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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A captive colony of collared lemmings (Dicrostonyx groenlandicus) from northern Alaska produced a male-biased sex ratio of 67% males for about three generations. These lemmings have a pair of autosomes fused to the sex chromosomes. Thus, males have two copies of some (formerly autosomal) sex-linked genes: One set is X-linked; the other can be described as Y-linked. Given such a karyotype, deleterious recessive alleles on the autosomal portion of the X chromosome are more resistant to selection than truly autosomal loci because they can be eliminated by homozygosity only in females. The male-bias could have resulted from one or more lethals carried on the formerly autosomal arm of the X chromosome. As inbreeding coefficients approached 0.3, the lethal was apparently homozygous in half of the homogametic (female) zygotes. This phenomenon may explain the excess of males and XY females attributed to meiotic drive in Dicrostonyx torquatus from Siberia. If under the natural mating system, inbreeding depression limits fitness, then fusion of autosomal chromatin to the sex chromosomes could be an adaptation to reduce inbreeding depression in heterogametic individuals.
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PMID:A male-biased natal sex-ratio in inbred collared lemmings, Dicrostonyx groenlandicus. 968 38

Fatigue and shortening-induced deactivation, two conditions that both lead to reversible depression of the mechanical performance of striated muscle are briefly reviewed. Fatigue. Isolated fibres from frog skeletal muscle (1-3 degrees C) that are stimulated to produce a 1 s fused tetanus at 15 s intervals are brought into a state of myofibrillar fatigue, (tetanic force reduced to 70-75% of the control) that is attributable to reduced performance of the myofibrils with no significant change in activation of the contractile system. A more intense stimulation programme (a single stimulus applied at 1-2 s intervals) reduces the tetanic force below 70% of the rested-state level. Under these conditions, failure of activation becomes increasingly important as a cause of the force decline. Deficient inward spread of activation is likely to account for at least part of the force decline after a period of intense fatiguing stimulation. Shortening-induced deactivation. Striated muscle that is allowed to shorten during activity loses some of its capacity to produce force, full restoration of the contractile strength being attained 1-2 s after the shortening phase. The depressant effect of shortening is demonstrable in skinned preparations as well as in intact muscle fibres and the magnitude of the effect is dependent on the state of activation of the muscle fibre when the movement occurs. The experimental evidence supports the view that sliding of the thick and thin filaments during activity reduces the affinity for calcium at the regulatory sites on the thin filament, leading to a transitory deactivation of the contractile system.
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PMID:Fatigue vs. shortening-induced deactivation in striated muscle. 872 78

Through expression of a glucocorticoid receptor (GR) antisense RNA in brain, we have produced transgenic mice with an hyperactive hypothalamic-pituitary-adrenocortical (HPA) system similar to that seen in depressed patients. This model supports the hypothesis that disturbed corticosteroid receptor regulation could be the primary factor responsible for both the CRH/AVP hyperdrive that leads to increased activity of the HPA system, and the premature escape from the cortisol suppressant action of dexamethasone seen in affective disorders. Although normalisation of the hyperactive HPA system occurs during successful antidepressant therapy of depressive illness, these improvements do not correlate with changes in monoaminergic neurotransmitter systems, suggesting that unknown mechanisms of action may be operative. Work from my laboratory was the first to show that different types of antidepressants increased glucocorticoid receptor (GR) mRNA. We found increased GR mRNA levels irrespective of the preferential inhibitory action of antidepressant on the monoamine neurotransmitter re-uptake and showed increased GR gene transcription in antidepressant-treated mouse fibroblast cells that do not possess monoamine re-uptake mechanisms. We measured changes in glucocorticoid response in cells transfected with a glucocorticoid-sensitive reporter plasmid (MMTV-CAT) and observed increased glucocorticoid-stimulated CAT activity when the cells were treated with antidepressant. A different chimaeric gene construct consisting of a fragment of the GR gene promoter region fused to the CAT gene allowed more direct measurement of antidepressant action and increased CAT activity was also seen when cells transfected with this construct were treated with antidepressant. Finally, GR mRNA concentration and glucocorticoid binding activity were increased in brain tissues of animals chronically treated with antidepressant. The time course of antidepressant actions on corticosteroid receptors coincides with their long-term actions on HPA system activity and follows closely that of clinical improvement of depression. This suggests that antidepressant-induced changes in brain corticosteroid receptors may underlie the observed simultaneous decrease in circulating ACTH and corticosterone levels and the decreased adrenal size. Some of these effects may be mediated through CRH since, in antidepressant-treated transgenic mice hypothalamic CRH mRNA levels were decreased. From this work we have formulated the hypothesis that a primary action of antidepressants could be the stimulation of corticosteroid receptor gene expression that renders the HPA system more susceptible to feedback inhibition by cortisol. The resultant decrease in HPA system activity could induce secondary changes in glucocorticoid-sensitive gene expression and lead to redressment of neurotransmitter imbalance. This work opens up a completely new insight into antidepressant drug action and suggests a line of approach to the development of new drugs by focusing on this action.
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PMID:Modulation of glucocorticoid receptor gene expression by antidepressant drugs. 885 29

