The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is regulated by the p53 and Egr-1 tumor suppressor pathways. Many anti-cancer drugs and chemicals induce NAG-1 expression, but the mechanisms are not fully understood. Transgenic mice expressing human NAG-1 are resistant to intestinal and prostate cancer, suggesting that NAG-1 is a tumor suppressor. Proteasome inhibitors exhibit anti-glioblastoma activities in preclinical studies. Here, we show that the proteasome inhibitors MG132 and bortezomib induced NAG-1 expression and secretion in glioblastoma cells. MG132 increased NAG-1 expression through transcriptional and post-transcriptional mechanisms. At the transcriptional level, the induction of NAG-1 required the −133 to +41 bp region of the promoter. At post-transcriptional levels, MG132 stabilized NAG-1 mRNA by increasing the half-life from 1.5 h to > 8 h. Because of the dramatic increase in mRNA stability, this is likely the major contributor to MG132-mediated NAG-1 induction. Further probing into the mechanism revealed that MG132 increased phosphorylation of the p38 MAPK pathway. Consequently, inhibiting p38 phosphorylation blocked activation of the NAG-1 promoter and decreased mRNA stability, indicating that p38 MAPK activation mediates both MG132-dependent promoter activation and mRNA stabilization of NAG-1. We propose that the induction of NAG-1 by p38 MAPK is a potential contributor to the anti-glioblastoma activity of proteasome inhibitors.
NAG-1/GDF15; MG132; glioblastoma; p38 MAPK
We aimed to examine the association between BMI and the risk of death from pancreas cancer in a pooled analysis of data from the Asia Cohort Consortium.
The data for this pooled-analysis included 883,529 men and women from 16 cohort studies in Asian countries. Cox proportional-hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for pancreas cancer mortality in relation to BMI. Seven predefined BMI categories (<18.5, 18.5–19.9, 20.0–22.4, 22.5–24.9, 25.0–27.4, 27.5–29.9, ≥30) were used in the analysis, with BMI of 22.5–24.9 serving as the reference group. The multivariable analyses were adjusted for known risk factors, including age, smoking, and history of diabetes.
We found no statistically significant overall association between each BMI category and risk of death from pancreas cancer in all Asians, and obesity was unrelated to mortality risk in both East Asians and South Asians. Age, smoking, and history of diabetes did not modify the association between BMI and risk of death from pancreas cancer. In planned subgroup analyses among East Asians, an increased risk of death from pancreas cancer among those with a BMI<18.5 was observed for individuals with a history of diabetes; HR = 2.01(95%CI: 1.01–4.00) (p for interaction=0.07).
The data do not support an association between BMI and risk of death from pancreas cancer in these Asian populations.
body mass index; insulin resistance; obesity; overweight; pancreatic cancer
The Hermansky–Pudlak Syndrome Type 4 (HPS4) gene, which encodes a subunit protein of the biogenesis of lysosome-related organelles complex (BLOC)-3, which is involved in late endosomal trafficking, is associated with schizophrenia; however, its clinical relevance in schizophrenia remains unknown. The purpose of the present study was to investigate whether HPS4 is associated with cognitive functions in patients with schizophrenia and healthy controls and with the clinical profiles of patients with schizophrenia.
We investigated the association of variants of HPS4 with clinical symptoms and cognitive function in Japanese patients with schizophrenia (n = 240) and age-matched healthy control subjects (n = 240) with single nucleotide polymorphisms (SNP)- or haplotype-based linear regression. We analyzed five tagging SNPs (rs4822724, rs61276843, rs9608491, rs713998, and rs2014410) of HPS4 and 2–5 locus haplotypes of these five SNPs. The cognitive functions of patients and healthy subjects were evaluated with the Brief Assessment of Cognition in Schizophrenia, Japanese-language version, and the patients were assessed for their symptomatology with the Positive and Negative Symptom Scale (PANSS).
In patients with schizophrenia, rs713998 was significantly associated with executive function under the dominant genetic model (P = 0.0073). In healthy subjects, there was a significant association between working memory and two individual SNPs under the recessive model (rs9608491: P = 0.001; rs713998: P = 0.0065) and two haplotypes (rs9608491-713998: P = 0.0025; rs61276843-9608491-713998: P = 0.0064). No significant association was found between HPS4 SNPs and PANSS scores or premorbid IQ, as measured by the Japanese version of the National Adult Reading Test.
