Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism in Children with Henoch-Schonlein Purpua Nephritis

This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN cases and 100 healthy children was studied by using the polymerase chain reactions (PCR). Its relation to the clinical manifestation, pathological classification and prognosis of HSPN was analyzed accordingly. The results showed that: (1) there was a significantly higher frequency for DD genotype in HSPN children (P<0.01); (2) DD genotype was more frequently seen in HSPN children with gross hematuria and massive proteinuria (P<0.05), while DI genotype was more common in HSPN children group with renal insufficiency (P<0.05); (3) although mesangial proliferative lesion was most frequently observed in 21 biopsied HSPN children, and DD genotype frequency was still higher in children with severe pathology (Class Ⅲ Ⅳ); (4)II genotype was significantly frequent in HSPN children with complete remission in the follow-up of 32 HSPN children. It was concluded that the deletion allele of ACE gene might play a role, at least to some extent, in the occurrence, deterioration and progression in juvenile HSPN.

Correlation between the Insertion/Deletion Mutations of Prion Protein Gene and BSE Susceptibility and Milk Performance in Dairy Cows

Objective To investigate the 23 bp and 12 bp insertion/deletion(indel)mutations within the bovine prion protein(PRNP)gene in Chinese dairy cows,and to detect the associations of two indel mutations with BSE susceptibility and milk performance.Methods Based on bovine PRNP gene sequence,two pairs of primers for testing the 23 bp and 12 bp indel mutations were designed.The PCR amplification and agarose electrophoresis were carried out to distinguish the different genotypes within the mutations.Moreover,based on previous data from other cattle breeds and present genotypic and allelic frequencies of two indels mutations in this study,the corrections between the two indel mutations and BSE susceptibility were tested,as well as the relationships between the mutations and milk performance traits were analyzed in this study based on the statistical analyses.Results In the analyzed Chinese Holstein population,the frequencies of two"del"alleles in 23 bp and 12 bp indel muations were more frequent.The frequency of haplotype of 23del-12del was higher than those of 23del-12ins and 23ins-12del.From the estimated r2and D’values,two indel polymorphisms were linked strongly in the Holstein population(D’=57.5%,r2=0.257).Compared with the BSE-affected cattle populations from the reported data,the significant differences of genotypic and allelic frequencies were found among present Holstein and some BSE-affected populations(P<0.05 or P<0.01).Similarly,there were significant frequency distribution differences of genotypes and alleles among Chinese Holstein and several previous reported healthy dairy cattle(P<0.05 or P<0.01).Moreover,association of genotype and combined genotypes of two indel polymorphisms with milk performance and resistant mastitis traits were analyzed in Holstein population,but no significant differences were found(P>0.05).Conclusions These observations revealed that the influence of two indel mutations within the bovine PRNP gene on BSE depended on the breed and they did not affect the milk production traits,which layed the foundation for future selection of resistant animals,and for improving health conditions for dairy breeding against BSE in China.

Association study between the angiotensin converting enzyme gene insertion/deletion polymorphism and Qinghai Han Chinese with congenital heart disease

Objective: The aim of this work is to determine whether the angiotensin converting enzyme(ACE) I/D(insertion/deletion) polymorphism is associated with the susceptibility to congenital heart disease(CHD) in the Qinghai Han Chinese. Methods: This study enrolled 59 CHD patients and 193 CHD controls from Qinghai Cardiovascular Diseases Vocational Hospital. Blood samples were collected from each of the patient and control groups. The ACE-I/D polymorphism was detected by polymerase chain reaction(PCR). Results: The genotype frequencies of ACE-I/D for II, ID, DD in patients and controls were 0.475, 0.441, 0.085 and 0.430, 0.446, 0.124, respectively. The allelic frequencies of I and D were 0.650, 0.350 and 0.695, 0.305, respectively. The OR of ID, DD and D alleles relative to II for CHD was 1.116(0.604-2.060), 1.619(0.564-4.648) and 1.211(0.777-1.889). There was no significant difference of the genotypic and the allelic frequencies in ACE-I/D polymorphism between the patient and control groups. Conclusion: There is no relation between ACE-I/D polymorphism and CHD in current Qinghai Han Chinese.

