADF than Pathfinder extrusa. Extrusa from all three strains appeared to be of higher quality than top or whole plant hand-clipped samples. In vitro organic matter disappearance tended to be highest for Trailblazer top hand-clipped samples. Composition of hand-clipped samples among strains was not significantly different. Mature crossbred wethers were used to compare Trailblazer and Pathfinder switchgrass hay in a digestion trial. No differences (P greater than .1) were detected between strains for DMI or apparent digestibility of DM, NDF, ADF and CP. Extrusa from Trailblazer switchgrass that had been selected for whole plant IVDMD had higher IVOMD; however, there was no indication that steers selected a differentially higher IVOMD for one strain than another.

Animal Feed↗

Method for comparing selectivities of unlabeled subpopulation-selective ligands: application to muscarinic receptors.

A method for comparing the selectivities of two unlabeled ligands by simultaneous competition for the binding of a nonselective labeled ligand has been illustrated by computer simulations. Experimental application of this approach indicated that the subpopulations of muscarinic receptors that are distinguished by the use of quaternary antagonists are not related to the M1 and M2 subtypes (based on pirenzepine). However, the quaternary agonist carbachol was found to express both modes of selectivity. The method should be particularly useful in the evaluation of new ligands when labeled selective ligands are unavailable. Further, this method complements experiments that can be carried out with a labeled selective ligand, since it emphasizes the contribution of the sites for which the selective ligand has low affinity.

Animals↗

Effects of selection for growth and selection diet on eggshell quality and embryonic development in Japanese quail.

Decreased hatchability in Japanese quail following selection for growth and relative improvements in hatchability following selection during goitrogen treatment were investigated. An unselected quail line (Line C) and lines selected for high 4-wk body weight while being fed diets containing either 20% CP and .2% thiouracil (TU) (Line T), or 28% CP and no TU (Lines P and H-CD) were used. Egg weight loss between 0 and 4, and 0 and 14 days of incubation, hatchability, and developmental stage of embryonic mortalities were determined in Experiment 1. Length of the incubation period, and percentages of body water and dry body weight were determined for 10- and 14-day embryos and 18-day-old chicks in Experiment 2. Eggshell quality was determined in Experiment 3. Hatchability was lower in selected than in unselected quail due to increased early and late embryonic mortality. Egg weight loss during incubation was greater in Line P than in Line C eggs. Weight loss, measured across lines, was lower in eggs that hatched than in those in which embryos died early. Percentage body water was higher in Line C than in Lines P and T at 14 and 18 days of incubation; however, percentage body water in Line T was lower than Line P at 14 days. Percentage of dry body weight was greater in Lines P and T than in Line C at 14 and 18 days. Eggshell thickness was greater in Line H-CD when compared with Line C. Increases in eggshell permeability occurring during selection for growth were associated with increased embryonic mortality and decreased hatchability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Response selection involves executive control: evidence from the selective interference paradigm.

In the present study, we investigated whether response selection involves executive control, using the selective interference paradigm within Baddeley's (1986) working memory framework. The interference from response selection was estimated by comparing the patterns of dual-task interference of simple and choice RT tasks with those of a number of established working memory tasks. In Experiment 1, we compared impairment of forward and backward verbal serial recall from the RT tasks and articulatory suppression. Experiment 2 measured the adverse effects of the RT tasks and matrix tapping on forward and backward visuospatial serial recall. Finally, in Experiment 3, we examined the impairment from the RT tasks with two measures of executive control--namely, letter and category fluency. Altogether, the three experiments demonstrated that response selection interferes with executive control and that the interference is not produced at the level of working memory's slave systems, which supports the assumption of executive involvement in response selection.

Choice Behavior↗

Murine CD4 T cells selected in a highly disparate xenogeneic porcine thymus graft do not show rapid decay in the absence of selecting MHC in the periphery.

