Mechanisms of developmental regulation in globin loci

The role of the c-myc oncogene has been little investigated in uveal melanoma. In this study an analysis of c-myc oncoprotein expression was undertaken using flow cytometry in 71 patients with posterior uveal melanoma. Nuclear c-myc oncoprotein was detected in all of the tumours, and survival analysis revealed a significant association between high oncoprotein positivity and improved survival (log rank test: chi2 = 6.47, P = 0.01). Multifactorial analysis using Cox's proportional hazards model revealed nuclear c-myc oncoprotein to be an independent prognostic marker more accurate than other clinicopathological parameters (log rank test: chi2 = 6.61, P = 0.01). However, this result of high oncoprotein expression correlating with improved outcome is surprising and in contrast to our previous studies using the same method on cutaneous melanoma, where high levels of nuclear c-myc expression have been found to correlate with poor outcome both in primary and secondary disease. This study suggests that the pattern of oncogene expression in uveal melanoma is distinct from cutaneous melanoma and that the underlying biology of these tumours is different.     

Disorders of temperature regulation

A remarkably effective and efficient thermoregulatory apparatus enables humans to maintain a normal body temperature despite widely varying and changing environmental and internal thermal conditions. Nevertheless, extreme ambient cold or heat and exhaustive exercise stress can overwhelm these defenses, leading to dangerous hypothermia or hyperthermia, respectively.     

Mechanisms of EGF receptor regulation in breast cancer cells

Overexpression of the EGF receptor in breast cancer correlates with poor prognosis and failure on endocrine therapy for both ER-/EGFR+ and ER+/EGFR+ tumors, suggesting a role for EGFR in the progression to hormone independence. The identification of specific DNAse I hypersensitive site patterns for the EGFR gene in ER+ vs. ER- cells implicates regions of the EGFR first intron in up-regulation of EGFR, while estrogen regulation studies indicate the involvement of a repressor(s) in the maintenance of low levels of EGFR. Based on these findings, a multi-step model is proposed for the progression of breast cancer from a hormone-dependent, ER+/EGFR-phenotype to an aggressive, hormone-independent, ER-/EGFR+ stage.     

Mechanisms and clinical significance of cell volume regulation

A wide variety of factors challenge constancy of cell volume. Alterations of cell volume activate diverse cell volume regulatory mechanisms including ion transport, osmolyte accumulation, metabolism and expression of appropriate genes. A wealth of cellular signalling pathways link cell volume to the respective regulatory mechanisms. Cell volume emerges as a pathophysiologically important parameter in several diseases including diabetes mellitus, uraemia, hepatic insufficiency and hypercatabolic states. The role of altered cell volume in disease is a challenge which requires more experimental research and clinical investigation.     

An NK1 receptor antagonist affects the circadian regulation of locomotor activity in golden hamsters

The objective of this study was to evaluate the impact of a feeding supplementation program on the growth of undernourished children younger than 5 years in the city of Guariba, state of S?o Paulo, Brazil. The sample consisted of 469 malnourished children enrolled in a feeding supplementation program sponsored by the State Health Secretariat. The children were divided into four groups according to how long they had been enrolled in the program: in group 1, the children had been enrolled for up to 12 months; in group 2, from 12 to 24 months; in group 3 from 24 to 36 months; and in group 4 the children had been enrolled for more than 35 months. Percentiles for weight/age, height/age and weight/height were calculated for each child. To assess the impact of the program, reference curves for the anthropometric profile were constructed based on expected variations in population percentiles. The changes observed in each group were analyzed statistically (McNemar). Groups 1 and 2 presented weight recovery and gains in the weight/height ratios for the most severely malnourished children; in group 3, the weight/height ratio was maintained and there was a discrete tendency towards weight recovery, which was reversed in group 4, in which the weight was again low in relation to height. The feeding supplementation program temporarily minimized severe nutritional deficiencies but was not sufficient to recover and maintain normal growth.     

Serotonin regulation of aggressive behavior in male golden hamsters (Mesocricetus auratus).