高血压患者ACE基因Insertion/Deletion多态性中的罕见突变1例

高血压是最强的心血管危险因素之一,目前我国高血压的患病人数已达约2.45亿[1]。《中国心血管健康与疾病报告2021》数据显示,我国≥18岁成人高血压知晓率41.0%,治疗率34.9%,控制率仅11.0%。在高血压的用药治疗方面,由于用药种类繁多,且存在药物反应的个体差异,通常会导致抗高血压药物的疗效不佳或不良反应[2]。2015年,国家卫生和计划生育委员会发布的《药物代谢酶和药物作用靶点基因检测技术指南(试行)》[3]。

Lack of association between ADRA2B-4825 gene insertion/deletion poly- morphism and migraine in Chinese Han population

Objective The present study aimed to estimate the association between susceptibility to migraine and the 12nucleotide insertion/deletion （indel） polymorphism in promoter region ofα 2B -adrenergic receptor gene （ADRA2B）.Methods A case-control study was carried out in Chinese Han population,including 368 cases of migraine and 517 controls.Genomic DNA was extracted from blood samples,and DNA fragments containing the site of polymorphism were amplified by PCR.Data were adjusted for sex,age,migraine history and family history,and analyzed using a logistic regression model.Results There was no association between indel polymorphism and migraine,at either the allele or the genotype level.Conclusion These findings do not support a functional significance of ADRA2B indel polymorphism at position-4825 relative to the start codon in the far upstream region of the promoter in the present migraine subjects.

Association of angiotensin converting enzyme gene insertion/deletion polymorphism with essential hypertension in south Indian population

Genetic,environmental and demographic factors contribute to the development of essential hypertension.Genetic polymorphism of Rennin-angiotensin-aldosterone system(RAAS)has been extensively studied to determine the genetic susceptibility to hypertension.The insertion/deletion(I/D)angiotensin converting enzyme(ACE)polymorphism has been established as a cardiovascular risk factor in some population,but its association with essential hypertension is controversial.This study sought to determine the association of I/D polymorphism of the ACE gene in south Indian essential hypertensive subjects.A total of 208 clinically diagnosed essential hypertensive patients without any associated diseases and 220 healthy control subjects were included in this study.Distribution and allelic frequency of Insertion(I)and Deletion(D)polymorphism at the 287 base pair Alu repeat sequence in the intron 16 of ACE gene were analyzed.The distribution of II,ID,DD genotypes of ACE gene was 28.3%,32.6%and 38.9%respectively in essential hypertensive patients and to 53.6%,26.3%and 20%in controls.The allele frequency for D allele is 0.58 in essential hypertension as compared to 0.34 of control subjects.The genotype and allele frequency of ACE gene polymorphism is significantly differed in patients when compared to controls.In conclusion,the I/D polymorphism of ACE gene is associated with Indian essential hypertension.

Ethnic differences in the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and peripheral vascular disease: A meta-analysis

Background: Several studies have investigated the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain controversial. Therefore, we conducted the current meta-analysis to evaluate this relationship in the general population of different ethnicities. Methods: We searched PubMed, Embase, Web of Science, Wanfang Database, and CNKI to identify eligible studies. Random-effect models were applied to estimate the pooled odds ratio (OR) with a 95％ confidence interval (CI), regardless of between-study heterogeneity. Results: A total of 13 studies with 1966 cases and 6129 controls were included in this meta-analysis. The pooled ORs for the association between ACE I/D polymorphism and PVD risk were not statistically significant in the overall population under all genetic models. In further ethnicity-stratified analyses, we found a statistically significant association of ACE I/D polymorphism with PVD susceptibility in Asians under most models. However, the association among Caucasians did not reach statistical significance. Conclusion: ACE I/D polymorphism might be associated with susceptibility to PVD in the Asian population, but there was no clear evidence indicating a similar significant relationship among Caucasians.

