Caenorhabditis elegans SNAP-29 is required for the proper morphology and functions of the Golgi and endosomes and general exocytosis.
It is generally accepted that soluble N-ethylmaleimide–sensitive factor attachment protein receptors mediate the docking and fusion of transport intermediates with target membranes. Our research identifies Caenorhabditis elegans homologue of synaptosomal-associated protein 29 (SNAP-29) as an essential regulator of membrane trafficking in polarized intestinal cells of living animals. We show that a depletion of SNAP-29 blocks yolk secretion and targeting of apical and basolateral plasma membrane proteins in the intestinal cells and results in a strong accumulation of small cargo-containing vesicles. The loss of SNAP-29 also blocks the transport of yolk receptor RME-2 to the plasma membrane in nonpolarized oocytes, indicating that its function is required in various cell types. SNAP-29 is essential for embryogenesis, animal growth, and viability. Functional fluorescent protein–tagged SNAP-29 mainly localizes to the plasma membrane and the late Golgi, although it also partially colocalizes with endosomal proteins. The loss of SNAP-29 leads to the vesiculation/fragmentation of the Golgi and endosomes, suggesting that SNAP-29 is involved in multiple transport pathways between the exocytic and endocytic organelles. These observations also suggest that organelles comprising the endomembrane system are highly dynamic structures based on the balance between membrane budding and fusion and that SNAP-29–mediated fusion is required to maintain proper organellar morphology and functions.
AIM: To compare the outcome of surgical treatment of colorectal adenocarcinoma in elderly and younger patients.
METHODS: The outcomes of 122 patients with colorectal adenocarcinoma who underwent surgical treatment between January 2004 and June 2009 were analyzed. The clinicopathological and blood biochemistry data of the younger group (< 75 years) and the elderly group (≥ 75 years) were compared.
RESULTS: There were no significant differences between the two groups in operation time, intraoperative blood loss, hospital stay, time to resumption of oral intake, or morbidity. The elderly group had a significantly higher rate of hypertension and cardiovascular disease. The perioperative serum total protein and albumin levels were significantly lower in the elderly than in the younger group. The serum carcinoembryonic antigen level was lower in the elderly than in the younger group, and there was a significant decreasing trend after the operation in the elderly group.
CONCLUSION: The short-term outcomes of surgical treatment in elderly patients with colorectal adenocarcinoma were acceptable. Surgical treatment in elderly patients was considered a selectively effective approach.
Colorectal tumor; Elderly patient; Morbidity; Carcinoembryonic antigen; C-reactive protein
A randomized control trial was performed to test whether a lifestyle intervention program, carried out in a primary healthcare setting using existing resources, can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance (IGT). The results of 3 years' intervention are summarized.
Through health checkups in communities and workplaces, 304 middle-aged IGT subjects with a mean body mass index (BMI) of 24.5 kg/m2 were recruited and randomized to the intervention group or control group. The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational materials provided by the study group.
After 1 year, the intervention had significantly improved body weight (-1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control; p = 0.023) and daily non-exercise leisure time energy expenditure (25 ± 113 vs. -3 ± 98 kcal; p = 0.045). Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years. The 3-year cumulative incidence tended to be lower in the intervention group (14.8% vs.8.2%, log-rank test: p = 0.097). In a sub-analysis for the subjects with a BMI > 22.5 kg/m2, a significant reduction in the cumulative incidence was found (p = 0.027).
The present lifestyle intervention program using existing healthcare resources is beneficial in preventing diabetes in Japanese with IGT. This has important implications for primary healthcare-based diabetes prevention.
