Interplay between stress response genes associated with attention‐deficit hyperactivity disorder and brain volume

The glucocorticoid receptor plays a pivotal role in the brain's response to stress; a haplotype of functional polymorphisms in the NR3C1 gene encoding this receptor has been associated with attention‐deficit hyperactivity disorder (ADHD). The serotonin transporter (5‐HTT) gene polymorphism 5‐HTTLPR is known to influence the relation between stress exposure and ADHD severity, which may be partly because of its reported effects on glucocorticoid levels. We therefore investigated if NR3C1 moderates the relation of stress exposure with ADHD severity and brain structure, and the potential role of 5‐HTTLPR. Neuroimaging, genetic and stress exposure questionnaire data were available for 539 adolescents and young adults participating in the multicenter ADHD cohort study NeuroIMAGE (average age: 17.2 years). We estimated the effects of genetic variation in NR3C1 and 5‐HTT, stress exposure and their interactions on ADHD symptom count and gray matter volume. We found that individuals carrying the ADHD risk haplotype of NR3C1 showed significantly more positive relation between stress exposure and ADHD severity than non‐carriers. This gene–environment interaction was significantly stronger for 5‐HTTLPR L‐allele homozygotes than for S‐allele carriers. These two‐ and three‐way interactions were reflected in the gray matter volume of the cerebellum, parahippocampal gyrus, intracalcarine cortex and angular gyrus. Our findings illustrate how genetic variation in the stress response pathway may influence the effects of stress exposure on ADHD severity and brain structure. The reported interplay between NR3C1 and 5‐HTT may further explain some of the heterogeneity between studies regarding the role of these genes and hypothalamic–pituitary–adrenal axis activity in ADHD.     

Cloning of the ethidium efflux gene from Escherichia coli

The gene specifying the ethidium efflux system of Escherichia coli has been cloned on a 3.2 kbp HindIII fragment and located on a 1.2 kbp fragment within this. Cross-resistance studies indicate that the system has a broad specificity for monovalent cations and the gene shows no hybridisation with similar genes found in Staphylococci.     

拟南芥COPT家族蛋白研究进展

铜(Cu)是植物必需的微量元素, 作为多种酶的辅因子参与许多植物生理生化反应。Cu缺乏和过量均影响植物正常生长发育, 因此植物进化出精妙复杂的调控网络来严格控制植物体内的Cu含量。植物Cu转运蛋白COPT家族成员与Cu有很高的亲和力, 能够调节植物对Cu的吸收和转运, 在维持植物体内Cu稳态平衡过程中发挥重要作用。COPT蛋白涉及不同的Cu转运功能, 如从外界环境中摄取Cu、从细胞器中输出Cu、长距离运输Cu以及在不同器官间动用和再分配Cu。此外, COPT蛋白在其它离子的稳态平衡维持、昼夜节律性生物钟调控、植物激素合成和植物对激素信号的感受过程中也发挥重要作用。该文综述了模式植物拟南芥(Arabidopsis thaliana) COPT家族各成员的表达和定位、调控机制以及生物学功能等方面的最新进展。     

Effect of Pressure on the Release of Radioactive Glycine and γ-Aminobutyric Acid from Spinal Cord Synaptosomes

Exposure to high hydrostatic pressure produces neurological changes referred to as the high-pressure nervous syndrome (HPNS). Manifestations of HPNS include tremor, EEG changes, and convulsions. These symptoms suggest an alteration in synaptic transmission, particularly with inhibitory neural pathways. Because spinal cord transmission has been implicated in HPNS, this study investigated inhibitory neurotransmitter function in the cord at high pressure. Guinea pig spinal cord synaptosome preparations were used to study the effect of compression to 67.7 atmospheres absolute on [3H]glycine and [3H]gamma-aminobutyric acid ([3H]GABA) release. Pressure was found to exert a significant suppressive effect on the depolarization-induced calcium-dependent release of glycine and GABA by these spinal cord presynaptic nerve terminals. This study suggests that decreased tonic inhibitory regulation at the level of the spinal cord contributes to the hyperexcitability observed in animals with compression to high pressure.     

