GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • BMJ  (21)
  • 1
    Online Resource
    Online Resource
    Homozygous mutations in DZIP1 can induce asthenoteratospermia with severe MMAF
    BMJ ; 2020
    In:  Journal of Medical Genetics Vol. 57, No. 7 ( 2020-07), p. 445-453
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 57, No. 7 ( 2020-07), p. 445-453
    Abstract: Asthenoteratospermia, one of the most common causes for male infertility, often presents with defective sperm heads and/or flagella. Multiple morphological abnormalities of the sperm flagella (MMAF) is one of the common clinical manifestations of asthenoteratospermia. Variants in several genes including DNAH1 , CEP135 , CATSPER2 and SUN5 are involved in the genetic pathogenesis of asthenoteratospermia. However, more than half of the asthenoteratospermia cases cannot be explained by the known pathogenic genes. Methods and results Two asthenoteratospermia-affected men with severe MMAF (absent flagella in 〉 90% spermatozoa) from consanguineous families were subjected to whole-exome sequencing. The first proband had a homozygous missense mutation c.188G 〉 A (p.Arg63Gln) of DZIP1 and the second proband had a homozygous stop-gain mutation c.690T 〉 G (p.Tyr230*). Both of the mutations were neither detected in the human population genome data (1000 Genomes Project, Exome Aggregation Consortium) nor in our own data of a cohort of 875 Han Chinese control populations. DZIP1 encodes a DAZ (a protein deleted in azoospermia) interacting protein, which was associated with centrosomes in mammalian cells. Immunofluorescence staining of the centriolar protein Centrin1 indicated that the spermatozoa of the proband presented with abnormal centrosomes, including no concentrated centriolar dot or more than two centriolar dots. HEK293T cells transfected with two DZIP1 -mutated constructs showed reduced DZIP1 level or truncated DZIP1. The Dzip1 -knockout mice, generated by the CRSIPR-Cas9, revealed consistent phenotypes of severe MMAF. Conclusion Our study strongly suggests that homozygous DZIP1 mutations can induce asthenoteratospermia with severe MMAF. The deficiency of DZIP1 induces sperm centrioles dysfunction and causes the absence of flagella.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmedgenet-2019-106479
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2009590-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Homozygous mutations in SPEF2 induce multiple morphological abnormalities of the sperm flagella and male infertility
    BMJ ; 2020
    In:  Journal of Medical Genetics Vol. 57, No. 1 ( 2020-01), p. 31-37
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 57, No. 1 ( 2020-01), p. 31-37
    Abstract: Male infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) is a genetically heterogeneous disorder. Previous studies revealed several MMAF-associated genes, which account for approximately 60% of human MMAF cases. The pathogenic mechanisms of MMAF remain to be illuminated. Methods and results We conducted genetic analyses using whole-exome sequencing in 50 Han Chinese probands with MMAF. Two homozygous stop-gain variants (c.910C 〉 T (p.Arg304*) and c.3400delA (p.Ile1134Serfs*13)) of the SPEF2 ( sperm flagellar 2 ) gene were identified in two unrelated consanguineous families. Consistently, an Iranian subject from another cohort also carried a homozygous SPEF2 stop-gain variant (c.3240delT (p.Phe1080Leufs*2)). All these variants affected the long SPEF2 transcripts that are expressed in the testis and encode the IFT20 (intraflagellar transport 20) binding domain, important for sperm tail development. Notably, previous animal studies reported spontaneous mutations of SPEF2 causing sperm tail defects in bulls and pigs. Our further functional studies using immunofluorescence assays showed the absence or a remarkably reduced staining of SPEF2 and of the MMAF-associated CFAP69 protein in the spermatozoa from SPEF2 -affected subjects. Conclusions We identified SPEF2 as a novel gene for human MMAF across the populations. Functional analyses suggested that the deficiency of SPEF2 in the mutated subjects could alter the localisation of other axonemal proteins.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmedgenet-2019-106011
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2009590-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Biallelic mutations in CFAP65 cause male infertility with multiple morphological abnormalities of the sperm flagella in humans and mice
    BMJ ; 2020
    In:  Journal of Medical Genetics Vol. 57, No. 2 ( 2020-02), p. 89-95
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 57, No. 2 ( 2020-02), p. 89-95