Trial registration number
Melanogenesis substrate, N-propionyl-cysteaminylphenol (NPrCAP), is selectively incorporated into melanoma cells and inhibits their growth by producing cytotoxic free radicals. Magnetite nanoparticles also disintegrate cancer cells and generate heat shock protein (HSP) upon exposure to an alternating magnetic field (AMF). This study tested if a chemo-thermo-immunotherapy (CTI therapy) strategy can be developed for better management of melanoma by conjugating NPrCAP on the surface of magnetite nanoparticles (NPrCAP/M). We examined the feasibility of this approach in B16 mouse melanoma and evaluated the impact of exposure temperature, frequency, and interval on the inhibition of re-challenged melanoma growth. The therapeutic protocol against the primary transplanted tumor with or without AMF exposure once a day every other day for a total of three treatments not only inhibited the growth of the primary transplant but also prevented the growth of the secondary, re-challenge transplant. The heat-generated therapeutic effect was more significant at a temperature of 43°C than either 41°C or 46°C. NPrCAP/M with AMF exposure, instead of control magnetite alone or without AMF exposure, resulted in the most significant growth inhibition of the re-challenge tumor and increased the life span of the mice. HSP70 production was greatest at 43°C compared to that with 41°C or 46°C. CD8+T cells were infiltrated at the site of the re-challenge melanoma transplant.
peptide; cancer vaccine; immunotherapy; colon cancer; CTL
Considerable interest has been focused on telomerase because of its potential use in assays for cancer diagnosis, and for anti-telomerase drugs as a strategy for cancer chemotherapy. A number of assays based on the polymerase chain reaction (PCR) have been developed for evaluation of telomerase activity. To overcome the disadvantages of the conventional telomerase assay [telomeric repeat amplification protocol (TRAP)] related to PCR artifacts and troublesome post-PCR procedures, we have developed a telomeric repeat elongation (TRE) assay which directly measures telomerase activity as the telomeric elongation rate by biosensor technology using surface plasmon resonance (SPR). 5′-Biotinylated oligomers containing telomeric repeats were immobilized on streptavidin-pretreated dextran sensor surfaces in situ using the BIACORE apparatus. Subsequently, the oligomers associated with the telomerase extracts were elongated in the BIACORE apparatus. The rate of TRE was calculated by measuring the SPR signals. We examined elongation rates by the TRE assay in 18 cancer and three normal human fibroblast cell lines, and 12 human primary carcinomas and matching normal tissues. The elongation rates increased in a concentration- and time-dependent manner. Those of cancer cells were two to 10 times higher than fibroblast cell lines and normal tissues. Telomerase activities and its inhibitory effects of anti-telomerase agents as measured by both the TRE and TRAP assays showed a good correlation. Our assay allows precise quantitative comparison of a wide range of human cells from somatic cells to carcinoma cells. TRE assay is suitable for practical use in the assessment of telomerase activity in preclinical and clinical trials of telomerase-based therapies, because of its reproducibility, rapidity and simplicity.
Surgical trauma impairs intraoperative insulin sensitivity and is associated with postoperative adverse events. Recently, preprocedural statin therapy is recommended for patients with coronary artery disease. However, statin therapy is reported to increase insulin resistance and the risk of new-onset diabetes. Thus, we investigated the association between preoperative statin therapy and intraoperative insulin sensitivity in nondiabetic, dyslipidemic patients undergoing coronary artery bypass grafting.
RESEARCH DESIGN AND METHODS
In this prospective, nonrandomized trial, patients taking lipophilic statins were assigned to the statin group and hypercholesterolemic patients not receiving any statins were allocated to the control group. Insulin sensitivity was assessed by the hyperinsulinemic-normoglycemic clamp technique during surgery. The mean, SD of blood glucose, and the coefficient of variation (CV) after surgery were calculated for each patient. The association between statin use and intraoperative insulin sensitivity was tested by multiple regression analysis.
We studied 120 patients. In both groups, insulin sensitivity gradually decreased during surgery with values being on average ∼20% lower in the statin than in the control group. In the statin group, the mean blood glucose in the intensive care unit was higher than in the control group (153 ± 20 vs. 140 ± 20 mg/dL; P < 0.001). The oscillation of blood glucose was larger in the statin group (SD, P < 0.001; CV, P = 0.001). Multiple regression analysis showed that statin use was independently associated with intraoperative insulin sensitivity (β = −0.16; P = 0.03).
