Role of PRMTs in cancer: Could minor isoforms be leaving a mark?

Protein arginine methyltransferases(PRMTs) catalyze the methylation of a variety of protein substrates, many of which have been linked to the development, progression and aggressiveness of different types of cancer. Moreover, aberrant expression of PRMTs has been observed in several cancer types. While the link between PRMTs and cancer is a relatively new area of interest, the functional implications documented thus far warrant further investigations into its therapeutic potential. However, the expression of these enzymes and the regulation of their activity in cancer are still significantly understudied. Currently there are nine main members of the PRMT family. Further, the existence of alternatively spliced isoforms for several of these family members provides an additional layer of complexity. Specifically, PRMT1, PRMT2, CARM1 and PRMT7 have been shown to have alternative isoforms and others may be currently unrealized. Our knowledge with respect to the relative expression and the specific functions of these isoforms is largely lacking and needs attention. Here we present a review of the current knowledge of theknown alternative PRMT isoforms and provide a rationale for how they may impact on cancer and represent potentially useful targets for the development of novel therapeutic strategies.

Effect of a fermented milk containing Bifidobacterium lactis DN-173010 on Chinese constipated women

AIM: To investigate the effect of a fermented milk containing Bifidobacterium lactis DN-173010 and yogurt strains (BIO) on adult women with constipation in Beijing.METHODS: A total of 135 adult females with constipation were randomly allocated to consume for 2 wk either 100 g of the test fermented milk or 100 g of an acidified milk containing non-living bacteria (control).Stool frequency,defecation condition scores,stool consistency and food intake were recorded at baseline and after 1 and 2 wk in an intention-to-treat population of 126 subjects.In parallel,safety evaluation parameters were performed.RESULTS: At baseline,no differences were found between groups.Following consumption of test product,stool frequency was significantly increased after 1 wk (3.5 ± 1.5 vs 2.4 ± 0.6,P < 0.01) and 2 wk (4.1 ± 1.7 vs 2.4 ± 0.6,P < 0.01),vs baseline.Similarly,after 1 and 2 wk,of test product consumption,defecation condition (1.1 ± 0.9 vs 1.9 ± 1.2,P < 0.01 and 0.8 ± 1.0 vs 1.9 ± 1.2,P < 0.01,respectively) and stool consistency (1.0 ± 0.8 vs 1.5 ± 1.1,P < 0.01 and 0.6 ± 0.8 vs 1.5 ± 1.1,P < 0.01,respectively) were significantly improved.Compared with the control group,stool frequency was also significantly increased (3.5 ± 1.5 vs 2.5 ± 0.9,P < 0.01 and 4.1 ± 1.7 vs 2.6 ± 1.0,P < 0.01,respectively),and defecation condition (1.1 ± 0.9 vs 1.6 ± 1.1,P < 0.01 and 0.8 ± 1.0 vs 1.6 ± 1.1,P < 0.01,respectively) and stool consistency (1.0 ± 0.8 vs 1.4 ± 1.0,P < 0.05 and 0.6 ± 0.8 vs 1.3 ± 1.0,P < 0.01,respectively) significantly decreased after 1 and 2 wk of product consumption.During the same period,food intake did not change between the two groups,and safety parameters of the subjects were within normal ranges.CONCLUSION: This study suggests a beneficial effect of a fermented milk containing B.lactis DN-173010 on stool frequency,defecation condition and stool consistency in adult women with constipation constipated women after 1 and 2 wk of consumption.

Characterization of the Xenopus homolog of animmediate early gene associated with cell activation: sequence analysis and regulation of its expression by thyroid hormone during amphibian metamorphosis

The complex transformation of a tadpole to a frogduring amphibian development is under the control of thyroid hormone (T3). T3 is known to regulate gene transcription through its nuclear receptors. We have previouslyisolated many genes which are up-regulated by T3 in theintestine of Xenopus laevis tadpoles. We have now cloneda full- length cDNA for one such gene (IU12). Sequenceanalysis shows that the IU12 cDNA encodes a plasmamembrane protein with 12 transmembrane domains andhomologous to a mammalian gene associated with cell activation and organ development. Similarly, we have foundthat IU12 is activated during intestinal remodeling whenboth cell death and proliferation take place. Furthermore,IU12 is an early T3-response gene and its expression in theintestine during T3-induced metamorphosis mimics thatduring normal development. These results argue for a roleof IU12 in the signal transduction pathways leading to intestinal metamorphosis.

