340 research outputs found
New imaging techniques project the cellular and molecular alterations underlying bicuspid aortic valve development
No full textBicuspid aortic valve (BAV) disease is the most common congenital cardiac malformation associated with an increased lifetime risk and a high rate of surgically-relevant valve deterioration and aortic dilatation. Genomic data revealed that different genes are associated with BAV. A dominant genetic factor for the recent past was the basis to the recommendation for a more extensive aortic intervention. However very recent evidence that hemodynamic stressors and alterations of wall shear stress play an important role independent from the genetic trait led to more conservative treatment recommendations. Therefore, there is a current need to improve the ability to risk stratify BAV patients in order to obtain an early detection of valvulopathy and aortopathy while also to predict valve dysfunction and/or aortic disease development. Imaging studies based on new cutting-edge technologies, such us 4-dimensional (4D) flow magnetic resonance imaging (MRI), two-dimensional (2D) or three-dimensional (3D) speckle-tracking imaging (STI) and computation fluid dynamics, combined with studies demonstrating new gene mutations, specific signal pathways alterations, hemodynamic influences, circulating biomarkers modifications, endothelial progenitor cell impairment and immune/inflammatory response, all detected BAV valvulopathy progression and aortic wall abnormality. Overall, the main purpose of this review article is to merge the evidences of imaging and basic science studies in a coherent hypothesis that underlies and thus projects the development of both BAV during embryogenesis and BAV-associated aortopathy and its complications in the adult life, with the final goal to identifying aneurysm formation/rupture susceptibility to improve diagnosis and management of patients with BAV-related aortopathy
Molecular basis of functional myogenic specification of Bona Fide multipotent adult cardiac stem cells
No full textIschemic Heart Disease (IHD) remains the developed world's number one killer. The improved survival from Acute Myocardial Infarction (AMI) and the progressive aging of western population brought to an increased incidence of chronic Heart Failure (HF), which assumed epidemic proportions nowadays. Except for heart transplantation, all treatments for HF should be considered palliative because none of the current therapies can reverse myocardial degeneration responsible for HF syndrome. To stop the HF epidemic will ultimately require protocols to reduce the progressive cardiomyocyte (CM) loss and to foster their regeneration. It is now generally accepted that mammalian CMs renew throughout life. However, this endogenous regenerative reservoir is insufficient to repair the extensive damage produced by AMI/IHD while the source and degree of CM turnover remains strongly disputed. Independent groups have convincingly shown that the adult myocardium harbors bona-fide tissue specific cardiac stem cells (CSCs). Unfortunately, recent reports have challenged the identity and the endogenous myogenic capacity of the c-kit expressing CSCs. This has hampered progress and unless this conflict is settled, clinical tests of repair/regenerative protocols are unlikely to provide convincing answers about their clinical potential. Here we review recent data that have eventually clarified the specific phenotypic identity of true multipotent CSCs. These cells when coaxed by embryonic cardiac morphogens undergo a precisely orchestrated myogenic commitment process robustly generating bona-fide functional cardiomyocytes. These data should set the path for the revival of further investigation untangling the regenerative biology of adult CSCs to harness their potential for HF prevention and treatment
Combining cell and gene therapy to advance cardiac regeneration
No full textThe characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial. The in vivo test of somatic reprogramming and cardioregenerative non-coding RNAs revived the interest in gene therapy for myocardial regeneration. The latter, together with the advent of genome editing, has prompted most recent efforts to produce genetically-modified allogeneic CSCs that secrete cardioregenerative factors to optimize effective myocardial repair. Expert opinion: The current war against heart failure epidemics in western countries seeks to find effective treatments to set back the failing hearts prolonging human lifespan. Off-the-shelf allogeneic-genetically-modified CSCs producing regenerative agents are a novel and evolving therapy set to be affordable, safe, effective and available at all times for myocardial regeneration to either prevent or treat heart failure
The use and abuse of Cre/Lox recombination to identify adult cardiomyocyte renewal rate and origin