Preoperative use of lipophilic statins is associated with increased insulin resistance during cardiac surgery in nondiabetic, dyslipidemic patients.
A 77-year-old woman complained of epigastralgia, and a tumor (5 cm in diameter) of the gallbladder neck was detected by image analysis. Following cholecystectomy, the tumor was pathologically diagnosed as intraductal papillary neoplasm (IPN), gastric type, with associated invasive carcinoma. About 10 mo later, intraluminal multiple masses (3 foci, up to 1.8 cm) were noted in the extrahepatic bile duct, and the resected specimen showed that all tumors had similar gross and microscopic features as seen in gallbladder IPN without invasion, and they were synchronous multiple lesions. This case showed a papillary tumor of the gallbladder of gastric phenotype, and confirmed that the gallbladder is a target of IPN in addition to the bile ducts.
Intraductal papillary neoplasm; Intracystic papillary neoplasm; Gastric type; Metachronous occurrence; Synchronous occurrence
Chronic obstructive pulmonary disease is a common disability among elderly subjects with a heavy cigarette smoking habit. In contrast to the population that is susceptible to smoking, in whom pulmonary function worsens with the length of exposure to cigarette smoke, there are elderly individuals whose pulmonary function is not impaired. However, to date, the characteristics of this resistant smoking population have not been investigated. We aimed to identify a biomarker in individuals in whom lung health is maintained despite smoking. Blood sampling and spirometry were performed on 3,257 subjects who participated in a community-based annual health check in Takahata, Japan, from 2004 to 2006. We selected 117 elderly smokers (age ≥70, Brinkman index ≥600, smoking years ≥30). The ‘smoking resistant’ group met the following criteria: FEV1/FVC ≥0.7, and FEV1%predicted ≥80. Spirometry was re-evaluated in 147 male, current smokers in 2009. Baseline serum iron (sFe) levels were higher in the smoke resistant group compared with the non-resistant group. In those with low sFe levels, FEV1/FVC was reduced in male subjects. These spirometric measures were positively associated with sFe levels in men. Multiple linear regression analysis revealed that sFe levels were predictive for spirometric values, independent of other clinical factors. In addition, sFe levels were predictive for a decline in FEV1.Serum iron levels may be a biomarker for the spirometric susceptibility of individuals to cigarette smoke.
Alveolar macrophages (AMs) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated that the transcription factor, MafB, increased in the AMs of mice exposed to cigarette smoke, and in those of human patients with COPD. The aim of this study was to evaluate the role of MafB in AMs using newly established transgenic (TG) mice that specifically express dominant negative (DN) MafB in macrophages under the control of macrophage scavenger receptor (MSR) enhancer-promoter. We performed cell differential analyses in bronchoalveolar lavage cells, morphological analyses with electron microscopy, and flow cytometry-based analyses of surface markers and a phagocytic capacity assay in macrophages. AM number in the TG mice was significantly decreased compared with wild-type (WT) mice. Morphologically, the high electron density area in the nucleus increased, the shape of pseudopods on the AMs was altered, and actin filament was less localized in the pseudopods of AMs of TG mice, compared with WT mice. The expression of surface markers, F4/80 and CD11b, on peritoneal macrophages in TG mice was reduced compared with WT mice, while those on AMs remained unchanged. Phagocytic capacity was decreased in AMs from TG mice, compared with WT mice. In conclusion, MafB regulates the phenotype of macrophages with respect to the number of alveolar macrophages, the nuclear compartment, cellular shape, surface marker expression, and phagocytic function. MSR-DN MafB TG mice may present a useful model to clarify the precise role of MafB in macrophages.
Patient: Female, 28
Final Diagnosis: Single intrauterine fetal death
Clinical Procedure: —
Specialty: Obstetrics and Gynecology
Single fetal death in monochorionic twin pregnancy may result in poor perinatal outcome of the surviving twin, including neurologic sequelae, other organ injury, and death. In most reported cases of poor perinatal outcome in the surviving twin, monochorionic co-twin death occured after more than 20 weeks of gestation, while few with earlier occurrence have been presented.
