New recessive compound heterozygous variants of RP1L1 in RP1L1 maculopathy

AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.

Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

Safety and efficacy of transcatheter arterial embolization in autosomal dominant polycystic kidney patients with gross hematuria: Six case reports

BACKGROUND To retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating autosomal dominant polycystic kidney disease(ADPKD)patients with gross hematuria.CASE SUMMARY The purpose of this study is to retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating ADPKD patients with gross hematuria.Materials and methods:During the period from January 2018 to December 2019,renal transcatheter arterial embolization was carried out on 6 patients with polycystic kidneys and gross hematuria.Renal arteriography was performed first,and then we determined the location of the hemorrhage and performed embolization under digital subtraction angiography monitoring.Improvements in routine blood test results,routine urine test results,urine color and postoperative reactions were observed and analyzed.Results:Renal transcatheter arterial embolization was successfully conducted in 6 patients.The indices of 5 patients and the color of gross hematuria improved after surgery compared with before surgery.No severe complication reactions occurred.CONCLUSION For autosomal dominant polycystic kidney syndrome patients with gross hematuria,transcatheter arterial embolization was safe and effective.

Complex adaptive system theory,agent-based modeling,and simulation in dominant technology formation

Dominant technology formation is the key for the hightech industry to“cross the chasm”and gain an established foothold in the market(and hence disrupt the regime).Therefore,a stimulus-response model is proposed to investigate the dominant technology by exploring its formation process and mechanism.Specifically,based on complex adaptive system theory and the basic stimulus-response model,we use a combination of agent-based modeling and system dynamics modeling to capture the interactions between dominant technology and the socio-technical landscape.The results indicate the following:(i)The dynamic interaction is“stimulus-reaction-selection”,which promotes the dominant technology’s formation.(ii)The dominant technology’s formation can be described as a dynamic process in which the adaptation intensity of technology standards increases continuously until it becomes the leading technology under the dual action of internal and external mechanisms.(iii)The dominant technology’s formation in the high-tech industry is influenced by learning ability,the number of adopting users and adaptability.Therein,a“critical scale”of learning ability exists to promote the formation of leading technology:a large number of adopting users can promote the dominant technology’s formation by influencing the adaptive response of technology standards to the socio-technical landscape and the choice of technology standards by the socio-technical landscape.There is a minimum threshold and a maximum threshold for the role of adaptability in the dominant technology’s formation.(iv)The socio-technical landscape can promote the leading technology’s shaping in the high-tech industry,and different elements have different effects.This study promotes research on the formation mechanism of dominant technology in the high-tech industry,presents new perspectives and methods for researchers,and provides essential enlightenment for managers to formulate technology strategies.

Species’ geographical range, environmental range and traits lead to specimen collection preference of dominant plant species of grasslands in Northern China

Many different factors,such as species traits,socio-economic factors,geographical and environmental factors,can lead to specimen collection preference.This study aims to determine whether grassland specimen collection in China is preferred by species traits(i.e.,plant height,flowering and fruiting period),environmental range(i.e.,the temperature and precipitation range)and geographical range(i.e.,distribution range and altitudinal range).Ordinary least squares models and phylogenetic generalized linear mixed models were used to analyze the relationships between specimen number and the explanatory variables.Random Forest models were then used to find the most parsimonious multivariate model.The results showed that interannual variation in specimen number between 1900 and 2020 was considerable.Specimen number of these species in southeast China was notably lower than that in northwest China.Environmental range and geographical range of species had significant positive correlations with specimen number.In addition,there were relatively weak but significant associations between specimen number and species trait(i.e.,plant height and flowering and fruiting period).Random Forest models indicated that distribution range was the most important variable,followed by flowering and fruiting period,and altitudinal range.These findings suggest that future floristic surveys should pay more attention to species with small geographical range,narrow environmental range,short plant height,and short flowering and fruiting period.The correction of specimen collection preference will also make the results of species distribution model,species evolution and other works based on specimen data more accurate.