    Abstract: Male infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre flagella resulting in severely decreased motility. Previous studies reported several MMAF-associated genes accounting for approximately half of MMAF cases. Methods and result We conducted genetic analysis using whole-exome sequencing in 88 Han Chinese MMAF probands. CFAP65 homozygous mutations were identified in four unrelated consanguineous families, and CFAP65 compound heterozygous mutations were found in two unrelated cases with MMAF. All these CFAP65 mutations were null, including four frameshift mutations (c.1775delC [p.Pro592Leufs*8], c.3072_3079dup [p.Arg1027Profs*41] , c.1946delC [p.Pro649Argfs*5] and c.1580delT [p.Leu527Argfs*31] ) and three stop-gain mutations (c.4855C 〉 T [p.Arg1619*], c.5270T 〉 A [p.Leu1757*] and c.5341G 〉 T [p.Glu1781*]). Additionally, two homozygous CFAP65 variants likely affecting splicing were identified in two MMAF-affected men of Tunisian and Iranian ancestries, respectively. These biallelic variants of CFAP65 were verified by Sanger sequencing and were absent or very rare in large data sets aggregating sequence information from various human populations. CFAP65 , encoding the cilia and flagella associated protein 65, is highly and preferentially expressed in the testis. Here we also generated a frameshift mutation in mouse orthologue Cfap65 using CRISPR-Cas9 technology. Remarkably, the phenotypes of Cfap65 -mutated male mice were consistent with human MMAF. Conclusions Our experimental observations performed on both human subjects and on Cfap65 -mutated mice demonstrate that the presence of biallelic mutations in CFAP65 causes the MMAF phenotype and impairs sperm motility.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmedgenet-2019-106344
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2009590-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Novel homozygous CFAP69 mutations in humans and mice cause severe asthenoteratospermia with multiple morphological abnormalities of the sperm flagella
    BMJ ; 2019
    In:  Journal of Medical Genetics Vol. 56, No. 2 ( 2019-02), p. 96-103
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 56, No. 2 ( 2019-02), p. 96-103
    Abstract: Male infertility is a major issue of human reproduction health. Asthenoteratospermia can impair sperm motility and cause male infertility. Asthenoteratospermia with multiple morphological abnormalities of the flagella (MMAF) presents abnormal spermatozoa with absent, bent, coiled, short and/or irregular-calibre flagella. Previous studies on MMAF reported that genetic defects in cilia-related genes (eg, AKAP4 , DNAH1 , CFAP43 , CFAP44 and CFAP69 ) are the major cause of MMAF. However, the known MMAF-associated genes are only responsible for approximately 30% to 50% of human cases. We further investigated the cases with MMAF in search of additional genes mutated in this condition. Methods and results We conducted whole exome sequencing in a male individual with MMAF from a consanguineous Han Chinese family. Sanger sequencing was also conducted in additional individuals with MMAF. Intriguingly, a homozygous frameshift mutation (p.Leu357Hisfs*11) was identified in the gene encoding CFAP69 (cilia and flagella-associated protein 69), which is highly expressed in testis. The subsequent Sanger sequencing of the CFAP69 coding regions among 34 additional individuals with MMAF revealed a case with homozygous nonsense mutation (p.Trp216*) of CFAP69 . Both of these CFAP69 loss-of-function mutations were not present in the human population genome data archived in the 1000 Genomes Project and ExAC databases, nor in 875 individuals of two Han Chinese control populations. Furthermore, we generated the knockout model in mouse orthologue Cfap69 using the CRISPR-Cas9 technology. Remarkably, male Cfap69 -knockout mice manifested with MMAF phenotypes. Conclusion Our experimental findings elucidate that homozygous loss-of-function mutations in CFAP69 can lead to asthenoteratospermia with MMAF in humans and mice.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    URL: Article
    DOI: 10.1136/jmedgenet-2018-105486
    DOI: 10.1136/jmedgenet-2018-105486.supp1
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2009590-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Metabolic syndrome is associated with and predicted by resting heart rate: a cross-sectional and longitudinal study
    BMJ ; 2015
    In:  Heart Vol. 101, No. 1 ( 2015-01-01), p. 44-49
    Details
    In: Heart, BMJ, Vol. 101, No. 1 ( 2015-01-01), p. 44-49
    Type of Medium: Online Resource
    ISSN: 1355-6037 , 1468-201X
    URL: Article
    DOI: 10.1136/heartjnl-2014-305685
    Language: English
    Publisher: BMJ
    Publication Date: 2015
    detail.hit.zdb_id: 2378689-9