CD4 repopulation can be achieved in T cell-depleted, thymectomized mice grafted with xenogeneic porcine thymus tissue. These CD4 T cells are specifically tolerant of the xenogeneic porcine thymus donor and the recipient, but are positively selected only by porcine MHC. Recent studies suggest that optimal peripheral survival of naive CD4 T cells requires the presence of the same class II MHC in the periphery as that of the thymus in which they were selected. These observations would suggest that T cells selected on porcine thymic MHC would die rapidly in the periphery, where porcine MHC is absent. Persistent CD4 reconstitution achieved in mice grafted with fetal porcine thymus might be due to increased thymic output to compensate for rapid death of T cells in the periphery. Comparison of CD4 T cell decay after removal of porcine or murine thymic grafts ruled out this possibility. No measurable role for peripheral murine class II MHC in maintaining the naive CD4 pool originating in thymic grafts was demonstrable. However, mouse class II MHC supported the conversion to, survival, and/or proliferation of memory-type CD4 cells selected in fetal porcine thymus. Thus, the same MHC as that mediating positive selection in the thymus is not critical for maintenance of the memory CD4 cell pool in the periphery. Our results support the interpretation that xenogeneic thymic transplantation is a feasible strategy to reconstitute CD4 T cells and render recipients tolerant of a xenogeneic donor.

Amino Acid Sequence↗

Selecting interspecific human-mouse and Chinese hamster-mouse hybrids using a new half-selection technique with a polyene antibiotic.

Interspecific human-mouse and Chinese hamster-mouse hybrids were isolated from polyethylene glycol fused cells by a new half-selection technique employing a structurally modified polyene macrolide antibiotic, amphotericin B methyl ester (AME), and HAT media. Unfused parental cells were killed as a result of innate sensitivity to AME or their genetic deficiency, absence of thymidine kinase (TK-) or hypoxanthine guanine-phosphoribosyl transferase (HGPRT-). In contrast, hybrid colonies were isolated after two to three weeks growth in three or four changes of HAT-AME media and subsequent growth in HAT media alone. The ability of hybrid cells to proliferate using this selective protocol indicates that genetic complementation resulted, and polyene antibiotic resistance was expressed as a dominant phenotypic property in the hybrids. Hybrid selection was dependent on: (1) the number of cells of each parental cell type co-cultivated; (2) the level of polyene antibiotic administered; and (3) the time interval before selection was initiated. The half-selection technique described in this report is simple to use, very effective in eliminating unfused parental cells and increases the potential types of hybrids which can be formed. Only one parental cell type need contain a biochemical defect, whereas the second parental type can be genetically normal.

Amphotericin B↗

The effects of selective and non-selective monoamine oxidase (MAO) inhibitors on conflict behavior in the rat.

Conflict behavior in rats was examined over the course of several weeks of chronic treatment with selective and non-selective monoamine oxidase inhibitors (MAOIs). In daily 10min sessions, rats were trained to drink from a tube which was occasionally electrified (0.5mA). Electrification was signalled by the presence of a tone. Within 3-4 weeks, control (i.e. non-drug) conflict behavior had stabilized (30-40 shocks and 8-12ml water/session) and drug testing began. Chronic administration (two injections/day for 8 weeks) with a non-selective (i.e. MAO-A and MAO-B inhibiting) dose of pargyline (15mg/kg) resulted in a time-dependent increase in punished responding. In contrast, chronic administration of the MAO-A selective inhibitor (clorgyline; 1.0mg/kg, 2mg/kg), the MAO-B selective inhibitor deprenyl (5mg/kg) or MAO-B inhibiting doses of pargyline (1.0mg/kg, 5mg/kg) were without effect. Finally, chronic treatment with the combination of a low dose of clorgyline (1.0mg/kg) and a low dose of pargyline (1.0mg/kg) did result in a time-dependent increase in punished responding. These results suggest that inhibition of both MAO-A and MAO-B is required for the eventuation of the anxiolytic effect resulting from chronic MAOI treatment.

Journal Article↗

[Does 'selective binding profile' result in 'selective treatment'?].