Clinical and genetic diagnosis of autosomal dominant osteopetrosis typeⅡin a Chinese family:A case report

BACKGROUND Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts.Approximately,80%of autosomal dominant osteopetrosis type II(ADO-II)patients were usually affected by heterozygous dominant mutations in the chloride voltage-gated channel 7(ClCN7)gene and present early-onset osteoarthritis or recurrent fractures.In this study,we report a case of persistent joint pain without bone injury or underlying history.CASE SUMMARY We report a 53-year-old female with joint pain who was accidentally diagnosed with ADO-II.The clinical diagnosis was based on increased bone density and typical radiographic features.Two heterozygous mutations in the ClCN7 and Tcell immune regulator 1(TCIRG1)genes by whole exome sequencing were identified in the patient and her daughter.The missense mutation(c.857G>A)occurred in the CLCN7 gene p.R286Q,which is highly conserved across species.The TCIRG1 gene point mutation(c.714-20G>A)in intron 7(near the splicing site of exon 7)had no effect on subsequent transcription.CONCLUSION This ADO-II case had a pathogenic CLCN7 mutation and late onset without the usual clinical symptoms.For the diagnosis and assessment of the prognosis for osteopetrosis,genetic analysis is advised.

Investigation of Demographic and Clinical Data of Patients with Autosomal Dominant Polycystic Kidney Disease

Background: Autosomal dominant polycystic kidney disease (ADPKD) is an important etiological factor causing chronic kidney disease (CKD), cardiovascular diseases and hypertension (HT). The purpose of the present study is to investigate the clinical information and demographic characteristics of autosomal dominant polycystic kidney disease patients who received treatment at our hospital for the last five years. Material and Method: Among 21400 people who sought care at Siirt State Hospital Urology and Nephrology Outpatient Clinics between January 2015 and January 2020 for various reasons, a total of 36 patients experiencing autosomal dominant polycystic kidney disease were included in the present research. Retrospective patient file access was used to gather demographic information and laboratory data. Results: The study included 36 patients in all, 25 (69.4%) male and 11 (30.6%) female. The patient’s average age was 50.8 ± 19.0. The average age at diagnosis was 43.4 ± 17.2. Family history was positive in 29 (80.5%) of the patients. There were hypertension in 27 (75.0%) patients, coronary artery disease in five (13.9%) patients, diabetes mellitus in five (13.9%) patients, left ventricular hypertrophy in 18 (50%) patients, proteinuria in 11 (30.6%) patients, and six (16.7%) patients had macroscopic hematuria. Liver cysts were found in 23 (63.9%) of the patients and nephrolithiasis in eight (22.2%). Discussion: Hypertension is the most common finding when clinical and demographic data of autosomal dominant polycystic kidney disease are examined. Providing blood pressure control reduces the risk of death due to left ventricular hypertrophy and slows down the rate at which chronic kidney disease progresses. The rate was found to be 80.5% for patients with a positive family history. It may be possible to diagnose and treat people with autosomal dominant polycystic kidney disease earlier by screening their family members.

Compound heterozygous mutations in tripeptidyl peptidase 1 cause rare autosomal recessive spinocerebellar ataxia type 7:A case report

BACKGROUND Spinocerebellar ataxia recessive type 7(SCAR7)is a rare clinical manifestation beginning in childhood or adolescence.SCAR7 is caused by tripeptidyl peptidase 1(TPP1)gene mutations,and presents with cerebellar ataxia,pyramidal signs,neurocognitive impairment,deep paresthesia,and cerebellar atrophy.CASE SUMMARY Here,we describe a 25-year-old female patient in China who presented with increasing difficulty walking,falling easily,shaking limbs,instability holding items,slurred speech,coughing when drinking,palpitations,and frequent hunger and overeating.Magnetic resonance imaging showed cerebellar atrophy.Whole exome sequencing detected two compound heterozygous mutations in the TPP1 gene:c.1468G>A p.Glu490Lys and c.1417G>A p.Gly473Arg.Considering the patient’s clinical presentation and genetic test results,we hypothesized that complex heterozygous mutations cause TPP1 enzyme deficiency,which may lead to SCAR7.CONCLUSION We report the first case of SCAR7 from China.We also identify novel compound heterozygous mutations in the TPP1 gene associated with SCAR7,expanding the range of known disease-causing mutations for SCAR7.

