Human monocyte heat shock protein 72 responses to acute hypoxic exercise after 3 days of exercise heat acclimation

The aim of this study was to determine whether short-term heat acclimation (STHA) could confer increased cellular tolerance to acute hypoxic exercise in humans as determined via monocyte HSP72 (mHSP72) expression. Sixteen males were separated into two matched groups. The STHA group completed 3 days of exercise heat acclimation; 60 minutes cycling at 50% V˙O2peak in 40°C 20% relative humidity (RH). The control group (CON) completed 3 days of exercise training in 20°C, 40% RH. Each group completed a hypoxic stress test (HST) one week before and 48 hours following the final day of CON or STHA. Percentage changes in HSP72 concentrations were similar between STHA and CON following HST1 (P=0.97). STHA induced an increase in basal HSP72 (P=0.03) with no change observed in CON (P=0.218). Basal mHSP72 remained elevated before HST2 for the STHA group (P0.05). Percent change in mHSP72 was lower after HST2 in STHA compared to CON (P=0.02). The mHSP72 response to hypoxic exercise was attenuated following 3 days of heat acclimation. This is indicative of improved tolerance and ability to cope with the hypoxic insult, potentially mediated in part by increased basal reserves of HSP72

The Caries Phenomenon: A Timeline from Witchcraft and Superstition to Opinions of the 1500s to Today's Science

This historical treatise follows the documented timeline of tooth decay into today's understanding, treatment, and teaching of caries biology. Caries has been attributed to many different causes for several millennia, however, only since the late 1900s has research revealed its complex multifactorial nature. European writers of the 1600s to 1700s held views that general health, mechanical injuries, trauma, and sudden temperature changes all caused caries—holding a common belief that decay was due to chemical agents, faulty saliva, and food particles. Until the early 1800s most writers believed that caries was due to inflammation from surrounding diseased alveolar bone. Today's science has demonstrated that caries is caused by indigenous oral microorganisms becoming a dynamic biofilm, that in the presence of fermentable sugars produce organic acids capable of dissolving inorganic enamel and dentin followed by the proteolytic destruction of collagen leaving soft infected dentin. As bacteria enter the pulp, infection follows

Scaling device for photographic images

A scaling device projects a known optical pattern into the field of view of a camera, which can be employed as a reference scale in a resulting photograph of a remote object, for example. The device comprises an optical beam projector that projects two or more spaced, parallel optical beams onto a surface of a remotely located object to be photographed. The resulting beam spots or lines on the object are spaced from one another by a known, predetermined distance. As a result, the size of other objects or features in the photograph can be determined through comparison of their size to the known distance between the beam spots. Preferably, the device is a small, battery-powered device that can be attached to a camera and employs one or more laser light sources and associated optics to generate the parallel light beams. In a first embodiment of the invention, a single laser light source is employed, but multiple parallel beams are generated thereby through use of beam splitting optics. In another embodiment, multiple individual laser light sources are employed that are mounted in the device parallel to one another to generate the multiple parallel beams

Biophysical implications of lipid bilayer rheometry for mechanosensitive channels

The lipid bilayer plays a crucial role in gating of mechanosensitive (MS) channels. Hence it is imperative to elucidate the rheological properties of lipid membranes. Herein we introduce a framework to characterize the mechanical properties of lipid bilayers by combining micropipette aspiration (MA) with theoretical modeling. Our results reveal that excised liposome patch fluorometry is superior to traditional cell-attached MA for measuring the intrinsic mechanical properties of lipid bilayers. The computational results also indicate that unlike the uniform bilayer tension estimated by Laplace's law, bilayer tension is not uniform across the membrane patch area. Instead, the highest tension is seen at the apex of the patch and the lowest tension is encountered near the pipette wall. More importantly, there is only a negligible difference between the stress profiles of the outer and inner monolayers in the cellattached configuration, whereas a substantial difference (~30%) is observed in the excised configuration. Our results have farreaching consequences for the biophysical studies of MS channels and ion channels in general, using the patch-clamp technique, and begin to unravel the difference in activity seen between MS channels in different experimental paradigms

Disruption of membrane cholesterol organization impairs the activity of PIEZO1 channel clusters

The human mechanosensitive ion channel PIEZO1 is gated by membrane tension and regulates essential biological processes such as vascular development and erythrocyte volume homeostasis. Currently, little is known about PIEZO1 plasma membrane localization and organization. Using a PIEZO1-GFP fusion protein, we investigated whether cholesterol enrichment or depletion by methyl-β-cyclodextrin (MBCD) and disruption of membrane cholesterol organization by dynasore affects PIEZO1-GFP’s response to mechanical force. Electrophysiological recordings in the cell-attached configuration revealed that MBCD caused a rightward shift in the PIEZO1-GFP pressure–response curve, increased channel latency in response to mechanical stimuli, and markedly slowed channel inactivation. The same effects were seen in native PIEZO1 in N2A cells. STORM superresolution imaging revealed that, at the nanoscale, PIEZO1-GFP channels in the membrane associate as clusters sensitive to membrane manipulation. Both cluster distribution and diffusion rates were affected by treatment with MBCD (5 mM). Supplementation of polyunsaturated fatty acids appeared to sensitize the PIEZO1-GFP response to applied pressure. Together, our results indicate that PIEZO1 function is directly dependent on the membrane composition and lateral organization of membrane cholesterol domains, which coordinate the activity of clustered PIEZO1 channels