It has been believed that the 'selective binding profile' may result in the 'selective treatment' for a disease. However, typical antipsychotics with the selective affinity for dopamine D2 receptor produce antipsychotic efficacy against positive symptoms accompanied with extrapyramidal side effects. Serotonin-dopamine-antagonists produce fewer EPS, since they have a potent antagonistic activity for 5-HT2A receptor besides the dopamine D2 antagonism. The disinhibition of diminished glutamatergic transmission and alpha 1 antagonism by MARTAs (Multi-Acting-Acting-Receptor-Targeted-Antipsychotics) can reduce positive symptoms of schizophrenic patients, and the 5-HT2A antagonitic and anticholinergic activities of the drugs may reduce the EPS. Moreover, MARTAs increase intracellular concentrations of dopamine and norepinephrine in the prefrontal cortex and disinhibit the diminished glutamatergic transmission, which are expected to improve the negative symptoms, anxiety and depressive symptoms, and cognitive impairment that are difficult to be treated by other existing antipsychotics. These important biological changes are induced by the antagonism of 5-HT2A, 5-HT2C, alpha 1-adrenergic and muscarinic receptors by MARTAs. Thus a multireceptorial profile of MARTA is considered to result in the improved treatment. Therefore 'selective binding profile' does not always mean 'selective treatment.' Instead, if a breakthrough drug is to be developed for the treatment of refractory diseases, it may be necessary to rethink the ordinary strategy targeting for a single receptor.

Antipsychotic Agents↗

Development of selective attention: perceptual load influences early versus late attentional selection in children and adults.

The moderating effect of perceptual load on visual selective attention was examined in 2 studies. In Study 1, children and young adults searched displays of varying set size flanked by irrelevant distractors. Children's performance was as efficient as adults' under conditions of high but not low loads, suggesting that early selection engages rapidly maturing neural systems and late selection engages later-maturing systems. In Study 2, 4 age groups were tested, and place markers were set at empty locations to examine perceptual grouping effects. Study 1's pattem was replicated in all age groups, with onset of early selection occurring at lower loads for younger children. Overall, children initiated early selection at lower loads to compensate for immature anterior-system interference control processes.

Adult↗

[Case report: reversible acute renal failure following therapy with both ketorolac (non-selective non-steroidal anti-inflammatory drug NSAID) and celecoxib (COX-2 selective) in the same patient].

BACKGROUND: We present the case of acute renal failure complicating the course of therapy with both ketorolac (non-selective Non-Steroidal Anti-inflammatory Drug, NSAID), and celecoxib (COX-2 Selective Inhibitor) in an elderly woman with chronic liver disease, heart failure and chronic renal failure. The main effect of NSAIDs is the inhibition of cyclooxygenase (COX), the enzyme involved in prostaglandins synthesis. The nephrotoxicity of NSAIDs is linked to this effect since prostaglandins not only act in response to inflammatory stimuli, but also play a role as modulators of some physiological renal functions. Under conditions of reduced renal perfusion, acute renal failure secondary to NSAIDs use may occur if the vasoconstrictive forces stimulated to maintain the filtrating function are not balanced by prostaglandin-induced vasodilatation. About ten years ago, two COX isoforms were demonstrated: COX-1 whose products are involved in regulating physiological functions and COX-2 which is expressed by a number of inflammatory stimuli. The discovery of molecular differences between COX-1 and COX-2 allowed the development of pharmacological agents selectively inhibiting COX-1 or COX-2. Selective inhibitors of COX-2 are now available. However, COX-1 products are involved in inflammatory reactions, whereas COX-2 products play a physiological role in many tissues and organs, including the kidney. These observations raised many doubts regarding the renal safety of COX-2 Inhibitors before they became commercially available. These doubts have been recently confirmed in the Literature. CONCLUSIONS: The case we report seems to confirm that, in patients at risk, the renal adverse effects of non-selective NSAIDs and of COX-2 Inhibitors could be the same due to the similar physiological role of COX-1 and COX-2-dependent prostaglandins.

Acute Kidney Injury↗