Autosomal dominant non-syndromic hearing loss caused by a novel mutation in MYO7A:A case report and review of the literature

BACKGROUND Variants in the MYO7A gene commonly result in Usher syndrome,and in rare cases lead to autosomal dominant non-syndromic deafness(DFNA11).Currently,only nine variants have been reported to be responsible for DFNA11 and their clinical phenotypes are not identical.Here we present a novel variant causing DFNA11 identified in a three-generation Chinese family.CASE SUMMARY The proband was a 53-year-old Han male who presented with post-lingual bilateral symmetrical moderate sensorineural hearing loss.We learned from the patient’s medical history collection that multiple family members also had similar hearing loss,generally occurring around the age of 40.Subsequent investigation by high-throughput sequencing identified a novel MYO7A variant.To provide evidence supporting that this variant is responsible for the hearing loss in the studied family,we performed Sanger sequencing on 11 family members and found that the variant co-segregated with the deafness phenotype.In addition,the clinical manifestation of the 11 affected family members was found to be lateonset bilateral slowly progressive hearing loss,inherited in this family in an autosomal dominant manner.None of the affected family members had visual impairment or vestibular symptoms;therefore,we believe that this novel MYO7A variant is responsible for the rare DFNA11 in this family.CONCLUSION We report a novel variant leading to DFNA11 which further enriches the collection of MYO7A variants,and our review of the nine previous variants that have been identified to cause DFNA11 provides a reference for clinical genetic counseling.

SCR-22 of pollen-dominant S haplotype class is recessive to SCR-44 of pollenrecessive S haplotype class in Brassica rapa

SCR/SP11 encodes the male determinant of recognition specificity of self-incompatibility(SI)in Brassica species and is sporophytically expressed in the anther tapetum.Based on dominance relationships in pollen and nucleotide sequence similarity,the S haplotypes in Brassica have been classified as class I or class II,with class-I S haplotypes being dominant over class-II S haplotypes.Here,we revealed that S-22 in B.rapa belonging to class I is recessive to class-II S-44 and class-I S-36 in pollen,whereas it is dominant over S-60,S-40,and S-29 based on pollination tests.SCR/SP11 of S-22(SCR-22)was sequenced,revealing that the deduced amino-acid sequence of SCR-22 has the longest C-terminal domain among the SCR/SP11 sequences.The expression of SCR-22 was found to be suppressed in S-22/S-44 and S-22/S-36 heterozygotes.Normal transcription of SCR-44 was considered to be due to the transcription suppression of Smi sRNA of the S-22 haplotype and a very low methylation state of the SCR-44 promoter region in the tapetum of S-22/S-44 heterozygotes.In SCR-22,only the cytosine residue located at the–37 bp position of the promoter region was hypermethylated in the tapetum of S-22/S-44 heterozygotes,and few methylated cytosines were detected in the promoter and coding regions of SCR-22 in S-22/S-36 heterozygotes.SCR-22 was also expressed in microspores in S-22 homozygotes but not in S-22/S-44 and S-22/S-36 heterozygotes.These results suggest that a mechanism different from class-II SCR/SP11 suppression may operate for the suppression of recessive class-I SCR-22 in S heterozygotes.

The notion of dominant terminology in bibliometric research

In this opinion paper, we introduce the expressions of dominant terminology and dominant term in the quantitative studies of science in analogy to the notion of dominant design in product development and innovation.

Clinical Characteristics of Macular Hole and Macular Epiretinal Membrane in Dominant and Nondominant Eyes

Ocular dominance(OD) is referred to the superiority of one eye over the other when the visual sense is produced[1]. This condition can be considered as a preference for the particular laterality of the eye during a mono-visual task or the relative contributions of visual signal transduction between eyes[2]. Empirically, OD tendencies are exhibited in habitual and subconscious behavior.

