理解运动行为抑制调控的新视角：乙酰胆碱门控氯离子通道受体

Acetylcholine, the first identified neurotransmitter, plays crucial roles in various brain functions. One well-known case is its involvement as an activating neurotransmitter in the regulation of locomotion. However, its inhibitory regulatory role, particularly in locomotion, remains poorly understood. In a study conducted by Polat et al., the authors investigated the inhibitory role of acetylcholine in locomotion in C. elegans. In this organism, the acetylcholine-gated chloride channel receptor consists of four subunits. The authors thoroughly examined the loss-of-function of each subunit in movement regulation. Interestingly, the mutant worms were still capable of performing various movements such as forward, backward crawling, and turning, suggesting that the overall movement was not significantly affected. However, quantitative behavior analysis revealed subtle yet significant differences in the timing and postures of the movement in these mutants. Furthermore, the authors employed optogenetics to stimulate a specific neuron involved in backward crawling and demonstrated that the loss-of-function of the receptors in individual neurons affects the transitioning between locomotion modes. This work provides evidence for the inhibitory regulatory role of acetylcholine in locomotion. The loss-of-function of acetylcholine-gated chloride channel receptors likely disrupts the balance of neuronal and circuit physiology, thereby affecting the regulation of locomotion. Moreover, this study highlights the powerful role of quantitative behavior analysis in discovering and understanding more sophisticated functions of neural circuits.     

The Asbury draft policy on ethical use of resources.

The general practice partners invited two medical ethicists (RC and TH) to meet them to develop the document. The partners met RC and TH for one and a half hours on eight occasions over one year and met without them on eight further occasions. The entire general practice also had an all day session to discuss in detail an advanced version of the draft. The developmental process was of great value to the partnership and has led to appreciable change in individuals'' views. The draft policy presented here is intended to start the ball rolling, so that proper guidelines will be developed at whatever level in the NHS is most appropriate. Comments and feedback are welcomed.     

Thalassomermis megamphis n. gen., n. sp. (Mermithidae: Nemata) from the Bathyal South Atlantic Ocean

Thalassomermis megamphis n. gen., n. sp. (Mermithidae: Nemata) was extracted from sediment collected off the coast of Brazil at a depth of approximately 1,000 m. Although the food of this new nematode is unknown, the reduction of the stoma and esophagus and presence of a trophosome indicate that it is parasitic in its juvenile stages. Thalassomermis megaraphis n. gen., n. sp. is assigned to Mermithidae because of its similarity to that family in the appearance of the cephalic sensory receptors, the long and tubular vagina, and copulatory muscles of the male extending posteriorly throughout most of the length of the tail. Thalassomermis megamphis n. gen., n. sp. differs from all other members of Mermithidae by the large, lenticular, intracuticular amphidial fovea with coiled, emergent terminal filaments as well as the small amphidial aperture situated over the center of the fovea.     

Posttetanic potentiation of human dorsiflexors

O'Leary, Deborah D., Karen Hope, and Digby G. Sale.Posttetanic potentiation of human dorsiflexors.J. Appl. Physiol. 83(6):2131-2138, 1997.Twitch contractions of the ankle dorsiflexors were evoked before and after applied 7-s tetanic stimulation at 100 Hzin 20 young adults. Torque decreased 15% during the tetanus. At 5 safter tetanus, twitch peak torque had potentiated 45%. Potentiationdeclined to 28% after 1 min, rose slightly to 33% at 2 min, anddeclined slowly with potentiation still 25% after 5 min. There waslarge intersubject variation in the amount of potentiation(5-140%) and its persistence (5 to 20 min). The muscle compoundaction potential (M wave) did not change significantly (from pretetanicvalue) at 5 s after tetanus but increased sharply (26%) at 2 min andthen subsided. Twitch half relaxation time (23%) decreasedsignificantly more than twitch rise time (13%) 5 s after tetanus andrecovered more slowly. Twitch rates of torque development (75%) andrelaxation (71%) increased similarly 5 s after tetanus and were stillelevated (~25%) at 5 min. The extent of twitch torque potentiationwas significantly inversely correlated with pretetanic twitch rise time(r = 0.69), half relaxation time (r = 0.61), andtwitch-to-tetanus ratio (r = 0.66). The data indicate that posttetanic potentiation has agreater effect on twitch half relaxation time than on time to peaktorque and is more prominent in muscles with a short twitch time courseand small twitch-to-tetanus ratio.