Influence of external barium and potassium on potassium efflux in depolarized frog sartorius muscles

Summary Efflux of⁴²K⁺ was measured in frog sartorius muscles equilibrated in depolarizing solutions with external K⁺ concentrations ([K⁺] _o ) between 75 and 300mm and NaCl concentrations of 60, 120, or 240mm. For several combinations of KCl and NaCl, steady-state internal potentials (V _i) were the same for different [K⁺] _o . For the range ofV _i examined, K⁺ efflux occurs principally through the K⁺ inward rectifier channels. When external K⁺ is removedV _i remains constant for 2 to 3 hr because of the high membrane conductance to Cl^–, but K⁺ efflux drops by about one order of magnitude.External Ba²⁺ in the presence or absence of external K⁺ produces an inhibition of K⁺ efflux described by a relation of the formu=(u₁/(1+C)[Ba²⁺] _o ))+u ₂, whereu is the uninhibited fraction of K⁺ efflux;u ₁, u₂ andC are constants; andu ₁+u₂=1.C depends both on [K⁺] _o andV _i. When [K⁺] _o 75mm, increasing [K⁺] _o at constantV _i reduces Ba²⁺ sensitivity. For constantV _i–30 mV, Ba²⁺ sensitivity is less when [K⁺] _o =0 than when [K⁺] _o 75mm. When [K⁺] _o =0, Ba²⁺ sensitivity decreases asV _i is made more positive. The dependence of the Ba²⁺ sensitivity onV _i at constant [K⁺] _o is greater when [K⁺] _o =0 than when [K⁺] _o 75mm.Both the activation of K⁺ efflux by external K⁺ and the Ba²⁺ inhibition of K⁺ efflux can be explained on the basis of two membrane control sites associated with each channel. When both sites are occupied by K⁺, the channels are in a high flux state. When one or both sites are empty, the channels are in a low, nonzero flux state. When Ba²⁺ occupies either site, K⁺ efflux is further reduced. The reduction of Ba²⁺-sensitivity by increasing [K⁺] _o at high [K⁺] _o is attributable to the displacement of Ba²⁺ from the control sites by K⁺. The increased Ba²⁺ sensitivity produced by going from [K⁺] _o =0 to [K⁺] _o >-75mm whenV _i–30 mV is attributable to states in which Ba²⁺ occupies one site and K⁺ the other when [K⁺] _o 0. The smallerV _i dependence of the Ba²⁺ sensitivity when [K⁺] _o 75mm compared to [K⁺] _o =0 is attributable to the necessity that Ba²⁺ displace K⁺ at the control sites when [K⁺] _o is high but not when [K⁺] _o =0.     

Measurements of amino acid transport in internally dialyzed giant axons

Summary It is shown that the axoplasmic composition of acidic and neutral amino acids can be controlled effectively by the method of internal dialysis. Direct assay for specific binding and measurement of diffusion coefficients in axoplasm show that there is no significant binding or compartmentalization of amino acids. The dependence of amino acid efflux on substrate concentration can be measured under well-defined, true steady-state conditions. The taurine efflux-concentration relation in theMyxicola giant axon conforms to a second-order Hill equation. This fact is consistent with either a cooperative process or a mechanism in which membrane translocation is not the rate-controlling step. The effluxes of taurine and glycine from squid axon are an order of magnitude smaller than inMyxicola. The efflux-concentration relations are essentially linear up to 200mm substrate concentration. This result may be produced by specific transporters which have very high asymmetry, or by simple diffusive leak in the absence of specific transporters.     

Growth,ionic balance,proton excretion,and nitrate reductase activity in Alnus and Hippophaë supplied with different sources of nitrogen

Summary Pre-cultivated, nodulated and non-nodulated plants of black alder (Alnus glutinosa) and sea buckthorn (Hippophaë rhamnoides ssp.rhamnoides) were grown on different N sources, with and without acidity control. Dry matter yields were lowest when plants were supplied with only NO ₃ ^– and were much greater when NH ₄ ⁺ was supplied either alone or in combination with NO ₃ ^– as long as the external pH was controlled; the final yields of the N₂-fixing plants were relatively low, especially withH. rhamnoides. Without acidity control, yields were greatly reduced in the presence of NH ₄ ⁺ .Proton or hydroxyl-ion effluxes, calculated on the basis of plant analyses, agreed well with measured excretion values. Without pH adjustment, the total proton efflux into the external solution was greater inA. glutinosa than inH. rhamnoides.Both species, but particularlyA. glutinosa, displayed the highest nitrate reductase activity in the roots.     