These findings suggested the involvement of HPS4 in the working memory of healthy subjects and in the executive function deficits in schizophrenia.
HPS4; Cognition; Working memory; Executive function; BACS; rs9608491; rs713998
The wearable sensor system developed by our group, which measured lower limb angles using Kalman-filtering-based method, was suggested to be useful in evaluation of gait function for rehabilitation support. However, it was expected to reduce variations of measurement errors. In this paper, a variable-Kalman-gain method based on angle error that was calculated from acceleration signals was proposed to improve measurement accuracy. The proposed method was tested comparing to fixed-gain Kalman filter and a variable-Kalman-gain method that was based on acceleration magnitude used in previous studies. First, in angle measurement in treadmill walking, the proposed method measured lower limb angles with the highest measurement accuracy and improved significantly foot inclination angle measurement, while it improved slightly shank and thigh inclination angles. The variable-gain method based on acceleration magnitude was not effective for our Kalman filter system. Then, in angle measurement of a rigid body model, it was shown that the proposed method had measurement accuracy similar to or higher than results seen in other studies that used markers of camera-based motion measurement system fixing on a rigid plate together with a sensor or on the sensor directly. The proposed method was found to be effective in angle measurement with inertial sensors.
Shochu wastewater (SW; alcoholic distillery wastewater) contains large amounts of organic compounds (25,000 – 60,000 COD mg/L), nitrogen (1,000 – 6,000 T-N mg/L), and phosphorus (500 – 1,000 T-P mg/L). Despite its high nutrient content, SW is highly perishable, which limits its utilization for animal feed and fertilizer. Therefore, SW is mainly treated by methane fermentation. On the other hand, a feed yeast, Candida utilis, can utilize various organic compounds and be utilized as a yeast extract source and animal feed. We previously bred a mutant, C. utilis UNA1, that accumulates a large amount of nitrogen. Here, we investigated the use of C. utilis UNA1 to treat highly concentrated SW. With fed-batch cultivation using a 5-L jar fermenter, controlling pH at 5.0 with H2SO4, 62.9% of DOC, 38.4% of DTN, and 44.5% of DTP were stably removed from non-diluted barley shochu wastewater (BSW), and about 16.7 kg of freeze-dried yeast biomass was obtained. The yeast sludge biomass generated from BSW contains about 60% crude protein. Furthermore, using H2SO4 to control pH increased the sulfur content of wastewater, which increased the methionine composition of yeast sludge biomass.
Candida utilis; Shochu wastewater; Treatment; Biomass production; Amino acid composition
Evaluation of balance control ability would become important in the rehabilitation training. In this paper, in order to make clear usefulness and limitation of a traditional simple inverted pendulum model in balance prediction in sit-to-stand movements, the traditional simple model was compared to an inertia (rotational radius) variable inverted pendulum model including multiple-joint influence in the balance predictions. The predictions were tested upon experimentation with six healthy subjects. The evaluation showed that the multiple-joint influence model is more accurate in predicting balance under demanding sit-to-stand conditions. On the other hand, the evaluation also showed that the traditionally used simple inverted pendulum model is still reliable in predicting balance during sit-to-stand movement under non-demanding (normal) condition. Especially, the simple model was shown to be effective for sit-to-stand movements with low center of mass velocity at the seat-off. Moreover, almost all trajectories under the normal condition seemed to follow the same control strategy, in which the subjects used extra energy than the minimum one necessary for standing up. This suggests that the safety considerations come first than the energy efficiency considerations during a sit to stand, since the most energy efficient trajectory is close to the backward fall boundary.
XMAP215msps and the EB1–Sentin duo act individually and cooperatively to accelerate microtubule growth and increase rescue events but also to promote frequent catastrophes.
