Cardiac hypertrophy is considered a necessary compensatory response to sustained elevations of left ventricular (LV) wall stress.
To test this, we inhibited calcineurin with cyclosporine (CsA) in the ...setting of surgically induced pressure overload in mice and examined in vivo parameters of ventricular volume and function using echocardiography. Normalized heart mass increased 45% by 5 weeks after thoracic aortic banding (TAB; heart weight/body weight, 8.3+/-0.9 mg/g mean+/-SEM versus 5. 7+/-0.1 mg/g unbanded, P<0.05). Similar increases were documented in the cell-surface area of isolated LV myocytes. In mice subjected to TAB+CsA treatment, we observed complete inhibition of hypertrophy (heart weight/body weight, 5.2+/-0.3 mg/g at 5 weeks) and myocyte surface area (endocardial and epicardial fractions). The mice tolerated abolition of hypertrophy with no signs of cardiovascular compromise, and 5-week mortality was not different from that of banded mice injected with vehicle (TAB+Veh). Despite abolition of hypertrophy by CsA (LV mass by echo, 83+/-5 mg versus 83+/-2 mg unbanded), chamber size (end-diastolic volume, 33+/-6 microL versus 37+/-1 microL unbanded), and systolic ejection performance (ejection fraction, 97+/-2% versus 97+/-1% unbanded) were normal. LV mass differed significantly in TAB+Veh animals (103+/-5 mg, P<0.05), but chamber volume (end-diastolic volume, 44+/-6 microL), ejection fraction (92+/-2%), and transstenotic pressure gradients (70+/-14 mm Hg in TAB+Veh versus 77+/-11 mm Hg in TAB+CsA) were not different.
In this experimental setting, calcineurin blockade with CsA prevented LV hypertrophy due to pressure overload. TAB mice treated with CsA maintain normal LV size and systolic function.
Background: A “headless” Myo10 that lacks a motor domain has been identified in the nervous system, but its functions are unknown.
Results: Headless Myo10 inhibits axon outgrowth and antagonizes the ...filopodia-inducing activity of full-length Myo10.
Conclusion: Full-length Myo10 is required for axon outgrowth, and headless Myo10 can inhibit full-length Myo10.
Significance: This study establishes opposing roles for headless and full-length Myo10 in axon outgrowth.
Myo10 is an unconventional myosin that localizes to and induces filopodia, structures that are critical for growing axons. In addition to the ∼240-kDa full-length Myo10, brain expresses a ∼165 kDa isoform that lacks a functional motor domain and is known as headless Myo10. We and others have hypothesized that headless Myo10 acts as an endogenous dominant negative of full-length Myo10, but this hypothesis has not been tested, and the function of headless Myo10 remains unknown. We find that cortical neurons express both headless and full-length Myo10 and report the first isoform-specific localization of Myo10 in brain, which shows enrichment of headless Myo10 in regions of proliferating and migrating cells, including the embryonic ventricular zone and the postnatal rostral migratory stream. We also find that headless and full-length Myo10 are expressed in embryonic and neuronal stem cells. To directly test the function of headless and full-length Myo10, we used RNAi specific to each isoform in mouse cortical neuron cultures. Knockdown of full-length Myo10 reduces axon outgrowth, whereas knockdown of headless Myo10 increases axon outgrowth. To test whether headless Myo10 antagonizes full-length Myo10, we coexpressed both isoforms in COS-7 cells, which revealed that headless Myo10 suppresses the filopodia-inducing activity of full-length Myo10. Together, these results demonstrate that headless Myo10 can function as a negative regulator of full-length Myo10 and that the two isoforms of Myo10 have opposing roles in axon outgrowth.
Abstract Introduction Total liquid ventilation (TLV) can cool down the entire body within 10–15 min in small animals. Our goal was to determine whether it could also induce ultra-fast and whole-body ...cooling in large animals using a specifically dedicated liquid ventilator. Cooling efficiency was evaluated under physiological conditions (beating-heart) and during cardiac arrest with automated chest compressions (CC, intra-arrest). Methods In a first set of experiments, beating-heart pigs were randomly submitted to conventional mechanical ventilation or hypothermic TLV with perfluoro-N-octane (between 15 and 32 °C). In a second set of experiments, pigs were submitted to ventricular fibrillation and CC. One group underwent continuous CC with asynchronous conventional ventilation (Control group). The other group was switched to TLV while pursuing CC for the investigation of cooling capacities and potential effects on cardiac massage efficiency. Results Under physiological conditions, TLV significantly decreased the entire body temperatures below 34 °C within only 10 min. As examples, cooling rates averaged 0.54 and 0.94 °C/min in rectum and esophageous, respectively. During cardiac arrest, TLV did not alter CC efficiency and cooled the entire body below 34 °C within 20 min, the low-flow period slowing cooling during CC. Conclusion Using a specifically designed liquid ventilator, TLV induced a very rapid cooling of the entire body in large animals. This was confirmed in both physiological conditions and during cardiac arrest with CC. TLV could be relevant for ultra-rapid cooling independently of body weight.
The newest introduction to echocardiography is a hand-carried ultrasound (HCU) device. It is a small echocardiographic machine that typically weighs less than 6 lb and can obtain echocardiographic ...images and data. However, neither the device nor the context of the examination fulfills the criteria for a comprehensive or complete echocardiographic examination. The American Society of Echocardiography believes that HCU will extend the concept of the "complete physical examination," allowing more rapid assessment of cardiovascular anatomy, function, and physiology. However, appropriate user-specific training (Level 1 at a minimum) and assumption of responsibility are essential to ensure the most accurate acquisition, interpretation, and use of the data.
ABSTRACT
We derive the spatially resolved star formation history (SFH) for a 96 deg2 area across the main body of the Large Magellanic Cloud (LMC), using the near-infrared photometry from the VISTA ...survey of the Magellanic Clouds (VMC). The data and analyses are characterized by a great degree of homogeneity and a low sensitivity to the interstellar extinction. 756 subregions of size 0.125 deg2 – corresponding to projected sizes of about $296\times 322\, \mathrm{pc}^{2}$ in the LMC – are analysed. The resulting SFH maps, with typical resolution of 0.2–0.3 dex in logarithm of age, reveal main features in the LMC disc at different ages: the patchy star formation at recent ages, the concentration of star formation on three spiral arms and on the Bar up to ages of ∼1.6 Gyr, and the wider and smoother distribution of older populations. The period of most intense star formation occurred roughly between 4 and 0.5 Gyr ago, at rates of $\sim \!0.3\, \mbox{$\mathrm{M}_{\odot }$}\mathrm{yr}^{-1}$. We compare young and old star formation rates with the observed numbers of RR Lyrae and Cepheids. We also derive a mean extinction and mean distance for every subregion, and the plane that best describes the spatial distribution of the mean distances. Our results cover an area about 50 per cent larger than the classical SFH maps derived from optical data. Main differences with respect to those maps are lower star formation rates at young ages, and a main peak of star formation being identified at ages slightly younger than 1 Gyr.
The reader is referred to the full-text version of the guidelines posted on the American College of Cardiology (ACC), American Heart Association (AHA), and North American Society for Pacing and ...Electrophysiology (NASPE) World Wide Web sites for a more detailed exposition of the rationale for these changes. ...degree AV block at any anatomic level, associated with any one of the following conditions:a. Bradycardia with symptoms presumed to be due to AV block. ...degree and advanced second-degree AV block at any anatomic level, associated with any one of the following conditions: a. Bradycardia with symptoms (including heart failure) presumed to be due to AV block.
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