Unusual presentation of glomus tympanicum tumour: New bone formation in the middle ear

The objective of this study is to increase awareness of the rare presentation, diagnostic difficulties and management of glomus tympanicum of the middle ear. A 49 years old male, with a background of hypertension and epilepsy, presented with a two month history of left sided conductive hearing loss, pulsatile tinnitus and headache. Clinically and radiologically a diagnosis of glomus tympanicum was made. Intraoperatively, extensive osteogenesis of the middle ear resulting in ossicular fixation and erosion was found. This patient required a two stage operation for full clearance of disease. A stapedectomy drill was used to drill off the bony overgrowth surrounding the ossicles resulting in improved hearing thresholds and full clearance of the disease at two year follow up. Glomus tympanicum can result in new bone formation in the middle ear with resultant ossicular fixation and conductive hearing loss. This can be effectively treated surgically with restoration of hearing.

Analysis of Electrical Dipoles Interaction Forces as a Function of the Distance and of the Form of Electrical Force Law

Here, we initially introduced and demonstrated two principles: orientation OR principle and attraction AT principle of electrical dipoles. The OR principle stipulates that any two electrical dipoles P1A, P1B, from two bodies A and B, at any distance in the free state each, will be reciprocally oriented parallel and in the same sense if the electrical interaction forces F between them are of decreasing type with distance r. If the electrical interaction forces F are of increasing type with distance, the two dipoles will be reciprocally oriented parallel but on the opposite sense. The AT principle stipulate that any two electrical dipoles P1A, P1B, at any distance in the free state each, will present always a reciprocal force of attraction FD in both cases of orientation accordingly to OR principle in case of any type of electrical force F decreasing or increasing with distance. These findings may complete our previous work where we found that FD force, between two electrical dipoles P1A, P1B considered at atomic and nuclear level, is in fact the actual gravitation Newton force FN. The paper must be considered together with this work for more consistency.

Selecting SNP markers reflecting population origin for cacao(Theobroma cacao L.)germplasm identification

Cacao is one of the most economically important agricultural commodities in the world,providing the principal ingredient for the global chocolate industry.Accurate genotype identification is essential for effective conservation and utilization of cacao germplasm.Here,we report the screening of 956 candidate SNPs,pre-selected from the 6 and 15K Theobroma cacao SNP Arrays using targeted Genotyping-by-Sequencing on 451 cacao germplasm accessions,representing ten known genetic groups from the tropical Americas.Based on call rate(No call rate<5%),Minor Allele Frequency(MAF>0.15)and Linkage Disequilibrium(LD≤0.5),a total of 219 SNPs were selected.The efficacy of these SNP markers for population classification was compared with the previous SSR-based analysis in cacao.The population assignment results of the retained 420 cacao accessions was highly comparable with the SSR study.The matrix of genetic distance between SSR and SNP markers is highly correlated(r=0.718;P<0.001).These results demonstrated the consistency in using the present SNP markers for cacao germplasm identification.This is our pilot project for the development of SNP markers reflecting population origin for cacao germplasm identification.These SNP markers and the selected reference germplasm for different populations are suitable for use in cacao germplasm management and crop improvement,including genotype identification,seed gardens and nursery accreditation,and cocoa authentication.Effort is being continued with the emphasis on selecting SNP markers for the detection of sub-population structures in the primary gene pool of T.cacao.

Evidence-based approach to providing informed consent for hip fracture surgery during the COVID-19 era

