维生素C通过调节PPAR-α靶基因抑制高脂饮食诱导非酒精性脂肪肝小鼠

目的 探讨维生素C是否通过调节PPAR-α靶基因抑制高脂饮食诱导非酒精性脂肪肝（nonalcoholic fatty liver disease,NAFLD）小鼠模型。方法 C57BL/6小鼠随机分为对照组、NAFLD组和维生素C组。每组均为10只小鼠。对照组采用普通饲料连续喂养15周;NAFLD组采用高脂饲料连续喂养15周;维生素C组采用高脂饲料及维生素C连续喂养15周。喂养15周后,利用代谢测量、组织学和基因表达检查NAFLD相关因素。结果 与NAFLD组小鼠相比,补充维生素C可抑制NAFLD小鼠体质量增加（P<0.05）。同时,维生素C组小鼠循环维生素C浓度显著高于NAFLD组（P<0.05）。维生素C可抑制肝脏脂肪变性（P<0.05）。同样,维生素C也可使NAFLD小鼠肝脏炎症、纤维化和凋亡相关基因mRNA水平降低（均P<0.05）。此外,维生素C小鼠血清丙氨酸转氨酶、天冬氨酸转氨酶、总胆固醇和低密度脂蛋白胆固醇水平低于NAFLD小鼠（均P<0.05）。最后,维生素C还能提高肝脏PPAR-α介导脂肪酸β氧化基因mRNA水平（均P<0.05）。结论 维生素C对NAFLD小鼠体质量增加、肝脏甘油三酯积累,以及肝脏炎症、纤维化和凋亡有抑制作用,这一过程可能部分是通过上调PPAR-α靶基因表达介导的。     

Imaging features of central nervous system haemangiopericytomas

Intracranial and spinal haemangiopericytomas are uncommon, durally based tumours. They macroscopically resemble meningiomas but are distinct histologically, have a more aggressive natural history and require different management. We present a pictorial review illustrating the radiological manifestations of these tumours that will aid in their preoperative identification.     

A reinvestigation of the cross-reactivity between Klebsiella and HLA-B27 in the aetiology of ankylosing spondylitis.

The existence of cross-reactivity between Klebsiella antigens and cells from donors who are HLA-B27 positive and exhibit ankylosing spondylitis (AS) has been reinvestigated. Cells and antisera from different laboratories have been tested together using simultaneously microcytoxicity, chromium release and enzyme linked immunosorbent assays (ELISA). No reproducible interaction has been found. Mitogenic stimulation did not induce cross-reactivity and 'transformation' of B27+AS- cells by Klebsiella culture supernatants failed. Two transformed cell lines from B27+ AS+ donors exhibited specific cross reaction with two anti-Klebsiella antisera but only by chromium release. Immunoprecipitation with these cells and antisera showed the absence of any AS+ -specific antigen. It is concluded that the involvement of Klebsiella in ankylosing spondylitis through simple immunological cross-reactivity or through interaction with HLA-B27 is unlikely.     

Novel proteins with binding specificity for DNA CTG repeats and RNA CUG repeats: implications for myotonic dystrophy

While an unstable CTG triplet repeat expansion is responsible for myotonic dystrophy, the mechanism whereby this genetic defect induces the disease remains unknown. To detect proteins binding to CTG triplet repeats, we performed bandshift analysis using as probes double- stranded DNA fragments having CTG repeats [ds(CTG)6-10] and single- stranded oligonucleotides having CTG repeats ss(CTG)8 or RNA CUG triplet repeats (CUG)8. The source of protein was nuclear and cytoplasmic extracts of HeLa cells, fibroblasts and myotubes. Proteins binding to the double-stranded DNA repeat [ds(CTG)6-10], were inhibited by nonlabeled ds(CTG)6-10, but not by a non-specific DNA fragment (USF/AD-ML). Another protein binding to ssCTG probe and RNA CUG probe was inhibited by nonlabeled (CTG)8 and (CUG)8. Nonlabeled oligos with different triplet repeat sequences, ss(CAG)8 or ss(CGG)8, did not inhibit binding to the ss(CTG)8 probe. However, when labeled as probes, the (CAG)8 and (CGG)8 bound to proteins distinct from the CTG proteins and binding was inhibited by nonlabeled (CAG)8 or (CGG)8 respectively. The protein binding only to the RNA repeat (CUG)8 was inhibited by nonlabeled (CUG)8 but not by nonlabeled single- or double-stranded CTG repeats. Furthermore, the CUG-BP exhibited no binding to an RNA oligonucleotide of triplet repeats of the same length but having a different sequence, CGG. The CUG binding protein was localized to the cytoplasm, whereas dsDNA binding proteins were localized to the nuclear extract. Thus, several trinucleotide binding proteins exist and their specificity is determined by the triplet sequence. The novel protein, CUG-BP, is particularly interesting since it binds to triplet repeats known to be present in myotonin protein kinase mRNA which is responsible for myotonic dystrophy.      