A Novel Insertion Solution for the Travelling Salesman Problem

The studypresents theHalfMax InsertionHeuristic (HMIH) as a novel approach to solving theTravelling SalesmanProblem (TSP). The goal is to outperform existing techniques such as the Farthest Insertion Heuristic (FIH) andNearest Neighbour Heuristic (NNH). The paper discusses the limitations of current construction tour heuristics,focusing particularly on the significant margin of error in FIH. It then proposes HMIH as an alternative thatminimizes the increase in tour distance and includes more nodes. HMIH improves tour quality by starting withan initial tour consisting of a ‘minimum’ polygon and iteratively adding nodes using our novel Half Max routine.The paper thoroughly examines and compares HMIH with FIH and NNH via rigorous testing on standard TSPbenchmarks. The results indicate that HMIH consistently delivers superior performance, particularly with respectto tour cost and computational efficiency. HMIH’s tours were sometimes 16% shorter than those generated by FIHand NNH, showcasing its potential and value as a novel benchmark for TSP solutions. The study used statisticalmethods, including Friedman’s Non-parametric Test, to validate the performance of HMIH over FIH and NNH.This guarantees that the identified advantages are statistically significant and consistent in various situations. Thiscomprehensive analysis emphasizes the reliability and efficiency of the heuristic, making a compelling case for itsuse in solving TSP issues. The research shows that, in general, HMIH fared better than FIH in all cases studied,except for a few instances (pr439, eil51, and eil101) where FIH either performed equally or slightly better thanHMIH. HMIH’s efficiency is shown by its improvements in error percentage (δ) and goodness values (g) comparedto FIH and NNH. In the att48 instance, HMIH had an error rate of 6.3%, whereas FIH had 14.6% and NNH had20.9%, indicating that HMIH was closer to the optimal solution. HMIH consistently showed superior performanceacross many benchmarks, with lower percentage error and higher goodness values, suggesting a closer match tothe optimal tour costs. This study substantially contributes to combinatorial optimization by enhancing currentinsertion algorithms and presenting a more efficient solution for the Travelling Salesman Problem. It also createsnew possibilities for progress in heuristic design and optimization methodologies.

A 9.5-kb deletion in the 1st intron of OsMADS51 enhances temperature sensitivity in rice

Temperature is an important environmental factor affecting heading date of rice.Despite its importance,genes responsible for temperature-sensitive heading in rice have remained elusive.Our previous study identified a quantitative trait locus qHd1 which advances heading date under high temperatures.A 9.5-kb insertion was found in the first intron of OsMADS51 in indica variety Zhenshan 97(ZS97).However,the function of this natural variant in controlling temperature sensitivity has not been verified.In this study,we used CRISPR/Cas9 to knock out the 9.5-kb insertion in ZS97.Experiments conducted under cotrolled conditions in phytotrons confirmed that deletion increased temperature sensitivity and advanced heading by downregulating the expression level of OsMADS51.One-hybrid assays in yeast,ChIP-quantitative polymerase chain reaction,electrophoretic mobility shift,and luciferase-based transient transactivation assays collectively confirmed that OsMADS51 affects heading date by regulation of heading date gene Ehd1.We further determined that the long non-coding RNA HEATINR is generated from the first intron of OsMADS51,offering an explanation for how the 9.5-kb insertion affects temperature sensitivity.We also found that OsMADS51 was strongly selected in early/late-season rice varieties in South China,possibly accounting for their strong temperature sensitivity.These insights not only advance our understanding of the molecular mechanisms underlying the temperature-responsive regulation of heading date in rice but also provide a valuable genetic target for molecular breeding.

Enhancing hydrogen evolution and oxidation kinetics through oxygen insertion into nickel lattice

Nickel-based materials,including metallic Ni and Ni oxide,have been widely studied in the exploration of non-precious-metal hydrogen electrocatalysts,but neither pure Ni nor NiO is ideal for the hydrogen evolution reaction(HER)and hydrogen oxidation reaction(HOR).In this paper,an oxygen insertion strategy was applied on nickel to regulate its hydrogen electrocatalytic performance,and the oxygen-inserted nickel catalyst was successfully obtained with the assistance of tungsten dioxide support(denoted as O-Ni/WO_(2)).The partial insertion of oxygen in Ni maintains the face-centered cubic arrangement of Ni atoms,simultaneously expanding the lattice and increasing the lattice spacing.Consequently,the adsorption strength of^(*)H and^(*)OH on Ni is optimized,thus resulting in superior electrocatalytic performance of0-Ni/WO_(2)in alkaline HER/HOR.The Tafel slope of O-Ni/WO_(2)@NF for HER is 56 mV dec^(-1),and the kinetic current density of O-Ni/WO_(2)for HOR reaches 4.85 mA cm^(-2),which is ahead of most currently reported catalysts.Our proposed strategy of inserting an appropriate amount of anions into the metal lattice could provide more possibilities for the design of high-performance catalysts.

