scholarly journals Tugging at the Heart Strings: The Septin Cytoskeleton in Heart Development and Disease

2020 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Kelsey Moore ◽  
Reece Moore ◽  
Christina Wang ◽  
Russell A. Norris
Keyword(s):  
Cardiovascular Diseases ◽  
Heart Development ◽  
Budding Yeast ◽  
Cellular Activity ◽  
Microtubule Organization ◽  
Vast Array ◽  
The Past ◽  
Temporal Function ◽  
Alternatively Spliced ◽  
Mammalian Genes

Septin genes were originally identified in budding yeast in 1971. Since their original discovery, at least 13 mammalian genes have now been found, which give rise to a vast array of alternatively spliced proteins that display unique spatial-temporal function across organs systems. Septin’s are now recognized as the 4th major component of the cytoskeleton. Their role in regulating ciliogenesis, actin and microtubule organization and their involvement in mechanotransduction clearly solidify their place as both a responder and driver of cellular activity. Although work on septin’s has escalated over the past decades, knowledge of septin function in the heart remains rudimentary. Whereas many cardiovascular diseases have been associated with genetic loci that include septin genes, new and additional concerted efforts will likely uncover previously unrecognized mechanisms by which the septin class of proteins contribute to clinical cardiac phenotypes. In this review, we place known function of septin proteins in the context of heart development and disease and provide perspectives on how increased knowledge of these proteins can mechanistically inform cardiac pathologies.

Abstract 250: Haploinsufficiency of Muscle-Enriched A-Type Lamin Interacting Protein (MLIP) Manifests as Enlarged Dilated Hearts

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Patrick Burgon ◽  
Julia Lockwood ◽  
Glenn Wells ◽  
Alexandre Blais
Keyword(s):  
Heart Development ◽  
Left Ventricular ◽  
Lamin A ◽  
Interacting Protein ◽  
Cellular Hypertrophy ◽  
Cellular Source ◽  
Alternatively Spliced ◽  
Normal Body Weight ◽  
Heart Size ◽  
And Function

Approximately 116 unique mutations in the lamin A/C gene have been described to date that are associated with dilated cardiomyopathy. We recently reported the discovery of MLIP through its interaction with lamin A/C. MLIP is expressed ubiquitously and most abundantly in heart, skeletal and smooth muscle of amniotes (mammals, reptiles and birds) and has no paralogous homologue suggesting no functional redundancy. The MLIP gene encodes at least seven, alternatively spliced, LMNA-interacting factors that possess several structural motifs not found in any other protein. The MLIP isoforms pattern of expression differs between each of the tissues with heart being the most heterogeneous. Down-regulation of lamin A/C expression by shRNA results in the up-regulation and mis-localization of MLIP. In addition to interacting and co-localizing with lamin A/C we also demonstrated that MLIP localizes to micro-domains in the nucleus with promyelocytic leukemia protein (PML) in close proximity to chromatin. MLIP's biological function still remains elusive. Eight week old hemizygous MLIP null mice develop enlarged hearts with a significant increase in heart to body weights (MLIP+/+ 5.62mg/g vs MLIP+/- 10.73mg/g, p<0.0001 n=7) with an overall 30% increase in the anterior-posterior ventricle length of MLIP hearts while maintaining a normal body weight (Figure). Echocardiographic analysis of MLIP+/- mice revealed that their hearts as having a significant (p3.93mm with a significant (p=0.011, n=12) reduction of left ventricular fractional shorting (LVFS) 31% when compare to littermate controls. Histological analysis of the hearts showed no overt phenotype other than an overall increase in the size of the MLIP+/- hearts. The cellular source for the increase in heart size and mass remains to be determined if it is the product of an increase in the number of cardiomyocytes due to aberrant hyperplasia or an increase in cardiomyocyte size through cellular hypertrophy. In conclusion, MLIP is a newly discovered lamin interacting protein that may serve as a transcriptional regulator that impact genes involved in heart development, growth and function and provides a new signaling paradigm.

scholarly journals The Effect of Service Quality on Satisfaction apropos Service Recipients of Divisional Secretariats in Colombo District in Sri Lanka

2017 ◽  
Vol 7 (1) ◽  
pp. 127
Author(s):  
Nayanananda Nilwala ◽  
Kennedy Gunawardana ◽  
R. S. Lalitha Fernando
Keyword(s):  
Regression Analysis ◽  
Correlation Analysis ◽  
Service Quality ◽  
Service Provider ◽  
Sampling Method ◽  
Social Economic ◽  
Relative Impact ◽  
Vast Array ◽  
The Public ◽  
The Past