Motor cortical activity in a memorized delay task

Summary Two rhesus monkeys were trained to move a handle on a two-dimensional (2D) working surface in directions specified by a light at the plane. They first captured with the handle a light on the center of the plane and then moved the handle in the direction indicated by a peripheral light (cue signal). The signal to move (go signal) was given by turning off the center light. The following tasks were used: (a) In the non-delay task the peripheral light was turned on at the same time as the center light went off. (b) In the memorized delay task the peripheral light stayed on for 300 ms and the center light was turned off 450–750 ms later. Finally, (c) in the non-memorized delay task the peripheral light stayed on continuously whereas the center light went off 750–1050 ms after the peripheral light came on. Recordings in the arm area of the motor cortex (N= 171 cells) showed changes in single cell activity in all tasks. In both delay tasks, the neuronal population vector calculated every 20 ms after the onset of the peripheral light pointed in the direction of the upcoming movement, which was instructed by the cue light. Moreover, the strength of the population signal showed an initial peak shortly after the cue onset in both the memorized and non-memorized delay tasks but it maintained a higher level during the memorized delay period, as compared to the non-memorized task. These results indicate that the motor cortex is involved in encoding and holding in memory directional information concerning a visually cued arm movement and that these processes can be visualized using neuronal population vector analysis.     

Cognitive spatial-motor processes

Summary Naive human subjects (N=18) were asked to move a manipulandum on a plane in directions other than going straight towards a visual stimulus. They were instructed verbally to generate a movement at an angle from a stimulus direction which varied in 2-dimensional (2-D) space from trial to trial in a pseudorandom fashion. Each subject performed eight sets of twenty consecutive trials: one for moving in the stimulus direction and seven for moving in directions at an angle from it. The angles were 5, 10, 15, 35, 70, 105 and 140°. Nine subjects were instructed to move in the clockwise (CW) departure and 9 to move in either (EI) the clockwise or the counterclockwise (CCW) departure, as they wished. The direction of the movement in 2-D space and the reaction time (RT) were measured. The mean angle achieved in a given set overshot the instruction angle, especially in the lower range (5–35°). The reaction time, (RT), of movements made at an angle from the stimulus direction showed two kinds of change: first, a step increase from the reaction time, RT₀, of movements in the stimulus direction, and second, superimposed upon it, a linear increase with the amplitude of the angle. The slope of the line was similar for the CW (2.37 ms/degree) and the EI case (2.28 ms/degree), but the step increase (y-intercept) for the EI case (84 ms) was substantially less than that of the CW case (155 ms). The linear increase of the RT with angle is compatible with the idea that performance in the task may involve a mental rotation of the imagined movement vector about its origin. The rotation would begin from the stimulus direction and end when the required angle is judged to have been reached; in addition, corrections of this angle at the end of the rotation could be made. The slope of 2.37 ms/degree observed in the CW case would correspond to a rotation rate of 422 degrees/s. The finding of a similar rate for the EI case indicates a similarity in strategy with regard to achieving a desired angle. In contrast, the lower intercept observed for the EI case suggests significant savings in processing information which is unconstrained with regard to angular departure. Assuming this model of internal motion, we analyzed the amplitude-accuracy relations using Fitts' (1954) approach to real movements. In accordance with Fitts' law, we found that the increase in RT, considered as a mental movement time, was a linear function of task difficulty which was calculated from the angle achieved and its variability. This indicates that Fitts' law holds for the hypothesized rotatory motion of the imagined movement vector, and that both real and imagined movements might be governed by similar amplitude-accuracy relations.     

Induction of the heat shock response of E. coli through stabilization of sigma 32 by the phage lambda cIII protein

The cIII protein of phage lambda favors the lysogenic response to infection by inhibiting the degradation of the lambda cII protein, which exerts the primary control on the developmental decision for lysis or lysogeny. To study the mechanism and scope of cIII-mediated regulation, we have used plasmid systems to examine the specific effect of cIII overproduction on the growth of Escherichia coli and the synthesis of bacterial proteins. We have found that maximal production of cIII prolongs the heat-induced synthesis of E. coli heat shock proteins and provokes elevated production of heat shock proteins even at low temperature. The overproduction of heat shock proteins is correlated with a rapid inhibition of cell growth, as judged by measurements of optical density. We suggest that an overactive heat shock response inhibits bacterial growth, either because excessive production of one or more of the proteins is highly deleterious or because only heat shock promoters are transcribed efficiently. To examine the effect of cIII on sigma 32, the specificity factor for the heat shock response, we have studied the stability of sigma 32 in cells carrying both cIII- and sigma 32-producing plasmids; the half-life of sigma 32 is increased fourfold in the presence of cIII. We conclude that overproduction of cIII provokes the heat shock response by increasing the steady-state level of active sigma 32. These studies also support the concept that the rate of expression of heat shock proteins is directly correlated with the amount of active sigma 32 and that regulation of the stability of sigma 32 may be an important factor for control of the heat shock response.