A 28-year-old primigravid woman was referred to our hospital at 18 3/7 weeks of gestation for perinatal management of single fetal death in a monochorionic-diamniotic twin pregnancy. Our first evaluation by ultrasonography revealed a dead twin sized at 16 weeks of gestation, and an alive one with normal size and appearance, together with 1 placenta and 2 amniotic cavities with normal fluid amounts. At 20 3/7 weeks of gestation, ultrasonography showed that the surviving twin had bilateral ventriculomegaly and dilatation all around the subarachnoid cavity despite a normal head size. Fetal magnetic resonance imaging revealed remarkable atrophy of the cerebral cortex. After counseling, the patient and family chose termination of pregnancy, and artificial abortion was performed at 21 weeks of gestation. The aborted fetuses were not anomalous. Autopsy pathological findings confirmed encephalomalacia in the surviving twin.
Recent development of imaging device make it possible that several abnormalities in central nervous system can be detected in detail at earlier gestational age. It is important to keep this condition in mind even though single fetal death occurred at early gestational age.
monochorionic twin; single intrauterine fetal death; encephalomalacia; fetal magnetic resonance imaging
There is considerable interest in using cell sheets for the treatment of various lesions as part of regenerative medicine therapy. Cell sheets can be prepared in temperature-responsive culture dishes and applied to injured tissue. For example, cartilage-derived cell sheets are currently under preclinical testing for use in treatment of knee cartilage injuries. The additional use of cryopreservation technology could increase the range and practicality of cell sheet therapies. To date, however, cryopreservation of cell sheets has proved impractical.
Here we have developed a novel and effective method for cryopreserving fragile chondrocyte sheets. We modified the vitrification method previously developed for cryopreservation of mammalian embryos to vitrify a cell sheet through use of a minimum volume of vitrification solution containing 20% dimethyl sulfoxide, 20% ethylene glycol, 0.5 M sucrose, and 10% carboxylated poly-L-lysine. The principal feature of our method is the coating of the cell sheet with a viscous vitrification solution containing permeable and non-permeable cryoprotectants prior to vitrification in liquid nitrogen vapor. This method prevented fracturing of the fragile cell sheet even after vitrification and rewarming. Both the macro- and microstructures of the vitrified cell sheets were maintained without damage or loss of major components. Cell survival in the vitrified sheets was comparable to that in non-vitrified samples.
We have shown here that it is feasible to vitrify chondrocyte cell sheets and that these sheets retain their normal characteristics upon thawing. The availability of a practical cryopreservation method should make a significant contribution to the effectiveness and range of applications of cell sheet therapy.
Cell sheet therapy; Chondrocyte sheet; Vitrification; Cryopreservation; Cartilage repair
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
LC3; autolysosome; autophagosome; flux; lysosome; phagophore; stress; vacuole
Ionizing radiation persistently reduces the pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus (DG) of the hippocampus, which may explain some of the learning deficits observed in patients treated with radiotherapy, particularly pediatric patients. A single dose of 8 Gy irradiation (IR) was administered to the brains of postnatal day 14 (P14) C57BL/6 mice and 1.0 × 105 bromodeoxyuridine-labeled, syngeneic NSPCs were injected into the hippocampus 1 day, 1 week or 6 weeks after IR. Cell survival and phenotype were evaluated 5 weeks after grafting. When grafted 1 day post-IR, survival and neuronal differentiation of the transplanted NSPCs were lower in irradiated brains, whereas the survival and cell fate of grafted cells were not significantly different between irradiated and control brains when transplantation was performed 1 or 6 weeks after IR. A young recipient brain favored neuronal development of grafted cells, whereas the older recipient brains displayed an increasing number of cells developing into astrocytes or unidentified cells. Injection of NSPCs, but not vehicle, induced astrogliosis and reduced thickness of the dorsal blade of the GCL after 5 months. In summary, we demonstrate that age and interval between IR and grafting can affect survival and differentiation of grafted NSPCs. The observed long-term gliosis and degeneration warrant caution in the context of NSPC grafting for therapeutical purposes.
