The Glycine-Alanine Dipeptide Repeat from C9orf72 Hexanucleotide Expansions Forms Toxic Amyloids Possessing Cell-to-Cell Transmission Properties

Hexanucleotide expansions, GGGGCC, in the non-coding regions of the C9orf72 gene were found in major frontotemporal lobar dementia and amyotrophic lateral sclerosis patients (C9FTD/ALS). In addition to possible RNA toxicity, several dipeptide repeats (DPRs) are translated through repeat-associated non-ATG-initiated translation. The DPRs, including poly(GA), poly(GR), poly(GP), poly(PR), and poly(PA), were found in the brains and spinal cords of C9FTD/ALS patients. Among the DPRs, poly(GA) is highly susceptible to form cytoplasmic inclusions, which is a characteristic of C9FTD/ALS. To elucidate DPR aggregation, we used synthetic (GA)₁₅ DPR as a model system to examine the aggregation and structural properties in vitro. We found that (GA)₁₅ with 15 repeats fibrillates rapidly and ultimately forms flat, ribbon-type fibrils evidenced by transmission electron microscopy and atomic force microscopy. The fibrils are capable of amyloid dye binding and contain a characteristic cross-β sheet structure, as revealed by x-ray scattering. Furthermore, using neuroblastoma cells, we demonstrated the neurotoxicity and cell-to-cell transmission property of (GA)₁₅ DPR. Overall, our results show the structural and toxicity properties of GA DPR to facilitate future DPR-related therapeutic development.     

Salivary Anionic Changes after Radiotherapy for Nasopharyngeal Carcinoma: A 1-Year Prospective Study

Objectives

To investigate the salivary anionic changes of patients with nasopharyngeal carcinoma (NPC) treated by radiotherapy.

Material and Methods

Thirty-eight patients with T1-4, N0-2, M0 NPC received conventional radiotherapy. Stimulated whole saliva was collected at baseline and 2, 6 and 12 months after radiotherapy. Salivary anions levels were measured using ion chromatography.

Results

A reduction in stimulated saliva flow and salivary pH was accompanied by sustained changes in anionic composition. At 2 months following radiotherapy, there was a significant increase in chloride, sulphate, lactate and formate levels while significant reductions in nitrate and thiocyanate levels were found. No further changes in these anion levels were observed at 6 and 12 months. No significant changes were found in phosphate, acetate, or propionate levels throughout the study period.

Conclusions

Conventional radiotherapy has a significant and prolonged impact on certain anionic species, likely contributing to increased cariogenic properties and reduced antimicrobial capacities of saliva in NPC patients post-radiotherapy.     

Clonal integration enhances survival and performance of Potentilla anserina, suffering from partial sand burial on Ordos plateau, China

On Ordos plateau, a semi-arid, desertified area in China, sand burial is a common stress factor for plants. The extent to which sand burial occurs is heterogeneous and unpredictable in space and in time. Therefore, clonal fragments (i.e., interconnected ramets of a clonal plant) often experience partial sand burial, with some ramets buried in sand while the rest may remain unburied. It was hypothesized that clonal fragments are able to benefit from clonal integration, in case they experience partial sand burial. A pot experiment was conducted with Potentilla anserina, a stoloniferous herb often found on Ordos plateau. We used clonal fragments consisting of four interconnected ramets. In the experiment, the two proximal (older) ramets were unburied while the two distal (younger) ramets were either unburied (control) or buried with a 2, 4 or 6 cm deep layer of sand (burial treatments). The stolon connection between the proximal and the distal ramets was either severed or left intact. Stolon severing dramatically decreased the survival of buried ramets. Stolon severing and sand burial had significant effects on plant performance in terms of biomass production, number of leaves and leaf area. A cost–benefit analysis based on performance measures shows that the proximal ramets supported their connected distal ramets and did not incur any cost from this resource export. These results suggest that clonal integration, which is one of the functionally most important consequences of clonal growth, contributes significantly to our test species' capacity to withstand partial sand burial on Ordos plateau, a semi-arid and desertified area of China.     

