Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor that leads to multiple endocrine tumors upon loss of its function. Menin functions as a transcriptional ...activator by tethering MLL complex to mediate histone H3 K4 methylation. It also functions as a repressor. However, the molecular mechanism of how menin contributes to the opposite outcome in gene expression is largely unknown. Here, we investigated the role of menin in the epigenetic regulation of transcription mediated by histone covalent modification. We show that the global methylation level of histone H3 K9, as well as H3 K4, was decreased in Men1(-/-) MEF cells. Consistently, menin was able to interact with the suppressor of variegation 3-9 homolog family protein, SUV39H1, to mediate H3 K9 methylation. This interaction decreased when patient-derived MEN1 mutation was introduced into the SUV39H1-interaction domain. We show that menin mediated different chromatin changes depending on target genes. Chromatin immunoprecipitation studies showed that menin directly associated with the GBX2 promoter and menin-dependent recruitment of SUV39H1 was essential for chromatin remodeling and transcriptional regulation. These results provide a molecular basis of how menin functions as a transcriptional repressor and suggest that menin-dependent integration of H3 K9 methylation might play an important role in preventing tumors.
This study examines the anatomic relationships and variability of the facial nerve trunk and its branches, with emphasis on the intraparotid connections between the divisions. Microdissections were ...performed on 30 Korean half-heads, and the facial nerve trunks and branches were exposed. The average depth of the stylomastoid foramen from the skin surface was 21.0 +/- 3.1 mm, and the distance between the stylomastoid foramen and the bifurcation of the temporofacial (upper) and cervicofacial (lower) divisions was 13.0 +/- 2.8 mm. In 26 of 30 dissections (86.7%), the facial nerve trunk bifurcated into two main divisions, and a trifurcation pattern was seen in the other four cases (13.3%). According to the origin of the buccal branches, we classified the branching patterns of the facial nerve into four categories. In type I (13.8% of cases), the buccal branches arose from the two main divisions of the trunk but not from other branches of the facial nerve. In type II (44.8% of cases), the buccal branches arising from the two main divisions were interconnected with the zygomatic branch. In type III (17.3% of cases), the marginal mandibular branch sent nerve twigs to the buccal branch, which originated from the upper and lower divisions. In type IV (17.3% of cases), the nerve twigs from the zygomatic and marginal mandibular branches merged to the buccal branch arising from the two main divisions. Communications between the facial and auriculotemporal nerve branches, which are known as "communicating auriculotemporal nerves," were observed in 28 of the 30 cases (93.3%). Familiarity with these common variations in the facial anatomy provides useful information for the surgeon in careful dissection, preservation of the facial nerve, and complete removal of the tumors in parotidectomies.
Background Standard-dose (36-Gy) total skin electron beam therapy (TSEBT) is a highly effective treatment in mycosis fungoides. However, the regimen is time-intensive and may be associated with ...significant toxicity. Objective We sought to evaluate the efficacy and tolerability associated with low-dose (12-Gy) TSEBT. Methods Data from 3 clinical trials using low-dose (12-Gy) TSEBT were pooled. In all trials, TSEBT-naïve patients with stage IB to IIIA mycosis fungoides were treated with TSEBT (12 Gy, 1 Gy per fraction over 3 weeks). The primary end point was clinical response rate. Secondary end points included time to response and duration of clinical benefit. Results In all, 33 patients enrolled. Eighteen were male; stages were 22 IB, 2 IIA, 7 IIB, and 2 IIIA. Overall response rate was 88% (29/33), including 9 patients with complete response. Median time to response was 7.6 weeks (3-12.4 weeks). Median duration of clinical benefit was 70.7 weeks (95% confidence interval 41.8-133.8 weeks). Toxicities from TSEBT were mild and reversible. Limitations Conclusions are limited because of the small number of patients. Conclusions Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with mycosis fungoides, which could be administered safely multiple times during the course of a patient's disease with acceptable toxicity profile.
Escherichia coli levels in surface water increase due to resuspension of sediment-bound bacteria by recreational boating activities at lake marinas.