    detail.hit.zdb_id: 1475501-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Psychometric properties of the Depression Stigma Scale (DSS) in Chinese cancer patients: a cross-sectional study
    BMJ ; 2019
    In:  BMJ Open Vol. 9, No. 7 ( 2019-07), p. e028429-
    Details
    In: BMJ Open, BMJ, Vol. 9, No. 7 ( 2019-07), p. e028429-
    Abstract: The Depression Stigma Scale (DSS) is commonly used to assess depression stigma in the general population and in people with depression. The DSS includes two 9-item subscales assumed to measure personal depression stigma (ie, personal perceptions of depression) and perceived depression stigma (ie, perceptions of how others perceive depression). The aim of the present study was to examine its psychometric properties in terms of validity and reliability in Chinese cancer patients. Design A cross-sectional study design. Participants and settings This study focused on 301 Chinese cancer patients recruited from two hospitals in Xi’an, China. Methods Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess the factor structure. Internal consistency was assessed using Cronbach’s alpha. To examine concurrent validity, symptoms of depression were used as the criterion. Results For each subscale of the DSS (ie, personal and perceived depression stigma), the EFA and CFA confirmed a two-factor structure: weak-not-sick (ie, perceiving that depression is not a real illness, but rather a sign of weakness) and discrimination (ie, perceiving that depressed people are discriminated against). The Cronbach’s alphas were adequate, ranging from 0.70 to 0.80. Symptoms of depression were positively but weakly correlated to personal and perceived depression stigma. Conclusions The DSS appeared to show satisfactory psychometric properties in our sample of cancer patients. Both personal depression stigma and perceived depression stigma subscales consisted of two underlying aspects.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2018-028429
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2599832-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Open and minimally invasive surgery for gastrointestinal stromal tumours: a systematic review and network meta-analysis protocol
    BMJ ; 2022
    In:  BMJ Open Vol. 12, No. 2 ( 2022-02), p. e050414-
    Details
    In: BMJ Open, BMJ, Vol. 12, No. 2 ( 2022-02), p. e050414-
    Abstract: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive system, and complete resection is the only way to provide a radical cure for resectable GISTs. Open surgery and minimally invasive approaches, including laparoscopy, robotic surgery and endoscopy, consist of the mainstream GIST resection. However, there is still a lack of evidence regarding which surgical outcomes and long-term prognosis would be better. Thus, we are planning to conduct a network meta-analysis and systematic review aiming to determine the comparative effectiveness among laparotomy, laparoscopy, endoscopy, robotic surgery, and laparoscopic and endoscopic cooperative surgery in GISTs. Method and analysis PubMed, EMBASE, the Cochrane Library and Web of Science will be searched for published studies to identify the proper literature comparing open resection, laparoscopy, endoscopy, robotic surgery, and laparoscopic and endoscopic cooperative surgery for resecting GISTs from inception to February 2021. Randomised controlled trials (RCTs) and non-randomised studies comparing at least two different interventions for GIST resection will be included. RCTs and non-randomised studies will be synthesised and analysed separately. Bayesian network meta-analysis will be performed to compare the surgical outcomes and long-term prognosis among the resection methods above. The included studies will be divided into several subgroups according to tumour location and size for further analysis. Sensitivity analysis will be performed to identify and explain heterogeneity to make our results robust. Meta-regression will serve as a supplementary method if data are available. The quality of evidence will be evaluated by the Grading of Recommendations, Assessment, Development and Evaluation. Ethics and dissemination No ethical approval is required for this network meta-analysis, as it is based on already published data. The findings of the review will be published in a peer-reviewed journal. PROSPERO registration number CRD42021237892.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2021-050414
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2599832-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Relationship Between Birth Weight and Asthma Diagnosis: A Cross-Sectional Survey Study Based on the National Survey of Children’s Health in the U.S.