Dynamic microtubules (MTs) are essential for various intracellular events, such as mitosis. In Drosophila melanogaster S2 cells, three MT tip-localizing proteins, Msps/XMAP215, EB1, and Sentin (an EB1 cargo protein), have been identified as being critical for accelerating MT growth and promoting catastrophe events, thus resulting in the formation of dynamic MTs. However, the molecular activity of each protein and the basis of the modulation of MT dynamics by these three factors are unknown. In this paper, we showed in vitro that XMAP215msps had a potent growth-promoting activity at a wide range of tubulin concentrations, whereas Sentin, when recruited by EB1 to the growing MT tip, accelerated growth and also increased catastrophe frequency. When all three factors were combined, the growth rate was synergistically enhanced, and rescue events were observed most frequently, but frequent catastrophes restrained the lengthening of the MTs. We propose that MT dynamics are promoted by the independent as well as the cooperative action of XMAP215msps polymerase and the EB1–Sentin duo.
Although there are many reports regarding radiation-induced microbleeds, its frequency,
relation to dose and latency after radiation are not fully elucidated. The purpose of this
study was to evaluate the frequency, latency, patient factors and dose relation of
radiation-induced microbleeds after cranial irradiation using phase-sensitive magnetic
resonance imaging (PSI) at 3.0 T.
Retrospective evaluation of 34 patients (age range, 13–78 years; mean, 49 years;
follow-up period, 3–169 months; mean 29 months) who had undergone cranial irradiation
using magnetic resonance (MR) imaging including PSI was performed. Twenty-three patients
received high-dose irradiation (44–60 Gy), and 11 patients received 24–30 Gy whole brain
irradiation. When microbleeds were detected on MR imaging in these high-dose irradiation
patients, dose distribution maps were reproduced by reviewing the clinical records.
Then the irradiated areas were divided into 6 radiation-dose classes: regions > 55 Gy,
45–55 Gy, 35–45 Gy, 25–35 Gy, 15–25 Gy and 5–15 Gy. The frequency of microbleeds in each
radiation-dose class was analyzed.
Microbleeds were detected in 7 (21%) of 34 patients on T2-weighted imaging, whereas
they were detected in 16 (47%) of the 34 patients on PSIs. The frequency of microbleeds was
higher than previously reported. The latency of radiation-induced microbleeds after
radiation was 3 months to 9 years (mean, 33 months). In high-dose irradiation patients, the
frequency of microbleeds significantly was associated with radiation dose. There were no
foci that were observed in regions that had received < 25 Gy.
Radiation-induced microbleeds occurred more frequently in the present study than has been
previously reported. PSI can be used to detect these vascular changes earlier than other
conventional MR imaging techniques.
cranial irradiation; magnetic resonance imaging; radiation injury; ;
Individuals with mental disorders have increased rates of obesity and metabolic syndrome.
Here we evaluated factors influencing obesity in individuals with mental disorders who were
attending psychiatric day-care facilities on an outpatient basis.
The subjects (n = 108) were outpatients attending hospital-based
rehabilitation programs. We assessed body fat, weight, height, waist circumference, body mass
index (BMI), blood pressure, Geriatric Depression Scale-15 (GDS) scores, frequency of day-care
visits, satisfaction with body shape, physical comorbidity and lifestyle habits. Lifestyle habits
were evaluated using Breslow's health index based on health-related choices.
The subjects were divided into 2 groups: obese group (BMI ≥ 25 kg/m2) and
non-obese group (BMI < 25 kg/m2). The physical parameters and attributes of both groups
were compared, and factors related to BMI were statistically analyzed. The prevalence of obesity was
47.2% in all patients, 42.4% in males and 54.8% in females. Weight, waist circumference, body fat and
systolic and diastolic blood pressure were significantly higher in the obese group than
in the non-obese group. Body fat, waist circumference, systolic blood pressure and diastolic blood pressure
exhibited significant positive correlations with BMI, whereas the frequency of day-care visits,
satisfaction with body shape, GDS score and Breslow's health index exhibited significant negative
correlations with BMI.
The present results showed that the prevalence of obesity was high in outpatients with mental
disorders. Improvement in lifestyle choices is necessary to prevent obesity and the onset of
metabolic syndrome in such patients.
Breslow’s health index; metabolic syndrome; mental disorder; obesity; psychiatric day-care facility
The PAR complex targets Tiam1 to adhesions, where it interacts with talin to promote adhesion-induced Rac1 activation, cell spreading, and migration.
