scholarly journals Homozygous mutations in DZIP1 can induce asthenoteratospermia with severe MMAF

2020 ◽  
Vol 57 (7) ◽  
pp. 445-453 ◽  
Author(s):  
Mingrong Lv ◽  
Wangjie Liu ◽  
Wangfei Chi ◽  
Xiaoqing Ni ◽  
Jiajia Wang ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Clinical Manifestations ◽  
Interacting Protein ◽  
Genome Data ◽  
Pathogenic Genes ◽  
Whole Exome ◽  
Exome Aggregation Consortium ◽  
Common Causes ◽  
Deleted In Azoospermia ◽  
The Common

BackgroundAsthenoteratospermia, 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 resultsTwo 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.ConclusionOur 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.

scholarly journals Clinical Manifestations Enticed in Clinical Cases of Canine Pyoderma

2017 ◽  
Vol 13 (02) ◽  
Author(s):  
Bansari Shah ◽  
Neha Rao ◽  
P. V. Parikh ◽  
D. M. Patel ◽  
D. S. Nauriyal
Keyword(s):  
Clinical Manifestations ◽  
Small Animal ◽  
Isolation And Identification ◽  
Common Causes ◽  
The Common ◽  
Clinical Cases

Canine pyoderma is one of the most common causes of dermatitis with worldwide occurrence in small animal practice. The condition is diagnosed on the basis of clinical manifestations, isolation and identification of causative organisms by bacteriological cultural examination. A study was conducted on 130 dogs diagnosed with canine pyoderma presented at the Veterinary Clinical Complex (VCC), Veterinary College, Anand. These included cases of surface pyoderma (15), superficial pyoderma (50), deep pyoderma (32) and secondary pyoderma (33). The common clinical manifestations observed were exudation of pus, pruritus, erythema, pustules, papules, crusts, epidermal collarettes and alopecia. Canine pyoderma found secondary to other dermatological afflictions illustrated manifestations associated with the underlying cause. Hence, the condition should be differentially diagnosed and treated accordingly.

Early signalling events of autophagy

2013 ◽  
Vol 55 ◽  
pp. 1-15 ◽  
Author(s):  
Laura E. Gallagher ◽  
Edmond Y.W. Chan
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Mammalian Cells ◽  
Mammalian Target Of Rapamycin ◽  
Interacting Protein ◽  
The Core ◽  
Autophagy Gene ◽  
Autophagy Induction ◽  
Cellular Pathways

Autophagy is a conserved cellular degradative process important for cellular homoeostasis and survival. An early committal step during the initiation of autophagy requires the actions of a protein kinase called ATG1 (autophagy gene 1). In mammalian cells, ATG1 is represented by ULK1 (uncoordinated-51-like kinase 1), which relies on its essential regulatory cofactors mATG13, FIP200 (focal adhesion kinase family-interacting protein 200 kDa) and ATG101. Much evidence indicates that mTORC1 [mechanistic (also known as mammalian) target of rapamycin complex 1] signals downstream to the ULK1 complex to negatively regulate autophagy. In this chapter, we discuss our understanding on how the mTORC1–ULK1 signalling axis drives the initial steps of autophagy induction. We conclude with a summary of our growing appreciation of the additional cellular pathways that interconnect with the core mTORC1–ULK1 signalling module.

scholarly journals Facial cleft? The first case of manitoba‐oculo‐tricho‐anal syndrome with novel mutations in China: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuchen Gu ◽  
Yimin Khoong ◽  
Xin Huang ◽  
Tao Zan
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Manifestations ◽  
Sporadic Case ◽  
Facial Cleft ◽  
Ocular Manifestations ◽  
First Case ◽  
Whole Exome ◽  
Chinese Girl ◽  
Low Prevalence