    BMJ ; 2023
    In:  BMJ Open Vol. 13, No. 12 ( 2023-12), p. e076884-
    Details
    In: BMJ Open, BMJ, Vol. 13, No. 12 ( 2023-12), p. e076884-
    Abstract: To assess the association between birth weight and childhood asthma risk using data from the 2019–2020 National Survey of Children’s Health database. Design Cross-sectional study. Setting The USA. Patients A representative cohort of American children. Exposure The exposure of this study was birth weight regardless of gestational age. Birth weight was divided into three groups: 〈 1500 g, 1500–2500 g and 〉 2500 g. Main outcome measures Primary outcomes were parent-reported diagnosis of asthma. Method The Rao-Scott χ 2 test was used to compare the groups. The main analyses examined the association between birth weight and parent-report asthma in children using univariable and multivariable logistic models adjusting for preterm birth, age, sex, race, family poverty, health insurance, smoking, maternal age. Subgroup analysis was performed based on interaction test. Results A total of 60 172 children aged 3–17 years were enrolled in this study; of these, 5202 (~8.6%) had asthma. Children with asthma were more likely to be born preterm, with low birth weight (LBW) or very LBW (VLBW). The incidence of asthma was the highest in VLBW children at 20.9% and showed a downward trend with an increase in birth weight class, with rates of 10.7% and 8.1% in the LBW and normal birthweight groups, respectively. Children with VLBW (OR 1.97; 95% CI 1.29 to 3.01) had higher odds of developing asthma in the adjusted analysis model. However, VLBW was only shown to be a risk factor for asthma among Hispanics, black/African-Americans and children between the ages of 6 and 12 years, demonstrating racial and age disparities. Conclusions VLBW increases the risk of childhood asthma; however, racial and age disparities are evident.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2023-076884
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2599832-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    High methionyl–tRNA synthetase expression predicts poor prognosis in patients with breast cancer
    BMJ ; 2020
    In:  Journal of Clinical Pathology Vol. 73, No. 12 ( 2020-12), p. 803-812
    Details
    In: Journal of Clinical Pathology, BMJ, Vol. 73, No. 12 ( 2020-12), p. 803-812
    Abstract: Methionyl–tRNA synthetase (MARS) is known to play a critical role in initiating translation and protection against cellular damages in vivo. The aim of this study was to clarify the role of MARS in breast cancer (BC) progression. Methods The expressions of MARS messenger RNA (mRNA) and protein in human BC tissues and adjacent non-cancerous tissues were detected by quantitative real-time PCR, western blot and immunohistochemistry. The prognostic potential of MARS in patients with BC was assessed by univariate and multivariate survival analyses. The association between the MARS expression and BC progression was further evaluated by the bioinformatics database of UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Database of Normal and Tumor Tissues (GENT). The role of MARS in the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of human breast cancer cell line (MCF-7 cells) was investigated after siRNA transfection. Results The expression level of MARS mRNA in the fresh BC tissues was significantly higher than that in the adjacent tissues. Immunohistochemistry showed that the expression level of MARS was closely associated with the clinicopathologial parameters of patients with BC, including the HER-2 status, Ki-67 status, molecular classification, tumour grade, N stage and tumour, node, metastasis (TNM) stage, and this finding was further confirmed by UALCAN database. The Kaplan-Meier analysis showed that high MARS expression and TNM stage were predictors of poor prognosis of patients with BC. The proliferation, migration and EMT capabilities of MCF-7 cells were significantly suppressed after MARS knockdown. An overview of UALCAN, GEPIA and GENT results suggested that MARS may be an oncogene of BC, as well as a potential therapeutic target of this malignant tumour. Conclusions High expression level of MARS in the human BC tissues was significantly associated with the unfavourable prognosis of patients with BC, suggesting that MARS may serve as a potential prognostic marker for the clinical diagnosis and prognostic prediction of BC.
    Type of Medium: Online Resource
    ISSN: 0021-9746 , 1472-4146
    URL: Article
    DOI: 10.1136/jclinpath-2019-206175
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2028928-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Mutation screening of the KIF5A gene in Chinese patients with amyotrophic lateral sclerosis
    BMJ ; 2019
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 90, No. 2 ( 2019-02), p. 245-246
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 90, No. 2 ( 2019-02), p. 245-246
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1136/jnnp-2018-318395
    DOI: 10.1136/jnnp-2018-318395.supp1
    DOI: 10.1136/jnnp-2018-318395.supp2
    DOI: 10.1136/jnnp-2018-318395.supp3
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 1480429-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...