Download or read book HIV 1 Quasispecies Heterogeneity Mediates Tat Function Molecular Epistasis and Neuropathogenesis written by Cassandra Spector and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over 38 million people worldwide continue to live with human immunodeficiency virus type 1 (HIV-1). HIV-1 remains a major public health concern due to chronic infection that cannot be cured by conventional antiretroviral therapies (ART). Infected cells continue to produce and secrete viral proteins, including the transactivator of transcription (Tat), even in viral load suppressed individuals. This predisposes people with HIV (PWH) to increased risk for developing HIV-1-associated comorbidities, such as HIV-1-associated neurocognitive disorder (HAND). The HIV-1 genome is susceptible to genetic diversification due to the error prone viral reverse transcriptase, as well as from adaptation in response to host restriction factors and immune selection pressures. This results in the formation of unique viral quasispecies (vQS) populations in individuals. Genetic variation within vQS may manifest in Tat as functional amino acid (AA) mutations. Tat's canonical function is to bind host factors and the HIV-1 transcription response element (TAR) RNA to enhance viral transcription efficiency, but also participates in pathogenic activities that contribute to overall HIV-1 pathogenesis and comorbidities. Previous studies have sought to characterize functional genetic variation between both Tat exons, which are separated by about 3 kilobases in the HIV-1 genome. However, prior sequencing technologies could not associate observed variants within and between exons from the same molecule of DNA. Therefore, the Pacific Biosciences (PacBio) Sequel platform was utilized to obtain long read sequences encompassing both Tat exons. PBMC gDNA from therapy-controlled participants of the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort was used to isolate tat-containing 4 kilobase amplicons to be sequenced. This sequencing dataset allowed for studies on viral diversity, co-occurring AAs, and functional conservation in Tat. Though deviations from expected occurrence composed a small proportion of observed co-variants, these presented potential variants of interest for future studies. AA functional sequence analyses displayed two patterns of conserved activity split across annotated Tat functions and demonstrated heterogeneity of Tat functional ability between vQS populations. Sequencing data from this study was applied to questions involving Tat's interactions with other viral proteins and its role in neuropathogenesis. Given the observed genetic diversity within tat, further studies investigated selection pressure between tat and rev, another HIV-1 gene that encodes a transcriptional regulatory protein and shares an overlapping reading frame with tat. Selection pressures observed on each overlapping gene segment as well as on individual overlapping codons supported the presence of segregated functional domain organization between the two genes. AA sequence logos of each gene further suggested adaptation of AAs that overlapped with functionally essential AAs in the opposite protein. To address the contribution of Tat AA variation to occurrence of HAND, Tat vQS sequences were associated with paired neuropsychological assessment test data administered to CARES Cohort participants. Neurocognitive phenotypes emerged that were led by dominant deficits in neurocognitive domains. Vectorization and dimensional reduction of Tat sample-specific sequences overlayed with domain deficit scores showed that sequence similarity between participants also associated with neurocognitive impairment in certain domains. Overall, these studies have led to advances in understanding Tat vQS composition and protein function in PWH. The data and results were applied to address questions on pathogenic mechanisms and the development of HIV-1 comorbidities involving Tat.
Download or read book Late Life Depression written by Steven P. Roose and published by Oxford University Press. This book was released on 2004-07-15 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: We live in an aging world. Illnesses that are prevalent and cause significant morbidity and mortality in older people will consume an increasing share of health care resources. One such illness is depression. This illness has a particularly devastating impact in the elderly because it is often undiagnosed or inadequately treated. Depression not only has a profound impact on quality of life but it is associated with an increased risk of mortality from suicide and vascular disease. In fact for every medical illness studied, e.g. heart disease, diabetes, cancer, individuals who are depressed have a worse prognosis. Research has illuminated the physiological and behavioral effects of depression that accounts for these poor outcomes. The deleterious relationship between depression and other illnesses has changed the concept of late-life depression from a "psychiatric disorder" that is diagnosed and treated by a psychiatrist to a common and serious disorder that is the responsibility of all physicians who care for patients over the age of 60.This is the first volume devoted to the epidemiology, phenomenology, psychobiology, treatment and consequences of late-life depression. Although much has been written about depressive disorders, the focus has been primarily on the illness as experienced in younger adults. The effects of aging on the brain, the physiological and behavioral consequences of recurrent depression, and the impact of other diseases common in the elderly, make late-life depression a distinct entity. There is a compelling need for a separate research program, specialized treatments, and a book dedicated to this disorder. This book will be invaluable to psychiatrists, gerontologists, clinical psychologists, social workers, students, trainees, and others who care for individuals over the age of sixty.