BACKGROUND Hip fractures are the most common reason for inpatient orthopaedic trauma admission.Urgent surgical intervention for hip fractures has remained a clinical priority throughout the coronavirus disease 2019(COVID-19)pandemic.Despite this,there is a paucity of clinical guidance addressing the informed consent process for hip fracture surgery in COVID-19 positive patients.This is of paramount medicolegal importance in a high-risk patient population.AIM To quantify the additional perioperative risks for COVID-19 positive patients undergoing hip fracture surgery and provide clinicians with an evidence-based framework to establish an informed consent process.METHODS Two hundred and fifty nine consecutive patients undergoing surgical intervention for hip fractures in four hospitals in the United Kingdom were recruited.51 patients were confirmed positive for COVID-19.Predefined outcomes were analyzed over a 30-d postoperative period.COVID-19 positive and COVID-19 negative patients were compared after adjustment for confounding factors.RESULTS COVID-19 positive patients had more intensive care admissions(27%vs 5%,P<0.001),longer inpatient stays(median 23 d vs 9 d,P<0.001)and a higher 30-d mortality(29%vs 10%,P=0.001)than COVID-19 negative patients.Postoperative complications were evident in 74.5%of COVID-19 positive patients.35.3%of COVID-19 positive patients suffered postoperative lower respiratory tract infections with 13.7%developing acute respiratory distress syndrome(ARDS)and 9.8%experiencing symptomatic thromboembolic events.CONCLUSION The COVID-19 pandemic has created uncertainty in the medical community worldwide and poses unique challenges in providing informed consent for surgery.COVID-19 positive patients undergoing hip fracture surgery should be consented for the additional risk of postoperative complications(including lower respiratory tract infection,ARDS,deep vein thrombosis and pulmonary embolism),increased requirement for intensive care admission,longer inpatient stay and higher risk of mortality.Further,clinicians must be transparent about the potential for unknown risks as research into the long-term surgical outcomes of COVID-19 positive patients continues to evolve.

An Analysis of the Origin of the Interaction Force between Electric Charges, including Justification of the ln<i>r</i>Term in the Completed Coulomb’s Law, in HM16 Ether

In this study, we demonstrate the correctness of our 2010 hypothesis regarding the need to complete Coulomb’s FC law with the term lnr, resulting in the completed FCC force. For this purpose, we consider the electrical interactions between charged microparticles (MPs), which develop as fundamental vibrations (FVs) in ether, producing the vibrational strains &epsilon;and &gamma;and the resulting stresses &sigma;and &tau;, as percussions of ether cells (ECs) upon the MP surface. The stresses &sigma;?and?&tau;produce a resultant force FP, due to the percussions which constitute the real electric force FCC. The spatial effect of ether on FP is demonstrated by an analytical method, considering the electrical interaction between MPs through various equidistant spatial paths li of FVs, modelled on the basis of the Huygens principle for waves. For this issue, we utilized a numerical calculation, which could be generalized. But this spatial effect of the ether leads at a very slow decreasing of the FP forces ratio rF when doubling the distance l, in contrast to Coulomb’s FC forces whose ratio rF?decreases accentuate with doubling l. Accordingly, the necessity of including the term ln r in the FCC force, which is limited to 1.0 for doubling l, at long distances, was justified.

Development of a Measurement Software for the Characterization of WORM Devices for Novel Memory Storage Applications

We hereby propose a software solution to perform high quality electrical measurements for the characterization of WORM (write-once read many), a new generation memory device which is being intensively studied for non-volatile data storage. The as-proposed software is completely based on .NET framework and sample C# code. The paper performed a relevant measurement based on this software. Working WORM devices, based on a polymeric matrix embedded with gold and copper sulfide nanoparticles, have been used for test measurements. The aim of this paper is to show the main steps to develop a fully working measurement software without using any expensive dedicated software.

The adenoviral E1A protein relieves gene repression by receptors in v/vo displaces corepressors and unliganded thyroid hormone

The human adenovirus type 5 early region 1A （E1A） is one of two oncogenes present in the adenovirus genome and functions by interfering with the activities of cellular regulatory proteins. The E1A gene is alternatively spliced to yield five products. Earlier studies have revealed that E1A can regulate the function of thyroid hormone （T3） receptors （TRs）. However, analysis in yeast compared with transfection studies in mammalian cell cultures yields surprisingly different effects. Here, we have examined the effect of E1A on TR function by using the frog oocyte in vivo system, where the effects of E1A can be studied in the context of chromatin. We demonstrate that different isoforms of E1A have distinct effects on TR function. The two longest forms inhibit both the repression by unliganded TR and activation by T3-bound TR. We further show that E1A binds to unliganded TR to displace the endogenous corepressor nuclear receptor corepressor, thus relieving the repression by unliganded TR. On the other hand, in the presence of T3, E1A inhibits gene activation by T3-bound TR indirectly, through a mechanism that requires its binding domain for the general coactivator p300. Taken together, our results thus indicate that E1A affects TR function through distinct mechanisms that are dependent upon the presence or absence of T3.

Determination of the Dynamic ITER Energy Confinement Time Scalings

We derive the differential equation, which is satisfied by the ITER scalings for the dynamic energy confinement time. We show that this differential equation can also be obtained from the differential equation for the energy confinement time, derived from the energy balance equation, when the plasma is near the steady state. We find that the values of the scaling parameters are linked to the second derivative of the power loss, estimated at the steady state. As an example of an application, the solution of the differential equation for the energy confinement time is compared with the profile obtained by solving numerically the balance equations (closed by a transport model) for a concrete Tokamak-plasma.

Thermogravimetric Analysis of Zirconia-Doped Ceria for Thermochemical Production of Solar Fuel

Developing an efficient redox material is crucial for thermochemical cycles that produce solar fuels (e.g. H2 and CO), enabling a sustainable energy supply. In this study, zirconia-doped cerium oxide (Ce1-xZrxO2) was tested in CO2-splitting cycles for the production of CO. The impact of the Zr-content on the splitting performance was investigated within the range 0 ≤ x < 0.4. The materials were synthesized via a citrate nitrate auto combustion route and subjected to thermogravimetric experiments. The results indicate that there is an optimal zirconium content, x = 0.15, improving the specific CO2-splitting performance by 50% compared to pure ceria. Significantly enhanced performance is observed for 0.15 ≤ x ≤ 0.225. Outside this range, the performance decreases to values of pure ceria. These results agree with theoretical studies attributing the improvements to lattice modification. Introducing Zr4+ into the fluorite structure of ceria compensates for the expansion of the crystal lattice caused by the reduction of Ce4+ to Ce3+. Regarding the reaction conditions, the most efficient composition Ce0.85Zr0.15O2 enhances the required conditions by a temperature of 60 K or one order of magnitude of the partial pressure of oxygen p(O2) compared to pure ceria. The optimal composition was tested in long-term experiments of one hundred cycles, which revealed declining splitting kinetics.

The midwives service scheme:a qualitative comparison of contextual determinants of the performance of two states in central Nigeria

Background:The federal government of Nigeria started the Midwives Service Scheme in 2009 to address the scarcity of skilled health workers in rural communities by temporarily redistributing midwives from urban to rural communities.The scheme was designed as a collaboration among federal,state and local governments.Six years on,this study examines the contextual factors that account for the differences in performance of the scheme in Benue and Kogi,two contiguous states in central Nigeria.Methods:We obtained qualitative data through 14 in-depth interviews and 2 focus group discussions:14 government officials at the federal,state and local government levels were interviewed to explore their perceptions on the design,implementation and sustainability of the Midwives Service Scheme.In addition,mothers in rural communities participated in 2 focus group discussions(one in each state)to elicit their views on Midwives Service Scheme services.The qualitative data were analysed for themes.Results:The inability of the federal government to substantially influence the health care agenda of sub-national governments was a significant impediment to the achievement of the objectives of the Midwives Service Scheme.Participants identified differences in government prioritisation of primary health care between Benue and Kogi as relevant to maternal and child health outcomes in those states:Kogi was far more supportive of the Midwives Service Scheme and primary health care more broadly.High user fees in Benue was a significant barrier to the uptake of available maternal and child health services.Conclusion:Differential levels of political support and prioritisation,alongside financial barriers,contribute substantially to the uptake of maternal and child health services.For collaborative health sector strategies to gain sufficient traction,where federating units determine their health care priorities,they must be accompanied by strong and enforceable commitment by sub-national governments.

熔封过程对挥发性有机物溶液标准物质的量值影响研究

本文研究了挥发性有机物溶液标准物质在熔封过程中影响量值稳定的主要因素以及对定值结果的不确定度贡献。通过实验考察溶质沸点在-13.4℃至220℃的7种挥发性有机物溶液标准物质在不同条件下熔封,使用外标法准确测定熔封前后溶液的量值变化。研究结果表明,以甲醇为溶剂,溶质沸点在-13.4℃至80℃范围内的挥发性有机物溶液的最佳冷却温度为-20℃,溶质沸点在80℃至220℃范围内溶液的冷却温度相对较高。溶质沸点越低,对挥发性有机物溶液的分液方式要求越高,全密闭管路的分液方式最佳。在安瓿瓶熔封过程中使用冷却套管,可以有效的减少火焰热效应对溶液的影响。对实验考察的7种挥发性有机物溶液标准物质的不确定度可降低至1%以内。

Are we ready to use new endoscopic scores for ulcerative colitis?