Abstract Background Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare syndrome with only 27 cases reported worldwide so far, but none was reported in the population of Eastern Asia. Such extremely low prevalence might be contributed by misdiagnosis due to its similarities in ocular manifestations with facial cleft. In our study, we discovered the first case of MOTA syndrome in the population of China, with 2 novel FRAS1 related extracellular matrix 1 (FREM1) gene stop-gain mutations confirmed by whole exome sequencing. Case presentation A 12-year-old Chinese girl presented with facial cleft-like deformities including aberrant hairline, blepharon-coloboma and broad bifid nose since birth. Whole exome sequencing resulted in the identification of 2 novel stop-gain mutations in the FREM1 gene. Diagnosis of MOTA syndrome was then established. Conclusions We discovered the first sporadic case of MOTA syndrome according to clinical manifestations and genetic etiology in the Chinese population. We have identified 2 novel stop-gain mutations in FREM1 gene which further expands the spectrum of mutational seen in the MOTA syndrome. Further research should be conducted for better understanding of its mechanism, establishment of an accurate diagnosis, and eventually the exploitation of a more effective and comprehensive therapeutic intervention for MOTA syndrome.

scholarly journals Novel variants in DNAH9 lead to nonsyndromic severe asthenozoospermia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dongdong Tang ◽  
Yanwei Sha ◽  
Yang Gao ◽  
Jingjing Zhang ◽  
Huiru Cheng ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Sperm Morphology ◽  
Immunofluorescence Staining ◽  
Compound Heterozygous ◽  
Sperm Tail ◽  
Transmission Electron ◽  
Whole Exome ◽  
Detailed Medical History ◽  
Novel Variants ◽  
Common Causes

Abstract Background Asthenozoospermia is one of the most common causes of male infertility, and its genetic etiology is poorly understood. DNAH9 is a core component of outer dynein arms in cilia and flagellum. It was reported that variants of DNAH9 (OMIM: 603330) might cause primary ciliary dyskinesia (PCD). However, variants in DNAH9 lead to nonsyndromic severe asthenozoospermia have yet to be reported. Methods Whole exome sequencing (WES) was performed for two individuals with nonsyndromic severe asthenozoospermia from two non-consanguineous families, and Sanger sequencing was performed to verify the identified variants and parental origins. Sperm routine analysis, sperm vitality rate and sperm morphology analysis were performed according the WHO guidelines 2010 (5th edition). Transmission electron microscopy (TEM, TECNAI-10, 80 kV, Philips, Holland) was used to observe ultrastructures of sperm tail. Quantitative realtime-PCR and immunofluorescence staining were performed to detect the expression of DNAH9-mRNA and location of DNAH9-protein. Furthermore, assisted reproductive procedures were applied. Results By WES and Sanger sequencing, compound heterozygous DNAH9 (NM_001372.4) variants were identified in the two individuals with nonsyndromic severe asthenozoospermia (F1 II-1: c.302dupT, p.Leu101fs*47 / c.6956A > G, p.Asp2319Gly; F2 II-1: c.6294 T > A, p.Phe2098Leu / c.10571 T > A, p.Leu3524Gln). Progressive rates less than 1% with normal sperm morphology rates and normal vitality rates were found in both of the two subjects. No respiratory phenotypes, situs inversus or other malformations were found by detailed medical history, physical examination and lung CT scans etc. Moreover, the expression of DNAH9-mRNA was significantly decreased in sperm from F1 II-1. And expression of DNAH9 is lower in sperm tail by immunofluorescence staining in F1 II-1 compared with normal control. Notably, by intracytoplasmic sperm injection (ICSI), F1 II-1 and his partner successfully achieved clinical pregnancy. Conclusions We identified DNAH9 as a novel pathogenic gene for nonsyndromic severe asthenospermia, and ICSI can contribute to favorable pregnancy outcomes for these patients.

scholarly journals Excited delirium syndrome from psychostimulant abuse can mimic a violent scene of death

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shatishraj Jothee ◽  
Mohamed Swarhib Shafie ◽  
Faridah Mohd Nor
Keyword(s):  
Clinical Manifestations ◽  
The Body ◽  
Law Enforcement Agencies ◽  
Manner Of Death ◽  
Case Presentation ◽  
Excited Delirium ◽  
The Common ◽  
Violent Scene ◽  
Naked Body ◽  
Psychostimulant Abuse