Identification and characterization of FpRco1 in regulating vegetative growth and pathogenicity based on T-DNA insertion in Fusarium pseudograminearum

Fusarium pseudograminearum is a devastating pathogen that causes Fusarium crown rot(FCR)in wheat and poses a significant threat to wheat production in terms of grain yield and quality.However,the mechanism by which F.pseudograminearum infects wheat remains unclear.In this study,we aimed to elucidate these mechanisms by constructing a T-DNA insertion mutant library for the highly virulent strain WZ-8A of F.pseudograminearum.By screening this mutant library,we identified nine independent mutants that displayed impaired pathogenesis in barley leaves.Among these mutants,one possessed a disruption in the gene FpRCO1 that is an ortholog of Saccharomyces cerevisiae RCO1,encoding essential component of the Rpd3S histone deacetylase complex in F.pseudograminearum.To further investigate the role of FpRCO1 in F.pseudograminearum,we employed a split-marker approach to knock out FpRCO1 in F.pseudograminearum WZ-8A.FpRCO1 deletion mutants exhibit reduced vegetative growth,conidium production,and virulence in wheat coleoptiles and barley leaves,whereas the complementary strain restores these phenotypes.Moreover,under stress conditions,the FpRCO1 deletion mutants exhibited increased sensitivity to NaCl,sorbitol,and SDS,but possessed reduced sensitivity to H_(2)O_(2)compared to these characteristics in the wild-type strain.RNA-seq analysis revealed that deletion of FpRCO1 affected gene expression(particularly the downregulation of TRI gene expression),thus resulting in significantly reduced deoxynivalenol(DON)production.In summary,our findings highlight the pivotal role of FpRCO1 in regulating vegetative growth and development,asexual reproduction,DON production,and pathogenicity of F.pseudograminearum.This study provides valuable insights into the molecular mechanisms underlying F.pseudograminearum infection in wheat and may pave the way for the development of novel strategies to combat this devastating disease.

An efficient method for constructing a random insertional mutant library for forward genetics in Nannochloropsis oceanica

Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.

Velamentous Cord Insertion: Interest of Antenatal Diagnosis and Review of the Literature

Velamentous insertion of the umbilical cord corresponds to the insertion of the cord directly on amniotic membranes. It is a rare situation whose frequency varies from 0.5% to 1.69% of single pregnancies. It must be diagnosed during the morphological ultrasound of the 2nd trimester, actively looking for the association with a vasa previa, due to the risk of fetal haemorrhagic threat. We report an antenatal diagnosis of velamentous cord insertion and its management with literature review.

Treatment of benign rectal stricture caused by repeated anal insertion by endoscopy and balloon dilation:A case report

BACKGROUND Benign rectal strictures can be categorized as primary(disease-related)and secondary(surgical anastomosis-related).Secondary strictures arise from surgical complications,whereas primary strictures have diverse etiologies,including various inflammatory conditions.Benign strictures are usually managed by surgery and endoscopy.We present an unusual etiology of benign rectal stricture caused by the repeated insertion of foreign objects into the rectum for sexual purposes,resulting in rectal injury and subsequent chronic inflammation.CASE SUMMARY A 53-year-old man presented to the outpatient clinic of the Colorectal Surgery Department with symptoms of chronic constipation and bloody stools.The patient previously experienced rectal injury due to foreign object insertion for sexual purposes.Colonoscopy revealed benign circumferential narrowing of the rectum.He underwent treatment by endoscopic argon plasma coagulation and balloon dilation and follow-up as an outpatient for 4 months.A colonoscopy at the end of the follow-up period revealed no evidence of rectal stricture relapse.CONCLUSION A history of rectal injury,followed by chronic inflammation,should be considered in patients with benign rectal strictures.Management with endoscopic argon plasma coagulation and balloon dilation can prevent the need for surgical resection of benign rectal strictures.

Relationship between insertion/deletion polymorphism of angiotensin converting enzyme gene and type 2 diabetic kidney disease

Objective To explore the interaction of angiotensinconverting enzyme (ACE) insertion /deletion(I /D) polymorphism( rs1799752 ) with diabetic kidney disease(DKD) development as well as its interaction with smokingand obesity in Chinese type 2 diabetic mellitus(T2DM) using an improved experiment method. MethodsFrom June 2016 to March 2018,300 T2DM patientswith DKD [DKD( +)]and 300 T2DM patients withoutDKD [DKD ( - )] were selected from China-JapanFriendship Hospital. The improved Triple Primer Methodthat combined PCR with capillary electrophoresis was establishedin this study to detect the ACE genotype. Therelevant clinical data as well as the frequencies of genotypeand allele of ACE gene I /D polymorphism betweenthe two groups were statistically analyzed. Patients werefurther grouped based on smoking status and obesity formultivariate regression.