Synaptic depression was studied using capacitance measurements in synaptic terminals of retinal bipolar neurons. Single 250 msec depolarizations evoked saturating capacitance responses averaging approximately 150 fF, whereas trains of 250 msec depolarizations produced plateau capacitance increases of approximately 300 fF. Both types of stimuli were followed by pronounced synaptic depression, which recovered with a time constant of approximately 8 sec after single pulses but required >20 sec for full recovery after pulse trains. Inactivation of presynaptic calcium current could not account for depression, which is attributed instead to depletion of releasable and reserve vesicle pools that are recruited and replenished at different rates. Recovery from depression was normal in the absence of fast endocytosis, suggesting that replenishment was from a reserve pool of preformed vesicles rather than from preferential recycling of recently fused vesicles. Given the in vivo light response of the class of bipolar neuron studied here, it is likely that, under at least some illumination conditions, the cells produce a fast and phasic bout of exocytosis rather than tonic release.
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PMID:Depletion and replenishment of vesicle pools at a ribbon-type synaptic terminal. 904 21

Tammar wallaby spermatozoa undergo maturation during transit through the epididymis. This maturation differs from that seen in eutherian mammals because in addition to biochemical and functional maturation there are also major changes in morphology, in particular formation of the condensed acrosome and reorientation of the sperm head and tail. Of spermatozoa released from the testes, 83% had a large immature acrosome. By the time spermatozoa reached the proximal cauda epididymis 100% of sperm had condensed acrosomes. Similarly 86% of testicular spermatozoa had immature thumb tack or T shape head-tail orientation while only 2% retained this immature morphology in the corpus epididymis. This maturation is very similar to that reported for the common brush tail possum, Trichosurus vulpecula. However, morphological maturation occurred earlier in epididymal transit in the tammar wallaby. By the time spermatozoa had reached the proximal cauda epididymis no spermatozoa had an immature acrosome and thumbtack orientation. Associated with acrosomal maturation was an increase in acrosomal thiols and the formation of disulphides which presumably account for the unusual stability of the wallaby sperm acrosome. The development of motility and progressive motility of tammar wallaby spermatozoa is similar to that of other marsupials and eutherian mammals. Spermatozoa are immotile in the testes and the percentage of motile spermatozoa and the strength of their motility increases during epididymal transit. During passage through the caput and corpus epididymis, spermatozoa first became weakly motile in the proximal caput and then increasingly progressively motile through the corpus epididymis. Tammar wallaby spermatozoa collected from the proximal cauda epididymis had motility not different from ejaculated spermatozoa. Ultrastructural studies indicated that acrosomal condensation involved a complex infolding of the immature acrosome. At spermiation the acrosome of tammar wallaby spermatozoa was a relatively large flat or concave disc which projected laterally and anteriorly beyond the limits of the nucleus. During transit of the epididymal caput and proximal corpus the lateral projections folded inwards to form a cup like structure the sides of which eventually met and fused. The cavity produced by this fusion was lost as the acrosome condensed to its mature form as a small button-like structure contained within the depression on the anterior end of the nucleus. During this process the dorsal surface of the immature acrosome and its outer acrosomal membrane and overlying plasma membrane were engulfed into the acrosomal matrix. This means that the dorsal surface of the acrosomal region of the testicular tammar wallaby sperm head is a transient structure. The dorsal acrosomal surface of the mature spermatozoon appears ultrastructurally to be the relocated ventral surface of the acrosomal projections which previously extended out beyond the acrosomal depression on the dorsal surface of the nucleus of the immature spermatozoon.
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PMID:Posttesticular development of spermatozoa of the tammar wallaby (Macropus eugenii). 906 49

