Cellular and molecular biology of Alzheimer's disease

Alzheimer's disease results from the degeneration of neurons. Degenerating nerve cells express atypical proteins, and amyloid is deposited. We suggest that some of these events are strongly influenced by genetic factors and age. Animal models should be useful in investigating the pathogenic mechanisms that lead to the brain abnormalities seen in this disease.     

Effector cell expression of NK1.1, a murine natural killer cell-specific molecule, and ability of mice to reject bone marrow allografts

The rejection of Hh-1 incompatible bone marrow cells in irradiated mice is mediated by NK cells and is genetically regulated. We tested the role of the NK-specific gene, NK1.1, in regulating the rejection of allogeneic bone marrow cell grafts. NK1.1+ mice, that are known to display strong resistance against Hh-1 incompatible grafts, were crossed to H-2/Hh-1 identical NK1.1-, poor responder mice, and the progeny were backcrossed to the poor responder parent. The segregating mice were individually typed for their expression of NK1.1 and the ability to resist Hh-1 incompatible bone marrow cells (BMC). A strong correlation was noted between expression of NK1.1 and rejection of H-2d/Hh-1d BMC. Our results support the idea that NK1.1 is one of the genes responsible for strong resistance to Hh-1d (determinant 2) but not for Hh-1j (determinant 3) BMC grafts. We suggest that the NK1.1 molecule functions as an accessory molecule in the cellular interactions involving the recognition of Hh-1 determinants.     

Oral inoculation with herpes simplex virus type 1 infects enteric neuron and mucosal nerve fibers within the gastrointestinal tract in mice.

Herpes simplex virus type 1 (HSV-1) is commonly encountered first during childhood as an oral infection. After this initial infection resolves, the virus remains in a latent form within innervating sensory ganglia for the life of the host. We have previously shown, using a murine model, that HSV-1 placed within the lumen of the esophagus gains access to nerves within the gut wall and establishes a latent infection in sensory ganglia (nodose ganglia) of the tenth cranial nerve (R. M. Gesser, T. Valyi-Nagy, S. M. Altschuler, and N. W. Fraser, J. Gen. Virol. 75:2379-2386, 1994). Peripheral processes of neurons in these ganglia travel through the vagus nerve and function as primary sensory receptors in most of the gastrointestinal tract, relaying information from the gut wall and mucosal surface to secondary neurons within the brain stem. In the work described here, we further examined the spread of HSV-1 through the enteric nervous system after oral inoculation. By immunohistochemistry, HSV-1 was found to infect myenteric ganglia in Auerbach's plexus between the inner and outer muscle layers of the gut wall, submucosal ganglia (Meisner's plexus), and periglandular ganglion plexuses surrounding submucosal glands. Virus-infected nerve fibers were also seen projecting through the mucosal layer to interact directly with surface epithelial cells. These intramucosal nerve fibers may be a conduit by which intraluminal virus is able to gain access to the enteric nervous system from the gastrointestinal lumen.     

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.     

Population dynamics of "null" and Thy1lo lymphocytes in mouse bone marrow: genesis of cells with natural killer cell lineage characteristics.