Comparison of growth and nutrient uptake capacities of three dominant species of Qinhuangdao green tides

Since 2015, green tides have been blooming in offshore waters of Qinhuangdao, with serious impacts on the local ecological environment and tourism. Ulva australis, Bryopsis plumosa, and U. prolifera are the dominant species of Qinhuangdao green tides, following a sequential succession pattern. Ulva prolifera is the dominant species,with the highest biomass and the greatest influence on the local ecological environment. To study the reason of green tide dominant species succession and U. profilera became the dominant species with the largest biomass,we compared and analyzed the growth and nutrient uptake capacity of the three algae. The results showed that temperature significantly affects the growth of the three species. Within the temperature range of the experimental setup, the optimum temperature for the growth of U. australis, B. plumosa and U. profilera is10℃, 15℃, and 20–25℃, respectively. Combined with the temperature variation trend during green tide bloom development, we believe that temperature is the key environmental factor for the succession of the dominant species. Ulva prolifera has a higher growth rate than U. australis and B. plumosa under the same nitrate,ammonium, and phosphate levels. Significant differences in the maximum absorption rate(R_(max)) and R_(max)/Ks(the relationship between uptake rate and substrate concentration) values indicated that U. prolifera had an apparent competitive advantage over U. australis and B. plumosa regarding nutrient uptake. Therefore, the strong growth and nutrient uptake capacities of U. prolifera might be the main reason for becoming the dominant species with the largest biomass in Qinhuangdao green tides.

Identification of the dominant loop of a dual-loop macro-reentry left atrial flutter without prior intervention using high-density mapping technology:A case report

BACKGROUND Left atrial flutter without prior cardiac interventions is uncommon,especially dual-loop macro-reentry atrial flutter.The critical step to ablate dual-loop macroreentry atrial flutter is to identify the dominant loop and key isthmus.Although entrainment mapping could help identify the dominant loop and key isthmus,it may alter or terminate tachycardia.High-density mapping allows the generation of electroanatomic maps without altering or terminating tachycardia.CASE SUMMARY Here,we report a case of symptomatic left atrial flutter without prior intervention.In this case,high-density mapping revealed a dual-loop macro-reentry around the mitral annulus and central scar of the anterior wall.The propagation result showed that the dominant loop was around the mitral annulus,and the key isthmus was between the central scar and mitral annulus.The atrial flutter terminated successfully after ablation was performed.CONCLUSION In this case,we demonstrate that high-density mapping technology may help identify the dominant loop of dual-loop atrial flutter without entrainment,which makes ablation easier.

Binary Archimedes Optimization Algorithm for Computing Dominant Metric Dimension Problem

In this paper,we consider the NP-hard problem of finding the minimum dominant resolving set of graphs.A vertex set B of a connected graph G resolves G if every vertex of G is uniquely identified by its vector of distances to the vertices in B.A resolving set is dominating if every vertex of G that does not belong to B is a neighbor to some vertices in B.The dominant metric dimension of G is the cardinality number of the minimum dominant resolving set.The dominant metric dimension is computed by a binary version of the Archimedes optimization algorithm(BAOA).The objects of BAOA are binary encoded and used to represent which one of the vertices of the graph belongs to the dominant resolving set.The feasibility is enforced by repairing objects such that an additional vertex generated from vertices of G is added to B and this repairing process is iterated until B becomes the dominant resolving set.This is the first attempt to determine the dominant metric dimension problem heuristically.The proposed BAOA is compared to binary whale optimization(BWOA)and binary particle optimization(BPSO)algorithms.Computational results confirm the superiority of the BAOA for computing the dominant metric dimension.

New Criteria for Judging Generalized Strictly Diagonally Dominant Matrix

Generalized strictly diagonally dominant matrices play a wide and important role in computational mathematics, mathematical physics, theory of dynamical systems, etc.But it is difficult to judge a matrix is or not generalized strictly diagonally dominant matrix.In this paper, by using the properties of α-chain diagonally dominant matrix, we obtain new criteria for judging generalized strictly diagonally dominant matrix, which enlarge the identification range.