     

Cryptic dehalogenase and chloroamidase genes in Pseudomonas putida and the influence of environmental conditions on their expression

Mutants of two strains of Pseudomonas putida expressed two cryptic chloroamidases (C-amidase and Hamidase) and one cryptic dehalogenase (DehII). The mutants were selected on either 2-chloropropionamide (2CPA) or 2-monochloropropionate (2MCPA), developing as papillae in parental colonies growing on a metabolisable support substrate. Mutants expressing C-amidase were selected if 2CPA was utilised as either a carbon or a nitrogen source. H-amidase mutants were selected only if 2CPA was used as a nitrogen source. Growth temperature and pH affected the frequency of papillae production, although different temperatures and pHs did not affect the overall growth characteristics of the parental colonies. Decreasing growth temperature increased the frequency of 2cpa⁺ papillae formation, but decreased the frequency of 2mcpa⁺ papillae formation. Low pH (6.0) prevented the formation of 2mcpa⁺ and 2cpa⁺ papillae. However, in the case of the 2cpa⁺ papillae, decreasing the growth temperature also allowed papillae formation at pH 6.0.Abbreviations CAA Chloroacetamide - 2CPA 2-Chloropropionamide - DCA Dichloroacetic acid - HAA Halogenated alkanoic acid - 2MCPA 2-Monochloropropionic acid     

Analogs of arachidonic acid methylated at C-7 and C-10 as inhibitors of leukotriene biosynthesis

The syntheses and biological activity of (all )-7,7-dimethyl-5-8,- 11,14-eicosatetraenoic acid, (all )-7,7,-dimethyl-5,8,11-eicosatrienoic acid, ( , -7,7-dimethyl-5,8-eicosadienoic acid, (all )-10,10-dimetyl- 5,8,11,14-eicosatetraenoic acid, (all -10,10-dimethyl-5,8,11-eicosatrienoic acid, and .-( , -15-hydroxy-7,7-dimethyl-5,8-eicosadienoic acid are described. These arachidonic acid analogs are all inhibitors of ionophore-induced SRS-A biosynthesis in rat peritoneal cells. Their mode of action may involve inhibition of phospholipase A₂ rather than Δ⁵-lipoxygenase. These compounds failed to exhibit significant activity in an model designed to detect inhibitors of antigen-induced, leukotriene-mediated bronchoconstriction is sensitized guinea pigs.     

Changes in fatty acid composition of winter wheat during frost hardening

Twelve day old winter wheat seedlings (cvs Kharkov, frost hardy and Champlein, less hardy) accumulated linolenic acid at the expense of linoleic acid during controlled hardening. The change was most pronounced in the roots, where it was not specific to the phospholipid fraction. It was less marked in the leaves, but occurred there mainly in the phospholipids. The lack of differences between fatty acid profiles of the two cultivars rules out the explanation of varietal differences in frost hardiness in winter wheat on the basis of major changes in fatty acid unsaturation.     

Structural properties of phospholipids in the rat liver inner mitochondrial membrane. A P-NMR study

1. 1. The ³¹P-NMR characteristics of intact rat liver mitochondria, mitoplasts and isolated inner mitochondrial membranes, as well as mitochondrial phosphatidylethanolamine and phosphatidylcholine, have been examined.

2. 2. Rat liver mitochondrial phosphatidylethanolamine hydrated in excess aqueous buffer undergoes a bilayer-to-hexagonal (H_II) polymorphic phase transition as the temperature is increased through 10°C, and thus prefers the H_II) arrangement at 37°C. Rat liver mitochondrial phosphatidylcholine, on the other hand, adopts the bilayer phase at 37°C.