The population dynamics of "null" small lymphocytes lacking B and T lineage markers in mouse bone marrow have been examined using a combination of immunolabeling and hydroxyurea (HU) deletion techniques. The binding of the B lineage-associated mAb, 14.8, and anti-Thy1.2 to bone marrow cells has been detected radioautographically. Null cells lacking 14.8 and Thy1.2 determinants (14.8- Thy1-) formed a substantial subset (12-14%) of bone marrow small lymphocytes, representing 0.5 x 10(6) cells per femur (2-3% of nucleated cells). HU treatment revealed an exceptionally rapid turnover of the null small lymphocyte population (T1/2, 7.5 hr) compared with 14.8+ cells (T1/2, 20.5 hr) and Thy1+ cells (T1/2, 53 hr). Small lymphocytes bearing low intensities of Thy1 (Thy1lo) were also rapidly renewed (T1/2, 28 hr) whereas those with high intensities of Thy1 (Thy1hi) were renewed only slowly (T1/2, 123 hr). During ontogeny, null small lymphocytes first appeared in the fetal liver by Day 11 and the fetal spleen by Day 16, but increased rapidly in the bone marrow in early postnatal life. Double immunolabeling techniques demonstrated that 10% of null small lymphocytes in the bone marrow expressed NK1.1 antigen, while larger proportions bound to tumor (YAC.1) cells in vitro and displayed Fc receptors. The NK1.1-bearing fraction of null small lymphocytes in bone marrow was depleted by HU treatment only after an initial delay. NK1.1 was also expressed on subsets of Thy1lo cells and Thy1hi cells. The results have revealed the continuous production in mouse bone marrow of null and Thy1lo small lymphocytes, totaling 1-3 x 10(7) cells/day and 1.2 x 10(6) cells/day, respectively. The findings suggest that the large-scale production of null lymphocytes in mouse bone marrow includes the genesis of NK lineage cells which express NK1.1 and Thy1lo during a period of terminal maturation.     

Continuous production of clinical dextran using two-stage reactor

Summary Clinical dextran with desired molecular weight was produced continuously in the two-stage reactor. Cells ofLeuconostoc meseteroides B512F cultivated in the first reactor were transferred to the second reactor where sucrose and primer were added for clinical dextran production. By using this two-stage reactor, the fraction of desired clinical dextran increased significantly when observed with gel permeation chromatography.     

H-Y antigen in X,i(Xq) gonadal dysgenesis: Evidence of X-linked genes in testicular differentiation

Summary Three years ago, we detected H-Y antigen in the white blood cells of a phenotypic female with several of the stigmata of Turner's syndrome, and the mosaic karyotype: 45,X/46,X,i(Xq). We surmised at the time that the isochromosome, i(Xq), may have contained occult Y-chromosome-derived material. We have now confirmed the presence of H-Y in this patient and we have obtained evidence for the presence of H-Y in four of five other similar patients, all of whom are notable for carrying at least a single cell line with the karyotype 46,X,i(Xq). Although we cannot categorically exclude the presence of Y-chromosomal genes in the cells of these patients, there is no cytogenetic evidence of structural rearrangement involving the Y in any of the cases. Expression of H-Y antigen in association with i(Xq) thus implies that H-Y structural genes are X-situated, or alternatively that they are autosomal and X-regulated. It would follow that the H-Y⁺ cellular phenotype per se is not a valid marker for the Y-chromosome, and that H-Y genes that have been mapped to the pericentric region of the Y may be regulatory.     

栓孔菌属漆酶高产菌株的初步筛选及其产酶条件的优化

利用显色反应对栓孔菌属(Trametes)进行了漆酶高产菌株的筛选,并对目标菌株的产酶条件进行了优化,在添加愈创木酚的固体培养基中,通过显色反应初步筛选出漆酶高产菌株东方栓孔菌Trametes orientalis Cui 6300;进一步通过单因子分析、正交试验和ABTS法确定了菌株Cui 6300的最适产酶条件:麦芽糖15 g/L,蛋白胨3 g/L,pH 4.8,Cu2+2.0 mmol/L,培养温度28°C,接种饼直径1.5 cm,此时酶活最高可达19.923 U/mL;同时探索了Cu2+浓度及添加时间对其菌丝生物量和漆酶活力的影响。研究表明,Cu2+最适添加浓度为2.0 mmol/L,添加时间为接种后第3天。     

瘦蛋白与皮肤创伤愈合

自1994年瘦蛋白（leptin）被发现以来,其生理作用得到广泛的研究。近年的研究表明,在高等动物的皮肤创伤愈合过程中,胶原与血管的生成、肉芽组织与上皮的再生以及组织的重建等因子,对皮肤的创伤愈合发挥着至关重要的作用,了解瘦蛋白与上述因子之间的相互关系与作用机制,有助于指导治疗,改善预后。