These studies examined the neurochemistry and neuroanatomy of the serotonin (5-HT) system innervating the anterior hypothalamus (AH) and the interaction of 5-HT receptor agonists with arginine vasopressin (AVP) in the regulation of offensive aggression in golden hamsters. Because specific 5-HT1A, 5-HT1B, and AVP V1A binding sites were observed within the AH by in vitro autoradiography, the hamsters were tested for offensive aggression after microinjections of AVP in combination with either the 5-HT1A agonist 8-hydroxy-2-(di-n-propylarnino) tetraline (DPAT) or the 5-HT1B agonist CGS-12066A (CGS) directly within the AH. Though treatment with DPAT resulted in a dose-dependent inhibition of AVP-facilitated offensive aggression, CGS was ineffective. In addition, a retrograde tracer was injected within the AH to localize the distribution of 5-HT neurons projecting to the area. Retrogradely labeled 5-HT neurons were found within the dorsal, median, and caudal linear raphe nuclei and are suspected to inhibit AVP-facilitated offensive aggression by an activation of 5-HT1A receptors in the AH. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral temperature regulation in the obese Zucker rat.

The behavioral thermoregulatory capability of lean (Fa/?) and obese (fa/fa) Zucker rats was investigated in an operant conditioning apparatus. Obese rats exposed to –9°C leverpressed for heat significantly more than lean rats, and consequently received more exogenous heat. Despite this increased heat intake, obese and lean animals demonstrated equivalent increases in core temperature. These results suggest that the obese (fa/fa) Zucker rat is not acting on a lowered thermoregulatory set point and is capable of behaviorally thermoregulating to compensate for poor heat absorption and/or a defect in metabolic heat production. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of water temperature in the regulation of water intake.

Performed 3 experiments on small groups (n = 2-6) of thirsty Carworth female albino rats. Cool water suppressed water intake. The suppression was apparent from the 1st min of drinking. Suppression occurred for both short (20-min) and long (100-min) daily drinking sessions, and occurred whether the water was available from a sipper tube or a bowl. When cellular hydration was delayed by giving Ss isotonic saline instead of water, the suppression by cooling was enhanced. Cool-water suppression of water intake appears to be a short-latency satiety mechanism that anticipates cellular and extracellular hydration. (27 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

高风温下热风炉操作对蓄热室温度分布的影响

提高风温过程中,热风炉蓄热室温度分布将产生相应的变化。本文针对首钢迁安钢铁有限责任公司2号高炉热风炉,数值模拟高风温下各种热风炉操作引起的蓄热室温度分布变化。研究结果表明:烟气温度每提高10 K,蓄热室高温区(不小于1 573 K)向下扩展0.25 m;烟气速度每升高1 m/s,高温区将向下扩展0.83 m,烟气出口温度提高25 K;高风温条件下应增加硅砖高度,并通过加强中温区格子砖的热容和热导率,提高中温区的蓄热量和热交换效率。     

Mechanisms in the simultaneous erosion-oxidation attack of nickel and cobalt at high temperature

An apparatus is described by which a specimen may be exposed to a well-defined erosive gas stream containing 20 μm alumina particles. Samples of nickel and cobalt were exposed to conditions of erosion and high temperature oxidation simultaneously, using 90 deg impact angle, at velocities up to 140 m/s^-1 and at temperatures up to 800 °C. From the results of erosion kinetics, surface morphologies, and cross section metallographic observations it is concluded that several definite regimes of interaction between erosion and oxidation exist. These regimes are described in qualitative terms, and it is shown how they arise as a result of the balance between the relative intensities of the erosion and oxidation processes.     

A study of the nycthemeral cycle of behavioural temperature regulation in man

1. Four human subjects were rendered hyperthermic and hypothermic by immersion in warm and cool water, at 02.00, 08.00, 14.00 and 20.00 hr. Bath and oesophageal temperatures and pulse rate were recorded. Temperature preference was determined by operant behaviour and vote. The core temperature set-point for behavioural thermoregulation was estimated from the behavioural results. 2. The results are in accord with those of previous studies of the nyethemeral cycling of autonomic responsiveness to heat and cold with a heating up phase before noon and a cooling down phase during the early night. 3. Subjective sensations and behavioural responses were also found to follow a nycthemeral cycle with a minimum before noon and a maximum at 20.00 hr. 4. The core temperature set point was 0-7 degrees C higher after noon than before noon with a small phase advance from resting core temperature. This result suggests that the nycthemeral cyclic change in body temperature is due to a nycthemeral cyclic change in the set-point near to which body temperature is kept by both autonomic and behavioural thermoregulatory responses.     

