Explore the vast range of titles available.

The Piezo1 calcium-permeable channel is revealed to have a role in the vascular cellular response to shear stress; a mouse knockout reveals that this channel is also important for normal vascular development. Feeling blood flow The calcium-permeable ion channel Piezo1 is known to be a sensor for noxious mechanical stimuli. Here David Beech and colleagues identify the channel as an important component in the vascular response to the frictional force or shear stress experienced by the walls of the blood vessel as the blood passes through. They show that Piezo1 channels act as blood flow sensors, important for the alignment of endothelial cells in response to flow. The lack of Piezo1 specifically in endothelial cells leads to abnormal vascular development. These findings have implications for understanding vascular physiology and how it is affected by disease processes such as atherosclerosis and cancer, in which alterations in shear stress and other mechanical forces are common. The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic 1 , 2 , 3 , 4 , 5 . Studies of sensory neurons have suggested Piezo proteins as subunits of Ca 2+ -permeable non-selective cationic channels for detection of noxious mechanical impact 6 , 7 , 8 . Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology.

This essay explains William James’s conception of happiness. While much has been written about James's conception of emotions, surprisingly little has been written about his conception of happiness. The few scholars who have addressed James’s conception of happiness have either failed to provide sufficient context or have taken too narrow a view of the matter. This essay combines a close reading of The Varieties of Religious Experience (1902) with examples from James's personal life to demonstrate how James developed a functionalist conception of happiness. James believed that unhappiness motivates the individual to adopt new mental habits and transform themselves until they can regain their happiness. This framework permits a considerable degree of flexibility, plurality, and experimentation. Although James believed that some strategies worked better than others, he was open to the possibility that individuals could attain happiness by many means.

Presentation of Case A 15-year-old right-handed girl was admitted to the hospital because of neutropenia and fever. A heart murmer was heard in early childhood and was ascribed to pulmonic stenosis. She was otherwise well until 4 1/2 years before entry, when a diagnosis of acute lymphoblastic leukemia without B-cell or T-cell markers was made. The administration of vincristine and prednisone was followed by a complete remission, but a single injection of L-asparaginase provoked an allergic reaction. Radiation in a dose of 2400 rad was given to the cranium, and six intrathecal doses of methotrexate were administered; cytologic examination of . . .

Presentation of Case First admission . An 11-year-old boy was admitted to the hospital because of a mediastinal mass. He was well until six weeks earlier, when a nasal voice and cervical lymphadenopathy were observed. One week before admission the cervical lymphadenopathy increased, and a dry cough developed, with intermittent wheezing and dyspnea. An x-ray film of the chest showed a mediastinal mass and a pleural effusion. The temperature was 36.9°C, the pulse 84, and the respirations 22. The blood pressure was 110/80 mm Hg. On examination he appeared well except for marked respiratory stridor in the supine position. Firm, . . .

Provocative results from the Viking landers on Mars (particularly the biology experiment) have stimulated considerable research. Although it does not seem likely that life presently exists, the early history of the planet is uncertain. Future activities may include roving vehicles on the surface and samples returned to Earth.

Army pediatricians in Iraq provide primary care and emergency stabilization to soldiers. The practice of military pediatrics necessitates additional training in psychiatric disorders and office gynecology including treatment of sexually transmitted diseases. The military pediatrician must be willing to care for the disorders of the older reservist, who currently account for 40% of US forces in Iraq.