Abstract Background Previous reported cases on excited delirium syndrome studied on the common clinical manifestations of the syndrome. The usual forensics implication for the syndrome is that death commonly is associated with restraint procedures by law enforcement agencies; however, not many cases reported highlights the difficulties in attributing a violent scene of death to the syndrome. Case presentation We present a case of a partially naked body found in an apartment unit under suspicious circumstances with multiple injuries. The scene of death was violent, and the body was found with blood wiped all over the floor and walls. Investigators believed a violent crime had occurred, and a suspect was reprimanded. However, upon autopsy, it was found that all injuries were superficially inflicted and were unlikely to have been part of an act of commission or caused his death. Internal examination found no remarkable pathology. Toxicology revealed a presence of psychostimulants, that is, methamphetamine, MDMA, and ethyl alcohol. Reconstruction of events by the witness, who was initially suspected of the ‘murder’, revealed that the injuries and his death could likely be explained by an episode of excited delirium. Conclusion The case highlights the challenges faced when attributing excited delirium syndrome as a cause of death. The syndrome can present with injuries from aggressive or bizarre behaviour, coupled with the destruction of property, which may confuse investigators on the possible manner of death.

scholarly journals From “Technical Newbies” to “Optimistic Politicians”

2019 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
James Prater ◽  
Konstantinos Kirytopoulos ◽  
Tony Ma
Keyword(s):  
Information Technology ◽  
Quantitative Research ◽  
Valuable Insight ◽  
Scheduling Problems ◽  
Information Technology Projects ◽  
Content Type ◽  
Common Causes ◽  
The Common ◽  
Project Estimation ◽  
Engineering Projects

Purpose Despite the advent of sophisticated control methods, there are still significant issues regarding late delivery of information technology projects. The purpose of this paper is to investigate the common causes of scheduling problems specifically in the information technology projects context. Design/methodology/approach Through a quantitative research, the importance of those causes, as well as the underpinning factors driving them, is explored. The causes are ranked according to their relative important index, and exploratory factor analysis is employed to reveal underlying dimensions (factors) of these causes. Findings From the analysis, four factors were extracted, namely, “Dataless Newbie,” “Technical Newbie,” “Pragmatic Futurist” and “Optimistic Politician.” These factors explain the different latent conditions that lead to scheduling problems in information technology projects. Practical implications The key contribution of this research is that it enlightens the latent conditions underpinning scheduling problems. Also, the evidence provides that schedule development for information technology projects is impacted by the same causes that impact engineering projects, and that applying a number of mitigation techniques widely used within the engineering area, such as reference class, would, no doubt, not only improve information technology schedules but also reduce the political pressures on the project manager. Originality/value This research provides a valuable insight into understanding the underlying factors for poor project estimation.

Carbon monoxide: mechanism of toxic action, pathogenesis and clinical manifestations of acute intoxication

2021 ◽  
pp. 4-9
Author(s):  
A. N. Grebenyuk ◽  
V. N. Bykov
Keyword(s):  
Carbon Monoxide ◽  
Clinical Manifestations ◽  
Acute Poisoning ◽  
Toxic Action ◽  
Acute Intoxication ◽  
Emergency Situations ◽  
Common Causes ◽  
The Central Nervous System ◽  
Regulatory Effects ◽  
Mitochondrial Cytochrome Oxidase

Introduction. Carbon monoxide (CO) remains one of the most common causes of acute poisoning and death, both in everyday life and in emergency situations, especially in fires.Material and methods. The paper summarizes information about the regulatory effects, mechanisms of toxic action, pathogenesis and clinical picture of intoxication, as well as predictors of the severity of CO poisoning.Results. The main mechanism of the toxic effect of CO is due to its ability to bind to the protohemal iron of hemoglobin (Hb) to form carboxyhemoglobin (HbCO). The toxicity of CO may also be enhanced by impaired functions of the myoglobin of the myocardium and skeletal muscles, mitochondrial cytochrome oxidase, and iron-containing enzymes of the antioxidant system. The leading link in the pathogenesis of acute CO intoxication is a violation of the oxygen transport function of hemoglobin and the associated development of hemic and tissue hypoxia. CO-induced cell and tissue damage due to the induction of mitochondrial dysfunction, oxidative stress, free radical hyperproduction, lipid peroxidation, inflammation, and apoptosis also play a role in the pathogenesis of intoxication.Conclusion. The mechanism of toxic action of CO, associated primarily with the formation of carboxyhemoglobin and the development of hypoxia, determines the clinical manifestations of acute intoxication, which depend on the concentration of CO and the duration of exposure, but are almost always associated with the central nervous system and cardiovascular system.

