miR-125b Promotes Early Germ Layer Specification through Lin28/let-7d and Preferential Differentiation of Mesoderm in Human Embryonic Stem Cells

Unlike other essential organs, the heart does not undergo tissue repair following injury. Human embryonic stem cells (hESCs) grow indefinitely in culture while maintaining the ability to differentiate into many tissues of the body. As such, they provide a unique opportunity to explore the mechanisms that control human tissue development, as well as treat diseases characterized by tissue loss, including heart failure. MicroRNAs are small, non-coding RNAs that are known to play critical roles in the regulation of gene expression. We profiled the expression of microRNAs during hESC differentiation into myocardial precursors and cardiomyocytes (CMs), and determined clusters of human microRNAs that are specifically regulated during this process. We determined that miR-125b overexpression results in upregulation of the early cardiac transcription factors, GATA4 and Nkx2-5, and accelerated progression of hESC-derived myocardial precursors to an embryonic CM phenotype. We used an in silico approach to identify Lin28 as a target of miR-125b, and validated this interaction using miR-125b knockdown. Anti-miR-125b inhibitor experiments also showed that miR-125b controls the expression of miRNA let-7d, likely through the negative regulatory effects of Lin28 on let-7. We then determined that miR-125b overexpression inhibits the expression of Nanog and Oct4 and promotes the onset of Brachyury expression, suggesting that miR-125b controls the early events of human CM differentiation by inhibiting hESC pluripotency and promoting mesodermal differentiation. These studies identified miR-125b as an important regulator of hESC differentiation in general, and the development of hESC-derived mesoderm and cardiac muscle in particular. Manipulation of miR-125b-mediated pathways may provide a novel approach to directing the differentiation of hESC-derived CMs for cell therapy applications

Heavy and light roles: myosin in the morphogenesis of the heart

Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin lightchain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed

Recurrent Respiratory Papillomatosis

Recurrent respiratory papillomatosis (RRP) is an acquired condition resulting in the growth of exophytic, wart-like lesions anywhere in the upper aerodigestive tract. This chapter will solely focus on papillomatosis affecting the larynx, the most affected site. While RRP is a benign condition, its recurrent nature makes it a source of morbidity due to the frequent need for surgical debulking and rare potential for airway obstruction or malignant transformation. Management has evolved significantly over the last 50 years, and understanding the evidence basis for diagnostic and treatment approaches is critically important

Visual mental rotation of possible and impossible objects

Participants were tested on two visual mental rotation tasks using three-dimensional “possible? and “impossible? shapes. Both types of stimuli can be easily encoded by their parts and how they are spatially organized. However, while possible shapes can also be easily encoded as a global image, it is more difficult to encode impossible shapes in such a way. Participants visually rotated both types of stimuli at comparable rates, reflecting that local representations were used in the process of visual mental rotation

Evidence-Based Laryngology

This text provides a critical look at the state of the evidence in the most compelling areas of laryngology. Rather than being a comprehensive text covering every single possible area, it focuses on published works in the 9 areas that are of the most interest to laryngologists as well as speech pathologists, general otolaryngologists, and head and neck oncologists managing laryngologic issues. The state of the literature is succinctly summarized and tabulated in each area, allowing the reader to see which areas have high-grade evidence (Levels 1 or 2) to support decision making, and which areas are in need of better quality studies. Each chapter is divided into three main sections: Diagnosis and Pathophysiology, Surgical management, and Non-surgical management. This makes it easier for the reader to browse to the area of interest in each section and to find the evidence basis for a given concept. Evidence-Based Laryngology will be an invaluable resource to otolaryngologists, residents, speech-language pathologists, and other clinicians who manage laryngological problems and would like to know the evidence basis behind different treatment options

Noise-Induced Tuning Curve Changes in Mechanoreceptors

) . J. Physiol. (Lond.) 244: 58P -- 59P, 1975. Conclusions JOHANSSON, R. S., LANDSTROM, U., AND LUNDSTROM, R. Responses of mechanoreceptive afferent units in the glabrous skin of the human hand The changes in tuning curves with noise modulation re- to sinusoidal skin displacements. Brain Res. 244: 17 -- 25, 1982. ported here have strong implications regarding models of JOHNSON, K. O. Reconstruction of population response to a vibratory stimulus in quickly adapting mechanoreceptive afferent fiber population in- sensory perception. Contemporary models of sensory per- nervating glabrous skin of the monkey. J. Neurophysiol. 37: 48 -- 72, ception assume that the tuning properties of receptors deter- 1974. mined in the absence of noise are preserved during everyday LAMOTTE,R.H.AND MOUNTCASTLE, V. B. Capacities of humans and mon- tasks. Our results show that this cannot be true. Therefore keys to discriminate between vibratory stimuli of different frequency somatic information tra..