Escherichia coli, a fecal coliform, and total ...coliforms were monitored between September 1999 and October 2001 in five marinas at Lake Texoma, located on the Oklahoma and Texas border. The general trend was that densities of
E. coli were lower in the summer season due to the lower loading of fecal material into Lake Texoma and the ecological conditions of the lake, such as more vigorous grazing by protozoa and less viability of
E. coli at an elevated temperature. The densities of total coliforms greatly increased in the summer.
E. coli levels increased with depth, and the bottom water samples had higher densities of
E. coli mainly due to their association with particles. There was a direct relationship between amount of gasoline sold, which was related to recreational boating activity, and the resuspension of
E. coli. This indicated that recreational boating activity in lake marinas may have resuspended bottom sediments with bound
E. coli, and the presence of
E. coli in marinas was not an indication of recent fecal contamination.
E. coli were detected in the largest densities at the boat dock points, followed by the gasoline filling station, and marina entrance. In addition, enumeration of bacteria in bottom sediment showed that the densities of
E. coli and total coliforms in sediment were much higher compared to those in lake water.
The myocyte enhancer factor 2 (MEF2) consists of a family of transcription factors that play important roles in a number of physiological processes from muscle cell differentiation to neuronal ...survival and T cell apoptosis. MEF2 has been reported to be associated with several distinct repressors including Cabin1(cain), MEF2-interacting transcriptional repressor (MITR), and HDAC4. It has been previously shown that Cabin1 is associated with MEF2 in a calcium-sensitive manner; activated calmodulin binds to Cabin1 and releases it from MEF2. However, it was not known whether the binding of HDAC4 and MITR to MEF2 is also regulated by calcium. We report that HDAC4 and MITR contain calmodulin-binding domains that overlap with their MEF2-binding domains. Binding of calmodulin to HDAC4 leads to its dissociation from MEF2, relieving MEF2 from the transcriptional repression by HDAC4. Together, HDAC4, MITR, and Cabin1 constitute a family of calcium-sensitive transcriptional repressors of MEF2.
Using an extended full-cycle carbon model from the Faustmann framework, which allows for management strategies of several uses concurrently implemented in the same area of forest, this paper ...investigates the selection of management objectives that are beneficial and optimal for forest plantations in Vietnam. Three scenarios are considered: Scenario 1 investigates the management objective of maximizing the land economic value (LEV) of timber as a single production. Scenario 2 investigates the joint production of timber and bioenergy sources. Scenario 3 analyzes the joint production of timber, bioenergy production, and carbon sequestration. The findings reveal that if growers pursue a timber management objective (Scenario 1), the farming business only provides considerable benefits under the government-subsidized credit scheme of 8.4%. For a higher non-subsidized interest rate of 15.24% of commercial banks, such gains reduce substantially and become negative value under the mean interest rate of 19.08% of private credit sources. Altering the management objective to a joint production of timber and raw bioenergy production (Scenario 2) will boost the LEV by a moderate level, but at the expense of timber production and thus carbon stock. However, the reduction tendency of timber and carbon balance is not substantial due mainly to the relatively small proportion of bioenergy production compared to timber production; therefore, decision-making frameworks targeting carbon uptake may be capable of incorporating such levels of confliction. Further internalizing the carbon value of the forest into management objectives generally leads to a longer rotation length, thus improving both carbon sequestration and income gains. Shifting the current timber-dominant management objective to a joint production of timber and bioenergy sources, or, alternatively, a joint production of timber, bioenergy production, and carbon sequestration when the carbon market is emerging, is a good alternative strategy for forest management in Vietnam.
This study was undertaken to investigate the effects of epidermal growth factor receptor (EGFR) mutation and its downstream signaling on response and survival in non-small-cell lung cancer (NSCLC) ...patients treated with gefitinib.
For 90 consecutive NSCLC patients who had received gefitinib, EGFR mutation was analyzed by DNA sequencing of exons 18, 19, 21, and 23 in the EGFR tyrosine kinase domain. Expressions of phosphorylated (p) -Akt and p-Erk were determined via immunohistochemistry. Response rate, time to progression (TTP), and overall survival were compared between each group according to EGFR mutation, as well as p-Akt and p-Erk expression.
Seventeen patients (18.9%; 95% CI, 10.8 to 27.0) harbored EGFR mutations. These mutations include deletions in exon 19 in seven patients, L858R in six patients, G719A in three patients, and a novel A859T in one patient. Response rate in patients with EGFR mutation was 64.7% (11 of 17 patients; 95% CI, 42.0 to 87.4), in contrast to 13.7% (10 of 73 patients; 95% CI, 5.8 to 21.6) in patients without mutation (P < .001). Moreover, these 17 patients with EGFR mutation had significantly prolonged TTP (21.7 v 1.8 months; P < .001) and overall survival (30.5 v 6.6 months; P < .001) compared with the remaining 73 patients without mutation. Although no significant correlation was detected between EGFR mutation and expressions of p-Akt or p-Erk, p-Akt overexpression was associated with prolonged TTP in patients with EGFR mutation.