No full textThe adult mammalian heart, including the human, is unable to regenerate segmental losses after myocardial infarction. This evidence has been widely and repeatedly used up-to-today to suggest that the myocardium, contrary to most adult tissues, lacks an endogenous stem cell population or more specifically a bona-fide cardiomyocyte-generating progenitor cell of biological significance. In the last 15 years, however, the field has slowly evolved from the dogma that no new cardiomyocytes were produced from shortly after birth to the present consensus that new cardiomyocytes are formed throughout lifespan. This endogenous regenerative potential increases after various forms of injury. Nevertheless, the degree/significance and more importantly the origin of adult new cardiomyocytes remains strongly disputed. Evidence from independent laboratories has shown that the adult myocardium harbours bona-fide tissue-specific cardiac stem cells (CSCs). Their transplantation and in situ activation have demonstrated the CSCs regenerative potential and have been used to develop regeneration protocols which in pre-clinical tests have shown to be effective in the prevention and treatment of heart failure. Recent reports purportedly tracking the c-kit+CSC's fate using Cre/lox recombination in the mouse have challenged the existence and regenerative potential of the CSCs and have raised scepticism about their role in myocardial homeostasis and regeneration. The validity of these reports, however, is controversial because they failed to show that the experimental approach used is capable to both identify and tract the fate of the CSCs. Despite these serious shortcomings, in contraposition to the CSCs, these publications have proposed the proliferation of existing adult fully-matured cardiomyocytes as the relevant mechanism to explain cardiomyocyte renewal in the adult. This review critically ponders the available evidence showing that the adult mammalian heart possesses a definable myocyte-generating progenitor cell of biological significance. This endogenous regenerative potential is expected to provide the bases for novel approaches of myocardial repair in the near future
If You Give an Author an Invitation…..Creative Tips for the Most Memorable Author Visit from Invitation to Thank You
No full textAuthor visits allow a child to make a real connection with writers and illustrators and build memories that last a lifetime. This presentation offers creative ideas and suggestions to help make the author visit experience an event worth celebrating
How to Host an Author Visit: Crafting an Unforgettable Experience for Your Students
No full textAuthor visits have amazing benefits for students, helping to motivate and inspire them. If you’ve never hosted an author before, however, it can be hard to know where to start! This presentation will cover why author visits can be a life-changing experience for your students, how to find authors to visit your school, and how to plan for the visit. The presentation will also include some ideas on how to fund author visits
Publishing Behind-The-Scenes: An Author and Her Literary Agent Talk Publishing
No full textMayonn Paasewe-Valchev is the author of a charming fantasy novel for middle grade readers and her literary agent is Sara Megibow of KT Literary. In a fiercely competitive industry, how did these two connect with HarperCollins for such a wildly successful book launch? Go behind the scenes in publishing to learn about what a literary agent does, what the author had to do to sign with that agent and how the manuscript went from laptop to bookshelf
Aquila and Predator: The Failure and Momentum of Drone Technologies in the U.S., 1970-2015
No full textThis article examines the technological and intellectual histories of unmanned aircraft systems (UAS) development in the U.S. from the 1970s until 2015. Borrowing from the field of science and technology studies, the author argues that although early drone development demonstrated a significant degree of heterogeneity (i.e., interpretive flexibility), the spectacular failure in 1987 of one program in particular—the Aquila Remotely Piloted Vehicle—thereafter contributed to a significant restricting of UAS potentialities. Aquila’s demise prompted a Congressional directive in 1988 to consolidate the disparate UAS development efforts within the U.S. Department of Defense (DoD) under one joint program, ushering in a means by which a singular exemplar artifact, the Predator, could emerge and stabilize as the prevailing UAS technological frame for the following three decades. This article further suggests the possibility that the restricting of UAS potentialities to Predator-like form had the deterministic effect of scripting U.S. policy in its war in Afghanistan, ultimately reducing the latter to a dubious campaign of strategically ineffectual “targeted killings”. If true, this claim establishes an indirect causal link between an obscure technology failure in the 1970-80s with a national strategic failure in the 2010-20s. By centering the Aquila as the subject of the article, the author intends to unbury an understudied attempt by the DoD to develop a drone type that differed drastically from Predator
The Value of Local Authors: A Survey of the Mission Statements and Submission Guidelines of Local Author Collections
No full textThis research examines the mission statements and submission guidelines of local author collections in public libraries to determine in what ways these collections emphasize the communities they represent, the extent to which all members of the community are represented by the collection, and how these collections are accessed by the community
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