Migrating cells acquire front-rear polarity with a leading edge and a trailing tail for directional movement. The Rac exchange factor Tiam1 participates in polarized cell migration with the PAR complex of PAR3, PAR6, and atypical protein kinase C. However, it remains largely unknown how Tiam1 is regulated and contributes to the establishment of polarity in migrating cells. We show here that Tiam1 interacts directly with talin, which binds and activates integrins to mediate their signaling. Tiam1 accumulated at adhesions in a manner dependent on talin and the PAR complex. The interactions of talin with Tiam1 and the PAR complex were required for adhesion-induced Rac1 activation, cell spreading, and migration toward integrin substrates. Furthermore, Tiam1 acted with talin to regulate adhesion turnover. Thus, we propose that Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration.
pneumonia; lymphadenitis; arthritis; Mycobacterium celatum; rpoB; rifampin; mutation; bacteria
Nonsteroidal anti-inflammatory drug-activated gene, NAG-1, a transforming growth factor-β member, is involved in tumor progression and development. The association between NAG-1 expression and development and progression of glioma has not been well defined. Glioblastoma cell lines have lower basal expression of NAG-1 than other gliomas and normal astrocytes. Most primary human gliomas have very low levels of NAG-1 expression. NAG-1 basal expression appeared to inversely correlate with tumor grade in glioma. Aberrant promoter hypermethylation is a common mechanism for silencing of tumor suppressor genes in cancer cells. In glioblastoma cell lines, NAG-1 expression was increased by the demethylating agent, 5-aza-2’-deoxycytidine. To investigate whether the NAG-1 gene was silenced by hypermethylation in glioblastoma, we examined DNA methylation status using genomic bisulfite sequencing. The NAG-1 promoter was densely methylated in several glioblastoma cell lines as well as in primary oligodendroglioma tumor samples, which have low basal expression of NAG-1. DNA methylation at two specific sites (−53 and +55 CpG sites) in the NAG-1 promoter was strongly associated with low NAG-1 expression. The methylation of the NAG-1 promoter at the −53 site blocks Egr-1 binding and thereby suppresses Nag-1 induction. Treatment of cells with low basal NAG-1 expression with NAG-1 inducer also did not increase NAG-1. Incubation with a demethylation chemical increased Nag-1 basal expression and subsequent incubation with a NAG-1 inducer increased NAG-1 expression. We concluded from these data that methylation of specific promoter sequences causes transcriptional silencing of the NAG-1 locus in glioma and may ultimately contribute to tumor progression.
NAG-1; GDF15; glioblastoma; DNA methylation
Mastermind-like 1 (MAML1) is a transcriptional co-activator in the Notch signaling pathway. Recently, however, several reports revealed novel and unique roles for MAML1 that are independent of the Notch signaling pathway. We found that MAML1 enhances the transcriptional activity of runt-related transcription factor 2 (Runx2), a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation. MAML1 significantly enhanced the Runx2-mediated transcription of the p6OSE2-Luc reporter, in which luciferase expression was controlled by six copies of the osteoblast specific element 2 (OSE2) from the Runx2-regulated osteocalcin gene promoter. Interestingly, a deletion mutant of MAML1 lacking the N-terminal Notch-binding domain also enhanced Runx2-mediated transcription. Moreover, inhibition of Notch signaling did not affect the action of MAML1 on Runx2, suggesting that the activation of Runx2 by MAML1 may be caused in a Notch-independent manner. Overexpression of MAML1 transiently enhanced the Runx2-mediated expression of alkaline phosphatase, an early marker of osteoblast differentiation, in the murine pluripotent mesenchymal cell line C3H10T1/2. MAML1−/− embryos at embryonic day 16.5 (E16.5) had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed. At E14.5, extended zone of collagen type II alpha 1 (Col2a1) and Sox9 expression, markers of chondrocyte differentiation, and decreased zone of collagen type X alpha 1 (Col10a1) expression, a marker of hypertrophic chondrocyte, were observed. These observations suggest that chondrocyte maturation was impaired in MAML1−/− mice. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.
To identify new molecules involved in bone and cartilage development and/or homeostasis, we utilized approximately 10,000 arrayed and addressable cDNA clones, which allowed systematic, efficient, and unbiased screening of cDNAs encoding factors that could activate critical bone differentiation activity via activation of Runx2, master regulator of bone development. We analyzed MAML1−/− mice to investigate the role of MAML1 in bone development. MAML1−/− embryos at embryonic day 14.5 and 16.5 had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed, indicated that chondrocyte maturation was impaired. This revealed that MAML1 plays an important role in proper bone development and may provide us with a new basis for identifying potential therapeutic targets for bone diseases.