External anions relieve DIDS inhibition of SO4 efflux from placental membrane vesicles

Sulphate efflux from human placental microvillus membrane vesicles was inhibited by external DIDS (K_I10 .6 M). This inhibition was partially reversed on addition of the translocated substrates sulphate or selenate to the external medium: selenite which is not translocated does not protect against DIDS inhibition. These findings show that the mechanism responsible for sulphate efflux can be modified by substrate in the external medium.Abbreviations DIDS 4-acetamido-4-isothiocyanostilbene-2-2-disulphonate     

Sucrose Efflux from the Maize Scutellum

Sucrose efflux from maize scutellum slices was promoted by high pH and by K+, Na+ or Rb+. Incubation in mannose (which drastically reduces the ATP level) caused high rates of sucrose efflux only when KCl was present at pH 8. The effects of triphenylmethylphosphonium ion (TPMP+, a lipid soluble cation) on sucrose efflux were similar to those of mannose plus KCl. Mannose and TPMP+ caused release of stored sucrose into the cytoplasm, but pH8 and KCl (mannose) or pH 8 (TPMP+) in the bathing solution were necessary for rapid efflux of sucrose. Rb⁺ uptake took place during sucrose efflux. In mannose, rates of Rb⁺ uptake and sucrose efflux were low at pH 5.6 and high at pH 8.0, although the time courses for uptake and efflux were different. It is concluded that sucrose efflux is electrogenic and that it occurs as sucrose-H⁺ symport. A scheme for sucrose transport across plasmalemma and tonoplast is presented.     

Stimulation by high external potassium of the sodium efflux in barnacle muscle fibers

Summary Single barnacle muscle fibers fromBalanus nubilus were used to study the effect of elevated external potassium concentration, [K] _o , on Na efflux, membrane potential, and cyclic nucleotide levels. Elevation of [K] _o causes a prompt, transient stimulation of the ouabain-insensitive Na efflux. The minimal effective concentrations is 20mm. The membrane potential of ouabain-treated fibers bathed in 10mm Ca²⁺ artificial seawater (ASW) or in Ca²⁺-free ASW decreases approximately linearly with increasing logarithm of [K] _o . The slope of the plot is slightly steeper for fibers bathed in Ca²⁺-free ASW. The magnitude of the stimulatory response of the ouabain-insensitive Na efflux to 100mmK _o depends on the external Na⁺ and Ca²⁺ concentrations, as well as on external pH, but is independent of external Mg²⁺ concentration. External application of 10^–4 m verapamil virtually abolishes the response of the Na efflux to subsequent K-depolarization. Stabilization of myoplasmic-free Ca²⁺ by injection of 250mm EGTA before exposure of the fiber to 100mm K _o leads to 60% reduction in the magnitude of the stimulation. Pre-injection of a pure inhibitor of cyclic AMP-dependent protein kinase reduces the response of the Na efflux to 100mm K _o by 50%. Increasing intracellular ATP, by injection of 0.5m ATP-Na₂ before elevation of [K] _o , fails to prolong the duration of the stimulation of the Na efflux. Exposure of ouabain-treated, cannulated fibers to 100mm K _o for time periods ranging from 30 sec to 10 min causes a small (60%), but significant, increase in the intracellular content of cyclic AMP with little change in the cyclic GMP level. These results are compatible with the view that the stimulatory response of the ouabain-insensitive Na efflux to high K _o is largely due to a fall in myoplasmicpCa resulting from activation of voltage-dependent Ca²⁺ channels and that an accompanying rise in internal cAMP accounts for a portion of this response.