Author: Taylor L Rudisill Publisher: ISBN: Category : Languages : en Pages : 87
Book Description
Emerging evidence suggests that altered neural connectivity, particularly at the level of synaptic connections, contributes to the pathology of many neurodevelopmental and neurodegenerative diseases. For instance, post-mortem Autistic patient brain samples have increased numbers of excitatory to inhibitory synaptic connections, referred to as an E/I imbalance [42]. Contrastingly, post-mortem brain samples from patients diagnosed with Alzheimer's disease have decreased numbers of synaptic connections [42]. In order to understand the mechanisms that underlie the formation of these synaptic circuits, we develop 3-D human cortical organoids ('mini-brains') from human-induced pluripotent stem cells (hIPSCs). Previous research demonstrates that rearrangements of the actomyosin cytoskeleton drive neural circuit formation, in particular the development and maturation of actin-enriched spines at excitatory synapses. This thesis work investigates how pharmacological regulation of actomyosin activity affects neuronal connectivity during neurite formation in 2-D and excitatory synapse formation in 3-D 'mini-brains'. The Rho-Kinase (ROCK) inhibitor, Y-27632, both inhibits non-muscle myosin II (NM-II) and leads to a corresponding increase in Rac-driven actin polymerization. In 2-D, Y-27632 promotes neurite formation. Specifically, Y-27632 increases the number, length, and branching of neurites in hIPSC-derived neurons. Furthermore, Y-27632 increases neurite persistence, while decreasing neurite protrusion and retraction rates. However, in 3-D, acute Y-27632 treatment increases excitatory synapse area, consistent with an increase in Rac-driven actin polymerization [39]. Thus, Y-27632 increases both neurite outgrowth and excitatory synapse formation and may serve as a potential therapeutic for neurodegenerative diseases associated with synapse loss such as Alzheimer's disease. This study demonstrates the need for physiologically-relevant brain models, such as 3-D cortical organoids, to assess the impact of drug therapies on developing neural circuits to potentially treat neurodevelopmental and neurodegenerative disorders.
Author: Philip H. Schwartz Publisher: Humana Press ISBN: 9781617792007 Category : Science Languages : en Pages : 468
Book Description
Almost daily, new technologies are being presented that move the field of human pluripotent stem cell research towards a future that may yield highly-effective, personalized medical treatments. Three enabling technologies at hand for human PSCs are 1) directed reprogramming of somatic cells, which eliminate many of the ethical issues associated with the derivation and use of human PSCs, increase genetic diversity of the available human PSC lines, and give rise to better in vitro human disease models; 2) the discovery that a Rho-associated protein Kinase (ROCK) inhibitor allows for efficient single cell passaging and cryopreservation, increasing the efficiency and reliability of hPSC culture; and 3) defined, animal-component-free media, which lay the groundwork for simplified scale-up for therapeutic applications, differentiation protocols, and toxicology screens. The aforementioned technologies can be found in Human Pluripotent Stem Cells: Methods and Protocols, a compilation of 33 detailed protocols in six categories of PSC research that cover laboratory essentials and the derivation of new PSC lines, including induced PSC lines, as well as their growth, maintenance, characterization, genetic manipulation, and differentiation. Written in the successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Human Pluripotent Stem Cells: Methods and Protocols serves as an ideal guide to scientists conducting their own pluripotent cell research programs and makes great strides towards furthering human knowledge and, ultimately, improving the human condition.
Author: George Comninel Publisher: Routledge ISBN: 1317487966 Category : Political Science Languages : en Pages : 311
Book Description
The International Workingmen’s Association was the prototype of all organizations of the Labour movement and the 150th anniversary of its birth (1864-2014) offers an important opportunity to rediscover its history and learn from its legacy. The International helped workers to grasp that the emancipation of labour could not be won in a single country but was a global objective. It also spread an awareness in their ranks that they had to achieve the goal themselves, through their own capacity for organization, rather than by delegating it to some other force; and that it was essential to overcome the capitalist system itself, since improvements within it, though necessary to pursue, would not eliminate exploitation and social injustice. This book reconsider the main issues broached or advanced by the International – such as labor rights, critiques of capitalism and the search for international solidarity – in light of present-day concerns. With the recent crisis of capitalism, that has sharpened more than before the division between capital and labour, the political legacy of the organization founded in London in 1864 has regained profound relevance, and its lessons are today more timely than ever. This book was published as a special issue of Socialism and Democracy.