A vast array of knowledge has been accumulated on the effect of service quality on customer satisfaction, particularly with a large number of studies over the past few years. However, the effect of service quality on satisfaction of service recipients in Divisional Secretariats in the Public Sector is relatively an unattended area by researchers. Hence, this study was carried out to evaluate the effect of service quality on satisfaction of service recipients of divisional secretariats. This particular organization was selected for the study as it is considered to be the most significant service provider in terms of statutory, social, economic and development in the country. A questionnaire survey and personal interviews were conducted to collect data by using the purposive sampling method. A modified questionnaire was prepared based on SERVQUAL instruments with two additional questions. A sample of 520 service recipients from 13 Divisional Secretariats in Colombo was drawn and it was represented by 40 from each division. Correlation analysis and multiple regression analysis were used to examine the relative impact of the service quality on satisfaction of service recipients. The study revealed that all the service quality attributes positively related to satisfaction of the service recipients. The findings of the study show that satisfaction of service recipients in terms of service quality has not met the expected level, which a divisional secretariat is deemed to provide for. 

scholarly journals Origin, Conservation, and Loss of Alternative Splicing Events that Diversify the Proteome in Saccharomycotina Budding Yeasts

2020 ◽  
Author(s):  
Jennifer E. Hurtig ◽  
Minseon Kim ◽  
Luisa J. Orlando-Coronel ◽  
Jellisa Ewan ◽  
Michelle Foreman ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Low Frequency ◽  
Common Mechanism ◽  
Duplicate Genes ◽  
Whole Genome ◽  
Genome Doubling ◽  
Whole Genome Doubling ◽  
Functional Consequences ◽  
Alternatively Spliced ◽  
Mammalian Genes

AbstractMany eukaryotes use alternative splicing to express multiple proteins from the same gene. However, while the majority of mammalian genes are alternatively spliced, other eukaryotes use this process less frequently. The budding yeast Saccharomyces cerevisiae has been successfully used to study the mechanism of splicing and the splicing machinery, but alternative splicing in yeast is relatively rare and has not been extensively studied. We have recently shown that the alternative splicing of SKI7/HBS1 is widely conserved, but that yeast and a few other eukaryotes have replaced this one alternatively spliced gene with a pair of duplicated unspliced genes as part of a whole genome doubling (WGD). Here we show that other examples of alternative splicing that were previously found to have functional consequences are widely conserved within the Saccharomycotina. We also show that the most common mechanism by which alternative splicing has disappeared is by the replacement of an alternatively spliced gene with duplicate genes. Saccharomycetaceae that diverged before WGD use alternative splicing more frequently than S. cerevisiae. This suggests that the WGD is a major reason for the low frequency of alternative splicing in yeast. We anticipate that whole genome doublings in other lineages may have had the same effect.

“I feel fine. Do I really need to take a cholesterol pill?”

HIV ◽  
2020 ◽  
pp. 189-200
Author(s):  
Arvind Nishtala ◽  
Matthew J. Feinstein
Keyword(s):  
Risk Factors ◽  
Antiretroviral Therapy ◽  
Cardiovascular Diseases ◽  
Chronic Condition ◽  
Clinical Manifestations ◽  
Epidemiological Studies ◽  
Communicable Diseases ◽  
Non Communicable Diseases ◽  
The Past ◽  
Traditional Risk Factors

With widespread antiretroviral therapy (ART) accessibility and uptake, HIV has transitioned in many ways to a chronic condition marked by heightened risks of non-communicable diseases. Several clinical and epidemiological studies over the past two decades have demonstrated elevated risks for cardiovascular diseases (CVDs) among people with HIV. These risks appear to be particularly elevated among people with histories of long periods of uncontrolled viremia and CD4 lymphopenia, and dovetail with traditional risk factors (such as smoking) that are common among people with HIV. This chapter presents a discussion of the evolving epidemiology, clinical manifestations, and putative mechanisms of CVDs among people with HIV.

scholarly journals Inhibitor of DNA binding in heart development and cardiovascular diseases

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Wenyu Hu ◽  
Yanguo Xin ◽  
Jian Hu ◽  
Yingxian Sun ◽  
Yinan Zhao
Keyword(s):  
Cardiovascular Diseases ◽  
Dna Binding ◽  
Heart Development ◽  
Inhibitor Of Dna Binding

scholarly journals Intercalated disc protein Xinβ is required for Hippo-YAP signaling in the heart

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Haipeng Guo ◽  
Yao Wei Lu ◽  
Zhiqiang Lin ◽  
Zhan-Peng Huang ◽  
Jianming Liu ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Heart Development ◽  
Genetic Interaction ◽  
Specific Cell ◽  
Cardiomyocyte Proliferation ◽  
Intercalated Disc ◽  
Knock Out ◽  
Genes Encoding ◽  
Knock Out Mice