Download or read book Brain Tumor Imaging written by Elke Hattingen and published by Springer. This book was released on 2015-09-02 with total page 166 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes the basics, the challenges and the limitations of state of the art brain tumor imaging and examines in detail its impact on diagnosis and treatment monitoring. It opens with an introduction to the clinically relevant physical principles of brain imaging. Since MR methodology plays a crucial role in brain imaging, the fundamental aspects of MR spectroscopy, MR perfusion and diffusion-weighted MR methods are described, focusing on the specific demands of brain tumor imaging. The potential and the limits of new imaging methodology are carefully addressed and compared to conventional MR imaging. In the main part of the book, the most important imaging criteria for the differential diagnosis of solid and necrotic brain tumors are delineated and illustrated in examples. A closing section is devoted to the use of MR methods for the monitoring of brain tumor therapy. The book is intended for radiologists, neurologists, neurosurgeons, oncologists and other scientists in the biomedical field with an interest in neuro-oncology.
Download or read book Tissue Engineered Vascular Grafts written by Beat H. Walpoth and published by Springer. This book was released on 2020-08-21 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiovascular diseases are still the leading cause of death in developed countries. Revascularization procedures such as coronary artery and peripheral bypass grafts, as well as access surgery represent a 2$ billion market yearly for the US alone. Despite intense research over many decades, no clinically suitable, shelf-ready, synthetic, vascular, small-caliber graft exists. There is therefore still a quest for such a clinical vascular prosthesis for surgical revascularization procedures and access surgery. Many approaches have been tried and are currently under investigation with promising results. These range from acellular and cell-based, stable or bio-degradable, synthetic scaffolds to biological or decellularized grafts, not forgetting self-assembly technologies for in vitro or in vivo VTE. All these approaches can be further enhanced by functionalization, e.g. with growth factors and drug elution. This updatable book aims to cover all the relevant aspects of Vascular Tissue Engineering (VTE) and novel alternatives to develop vascular grafts for clinical applications. The chapters in this book cover different aspects of manufacturing scaffolds with various polymers, mechanical characteristics, degradation rates, decellularization techniques, cell sheet assembly, 3-D printing and autologous mandril-based VTE. All the necessary in vitro tests such as biocompatibility and thrombogenicity are reviewed. Pre-clinical assessment of in vivo experimental models include patency, compliance, intimal hyperplasia, inflammatory reaction, cellular ingrowth and remodeling. Finally, early clinical trials will be periodically updated regarding results, regulatory aspects and post-marketing quality assessment. Furthermore, the reader should get an insight into various approaches, technologies and methods to better understand the complexity of blood surface and cell interactions in VTE. Translational research has yielded early human applications clearly showing the enormous need of research in the field to provide better solutions for our patients and this continuously updated book will hopefully become a reference in the field for life sciences.
Download or read book To Improve Health and Health Care written by and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Functional Neuroanatomy written by N. J. Strausfeld and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 445 pages. Available in PDF, EPUB and Kindle. Book excerpt: The "functional" in the title of this book not only reflects my personal bias about neuroanatomy in brain research, it is also the gist of many chapters which describe sophisticated ways to resolve structures and interpret them as dynamic entities. Examples are: the visualization of functionally identified brain areas or neurons by activity staining or intracellular dye-iontophoresis; the resolution of synaptic connections between physiologically identified nerve cells; and the biochemical identification of specific neurons (their peptides and transmitters) by histo- and immunocytochemistry. I personally view the nervous system as an organ whose parts, continuously exchanging messages, arrive at their decisions by the cooperative phenome non of consensus and debate. This view is, admittedly, based on my own ex perience of looking at myriads of nerve cells and their connections rather than studying animal behaviour or theorizing. Numerous structural studies have demonstrated that interneurons in the brain must receive hundreds of thousands of synapses. Many neurons receive inputs from several different sensory areas: each input conveys a message about the external world and possibly also about past events which are stored within the central nervous system. Whether an interneuron responds to a certain combination of inputs may be, literally, a matter of debate whose outcome is decided at the post synaptic membrane. A nerve cell responding to an overriding command is possibly a rare event.