In this article, the first isolation of Mycobacterium kyorinense specimens in Brazil is described. M. kyorinense is a recently identified species, with a few strains reported only in Japan. The Brazilian isolates were initially identified as Mycobacterium celatum by PCR restriction enzyme pattern analysis (PRA) with hsp65. However, biochemical tests indicated the same profile of M. kyorinense and distinguished them from M. celatum and Mycobacterium branderi. The sequencing of the hsp65, rpoB, and 16S rRNA genes allowed the accurate identification of isolates as M. kyorinense.
This report describes a case of rectal cancer with endoscopically observable white nodules caused by distal intramural lymphatic spread. A 57-year-old female presented to our hospital with frequent diarrhea and hemorrhoids. Computed tomography showed bilateral ovarian masses and three hepatic tumors diagnosed as rectal cancer metastases, and also showed multiple lymph node involvement. The patient was preoperatively diagnosed with stage IV rectal cancer. Colonoscopy demonstrated that primary rectal cancer existed 15 cm from the anal verge and that there were multiple white small nodules on the anal side of the primary tumor extending to the dentate line. Biopsies of the white spots were performed, and they were identified as adenocarcinoma. The patient underwent Hartmann’s procedure because of the locally advanced primary tumor. The white nodules were ultimately diagnosed as being caused by intramural lymphatic spreading because lymphatic permeation was strongly positive at the surrounding area. Small white nodules near a primary rectal cancer should be suspected of being intramural spreading. Endoscopic detection of white nodules may be useful for the diagnosis of distal intramural spread.
Rectal cancer; White nodule; Intramural spread; Lymphatic permeation
The TNFAIP3 gene, which encodes a ubiquitin-modifying enzyme (A20) involved in the negative regulation of NF-κB signaling, is frequently inactivated by gene deletions/mutations in a variety of B-cell malignancies. However, the detection of this in primary Hodgkin lymphoma (HL) specimens is hampered by the scarcity of Hodgkin Reed-Sternberg (HR-S) cells even after enrichment by micro-dissection.
We used anti-CD30 immunofluorescence with fluorescence in-situ hybridization (FISH) to evaluate the relative number of TNFAIP3/CEP6 double-positive signals in CD30-positive cells.
From a total of 47 primary classical Hodgkin lymphoma (cHL) specimens, 44 were evaluable. We found that the relative numbers of TNFAIP3/CD30 cells were distributed among three groups, corresponding to those having homozygous (11%), heterozygous (32%), and no (57%) deletions in TNFAIP3. This shows that TNFAIP3 deletions could be sensitively detected using our chosen methods.
Comparing the results with mutation analysis, TNFAIP3 inactivation was shown to have escaped detection in many samples with homozygous deletions. This suggests that TNFAIP3 inactivation in primary cHL specimens might be more frequent than previously reported.
FICTION analysis; Hodgkin lymphoma; TNFAIP3 gene; Homozygous deletion
In this study, we investigated the correlation between the microbiological characteristics of Clostridium difficile clinical isolates and the recurrence of C. difficile-associated disease (CDAD). Twenty C. difficile isolates recovered from 20 single infection cases and 53 isolates from 20 recurrent cases were analyzed by pulsed-field gel electrophoresis (PFGE) and PCR ribotyping, and the cytotoxicity, antimicrobial susceptibility, and sporulation/germination rates of the isolates were examined. Recurrent cases were divided into relapse or reinfection cases by the results of C. difficile DNA typing. Among the 20 recurrent cases, 16 cases (80%) were identified to be relapse cases caused by the initial strain and the remaining 4 cases (20%) were identified to be reinfection cases caused by different strains. All 73 isolates were susceptible to both vancomycin and metronidazole, but resistance against clindamycin, ceftriaxone, erythromycin, and ciprofloxacin was found in 87.7%, 93.2%, 87.7%, and 100% of the isolates, respectively. No correlations between DNA typing group, cytotoxicity, and sporulation rate of isolates and infection status, i.e., single, relapse, or reinfection, were observed. However, the isolates recovered from relapse cases showed a significantly higher germination rate when incubated in medium lacking the germination stimulant sodium taurocholate. These results indicate that the germination ability of C. difficile may be a potential risk factor for the recurrence of CDAD.