The nature of the infrared counterpart of IGR J19140+0951

The INTEGRAL observatory has been (re-)discovering new X-ray sources since the beginning of nominal operations in early 2003. These sources include X-ray binaries, Active Galactic Nuclei, cataclysmic variables, etc. Amongst the X-ray binaries, the true nature of many of these sources has remained largely elusive, though they seem to make up a population of highly absorbed high-mass X-ray binaries. One of these new sources, IGR J19140+0951, was serendipitously discovered on 2003 Mar 6 during an observation of the galactic microquasar GRS 1915+105. We observed IGR J19140+0951 with UKIRT in order to identify the infrared counterpart. Here we present the H- and K-band spectra. We determined that the companion is a B0.5-type bright supergiant in a wind-fed system, at a distance \la 5 kpc.Comment: 5 pages, 2 figures, accepted for publication in MNRA

Piezo1 Forms Specific, Functionally Important Interactions with Phosphoinositides and Cholesterol

Touch, hearing, and blood pressure regulation require mechanically gated ion channels that convert mechanical stimuli into electrical currents. One such channel is Piezo1, which plays a key role in the transduction of mechanical stimuli in humans and is implicated in diseases, such as xerocytosis and lymphatic dysplasia. There is building evidence that suggests Piezo1 can be regulated by the membrane environment, with the activity of the channel determined by the local concentration of lipids, such as cholesterol and phosphoinositides. To better understand the interaction of Piezo1 with its environment, we conduct simulations of the protein in a complex mammalian bilayer containing more than 60 different lipid types together with electrophysiology and mutagenesis experiments. We find that the protein alters its local membrane composition, enriching specific lipids and forming essential binding sites for phosphoinositides and cholesterol that are functionally relevant and often related to Piezo1-mediated pathologies. We also identify a number of key structural connections between the propeller and pore domains located close to lipid-binding sites

Delayed evaluation of combat-related penetrating neck trauma

ObjectiveThe approach to penetrating trauma of the head and neck has undergone significant evolution and offers unique challenges during wartime. Military munitions produce complex injury patterns that challenge conventional diagnosis and management. Mass casualties may not allow for routine exploration of all stable cervical blast injuries. The objective of this study was to review the delayed evaluation of combat-related penetrating neck trauma in patients after evacuation to the United States.MethodFrom February 2003 through April 2005, a series of patients with military-associated penetrating cervical trauma were evacuated to a single institution, prospectively entered into a database, and retrospectively reviewed.ResultsSuspected vascular injury from penetrating neck trauma occurred in 63 patients. Injuries were to zone II in 33%, zone III in 33%, and zone I in 11%. The remaining injuries involved multiple zones, including the lower face or posterior neck. Explosive devices wounded 50 patients (79%), 13 (21%) had high-velocity gunshot wounds, and 19 (30%) had associated intracranial or cervical spine injury. Of the 39 patients (62%) who underwent emergent neck exploration in Iraq or Afghanistan, 21 had 24 injuries requiring ligation (18), vein interposition or primary repair (4), polytetrafluoroethylene (PTFE) graft interposition (1), or patch angioplasty (1). Injuries occurred to the carotid, vertebral, or innominate arteries, or the jugular vein. After evacuation to the United States, all patients underwent radiologic evaluation of the head and neck vasculature. Computed tomography angiography was performed in 45 patients (71%), including six zone II injuries without prior exploration. Forty (63%) underwent diagnostic arteriography that detected pseudoaneurysms (5) or occlusions (8) of the carotid and vertebral arteries. No occult venous injuries were noted. Delayed evaluation resulted in the detection of 12 additional occult injuries and one graft thrombosis in 11 patients. Management included observation (5), vein or PTFE graft repair (3), coil embolization (2), or ligation (1).ConclusionsPenetrating multiple fragment injury to the head and neck is common during wartime. Computed tomography angiography is useful in the delayed evaluation of stable patients, but retained fragments produce suboptimal imaging in the zone of injury. Arteriography remains the imaging study of choice to evaluate for cervical vascular trauma, and its use should be liberalized for combat injuries. Stable injuries may not require immediate neck exploration; however, the high prevalence of occult injuries discovered in this review underscores the need for a complete re-evaluation upon return to the United States

The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels

The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. MscL represents an excellent model system to study the basic biophysical principles of mechanosensory transduction. However, understanding of the essential structural components that transduce bilayer tension into channel gating remains incomplete. Here using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may also represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics