Anatomical and functional recovery following spinal cord transection in the chick embryo

Following complete transection of the thoracic spinal cord at various times during embryonic development, chick embryos and posthatched animals exhibited various degrees of anatomical and functional recovery depending upon the age of injury. Transection on embryonic day 2 (E2), when neurogenesis is still occurring and before descending or ascending fiber tracts have formed, produced no noticeable behavioral or anatomical deficits. Embryos hatched on their own and were behaviorally indistinguishable from control hatchlings. Similar results were found following transection on E5, an age when neurogenesis is complete and when ascending and descending fiber tracts have begun to project through the thoracic region. Within 48 h following injury on E5, large numbers of nerve fibers were observed growing across the site of transection. By E8, injections of horse-radish peroxidase (HRP) administered caudal to the lesion, retrogradely labelled rostral spinal and brainstem neurons. Embryos transected on E5 were able to hatch and could stand and locomote posthatching in a manner that was indistinguishable from controls. Following spinal cord transections on E10, anatomical recovery of the spinal cord at the site of injury was not quite as complete as after E5 transection. Nonetheless, anatomical continuity was restored at the site of injury, axons projected across this region, and rostral spinal and brainstem neurons could be retrogradely labelled following HRP injections administered caudal to the lesion. At least part of this anatomical recovery may be mediated by the regeneration or regrowth of lesioned axons. Although none of the embryos transected on E10 that survived to hatching were able to hatch on their own, because several sham-operated embryos were also unable to hatch, we do not attribute this deficit to the spinal transection. When E10-transected embryos were aided in escaping from the shell, they were able to support their own weight, could stand, and locomote, and were generally comparable, behaviorally, to control hatchlings. Repair of the spinal cord following transection on E15 was considerably less complete compared to embryos transected on E2, E5, or E10. However, in some cases, a degree of anatomical continuity was eventually restored and a few spinal neurons rostral to the lesion could be retrogradely labelled with HRP. By contrast, labelled brainstem neurons were never observed following E15 transection. E15 transected embryos were never able to hatch on their own, and when aided in escaping from the shell, the hatchlings were never able to stand, support their own weight or locomote.(ABSTRACT TRUNCATED AT 400 WORDS)     

Structural aspects of nucleic acid-sensing Toll-like receptors

Invading pathogens elicit potent immune responses in cells through interactions between structurally conserved molecules derived from the pathogens and specialized innate immune receptors such as the Toll-like receptors (TLRs). Nucleic acid is one of the principal TLR ligands. Nucleic acid-sensing TLRs recognize an array of nucleic acids, including double-stranded RNA, single-stranded RNA, and DNAs with specific sequence motifs. Although ligand-induced dimerization is commonly observed followed by TLR activation, both the specific recognition mechanisms and the ligand–receptor interactions vary among different TLRs. In this review, we highlight our current understanding of how these receptors recognize their cognate ligands based on the recent advances in structural biology.     

Nupr1 deficiency downregulates HtrA1, enhances SMAD1 signaling,and suppresses age-related bone loss in male mice

Nuclear protein 1 (NUPR1) is a stress-induced protein activated by various stresses, such as inflammation and oxidative stress. We previously reported that Nupr1 deficiency increased bone volume by enhancing bone formation in 11-week-old mice. Analysis of differentially expressed genes between wild-type (WT) and Nupr1-knockout (Nupr1-KO) osteocytes revealed that high temperature requirement A 1 (HTRA1), a serine protease implicated in osteogenesis and transforming growth factor-β signaling was markedly downregulated in Nupr1-KO osteocytes. Nupr1 deficiency also markedly reduced HtrA1 expression, but enhanced SMAD1 signaling in in vitro-cultured primary osteoblasts. In contrast, Nupr1 overexpression enhanced HtrA1 expression in osteoblasts, suggesting that Nupr1 regulates HtrA1 expression, thereby suppressing osteoblastogenesis. Since HtrA1 is also involved in cellular senescence and age-related diseases, we analyzed aging-related bone loss in Nupr1-KO mice. Significant spine trabecular bone loss was noted in WT male and female mice during 6−19 months of age, whereas aging-related trabecular bone loss was attenuated, especially in Nupr1-KO male mice. Moreover, cellular senescence-related markers were upregulated in the osteocytes of 6−19-month-old WT male mice but markedly downregulated in the osteocytes of 19-month-old Nupr1-KO male mice. Oxidative stress-induced cellular senescence stimulated Nupr1 and HtrA1 expression in in vitro-cultured primary osteoblasts, and Nupr1 overexpression enhanced p16^ink4a expression in osteoblasts. Finally, NUPR1 expression in osteocytes isolated from the bones of patients with osteoarthritis was correlated with age. Collectively, these results indicate that Nupr1 regulates HtrA1-mediated osteoblast differentiation and senescence. Our findings unveil a novel Nupr1/HtrA1 axis, which may play pivotal roles in bone formation and age-related bone loss.     

Geographical Distribution of Adolescent Body Height with Respect to Effective Day Length in Japan: An Ecological Analysis

The height of Japanese youth raised in the northern region tends to be greater than that of youth raised in the southern region; therefore, a geographical gradient in youth body height exists. Although this gradient has existed for about 100 years, the reasons for it remain unclear. Consideration of the nutritional improvement, economic growth, and intense migration that has occurred in this period indicates that it is probably the result of environmental rather than nutritional or genetic factors. To identify possible environmental factors, ecological analysis of prefecture-level data on the body size of 8- to 17-year-old youth averaged over a 13-year period (1996 to 2008) and Japanese mesh climatic data on the climatic variables of temperature, solar radiation, and effective day length (duration of photoperiod exceeding the threshold of light intensity) was performed. The geographical distribution of the standardized height of Japanese adolescents was found to be inversely correlated to a great extent with the distribution of effective day length at a light intensity greater than 4000 lx. The results of multiple regression analysis of effective day length, temperature, and weight (as an index of food intake) indicated that a combination of effective day length and weight was statistically significant as predictors of height in early adolescence; however, only effective day length was statistically significant as a predictor of height in late adolescence. Day length may affect height by affecting the secretion of melatonin, a hormone that inhibits sexual and skeletal maturation, which in turn induces increases in height. By affecting melatonin production, regional differences in the duration of the photoperiod may lead to regional differences in height. Exposure to light intensity greater than 4000 lx appears to be the threshold at which light intensity begins to affect the melatonin secretion of humans who spend much of their time indoors.     

Optimal production of glutathione by controlling the specific growth rate of yeast in fed-batch culture

The optimal of the specific growth rate was obtained with simple mathematical model in a yeast fed-batch cultures. The model was based on the mass balance around the fed-batch system and the relationship between the specific growth rate, mu, and the specific production rate of glutathione, rho(G). The optimal profile of mu was calculated as a bang-bang type, That is mu, should start from the maximum value, mu(max) and should be kept at mu(max); then mu should be switched to mu(c), which gives a maximum value of rho(G). It was proven from the maximum principle that switching was needed only once, with the switching time from mu(max) to mu(c) depending on the final required glutathione content. Finally, this ideal profile of mu for the maximum production of glutathione was realized by manipulating the substrates feed rate in the fed-batch culture. Using the extended Kalman filter and a programmed-controller/feedback-compensator (PF) system, mu could be controlled at the optimal profile obtained. As a result, the maximum production of glutathione was accomplished fairly successfully. However, further improvement in the controller performance for mu is desired. The control strategy employed here can be applied to other batch reaction processes.     

Are Additional Trace Elements Necessary in Total Parenteral Nutrition for Patients with Esophageal Cancer Receiving Cisplatin-Based Chemotherapy?

It is known that cisplatin induces the excretion of zinc from the urine and thereby reduces its serum concentration. However, the fluctuation of these trace elements during or after cisplatin-based chemotherapy has not been evaluated. To answer this question, we performed a clinical study in esophageal cancer patients undergoing cisplatin-based chemotherapy. Eighteen patients with esophageal cancer who were not able to swallow food or water orally due to complete stenosis of the esophagus were evaluated. The patients were divided into a control group [total parenteral nutrition (TPN) alone for 28?days, ten cases] and an intervention group (TPN with additional trace elements for 28?days, eight cases). The serum concentrations of zinc, iron, copper, manganese, triiodothyronin (T3), and thyroxin (T4), as alternative indicators of iodine, were measured on days?0, 14, and 28 of treatment, and statistically analyzed on day?28. In the control group, the serum concentration of copper was significantly decreased from 135.4 (day?0) to 122.1???g/ml (day?14), and finally to 110.6???g/ml (day?28, p?=?0.015). The concentration of manganese was also significantly decreased from 1.34 (day?0) to 1.17???g/ml (day?14) and finally to 1.20 (day?28, p?=?0.049). The levels of zinc, iron, T3, and T4 were not significantly changed. In the intervention group, the supplementation with trace elements successfully prevented these decreases in their concentrations. TPN with supplementary trace elements is preferable and recommended for patients who are undergoing chemotherapy in order to maintain the patients?? nutrient homeostasis.     

Microbial communities associated with acetate-rich gas-petroleum reservoir surface facilities

We evaluated the microbial communities in acetate-rich production waters from separators of a high-temperature gas-petroleum reservoir in Higashi-Niigata, Japan. Bacterial and archaeal 16S rRNA gene libraries constructed from these waters were dominated by Acetobacterium-, Methanofollis-, and Methanosarcina-related sequences. The libraries constructed from enrichment cultures of the production waters were dominated by sequences related to the Acetobacterium- and Methanofollis-related sequences.     

Suppression of matrix metalloproteinase production in nasal fibroblasts by tranilast, an antiallergic agent, in vitro

Allergic rhinitis is an inflammatory disease characterized by nasal wall remodeling with intense infiltration of eosinophils and mast cells/basophils. Matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are the major proteolytic enzymes that induce airway remodeling. These enzymes are also important in the migration of inflammatory cells through basement membrane components. We evaluated whether tranilast (TR) could inhibit MMP production from nasal fibroblasts in response to tumor necrosis factor-alpha (TNF-alpha) stimulation in vitro. Nasal fibroblasts (NF) were established from nasal polyp tissues taken from patients with allergic rhinitis. NF (2 x 10(5) cells/mL) were stimulated with TNF-alpha in the presence of various concentrations of TR. After 24 hours, the culture supernatants were obtained and assayed for MMP-2, MMP-9, TIMP-1, and TIMP-2 levels by ELISA. The influence of TR on mRNA expression of MMPs and TIMPs in cells cultured for 12 hours was also evaluated by RT-PCR. TR at more than 5 x 10(-5) M inhibited the production of MMP-2 and MMP-9 from NF in response to TNF-alpha stimulation, whereas TIMP-1 and TIMP-2 production was scarcely affected. TR also inhibited MMP mRNA expression in NF after TNF-alpha stimulation. The present data suggest that the attenuating effect of TR on MMP-2 and MMP-9 production from NF induced by inflammatory stimulation may underlie the therapeutic mode of action of the agent in patients with allergic diseases, including allergic rhinitis.