关键词： myelodysplastic syndrome   U2AF1   TET2   alternative splicing  

摘要： Mutations in splicing factors are recurrent somatic alterations identified in myelodysplastic syndromes (MDS) and they frequently coincide with mutations in epigenetic factors. About 25% of patients present concurrent mutations in such pathways, suggesting a cooperative role in the pathogenesis of MDS. We focused on the splicing factor U2AF1 involved in the recognition of the 3 ' splice site during pre-mRNA splicing. Using a CRISPR/Cas9 system, we created heterozygous mice with a carboxy-terminal truncated U2af1 allele (U2af1(mut/+)), studied the U2af1(mut/+) hematopoietic system, and did not observe any gross differences in both young (12-13 weeks) and old (23 months) U2af1(mut/+) mice, except for a reduction in size of approximately 20%. However, hematopoietic stem/progenitor cells lacked reconstitution capacity in transplantation assays and displayed an aberrant RNA splicing by RNA sequencing. We also evaluated U2af1(mut/+) in conjunction with Tet2-deficiency. Novel double mutant U2af1(mut/+) Tet2(-/-) mice showed increased monogranulocytic precursors. Hematopoietic stem/progenitor cells were also enhanced and presented functional and transcriptomic alterations. Nonetheless, U2af1(mut/+) Tet2(-/-) mice did not succumb to MDS disease over a 6-month observation period. Collectively, our data suggest that cooperation between mutant U2af1 and Tet2 loss is not sufficient for MDS initiation in mice.

关键词： heat stress   high temperature   high-light   net CO2 assimilation   PSII efficiency   Vigna unguiculata  

摘要： We explored the effects, on photosynthesis in cowpea (Vigna unguiculata) seedlings, of high temperature and light-environmental stresses that often co-occur under field conditions and can have greater impact on photosynthesis than either by itself. We observed contrasting responses in the light and carbon assimilatory reactions, whereby in high temperature, the light reactions were stimulated while CO2 assimilation was substantially reduced. There were two striking observations. Firstly, the primary quinone acceptor (Q(A)), a measure of the regulatory balance of the light reactions, became more oxidized with increasing temperature, suggesting increased electron sink capacity, despite the reduced CO2 fixation. Secondly, a strong, O-2-dependent inactivation of assimilation capacity, consistent with down-regulation of rubisco under these conditions. The dependence of these effects on CO2, O-2 and light led us to conclude that both photorespiration and an alternative electron acceptor supported increased electron flow, and thus provided photoprotection under these conditions. Further experiments showed that the increased electron flow was maintained by rapid rates of PSII repair, particularly at combined high light and temperature. Overall, the results suggest that photodamage to the light reactions can be avoided under high light and temperatures by increasing electron sink strength, even when assimilation is strongly suppressed.

关键词： alternative splicing   gravitational unloading   m. soleus   sequencing   titin  

摘要： Abstract: Changes in titin alternative splicing in the rat soleus after seven-day gravitational unloading (the hindlimb unloading model) were studied by long-fragment PCR and nanopore sequencing. An increase in the proportion of shorter titin mRNA transcripts was found in m. soleus of the hindlimb suspended rats, which may have led to the translation of shorter variants of the N2A isoform of this protein. In the nuclear fraction of m. soleus of control and hindlimb suspended rats, no significant differences were found in the content of Rbm20, an RNA-binding protein involved, as is shown earlier, in the regulation of titin alternative splicing in mammalian cardiac muscle. It can be assumed that Rbm20 is not involved in the regulation of titin alternative splicing in the rat soleus muscle. © 2021, Pleiades Publishing, Inc.

摘要： In this Perspective Statement from The Obesity Society, the Clinical Committee discusses the use of weight loss supplements in the United States and the lack of regulatory oversight and rigorous testing of their efficacy and safety. A number of products and services claiming to promote weight loss are directly marketed to individuals with obesity and those wanting to lose weight. These products are not regulated as "drugs" by the Federal Drug Administration but, rather, are treated as dietary supplements if ingredients are "generally regarded as safe," requiring little or no testing to show efficacy or safety. Health care providers should be aware of the lack of evidence and deficiencies in regulatory oversight of dietary supplements marketed for weight loss. Regulatory authorities should protect consumers by ensuring accurate and safe marketing claims and preventing promotion of unproven and potentially unsafe products and claims.

关键词： core genes   dot plot analysis   phylogenetics   ranavirus  

摘要： Ranaviruses can infect both captive and wild cold-blooded vertebrates, leading to significant economic and environmental losses. With the cases of ranavirus infection increasing, many ranavirus genomic sequences were published, but little is known about ranavirus taxonomy on a whole-genome level. In this study, 44 ranaviruses core genes were identified in 32 ranaviruses genome sequences by using PanX. The neighbour-joining phylogenetic trees (NJ-tree) based on 44 ranaviruses core genes and 24 iridoviridae core genes and composition vector phylogenetic tree (CV-Tree) based on whole genome were constructed. The three of phylogenetic trees showed that 32 ranavirus isolates can be divided into 4 different subgroups including SGIV-like, EHNV-like, FV3-like and CMTV-like, and subgroups taxonomic position of three phylogenetic trees were consistent. However, the phylogenetic position of ToRV could not be determined if it belongs to FV3-like or CMTV-like group. Subsequently, we carried out dot plot analysis and confirmed that ToRV should belong to CMTV-like group. Based on dot plot analysis and phylogenetic trees, the taxonomic classification of ranaviruses was confirmed. Finally, four genes which are suitable for the construction of phylogenetic tree were selected from ranavirus core genes by recombination analysis, substitution saturation analysis and single-gene phylogenetic analysis. Phylogenetic tree based on concatenated sequences of the four selected genes showed that the classification of subgroups was identical with three of the phylogenetic trees. Conclusion: Our results confirmed taxonomic identification of ranaviruses;the four selected genes used in phylogenetic analysis will make taxonomic identification more convenient and accurate.