For ulcerative colitis(UC),the variability in inflammatory activity along the colon poses a challenge in management.The focus on achieving endoscopic healing in UC is evident,where the UC Endoscopic Index of Severity and Mayo Endoscopic Subscore are commonly used for evaluation.However,these indices primarily consider the most severely affected region.Liu et al recent study validates the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with Mayo Endoscopic Subscore(MES).Despite recommendation,certain aspects warrant further invest-igation.Fecal calprotectin,an intermediate target,correlates with TIGER and should be explored.Determining TIGER scores defining endoscopic remission and response,evaluating agreement with histological activity,and assessing inter-endoscopist agreement for TIGER require scrutiny.Exploring the correlation between TIGER and intestinal ultrasound,akin to MES,adds value.

应急监测用多组分挥发性有机物气体标准物质研制

介绍了瓶装1μmol/mol氮中52组分挥发性有机物气体标准物质的研制过程。所选52种目标组分满足中国环境标准HJ 1223—2021《环境空气挥发性有机物的应急测定便携式气相色谱-质谱法》中所规定的环境空气中有害挥发性有机物的监测需求,建立质谱选择离子扫描(SIM)的分析方法。通过气瓶筛选实验,选取配备硅烷化阀门的特殊气瓶作为充装容器,使用GC-MS研究目标化合物的均匀性及长期稳定性。结果表明:该气体标准物质分析平衡时间短,大幅提高分析效率,1年内稳定性良好,满足现场应急测定需求。同时,严格按照GB/T 5274.1—2018中给出的不确定度计算公式评定研制标物的不确定度,其相对扩展不确定度为U=5%(k=2)。

缩短藏区大型水电站大比例尺测图时间

针对西藏高海拔施工区地质条件的特殊性,采用传统大比例尺测图难点在于地形测量时间长,投入人员、设备多,并且该水电站地势险要,岸坡陡峭,两岸只有前期勘探时的一条施工便道供测量人员使用,在开展测量时不仅会花费较长的时间在路途中,而且工作效率极低,鉴于两岸植被稀少,碎屑流密集,表层岩土呈现风化状态,松散易塌滑,测量时存在很大的安全隐患。为彻底解决使用传统测量过程中过多消耗时间的问题,发现测区现场植被较少,遮挡物较少,基本为裸露的岩体,使用无人机D2000+LiDAR专业无人机测量技术来替代传统的全站仪测图方法。

考虑设防水准的群体建筑物震害预测方法

唐山地震、汶川地震等历史震害表明:抗震设防水准对建筑物抗震能力影响很大。为此,提出了一种考虑设防水准的群体建筑物的震害预测方法,根据已有地区的建筑物震害预测结果估计被模拟地区的震害矩阵,并将已有的震害预测矩阵分为设防结构和未设防结构两部分,分别计算主要震害影响因素的影响因子值,按各个影响因子所占的建筑面积比例赋予不同的权重系数,最终得到设防结构和未设防结构各自对应的综合影响系数,进而得出被模拟地区的震害矩阵。最后通过一个实例,验证了该方法的可行性和可靠性。实践证明:该方法思路清晰,计算参数少,大大提高了建筑物群体震害预测工作的效率。

创业企业如何有效进行要素资源分配——供给侧改革背景下一个跨层次被调节的中介模型

依托创业管理理论和企业成长理论,构建了一个跨层次被调节的中介作用模型。运用2010-2015年创业板上市公司数据,通过Mplus软件检验了投资挤占、资源冗余、行业周期性与企业绩效之间的关系。实证结果表明,创业企业投资挤占能够显著降低企业绩效,而资源冗余在其中起中介作用。按流动性进一步分析资源冗余发现,投资挤占会造成低流动资源冗余的增加和高流动资源冗余的减少进而负向影响创业企业绩效。最后,对于周期性行业中的创业企业,行业周期性会加剧企业投资挤占与低流动资源冗余的正向关系,同时又会减弱投资挤占与高流动资源冗余之间的负向关系。

遥感技术在地震应急基础数据库建设中的应用

基于地震应急基础数据库的需求,以快速、有效、准确的获取任意区域范围的建筑物基础信息数据为目的,通过应用面向对象特征提取技术从遥感图像上获取建筑物信息,并结合GIS技术将获取到的数据在空间地理坐标下网格化,得到建筑物基础信息空间网格数据库。本文详细介绍了数据库建设的技术路线和在震害评估系统中的应用,并以四川省为例验证了本方法的可行性和准确性,为地震应急工作提供了有效的数据支持,为开展更大范围的数据库建设工作提供了一种新的思路。