3. 3. Total inner mitochondrial membrane lipids, dispersed in an excess of aqueous buffer, exhibit ³¹P-NMR spectra consistent with a bilayer arrangement for the majority of the endogeneous phospholipids; the remainder exhibit spectra consistent with structure allowing isotropic motional averaging. Addition of Ca²⁺ results in hexagonal (H_II) phase formation for a portion of the phospholipids, as well as formation of ‘lipidic particles’ as detected by freeze-fracture techniques.

4. 4. Preparations of inner mitochondrial membrane at 4 and 37°C exhibit ³¹P-NMR spectra consistent with a bilayer arrangement of the large majority of the endogenous phospholipids which are detected. Approx. 10% of the signal intensity has characteristics indicating isotropic motional averaging processes. Addition of Ca²⁺ results in an increase in the size of this component, which can become the dominant spectral feature.

5. 5. Intact mitochondria, at 4°C, exhibit ³¹P-NMR spectra arising from both phospholipid and small water-soluble molecules (ADP, P_i, etc.). The phospholipid spectrum is characteristic of a bilayer arrangement. At 37°C the phospholipids again give spectra consistent with a bilayer; however, the labile nature of these systems is reflected by increased isotropic motion at longer (at least 30 min) incubation times.

6. 6. It is suggested that the uncoupling action of high Ca²⁺ concentrations on intact mitochondria may be related to a Ca²⁺-induced disruption of the integrity of the inner mitochondrial phospholipid bilayer. Further, the possibility that non-bilayer lipid structures such as inverted micelles occur in the inner mitochondrial membrane cannot be excluded.

Fluid transport and the dimensions of cells and interspaces of living Necturus gallbladder

The volume of the cells and lateral intercellular spaces were measured in living Necturus gallbladder epithelium. Under control conditions, the volume of the lateral spaces was 9% of the cell volume. Replacement of mucosal NaCl by sucrose or tetramethylammonium chloride (TMACl) caused intercellular spaces to collapse. During mucosal NaCl replacement, cell volume decreased to 79% of its control value. When NaCl was reintroduced into the mucosal bath, the intercellular spaces reopened and the cells returned to control volume. The NaCl active transport rate, calculated from the rate of cell volume decrease, was 266 pM/cm2.s, close to the observed rate of transepithelial salt transport. It was calculated from the decrease in cell volume that all of the intracellular NaCl was transported out of the cell during removal of mucosal NaCl. The flux of salt across the apical membrane, calculated from the rate of cell volume increase upon reintroducing mucosal NaCl, was 209 pM/cm2.s, in good agreement with estimates by other methods. The electrical resistance of the tight junctions was estimated to be 83.9% of the total tissue resistance in control conditions, suggesting that the lateral intercellular spaces normally offer only a small resistance to electrolyte movement.     

trans-dominant inhibition of human immunodeficiency virus type 1 Rev occurs through formation of inactive protein complexes.

The human immunodeficiency virus type 1 Rev protein controls expression of certain viral RNAs by binding to these RNAs in the nucleus. To investigate how dominant negative Rev mutants inhibit Rev function, we fused such mutants to hormone-dependent localization signals from the glucocorticoid receptor. Each was found to have fully potent inhibitory activity whether expressed in the nucleus or in the cytoplasm. Wild-type Rev colocalized with an inhibitory fusion protein, implying that the two proteins interact. The resulting complexes accumulated within nuclei in response to steroids but had no effect on expression of Rev-responsive mRNAs. A mutation known to block in vitro oligomerization of Rev abolished both complex formation and inhibitory activity of the mutant fusion proteins. Thus, trans-dominant inhibition of Rev does not require competition for nuclear substrates but may instead reflect the ability of a mutant to form nonfunctional complexes with the wild-type protein in vivo.