Screening of Candidate Pathogenic Genes for Spontaneous Abortion using Whole Exome Sequencing

2021 ◽  
Vol 24 ◽  
Author(s):  
Qingwen Zhu ◽  
Yiwen Zhou ◽  
Jiayi Ding ◽  
Li Chen ◽  
Jia Liu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Spontaneous Abortion ◽  
Gene Fusion ◽  
High Throughput Sequencing ◽  
Kegg Pathway ◽  
Novel Mutation ◽  
Common Disease ◽  
Pathogenic Genes ◽  
Whole Exome

Background: Spontaneous abortion is a common disease in obstetrics and reproduction. Objective: This study aimed to screen candidate pathogenic genes for spontaneous abortion using whole-exome sequencing. Methods: Genomic DNA was extracted from abortion tissues of spontaneous abortion patients and sequenced using the Illumina HiSeq2500 high-throughput sequencing platform. Whole exome sequencing was performed to select harmful mutations, including SNP and insertion and deletion sites, associated with spontaneous abortion. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and gene fusion analyses were performed. MUC3A and PDE4DIP were two novel mutation genes that were screened and verified by PCR in abortion tissues of patients. Results: A total of 83,633 SNPs and 13,635 Indel mutations were detected, of which 29172 SNPs and 3093 Indels were screened as harmful mutations. The 7 GO-BP, 4 GO-CC, 9 GO-MF progress, and 3 KEGG pathways were enriched in GO and KEGG pathway analyses. A total of 746 gene fusion mutations were obtained, involving 492 genes. MUC3A and PDE4DIP were used for PCR verification because of their high number of mutation sites in all samples. Conclusion: There are extensive SNPs and Indel mutations in the genome of spontaneous abortion tissues, and the effect of these gene mutations on spontaneous abortion needs further experimental verification.

scholarly journals Non-tuberculous Mycobacterium Disease: Radiologic Manifestation in an Infant presenting with Respiratory Distress

2017 ◽  
Vol 5 (1-2) ◽  
pp. 13-20
Author(s):  
Rupesh Gautam ◽  
Maria Isabel Atienza ◽  
Maika Noda ◽  
Mariaem Andres
Keyword(s):  
Hypersensitivity Pneumonitis ◽  
Pulmonary Infection ◽  
Clinical Manifestations ◽  
Distinct Group ◽  
Middle Lobe ◽  
Air Trapping ◽  
Pulmonary Tb ◽  
Radiologic Findings ◽  
The Common ◽  
Common Manifestation

Non-tuberculous mycobacterium (NTM) comprises distinct group of organisms with lymphadenitis and pulmonary infection as the common manifestation. The diagnosis of pulmonary disease is based on clinical manifestations, radiologic findings and microbiologic culture. The classic NTM infection may be indistinguishable from pulmonary TB. Non-classic infection has predilection to the middle lobe and lingula unlike tuberculosis which is commonly seen in the upper lobes. The disease may also present as hypersensitivity pneumonitis with ground glass like opacities, centrilobular nodules and air trapping on imaging. The knowledge of imaging manifestations of NTM will aid in timely diagnosis and treatment of the disease.Nepal Journal of Radiology Vol.5(1-2) 2015: 13-20

scholarly journals Investigation of Pathogenic Genes in Peri-Implantitis from Implant Clustering Failure Patients: A Whole-Exome Sequencing Pilot Study

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e99360 ◽  
Author(s):  
Soohyung Lee ◽  
Ji-Young Kim ◽  
Jihye Hwang ◽  
Sanguk Kim ◽  
Jae-Hoon Lee ◽  
...  
Keyword(s):  
Pilot Study ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pathogenic Genes ◽  
Whole Exome
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