Transcription of the repressible acid phosphatase gene (KIPHO5) in Kluyveromyces lactis is strongly regulated in response to the level of inorganic phosphate (Pi) present in the growth medium. We have begun a study of the promoter region of this gene in order to identify sequences involved in the phosphate control of KIPHO5 expression and to design new expression-secretion systems in K. lactis. Deletion analysis and directed mutagenesis revealed two major identical upstream activating sequences (UAS) CACGTG at positions -430 (USA1) and -192 (UAS2) relative to the ATG initiation codon. These sequences are identical to those described for Saccharomyces cerevisiae for the binding of Pho4p. Deletion or directed mutagenesis of either one or both UAS reduce KIPHO5 expression by the same amount (approximately 80%). When fused to the coding region of trout growth hormone cDNA (tGH-II), the promoter and signal peptide-encoding region of the phosphate-repressible KIPHO5 gene drives the expression of this gene and the secretion of the tGHII protein. Synthesis of tGHIIp in K. lactis transformants carrying this construct was found to be regulated by the Pi present in the medium; depression of heterologous protein expression can therefore be achieved by lowering the Pi concentration.
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PMID:Heterologous protein secretion directed by a repressible acid phosphatase system of Kluyveromyces lactis: characterization of upstream region-activating sequences in the KIPHO5 gene. 964 7

In certain Australian marsupials including the tammar wallaby (Macropus eugenii) and the brushtail possum (Trichosurus vulpecula), formation of the acrosome is not completed in the testis but during a complex differentiation process as spermatozoa pass through the epididymis. Using transmission and scanning electron microscopy this paper defined the process of acrosome formation in the epididymis, providing temporal and spatial information on the striking reorganisation of the acrosomal membranes and matrix and of the overlying sperm surface involved. On leaving the testis wallaby and possum spermatozoa had elongated 'scoop'-shaped acrosomes projecting from the dorsal surface of the head. During passage down the epididymis, this structure condensed into the compact button-like organelle found on ejaculated spermatozoa. This condensation was achieved by a complex process of infolding and fusion of the lateral projections of the 'scoop'. In the head of the epididymis the rims of the lateral scoop projections became shorter and thickened and folded inwards, to eventually meet midway along the longitudinal axis of the acrosome. As spermatozoa passed through the body of the epididymis the lateral projections fused together. Evidence of this fusion of the immature outer acrosomal membrane is the presence of vesicles within the acrosomal matrix which persist even in ejaculated spermatozoa. When spermatozoa have reached the tail of the epididymis the acrosome condenses into its mature form, as a small button-like structure contained within the depression on the anterior end of the nucleus. During the infolding process, the membranes associated with the immature acrosome are either engulfed into the acrosomal matrix (outer acrosomal membrane), or eliminated from the sperm head as tubular membrane elements (cytoplasmic membrane). Thus the surface and organelles of the testicular sperm head are transient structures in those marsupials with posttesticular acrosome formation and this must be taken into consideration in attempts to dissect the cell and molecular biology of fertilisation.
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PMID:Acrosome formation during sperm transit through the epididymis in two marsupials, the tammar wallaby (Macropus eugenii) and the brushtail possum (Trichosurus vulpecula). 1033 54