Can the occurrence of rare insertion/deletion polymor-phisms in human mtDNA be verified from phylogeny?

Due to its specific characteristics, such as ma-ternal inheritance and absence of recombination, each mtDNA belongs to certain monophyletic clade in the rooted mtDNA tree (haplogroup) according to the mutations it harbors. Rare mutation (excluding parallel mutation) occur-ring at multiple times in different haplogroups could thus be a potential reading error according to the mtDNA phylogeny. This experience has been widely used in double-checking the credibility of the rare mutations in human mtDNA sequences. However, no test has been performed so far for the feasibility of applying this strategy to the rare insertion/deletion (indel) events in mtDNA sequences. In this study, we attempted to relate the rare indels in mtDNAs to their haplogroup status in a total of 2352 individuals from 50 populations in China. Our results show that the insertion of A at position 16259 is restricted to a subclade of haplogroup C and can be verified. The other indel polymorphisms, which occur in the repeat of the deleted or inserted nucleotide(s), may not be distin-guished from phantom mutations from a phylogenetic point of view. Independently and multiply sequencing the frag-ment with the indel is the best and the most reliable way for confirmation.

Genetic diversity analysis of forty-three insertion/deletion loci for forensic individual identification in Han Chinese from Beijing based on a novel panel

Due to the virtues of no stutter peaks,low rates of mutation,and short amplicon sizes,insertion/deletion(InDei)polymorphism is an indispensable tool for analyzing degraded DNA samples from crime scenes for human identifications(Wang et al.,2021).Herein,a self-developed panel of 43 InDei loci constructed previously by our group was utilized to evaluate the genetic diversities and explore the genetic background of the Han Chinese from Beijing(HCB)including 301 random healthy individuals.

Efficient large fragment deletion in plants:double pairs of sgRNAs are better than dual sgRNAs

Dear Editor,Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)is a powerful and versatile gene editing system that has been extensively utilized in various animals and plants,which holds enormous potential and value for scientific research and breeding.However,single-targeted CRISPR can only induce a few base deletions,insertions,or substitution.Ideally,thesemutations result in premature termination of the protein encoded by the target gene,leading to a loss of function[1].

Atomic-scale insights of indium segregation and its suppression by GaAs insertion layer in InGaAs/AlGaAs multiple quantum wells

The In segregation and its suppression in InGaAs/AlGaAs quantum well are investigated by using high-resolution x-ray diffraction(XRD)and photoluminescence(PL),combined with the state-of-the-art aberration corrected scanning transmission electron microscopy(Cs-STEM)techniques.To facility our study,we grow two multiple quantum wells(MQWs)samples,which are almost identical except that in sample B a thin GaAs layer is inserted in each of the InGaAs well and AlGaAs barrier layer comparing to pristine InGaAs/AlGaAs MQWs(sample A).Our study indeed shows the direct evidences that In segregation occurs in the InGaAs/AlGaAs interface,and the effect of the Ga As insertion layer on suppressing the segregation of In atoms is also demonstrated on the atomic-scale.Therefore,the atomic-scale insights are provided to understand the segregation behavior of In atoms and to unravel the underlying mechanism of the effect of GaAs insertion layer on the improvement of crystallinity,interface roughness,and further an enhanced optical performance of InGaAs/AlGaAs QWs.

Complications Related to the Insertion Technique of Jadelle® Contraceptive Implants

Introduction: Contraceptive implants are one of the most effective methods of birth spacing. Jadelle® implants consist of two strands that are easy to insert and remove. Although their effectiveness is no longer in question, their use (insertion) requires a surgical procedure with the corollary possibility of complications. These are mainly insertions that are too deep (in the arm muscle), vascular and nerve damage. Material and Methods: Our study focused on complications related to implant insertion. It was a descriptive and retrospective study over thirty-four months, from October 2016 to July 2019, and concerned all patients seen in consultation and who presented a complication related to the insertion of contraceptive implants in the Department of Gynecology and Obstetrics of the National Hospital of Pikine. Results: We collected nine complications managed at the Gynecology and Obstetrics Department of the Centre Hospitalier National de Pikine from 2016 to 2019. These were insertions that were too deep with sometimes nerve damage, infection or incident during anesthesia. The operative procedures were based on the type of complication. Conclusion: Although Jadelle® has the advantage of having only 2 rods compared to its predecessor Norplant®, its use is also conditioned by insertion and removal procedures which may experience complications.