To improve the biodegradation of biodegradable plastic (BP) mulch films, 1227 fungal strains were isolated from plant surface (phylloplane) and evaluated for BP-degrading ability. Among them, B47-9 a strain isolated from the leaf surface of barley showed the strongest ability to degrade poly-(butylene succinate-co-butylene adipate) (PBSA) and poly-(butylene succinate) (PBS) films. The strain grew on the surface of soil-mounted BP films, produced breaks along the direction of hyphal growth indicated that it secreted a BP-degrading enzyme, and has directly contributing to accelerating the degradation of film. Treatment with the culture filtrate decomposed 91.2 wt%, 23.7 wt%, and 14.6 wt% of PBSA, PBS, and commercially available BP polymer blended mulch film, respectively, on unsterlized soil within 6 days. The PCR-DGGE analysis of the transition of soil microbial community during film degradation revealed that the process was accompanied with drastic changes in the population of soil fungi and Acantamoeba spp., as well as the growth of inoculated strain B47-9. It has a potential for application in the development of an effective method for accelerating degradation of used plastics under actual field conditions.
Biodegradable plastic; Leaf surface; Phylloplane fungi; Mulch film; PCR-DGGE
Three novel 1-alkyldaphnane-type diterpenes, stelleralides A–C (4–6), and five known compounds were isolated from the roots of Stellera chamaejasme L. The structures of 4–6 were elucidated by extensive spectroscopic analyses. Several isolated compounds showed potent anti-HIV activity. Compound 4 showed extremely potent anti-HIV activity (EC90 0.40 nM) with the lowest cytotoxicity (IC50 4.3 μM), and appears to be a promising compound for development into anti-AIDS clinical trial candidates.
Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement.
Laparoscopic surgery for colorectal disease has become widespread as a minimally invasive treatment. This is important because the increasing availability of new devices allows us to perform procedures with a reduced length of surgery and decreased blood loss. We herein report the results of a literature review of energy sources for laparoscopic colorectal surgery, focused especially on 6 studies comparing ultrasonic coagulating shears (UCS) and other instruments. We also describe our laparoscopic dissection techniques using UCS for colorectal cancer. The short-term outcomes of surgeries using UCS and Ligasure for laparoscopic colorectal surgery were superior to conventional electrosurgery. Some authors have reported that the length of surgery or blood loss when Ligasure was used for laparoscopic colorectal surgery is less than when UCS was used. On the other hand, a recent study demonstrated that there were no significant differences between the short-term outcomes of UCS and Ligasure for laparoscopic colorectal surgery. It is therefore suggested that the choice of technique used should be made according to the surgeon’s preference. We also describe our laparoscopic dissection techniques using UCS (Harmonic ACE) for colorectal cancer with regard to the retroperitoneum dissection, dissection technique, dissection technique around the feeding artery, and various other dissection techniques. We therefore review the outcomes of using various energy sources for laparoscopic colorectal surgery and describe our laparoscopic dissection techniques with UCS (Harmonic ACE) for colorectal cancer.
Laparoscopic surgery; Ultrasonic coagulating shears; Harmonic Scalpel; Ligasure; Colon and rectum; Dissection technique
The capacity of white-rot fungi to degrade wood lignin may be highly applicable to the development of novel bioreactor systems, but the mechanisms underlying this function are not yet fully understood. Lignin peroxidase (LiP) and manganese peroxidase (MnP), which are thought to be very important for the ligninolytic property, demonstrated increased activity in Phanerochaete chrysosporium RP-78 (FGSC #9002, ATCC MYA-4764™) cultures following exposure to 5 mM cyclic adenosine 3', 5'-monophosphate (cAMP) and 500 μM 3'-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that transcription of most LiP and MnP isozyme genes was statistically significantly upregulated in the presence of the cAMP and IBMX compared to the untreated condition. However, 100 μM calmodulin (CaM) inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), which had insignificant effects on fungal growth and intracellular cAMP concentration, not only offset the increased activity and transcription induced by the drugs, but also decreased them to below basal levels. Like the isozyme genes, transcription of the CaM gene (cam) was also upregulated by cAMP and IBMX. These results suggest that cAMP signaling functions to increase the transcription of LiP and MnP through the induction of cam transcription.