Predictions that anxious and nonanxious depression would differ in perceptual asymmetry (PA), as well as in sensitivity for perceiving emotional words, were evaluated using dichotic listening tasks. A total of 149 patients having a major depressive disorder (51 with and 98 without an anxiety disorder) and 57 healthy controls were tested on fused-word and complex tone tasks. The anxious and nonanxious depression groups showed a consistent difference in PA across tasks; that is, the anxious group had a larger left-ear advantage for tones and a smaller right-ear advantage for words when compared with the nonanxious group. There was no group difference in sensitivity for perceiving emotional words. Patients having an anxious depression appear to have a greater propensity to activate right than left-hemisphere regions during auditory tasks, whereas those having a nonanxious depression have the opposite hemispheric asymmetry.
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PMID:Perceptual asymmetry differences between major depression with or without a comorbid anxiety disorder: a dichotic listening study. 1036 33

One of the principal environmental adaptations of certain fishes inhabiting polar and northern coastal waters is the synthesis of antifreeze proteins (AFPs). AFPs bind to and prevent the growth of nascent ice crystals, thus depressing the serum freezing point. The transgenic expression of AFP holds great promise for conferring freeze resistance to commercially important plant and animal species. Since fish at the greatest risk of freezing have multiple AFP gene copies in order to synthesize higher levels of this protein, we have evaluated this evolutionary strategy as a way to maximize AFP expression in a model transgenic host, the fruit fly Drosophila melanogaster. A construct in which AFP genes of the Atlantic wolffish are fused to the Drosophila yolk protein 1,2 promoter/enhancer region was transferred to flies through P-element mediated transformation. Several independent transgenic fly lines were used in genetic crosses to obtain multi-insert lines. Haemolymph freezing point depression (thermal hysteresis) was greater in homozygotes relative to heterozygotes for a given insert. Similarly, multi-insert lines consistently displayed greater haemolymph AFP activity than the single insert lines from which they were derived. The thermal hysteresis value obtained with a fly line harboring 8 AFP gene copies, 0.43 degree C, represents the highest such value to date recorded in a transgenic host, and is even higher than the levels found in some AFP-producing fish.
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PMID:Increased gene dosage augments antifreeze protein levels in transgenic Drosophila melanogaster. 1039 66

Active shortening of respiratory muscle L2B from the crab Carcinus maenas results in contractile deactivation, seen as (1) a decline of force during the course of isovelocity shortening, (2) a reduction in the rate of force redevelopment following shortening, (3) a depression of the level of isometric force reached following shortening, and (4) an accelerated relaxation at the end of stimulation. The degree of deactivation increases with increasing distance of shortening, decreases with increasing shortening velocity, and is approximately linearly related to the work done during shortening. Deactivation lasts many seconds if stimulation is maintained, but is largely although not completely removed if the stimulation is temporarily interrupted so that the force drops towards the resting level. Deactivation for a given distance and velocity of shortening increases with increasing muscle length above the optimum length for force production. Stimulating muscle L2B at suboptimal frequencies gives tetanic contractions that are fully fused but of less than maximal amplitude. The depression of force following shortening, relative to the force during an isometric contraction, is independent of the stimulus frequency used to activate the muscle, indicating that deactivation is not a function of the background level of stimulus-controlled muscle activation upon which it occurs. Deactivation reduces the work required to restretch a muscle after it has shortened, but it also lowers the force and therefore the work done during shortening. The net effect of deactivation on work output over a full shortening/lengthening cycle is unknown.
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PMID:Work-dependent deactivation of a crustacean muscle. 1046 Jul 43


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