neurogenesis; radiotherapy; transplantation; grafting; astrogliosis; differentiation
In vivo two-photon microscopy has revealed vital information on neural activity for brain function, even in light of its limitation in imaging events at depths greater than several hundred micrometers from the brain surface. We developed a novel semiconductor-laser-based light source with a wavelength of 1030 nm that can generate pulses of 5-picosecond duration with 2-W output power, and a 20-MHz repetition rate. We also developed a system to secure the head of the mouse under an upright microscope stage that has a horizontal adjustment mechanism. We examined the penetration depth while imaging the H-Line mouse brain and demonstrated that our newly developed laser successfully images not only cortex pyramidal neurons spreading to all cortex layers at a superior signal-to-background ratio, but also images hippocampal CA1 neurons in a young adult mouse.
Cholangiocarcinomas (CCs) show intraluminal spread to bile ducts and periductal infiltration associated with vascular, lymphatic and perineural invasion in addition to direct penetration. Recently, the peribiliary gland networks located around the hilar and extrahepatic bile ducts have been reportedly to be involved in a variety of biliary diseases. However, the pathological features and roles of these networks in the carcinogenesis and progression of CCs remain to be explored. Recently, we experienced two cases of hilar CC showing a nodular sclerosing growth grossly and histologically well-differentiated adenocarcinomas, with an extensive involvement of the peribiliary gland networks. In situ like spread of carcinoma cells in the bile duct lumen was focal in one case and not identifiable in the other. In contrast, other 4 cases of ordinary hilar CC which were also well-differentiated adenocarcinomas, showed variable intraductal luminal spread and also extensive periductal infiltration irrespective of the peribiliary gland network. In conclusion, the present study showed a unique form of periductal spread of CCs with preferential and extensive involvement of the peribiliary gland networks.
Biliary tree; peribiliary glands; hilar cholangiocarcinoma
Megakaryocytes are generated by the differentiation of megakaryocytic progenitors; however, little information has been reported regarding how ionizing radiation affects the differentiation pathway and cellular responses. Human leukemia K562 cells have been used as a model to study megakaryocytic differentiation. In the present study, to investigate the effects of radiation on phorbol 12-myristate 13-acetate (PMA)-induced megakaryocytic differentiation of K562 cells, the cellular processes responsible for the expression of CD41 antigen (GPIIb/IIIa), which is reported to be expressed early in megakaryocyte maturation, were analyzed. The expression of CD41 antigens was significantly increased 72 h after treatment with both 4 Gy X-irradiation and PMA. In this fraction, two populations, CD41low and CD41high cells, were detected by flow cytometry. The CD41high cells sustained intracellular ROS at the initial level for up to 72 h, but CD41low cells had reduced ROS by 48 h. The maximum suppressive effect on CD41 expression was observed when N-acetyl cysteine, which is known to act as a ROS scavenger, was administered 48 h after PMA stimulation. When K562 cells were pretreated with mitogen-activated protein kinase (MAPK) pathway inhibitors, an ERK1/2 inhibitor and a p38 MAPK inhibitor, followed by X-irradiation and PMA stimulation, the reactivity profiles of both inhibitors showed the involvement of MAPK pathway. There is a possibility that the K562 cell population contains at least two types of radiosensitive megakaryocytic progenitors with respect to ROS production mechanisms, and intracellular ROS levels determine the extent of CD41 expression.
K562 cells; megakaryocytopoiesis; ROS; MAPK
Background:Metabolic syndrome (Mets) is reportedly associated with chronic obstructive pulmonary disease (COPD). However, the relationship between abdominal circumference (AC) and decline in FEV1 has not been elucidated. We aimed to investigate this relationship among male current smokers.
Methods:Spirometry was performed on subjects (n = 3,257) ≥ 40 years of age, who participated in a community-based annual health check in Takahata, Japan, from 2004 through 2006 (visit 1). Spirometry was re-evaluated, and AC was assessed in 147 of the male current smokers in 2009 (visit 2). The diagnosis of Mets was based on the criteria used in the Hisayama Study.