Phanerochaete chrysosporium; cAMP signaling; Calmodulin signaling; Lignin peroxidase; Manganese peroxidase
The microtubule plus end regulator EB1 brings Sentin and possibly a microtubule polymerase to microtubule plus ends to promote microtubule dynamics.
Highly conserved EB1 family proteins bind to the growing ends of microtubules, recruit multiple cargo proteins, and are critical for making dynamic microtubules in vivo. However, it is unclear how these master regulators of microtubule plus ends promote microtubule dynamics. In this paper, we identify a novel EB1 cargo protein, Sentin. Sentin depletion in Drosophila melanogaster S2 cells, similar to EB1 depletion, resulted in an increase in microtubule pausing and led to the formation of shorter spindles, without displacing EB1 from growing microtubules. We demonstrate that Sentin’s association with EB1 was critical for its plus end localization and function. Furthermore, the EB1 phenotype was rescued by expressing an EBN-Sentin fusion protein in which the C-terminal cargo-binding region of EB1 is replaced with Sentin. Knockdown of Sentin attenuated plus end accumulation of Msps (mini spindles), the orthologue of XMAP215 microtubule polymerase. These results indicate that EB1 promotes dynamic microtubule behavior by recruiting the cargo protein Sentin and possibly also a microtubule polymerase to the microtubule tip.
The use of biodegradable plastics can reduce the accumulation of environmentally persistent plastic wastes. The rate of degradation of biodegradable plastics depends on environmental conditions and is highly variable. Techniques for achieving more consistent degradation are needed. However, only a few microorganisms involved in the degradation process have been isolated so far from the environment. Here, we show that Pseudozyma spp. yeasts, which are common in the phyllosphere and are easily isolated from plant surfaces, displayed strong degradation activity on films made from poly-butylene succinate or poly-butylene succinate-co-adipate. Strains of P. antarctica isolated from leaves and husks of paddy rice displayed strong degradation activity on these films at 30°C. The type strain, P. antarctica JCM 10317, and Pseudozyma spp. strains from phyllosphere secreted a biodegradable plastic-degrading enzyme with a molecular mass of about 22 kDa. Reliable source of biodegradable plastic-degrading microorganisms are now in our hands.
Pseudozyma; Biodegradable plastic; Phyllosphere; Yeast
We found that Numb directly binds to p120. Numb depletion impaired E-cadherin internalization. aPKC phosphorylated Numb and inhibited its association with p120. In the Numb-depleted cells, the phosphomimetic Numb mutant failed to restore E-cadherin internalization. We propose the mode of action of Numb for intercellular adhesion downstream of aPKC.
Cadherin trafficking controls tissue morphogenesis and cell polarity. The endocytic adaptor Numb participates in apicobasal polarity by acting on intercellular adhesions in epithelial cells. However, it remains largely unknown how Numb controls cadherin-based adhesion. Here, we found that Numb directly interacted with p120 catenin (p120), which is known to interact with E-cadherin and prevent its internalization. Numb accumulated at intercellular adhesion sites and the apical membrane in epithelial cells. Depletion of Numb impaired E-cadherin internalization, whereas depletion of p120 accelerated internalization. Expression of the Numb-binding fragment of p120 inhibited E-cadherin internalization in a dominant-negative fashion, indicating that Numb interacts with the E-cadherin/p120 complex and promotes E-cadherin endocytosis. Impairment of Numb induced mislocalization of E-cadherin from the lateral membrane to the apical membrane. Atypical protein kinase C (aPKC), a member of the PAR complex, phosphorylated Numb and inhibited its association with p120 and α-adaptin. Depletion or inhibition of aPKC accelerated E-cadherin internalization. Wild-type Numb restored E-cadherin internalization in the Numb-depleted cells, whereas a phosphomimetic mutant or a mutant with defective α-adaptin-binding ability did not restore the internalization. Thus, we propose that aPKC phosphorylates Numb to prevent its binding to p120 and α-adaptin, thereby attenuating E-cadherin endocytosis to maintain apicobasal polarity.