Learning and long- and short-term memory in cockroaches

Intact cockroaches, headless insects and isolated segments of the animal were trained to avoid electric shocks, contingent upon an electric signal which was applied a fraction of a second prior to the shocks. The results showed that all the intact insects learned to avoid the shocks in approximately ten sessions, on a schedule of two daily sessions and ten trials per session. The retention of the learned responses was further tested; it showed that there was no decrement of avoidance reactions till the end of insect life in the experimental conditions. Furthermore, this retention of the learned behaviour was not affected by the severance of the head nor even by the isolation of a single ganglion, once the behaviour had been established.The learning ability of the headless animals, and of the isolated segments, was different. There is evidence that both types of preparations demonstrated some degree of learning, but a majority of them failed to reach the criterion of 100 per cent avoidances in a training schedule, exactly the same as for the intact cockroach. Nevertheless, if the headless insects were given a mass training of fourteen sessions per day, all of them reached the criterion. The retention of the isolated segment was found to be less than 1 day long, and that of the headless insects lasted at most 2 or 3 days after the last training session.It is interpreted that long-term memory can be established in the intact animals and, once it has been accomplished, the acquired behaviour can be retained by the lower portions of the central nervous system.     

转化淋巴细胞胰岛素受体酪氨酸蛋白激酶活性及细胞内源性底物的研究

本文对增殖期的淋巴细胞胰岛素依赖性酪氨酸蛋白激酶活性及内源性废物进行了分析研究。在纯化的健康人淋巴细胞中加入适量的植物血凝素(PHA),经过72h培养即成为转化淋巴细胞(增殖期淋巴细胞)。应用~(32)P参入实验,证实转化淋巴细胞胰岛素受体具有胰岛素依赖性的酪氨酸蛋白激酶活性,与未转化的对照组相比其活性增加约9倍。Scatchard分析表明转化后淋巴细胞膜表面胰岛素受体数增加3.5倍。应用抗酪氨酸磷酸酯抗体,对胰岛素作用前后的转化与未转化淋巴细胞内,酪氨酸残基磷酸化的蛋白进行了鉴定,结果表明:除了95kD受体β亚基自身磷酸化外,45kD蛋白质也明显磷酸化,我们命名它为PP45。我们认为PP45可能是淋巴细胞中胰岛素受体酪氨酸蛋白激酶的主要内源性废物,它的磷酸化是胰岛素信息传递过程级联反应的初始步骤。     

千金藤属植物小叶地不容中的生物碱(Ⅷ)

从小叶地不容(Steghania succitera Lo.et Tsoong)的块根中分得11种生物碱,根据理化性质及波谱测定,鉴定为克班宁(crebanine)(Ⅰ),四氢巴马汀(tetrahydropalmatine)(Ⅱ),去氢克班宁(dehydrocrebanine)(Ⅲ),巴马汀(palmatine)(Ⅳ),去氢紫堇单酚碱(dehydro-corydalmiae)(Ⅴ),克班宁硝酸盐(Ⅵ),氧代克班宁(oxocrebanine)(Ⅶ),紫堇单酚碱(corydalmine)(Ⅷ),phanostenine(Ⅸ),离木明碱 discretamine(Ⅹ),及 corypalmine(Ⅺ),化合物(Ⅳ)、(Ⅴ)、(Ⅵ)、(Ⅶ)、(Ⅸ)、(Ⅹ)和Ⅺ为首次报道从该植物中分得。     

Groin flap design and versatility

The groin flap is a reliable and well-established reconstructive option for pedicled or free-tissue transfer. Concern regarding its variable vascular origin and caliber has limited its use. To overcome this, a simplified guideline based on the transverse diameter of the patient's index and long fingers at the distal interphalangeal level has been developed. Thus "rule of two finger widths" positions the origin of the vascular pedicle from the femoral vessels two finger widths below the inguinal ligament, the upper flap border two finger widths above the inguinal ligament, the lower flap border two finger widths below the vascular origin, and both parallel to the flap axis, which lies along a line from the vascular origin to the anterosuperior iliac spine. This new groin flap design provides the necessary guidelines for vascular identification, accommodates pediatric and adult stature, and ensures primary donor-site closure if flap dimensions are within the prescribed boundaries. In addition, a new sartorius-cutaneous groin flap is presented. This combines the cutaneous groin flap with the proximal sartorius muscle (up to 15 cm), which is supplied by the deep vessels of the superficial circumflex iliac system. The sartorius-cutaneous groin flap further emphasizes the concept of single-pedicle compound or combined flaps and additionally enhances the extensive reconstructive versatility of previously described groin flaps. Over 200 pedicled and free groin flaps have been performed according to the "rule of two finger widths" over the past 5 years. There have been no complications related to flap design, such as difficulty with flap elevation, marginal necrosis, or donor-site closure.(ABSTRACT TRUNCATED AT 250 WORDS)