关键词： Flap coverage   keystone flap   nasal defect   nasal reconstruction   plastic surgery  

摘要： Nasal defect coverage has some challenging aspects for plastic surgeons because of the midfacial location of the nose and the relationship between convexities and concavities of nasal subunits. The authors described our experience with performing keystone flap (KF) nasal reconstruction in accordance with the facial aesthetic subunit concept and demonstrated the expanding versatility of KFs in nasal reconstruction. Between January 2017 and February 2020, 15 patients (average age, 72.07 +/- 13.00 years, range: 38-88 years) underwent KF reconstruction for nasal defects. We performed KF reconstruction in accordance with the facial aesthetic subunit concept. Data, including the defect causes and locations, defect sizes, flap sites and sizes, types of KFs, flap survival, complications, and follow-up period for each patient were reviewed retrospectively. Cosmetic outcomes were evaluated by independent plastic surgeons and patients through satisfactory postoperative surveys. Sixteen defects occurred in 15 patients. The defect sizes ranged from 0.8 x 1 cm to 2.5 x 3 cm. The flap sizes ranged from 1.5 x 3.5 cm to 4 x 6 cm. All defects were successfully covered with KFs from adjacent subunits. All flaps survived without any postoperative complications. At the mean follow-up period of 8.33 +/- 2.92 months, the objective cosmetic outcomes were rated favorably, and the average subjective patient satisfaction score was 7.93 +/- 1.28 on a scale of 1 to 10. We suggest that using KF reconstruction in consideration of the facial aesthetic subunit concept can be a promising alternative modality for covering nasal defects with outstanding aesthetic outcomes.

关键词： Quantile regression   Regularization techniques   Portfolio optimization   Performance evaluation  

摘要： We extend the analysis of investment strategies derived from penalized quantile regression models, introducing alternative approaches to improve state- of- art asset allocation rules. We make use of the post- model- selection estimation, which builds on two important choices: the specification of the penalty function and the selection of the optimal tuning parameter. Therefore, we first investigate whether and to what extent the performance of a given portfolio changes when moving from convex to nonconvex penalty functions. Second, we compare different methods to select the optimal tuning parameter, which controls the intensity of the penalization. Empirical analyses on real- world data show that these alternative methods outperform the standard LASSO, providing improvements in terms of risk, risk- adjusted return and portfolio concentration. This evidence becomes stronger when focusing on extreme risk, which is strictly linked to quantile regression.

关键词： Arterial switch operation   Lecompte manoeuvre   Autologous pericardium   PA bifurcation stenosis  

摘要： OBJECTIVES: Late complications of arterial switch operations (ASO) for transposition of the great arteries, such as neo-pulmonary artery (PA) stenosis and/or neoaortic regurgitation, have been reported. We developed an alternative reconstruction method called the longitudinal extension (LE) method to prevent PA bifurcation stenosis (PABS). METHODS: We identified 48 patients diagnosed with transposition of the great arteries and performed ASO using the Lecompte manoeuvre for neo-PA reconstruction. In 9 consecutive patients (from 2014), the LE method was performed (LE). Before 2014, conventional techniques were performed in 39 patients (C). The median body weight and age in the LE and C groups were 3.0 and 3.1kg and 12 and 26days, respectively. In the LE group, 1 patient underwent bilateral PA banding before ASO. In C, PA banding and arch repair were performed in 1 patient each. Patients who received concomitant procedures were included. RESULTS: The median follow-up in LE and C groups was 1.9 and 10.1years, respectively. Early mortality/late death was not found in group LE and in 1 patient in group C. Only 1 case required ascending aorta sliding plasty in LE, and 8 patients needed PA augmentation for PABS in C. The median velocity of right/left PA was measured as 1.6/1.9 m/s in LE and 2.1/2.3 m/s in C, so it showed a lower value in LE. CONCLUSIONS: Excellent mid-term results were obtained with the LE method. It was considered a useful procedure in preventing PABS, which is a primary late complication of ASO. Further follow-up and investigations are needed.

摘要： Rationale Guidelines recommend pre-/post-bronchodilator spirometry for diagnosing COPD, but resource constraints limit the availability of spirometry in primary care in low- and middle-income countries. Although spirometry is the diagnostic gold standard, we shall assess alternative tools for settings without spirometry. Methods A systematic literature review and meta-analysis was conducted, utilising Cochrane, CINAHL, Google Scholar, PubMed and Web of Science (search cut-off was May 01, 2020). Published studies comparing the accuracy of diagnostic tools for COPD with post-bronchodilator spirometry were considered. Studies without sensitivity/specificity data, without a separate validation sample and outside of primary care were excluded. Sensitivity, specificity and area under the curve (AUC) were assessed. Results Of 7578 studies, 24 were included (14635 participants). Hand devices yielded a larger AUC than questionnaires. The meta-analysis included 17 studies and the overall AUC of micro-spirometers (0.84, 95% CI 0.80-0.89) was larger when compared to the COPD population screener (COPD-PS) questionnaire (0.77, 95% CI 0.63-0.85) and the COPD diagnostic questionnaire (CDQ) (0.72, 95% CI 0.64-0.78). However, only the difference between micro-spirometers and the CDQ was significant. Conclusions The CDQ and the COPD-PS questionnaire were approximately equally accurate tools. Questionnaires ensured testing of symptomatic patients, but micro-spirometers were more accurate. A combination could increase accuracy but was not evaluated in the meta-analysis.