Medial amygdaloid lesions and the regulation of sociosexual behavioral patterns across the estrous cycle in female golden hamsters.

Two experiments were conducted to examine the behavioral effects of medial amygdaloid (M) lesions during the estrous cycle in female golden hamsters. In Experiment 1, males were paired with gonadally intact M-lesioned, sham-operated, or ovariectomized M-lesioned females and tested in large enclosures. Medial amygdaloid lesions reduced, significantly, the occurrence of precopulatory biting attack and vaginal scent-marking behavior in females. In contrast, M lesions produced a significant increase in the duration of copulation. Mating behavior was also observed for a brief period of time in 1 M-lesioned female during the diestrus period and in 2 ovariectomized animals. After copulation, M-lesioned females attacked their mating partner less frequently than did sham-lesioned animals, which suggests that M lesions may modulate the reduction of both pre- and postcopulatory aggressive behavior by common processes. The attenuation in aggressive responsiveness was further documented in Experiment 2, which shows that during intrasexual fights, M-lesioned females exhibited significantly fewer offensive agonistic responses than did sham-operated opponents. Collectively, the results demonstrate that M lesions produce significant alterations in both social and sexual response patterns and suggest that M may be a neural component of a forebrain inhibitory system regulating the display of feminine copulatory behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nitric oxide as a peripheral and central mediator in temperature regulation

In animals including humans nitric oxide (NO) serves as a biological messenger both peripherally at neuroeffector junctions and in the central nervous system where it modulates neuronal activity. Evidence for the involvement of NO in homeostatic control is accumulating also for temperature regulation in homeotherms. In the periphery an auxiliary role in the vasomotor control of convective heat transfer to heat dissipating surfaces and modulation of thermoregulatory heat generation, especially in brown adipose tissue as the site of nonshivering thermogenesis, are discussed as NO actions. At the central level a thermolytic role of NO in thermoregulation as well as in fever is assumed, however, experimental data opposing this view suggest that topical specificity may be important. At the level of single neurons, the observed interrelationships between thermosensitivity and responsiveness to NO are still not consistent enough to reconcile these data with the effects of NO-donors and inhibitors of NO-synthase on temperature regulation.     

Mechanisms of catalysis and allosteric regulation of yeast chorismate mutase from crystal structures

BACKGROUND: Chorismate mutase (CM) catalyzes the Claisen rearrangement of chorismate to prephenate, notably the only known enzymatically catalyzed pericyclic reaction in primary metabolism. Structures of the enzyme in complex with an endo-oxabicyclic transition state analogue inhibitor, previously determined for Bacillus subtilis and Escherichia coli CM, provide structural insight into the enzyme mechanism. In contrast to these bacterial CMs, yeast CM is allosterically regulated in two ways: activation by tryptophan and inhibition by tyrosine. Yeast CM exists in two allosteric states, R (active) and t (inactive). RESULTS: We have determined crystal structures of wild-type yeast CM cocrystallized with tryptophan and an endo-oxabicyclic transition state analogue inhibitor, of wild-type yeast CM co-crystallized with tyrosine and the endo-oxabicyclic transition state analogue inhibitor and of the Thr226-->Ser mutant of yeast CM in complex with tryptophan. Binding of the transition state analogue inhibitor to CM keeps the enzyme in a 'super R' state, even if the inhibitory effector tyrosine is bound to the regulatory site. CONCLUSIONS: The endo-oxabicyclic inhibitor binds to yeast CM in a similar way as it does to the distantly related CM from E. coli. The inhibitor-binding mode supports a mechanism by which polar sidechains of the enzyme bind the substrate in the pseudo-diaxial conformation, which is required for catalytic turnover. A lysine and a protonated glutamate sidechain have a critical role in the stabilization of the transition state of the pericyclic reaction. The allosteric transition from T-->R state is accompanied by a 15 degrees rotation of one of the two subunits relative to the other (where 0 degrees rotation defines the T state). This rotation causes conformational changes at the dimer interface which are transmitted to the active site. An allosteric pathway is proposed to include residues Phe28, Asp24 and Glu23, which move toward the activesite cavity in the T state. In the presence of the transition-state analogue a super R state is formed, which is characterised by a 22 degrees rotation of one subunit relative to the other.