Abstract Intercalated discs (ICD), specific cell-to-cell contacts that connect adjacent cardiomyocytes, ensure mechanical and electrochemical coupling during contraction of the heart. Mutations in genes encoding ICD components are linked to cardiovascular diseases. Here, we show that loss of Xinβ, a newly-identified component of ICDs, results in cardiomyocyte proliferation defects and cardiomyopathy. We uncovered a role for Xinβ in signaling via the Hippo-YAP pathway by recruiting NF2 to the ICD to modulate cardiac function. In Xinβ mutant hearts levels of phosphorylated NF2 are substantially reduced, suggesting an impairment of Hippo-YAP signaling. Cardiac-specific overexpression of YAP rescues cardiac defects in Xinβ knock-out mice—indicating a functional and genetic interaction between Xinβ and YAP. Our study reveals a molecular mechanism by which cardiac-expressed intercalated disc protein Xinβ modulates Hippo-YAP signaling to control heart development and cardiac function in a tissue specific manner. Consequently, this pathway may represent a therapeutic target for the treatment of cardiovascular diseases.

Arterial compliance in older people

2000 ◽  
Vol 10 (1) ◽  
pp. 43-54
Author(s):  
C. Rajkumar ◽  
S. Bonapace ◽  
C. J. Bulpitt
Keyword(s):  
Cardiovascular Diseases ◽  
Elderly Population ◽  
Arterial Compliance ◽  
The Elderly ◽  
Arterial System ◽  
Mortality And Morbidity ◽  
Risk Of Death ◽  
The Past ◽  
Life Expectancy At Birth ◽  
The Uk

IntroductionLongevity has lengthened in recent times. This has resulted in an increase in the elderly population, with life expectancy at birth in men in the UK being approximately 72.5 years and women, 78.5 years. Despite the risk of death from cardiovascular diseases decreasing in the past 40 years, these still continue to be the largest cause of mortality in the elderly. Cardiovascular mortality and morbidity are lower in women. However, this is not true in the later years of life. After the age of 80, the risk of cardiovascular problems increases to that of men. The cardiovascular changes occurring with aging consists of changes in the heart and arterial system.

scholarly journals Current trends and future perspectives in pelvic reconstructive surgery

2018 ◽  
Vol 14 ◽  
pp. 174550651877649 ◽  
Author(s):  
Mélanie Aubé ◽  
Le Mai Tu
Keyword(s):  
Pelvic Organ Prolapse ◽  
Surgical Repair ◽  
Treatment Options ◽  
Pelvic Organ ◽  
Review Article ◽  
Pelvic Reconstructive Surgery ◽  
Future Perspectives ◽  
Vast Array ◽  
The Past ◽  
Current Trends

Pelvic organ prolapse is a prevalent disorder with a high lifetime incidence of surgical repair. Pelvic organ prolapse surgery has greatly evolved over the past years, and pelvic floor reconstructive surgeons are faced with a vast array of treatment options for their patients. Our review article illustrates the current trends and future perspectives for the surgical treatment of pelvic organ prolapse.

scholarly journals Tailored Interventions to Improve Medication Adherence for Cardiovascular Diseases

2020 ◽  
Vol 11 ◽  
Author(s):  
Hai-Yan Xu ◽  
Yong-Ju Yu ◽  
Qian-Hui Zhang ◽  
Hou-Yuan Hu ◽  
Min Li
Keyword(s):  
Cardiovascular Disease ◽  
Medication Adherence ◽  
Cardiovascular Diseases ◽  
Healthcare Costs ◽  
Therapeutic Effects ◽  
Improve Medication Adherence ◽  
The Past ◽  
Tailored Interventions ◽  
Past Half Century ◽  
Past Half

Over the past half-century, medical research on cardiovascular disease (CVD) has achieved a great deal; however, medication adherence is unsatisfactory. Nearly 50% of patients do not follow prescriptions when taking medications, which limits the ability to maximize their therapeutic effects and results in adverse clinical outcomes and high healthcare costs. Furthermore, the effects of medication adherence interventions are disappointing, and tailored interventions have been proposed as an appropriate way to improve medication adherence. To rethink and reconstruct methods of improving medication adherence for CVD, the literature on tailored interventions for medication adherence focusing on CVD within the last 5 years is retrieved and reviewed. Focusing on identifying nonadherent patients, detecting barriers to medication adherence, delivering clinical interventions, and constructing theories, this article reviews the present state of tailored interventions for medication adherence in CVD and also rethinks the present difficulties and suggests avenues for future development.

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