Results:No significant relationships were observed between AC and spirometric parameters such as % predicted forced vital capacity (FVC), % predicted forced expiratory volume in 1 s (FEV1) and FEV1/FVC. However, decline in FEV1 was significantly correlated with AC. Multivariate logistic regression analysis showed that AC was a significant discriminating factor for decline in FEV1, independently of age, Brinkman index and change in body mass index from visit 1 to visit 2. At visit 2, there was a greater prevalence of decline in FEV1 among subjects with Mets (n=17) than among those without Mets. Although there were no differences in % predicted FVC, % predicted FEV1 or FEV1/FVC between subjects with or without Mets, the rate of decline in FEV1 was significantly greater in subjects with Mets than in those without.
Conclusions:This retrospective analysis suggested that measuring AC may be useful for discriminating male smokers who show a decline in FEV1.
decline in FEV1; abdominal circumference; smoker; health check.
To evaluate the effect of preoperative intravitreal bevacizumab (IVB) on surgical procedures, visual prognosis, and postoperative complications, especially postoperative vitreous hemorrhage, in cases with proliferative diabetic retinopathy (PDR).
Materials and Methods:
Seventy-one eyes of 54 consecutive patients (23 eyes of 18 women, 48 eyes of 36 men) were investigated in this study. Twenty-five eyes received IVB one to 30 days before the vitrectomy (Bevacizumab Group) and the other 46 eyes had the vitrectomy alone (Control Group). The surgical procedures, best-corrected visual acuities at baseline, 1, 3, and 6 months after the vitrectomy, and postoperative complications in the Bevacizumab Group were compared to the Control Group.
The patients were significantly younger in the Bevacizumab Group compared to the Control Group (P = 0.008). The incidence of preoperative vitreous hemorrhage, tractional retinal detachment, and iris neovascularization was significantly higher in the Bevacizumab Group than in the Control Group (P = 0.017, 0.041, and 0.018, respectively). The surgical procedures performed and the visual acuity at all time points was not significantly different between groups (P > 0.05, all comparisons). The incidence of early (≤4 weeks) postoperative vitreous hemorrhage was significantly higher in the Bevacizumab Group (27%) than in the Control Group (7%; P = 0.027) although the rate of late (>4 weeks) postoperative vitreous hemorrhage was not significantly different between groups (P > 0.05).
Vitrectomy with preoperative IVB may have no detrimental effect on surgical procedures and achieves the surgical outcomes for repair of PDR equal to vitrectomy alone despite the obvious selection bias of the patients in this study. However, special monitoring is highly recommended for early postoperative vitreous hemorrhage because bevacizumab in the vitreous may be washed out during vitrectomy.
Bevacizumab; Postoperative Vitreous Haemorrhage; Proliferative Diabetic Retinopathy; Vitrectomy; Vascular Endothelial Growth Factor
In the developing central nervous system, spontaneous activity appears well before the brain responds to external sensory inputs. One of the earliest activities is observed in the hindbrain and spinal cord, which is detected as rhythmic electrical discharges of cranial and spinal motoneurons or oscillations of Ca2+- and voltage-related optical signals. Shortly after the initial expression, the spontaneous activity appearing in the hindbrain and spinal cord exhibits a large-scale correlated wave that propagates over a wide region of the central nervous system, maximally extending to the lumbosacral cord and to the forebrain. In this review, we describe several aspects of this synchronized activity by focusing on the basic properties, development, origin, propagation pattern, pharmacological characteristics, and possible mechanisms underlying the generation of the activity. These profiles differ from those of the respiratory and locomotion pattern generators observed in the mature brainstem and spinal cord, suggesting that the wave is primordial activity that appears during a specific period of embryonic development and plays some important roles in the development of the central nervous system.
spontaneous activity; embryo; brainstem; spinal cord; development; synchronization
Background:Plasma fibrinogen is considered a biomarker of respiratory disease, owing to the relationship between plasma fibrinogen and pulmonary function established in Western populations. However, such a relationship has not yet been confirmed in an Asian population. We assessed this relationship in the general Japanese population.