Our data further support the importance of EGFR mutation with regard to gefitinib sensitivity. In addition to its predictive role, EGFR mutation confers significant survival benefits on NSCLC patients treated with gefitinib.
The growing demand for high-performance next-generation lithium (Li)-based batteries has brought Li-metal anodes into the spotlight, due to their high theoretical capacity (3,860 mAh g-1) and low ...electrochemical potential (-3.04 V vs. SHE). However, the practical application of Li-metal anodes faces formidable challenges, primarily associated with dendritic Li growth resulting from non-uniform ion flux. Although previous studies utilizing carbonaceous materials having pores and lithiophilic atoms have demonstrated powerful performances, the complex process involving pore creation and doping with heteroatoms still has limitations in terms of cost-effectiveness. This study introduces a lithiophilic nitrogen (N)-doped three-dimensional (3D) porous carbon (NLC) by simply reusing and carbonizing NH2-functionalized lignin (NL), an eco-friendly biopolymer derived from waste wood generated during the pulping process. The NLC offers macro-porous spaces with a rich array of N-doped sites, capable of accommodating and guiding Li deposition to facilitate uniform Li growth. The results demonstrate the effectiveness of the NLC as the Li growth guiding layer in Li-metal batteries. A full cell incorporating the NLC as a Li growth guiding layer, with NCM811 as cathodes, exhibits a remarkable capacity of 145. 57 mAh g-1 even at a high C-rate of 5C and capacity retention of 90.3% (167 mAh g-1) after 150 cycles at 1C. These findings represent significant advancements compared to conventional Li-metal batteries.
In this study we have examined the occurrence probability of solar proton events and their peak fluxes depending on three flare parameters (X‐ray peak flux, longitude, and impulsive time). For this ...we used NOAA solar energetic particle events from 1976 to 2006 and their associated X‐ray flare data. As a result, we selected 166 proton events that were associated with major flares: 85 events associated with X‐class flares and 81 events associated with M‐class flares. The occurrence probability especially strongly depends on three parameters as follows. (1) We found that about only 3.5% (1.9% for M‐class and 21.3% for X‐class) of the flares are associated with the proton events. (2) It is also found that this fraction strongly depends on longitude; for example, the fraction for 30°W < L ≤ 90°W is about three times larger than that for 30°E < L ≤ 90°E. (3) We also note that the occurrence probability of solar proton events associated with long‐duration (≥0.3 h) flares is about 2 (X‐class flare) to 7 (M‐class flare) times larger than that with short‐duration (<0.3 h) flares. (4) The largest difference is found between the eastern short‐duration M‐class flare group (0.3%) and the western long‐duration X‐class flare group (46.5%). In addition, the relationship between X‐ray flare peak flux and proton peak flux as well as its correlation coefficient are strongly dependent on longitude and impulsive time.
Background Optimum dose ratios of rimabotulinumtoxinB (BTX‐B) and onabotulinumtoxinA (BTX‐A) have not been determined for forehead wrinkles.
Objective To compare the efficacy and safety of BTX‐B ...and BTX‐A for the treatment of forehead lines.
Methods Twenty‐two women (mean age, 40 years) with symmetrical moderate to severe forehead lines were randomized to receive single intramuscular injections of BTX‐A and BTX‐B on either side of the forehead, at a potency ratio of 1 : 70 or 1 : 100. Subjects were followed‐up for 16 weeks. Four physicians evaluated patients’ photographs according to the 4‐point Facial Wrinkling Grade (FWG). Clinical Improvement Scale (CIS) was calculated by subtracting FWG score at each visit from that at baseline. Patient satisfaction scores and adverse events were also recorded.
Results Both BTX‐A and BTX‐B were effective for the treatment of forehead lines. At both potency ratios, BTX‐A had a longer duration of action than BTX‐B, while BTX‐B led to faster improvement than BTX‐A. There was no significant difference in CIS between 700 U and 1000 U BTX‐B treatments. Adverse effects were mild and transient.
Conclusion Both BTX‐A and BTX‐B were effective and well tolerated for the treatment of forehead wrinkles at potency ratios of 1 : 70 and 1 : 100.
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