Author: Leonora Buzanska Publisher: Springer ISBN: 3319934856 Category : Science Languages : en Pages : 334
Book Description
This book summarizes early pioneering achievements in the field of human neural stem cell (hNSC) research and combines them with the latest advances in stem cell technology, including reprogramming and gene editing. The powerful potential of hNSC to generate and repair the developing and adult CNS has been confirmed by numerous experimental in vitro and in vivo studies. The book presents methods for hNSC derivation and discusses the mechanisms underlying NSC in vitro fate decisions and their in vivo therapeutic mode of action. The long-standing dogma that the human central nervous system (CNS) lacks the ability to regenerate was refuted at the end of the 20th century, when evidence of the presence of neurogenic zones in the adult human brain was found. These neurogenic zones are home to human neural stem cells (hNSCs), which are capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. NSCs isolated from human CNS have a number of clinical advantages, especially the innate potential to differentiate into functional neural cells. Nevertheless, their full clinical exploitation has been hindered by limited access to the tissue and low expansion potential. The search for an alternative to CNS sources of autologous, therapeutically competent hNSCs was the driving force for the many studies proving the in vitro plasticity of different somatic stem cells to generate NSCs and their functional progeny. Now the era of induced pluripotent stem cells has opened entirely new opportunities to achieve research and therapeutic goals with the aid of hNSCs.
Author: Hans-Peter Landolt Publisher: Springer Nature ISBN: 3030112721 Category : Medical Languages : en Pages : 481
Book Description
This volume connects current ideas and concepts about sleep functions and circadian rhythms with the search for novel target-selective sleep-wake therapeutics. To do so, it provides a timely, state-of-the-art overview of sleep-wake mechanisms in health and disease, ongoing developments in drug discovery, and their prospects for the clinical treatment of sleep-disordered patients. It particularly focuses on the concept that sleep and wakefulness mutually affect each other, and the future therapeutic interventions with either sleep- or wake-promoting agents that are expected to not only improve the quality of sleep but also the waking behavior, cognition, mood and other sleep-associated physiological functions. The chapter 'Sleep Physiology, Circadian Rhythms, Waking Performance and the Development of Sleep-Wake Therapeutics' available open access under a CC BY 4.0 license at link.springer.com
Author: Jeffrey Noebels Publisher: OUP USA ISBN: 0199746540 Category : Medical Languages : en Pages : 1258
Book Description
Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.
Author: Rita Sattler Publisher: Springer ISBN: 331989689X Category : Medical Languages : en Pages : 321
Book Description
It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre--‐mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--‐ coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi--‐directional transcription and production of repeat associated non--‐ATG (RAN) translation products. This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer’s disease, Huntington’s disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters will therefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways.
Author: Giuseppe Perale Publisher: Woodhead Publishing ISBN: 0081028083 Category : Technology & Engineering Languages : en Pages : 348
Book Description
Spinal Cord Injury (SCI) Repair Strategies provides researchers the latest information on potential regenerative approaches to spinal cord injury, specifically focusing on therapeutic approaches that target regeneration, including cell therapies, controlled drug delivery systems, and biomaterials. Dr. Giuseppe Perale and Dr. Filippo Rossi lead a team of authoritative authors in academia and industry in this innovative reference on the field of regenerative medicine and tissue engineering. This book presents all the information readers need to understand the current and potential array of techniques, materials, applications and their benefits for spinal cord repair. - Covers current and future repair strategies for spinal cord injury repair - Focuses on key research trends, clinics, biology and engineering - Provides fundamentals on regenerative engineering and tissue engineering
Author: Taylor L Rudisill
Author: Philip H. Schwartz
Author: George Comninel
Author: Leonora Buzanska
Author: Lauri Saxén
Author: Hans-Peter Landolt
Author: Jeffrey Noebels
Author: Rita Sattler
Author: John W. Barnhill
Author: Giuseppe Perale