Methods:Totally, 3,257 men and women aged ≥40 years who participated in a community-based annual health checkup in Takahata, Japan, from 2004 to 2006, underwent spirometry, and their plasma fibrinogen levels were determined.
Results:We found an inverse relationship between spirometric measures (percent predicted forced vital capacity [%FVC] and forced expiratory volume in 1s [%FEV1], and FEV1/FVC) and plasma fibrinogen levels in men, but not in women. The plasma fibrinogen levels were significantly higher in subjects with restrictive, obstructive, and mixed ventilatory disorders than in those with normal spirometry results. Multiple linear regression analysis revealed that in men, plasma fibrinogen levels were predictive for %FVC and %FEV1 (independent of age, body mass index, and cigarette smoking) but not for FEV1/FVC.
Conclusions:Plasma fibrinogen was significantly associated with pulmonary function in Japanese men, and as such, plasma fibrinogen might be a potent biomarker for pulmonary dysfunction in men.
Chronic Obstructive Pulmonary Disease; Decline in FEV1; Fibrinogen; Pulmonary function; Smoker; Spirometry
Plant tissues that require structural rigidity synthesize a thick, strong secondary cell wall of lignin, cellulose and hemicelluloses in a complicated bridged structure. Master regulators of secondary wall synthesis were identified in dicots, and orthologs of these regulators have been identified in monocots, but regulation of secondary cell wall formation in monocots has not been extensively studied. Here we demonstrate that the rice transcription factors SECONDARY WALL NAC DOMAIN PROTEINs (SWNs) can regulate secondary wall formation in rice (Oryza sativa) and are potentially useful for engineering the monocot cell wall. The OsSWN1 promoter is highly active in sclerenchymatous cells of the leaf blade and less active in xylem cells. By contrast, the OsSWN2 promoter is highly active in xylem cells and less active in sclerenchymatous cells. OsSWN2 splicing variants encode two proteins; the shorter protein (OsSWN2S) has very low transcriptional activation ability, but the longer protein (OsSWN2L) and OsSWN1 have strong transcriptional activation ability. In rice, expression of an OsSWN2S chimeric repressor, driven by the OsSWN2 promoter, resulted in stunted growth and para-wilting (leaf rolling and browning under normal water conditions) due to impaired vascular vessels. The same OsSWN2S chimeric repressor, driven by the OsSWN1 promoter, caused a reduction of cell wall thickening in sclerenchymatous cells, a drooping leaf phenotype, reduced lignin and xylose contents and increased digestibility as forage. These data suggest that OsSWNs regulate secondary wall formation in rice and manipulation of OsSWNs may enable improvements in monocotyledonous crops for forage or biofuel applications.
NAC trascription factor; secondary cell wall; rice; genetic modification; CRES-T
Differentiation-induction therapy is an attractive approach in leukemia treatment. It has been suggested that the accumulation of intracellular reactive oxygen species (ROS) is involved in megakaryocytic differentiation induced by phorbol 12-myristate 13-acetate (PMA) in the K562 leukemia cell line. Therefore, a ROS-inducible technique could be a powerful method of differentiation induction. Accordingly, we hypothesized that ionizing radiation contributes to the acceleration of megakaryocytic differentiation through the accumulation of intracellular ROS in leukemia cells. In the present study, ionizing radiation was shown to promote PMA-induced megakaryocytic differentiation. Cells with high CD41 expression sustained intracellular ROS levels effectively. The enhancement of differentiation by ionizing radiation was found to be regulated through the mitogen-activated protein kinase (MAPK) pathway, involving both extracellular signal-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK. Ionizing radiation also controlled mRNA expression of the oxidative stress response gene heme oxygenase-1 (HO1). Consequently, we concluded that intracellular ROS, increased by ionizing radiation, modulate megakaryocytic differentiation downstream of the MAPK pathway.
K562 cells; megakaryocytopoiesis; ROS; MAPK