A novel frameshift mutation in CX46 associated with hereditary dominant cataracts in a Chinese family

AIM：To investigate the genetic mutations that are associated the hereditary autosomal dominant cataract in a Chinese family.METHODS：A Chinese family consisting of 20 cataract patients（including 9 male and 11 female） and 2 unaffected individuals from 5 generations were diagnosed to be a typical autosomal dominant cataract pedigree. Genomic DNA samples were extracted from the peripheral blood cells of the participants in this pedigree. Exon sequence was used for genetic mutation screening. In silico analysis was used to study the structure characteristics of connexin 46（CX46） mutant. Immunoblotting was conduceted for testing the expression of CX46.RESULTS：To determine the involved genetic mutations, 11 well-known cataract-associated genes（cryaa, cryab, crybb1, crybb2, crygc, crygd, Gja3, Gja8, Hsf4, Mip and Pitx3） were chosen for genetic mutation test by using exon sequencing. A novel cytosine insertion at position 1195 of CX46 c DNA（c.1194_1195ins C） was found in the samples of 5 tested cataract patients but not in the unaffected 2 individuals nor in normal controls, which resulted in 30 amino acids more extension in CX46Cterminus（cx46fs400） compared with the wild-type CX46. In silico protein structure analysis indicated that the mutant showed distinctive hydrophobicity and protein secondary structure compared with the wild-type CX46. The immunoblot results revealed that CX46 protein, which expressed in the aging cataract lens tissues, was absence in the proband lens. In contrast, CX50, alpha A-crystallin and alphaB-crystallin expressed equally in both proband and aging cataract tissues. Those results revealed that the cx46fs400 mutation could impair CX46 protein expression. CONCLUSION：The insertion of cytosine at position 1195 of CX46 cD NA is a novel mutation site that is associated with the autosomal dominant cataracts in this Chinese family. The C-terminal frameshift mutation is involved in regulating CX46 protein expression.

The Investigation of Main Pathogens Causing Dairy Cattle Recessive Mastitis in Eastern Hebei

[Objective]This paper aimed to determine the main pathogens causing dairy cattle recessive mastitis in eastern Hebei and provide certain reference for local veterinarians and cow farmers to prevent and cure the disease.[Method]512 cows from 5 different farms in eastern Hebei were selected,and LMT,milk ph test and somatic cell direct counting methods were combined and used to conduct recessive mastitis＇ s epidemiological investigation,as well as isolate and identify the pethogens.[Result]The results indicated that the incidence of recessive mastitis is 60.7%（311 / 512）,bacteria isolation rate reached 87.8%（273 /311）.Total 81 isolates,belonging to 3 classes and 5 types were identified in milk samples of positive milk area from 273 cows with recessive mastitis.Among which,19 isolates were Streptococcus,accounting for 23.45%.Staphylococcus had 31 isolates,accounting for 38.27%.Enterobacter had 3,accounting for 3.7%.Other unshaped had 28 isolates,accounting for 34.6%.[Conclusion] The main pathogens caused dairy cattle recessive mastitis in eastern Hebei were Streptococcus agalactiae and Staphylococcus aureus.

Utilization of eui Gene from a Recessive Tall Rice Mutant 02428h in Breeding

In order to improve the panicle extrusion of photo- and thermo-sensitive sterile line ‘Pei＇ai 64S＇ by using elongated uppermost internode （eul） gene of the wide compatibility rice mutant ‘02428h＇, a new photo- and thermo-sensitive sterile line ‘P8hS＇ characterized with elongated uppermost internode was developed by transferring the eui gene into Pei＇ai 64S through three successive backcrossing, Compared with Pei＇ai 64S, the plant height of P8hS was 35.6 cm higher resulted from the elongation of the uppermost and the second internodes from the top. The panicle extrusion of Pei＇ai 64S was completely improved and positive effects were found on the main economic characters of P8hS and its hybrids by introducing euigene into Pei＇ai 64S.

Simultaneous kidney transplantation and ipsilateral native nephrectomy in patients with autosomal dominant polycystic kidney disease

The simultaneous kidney transplantation and ipsilateral native nephrectomy for autosomal dominant polycystic kidney disease does not seem to be associated with increased rates of comorbidity and complications.This outcome can efficiently be achieved when the indication and surgical approach of native nephrectomy are properly justified.