Does geographic variation in thermal tolerance in Daphnia represent trade-offs or conditional neutrality?

Geographic variation in thermal tolerance in Daphnia seems to represent genetic load at the loci specifically responsible for heat tolerance resulting from conditional neutrality. We see no evidence of trade-offs between fitness-related traits at 25 °C vs. 10 °C or between two algal diets across Daphnia magna clones from a variety of locations representing the opposite ends of the distribution of long-term heat tolerance. Likewise, we found no evidence of within-environment trade-offs between heat tolerance and fitness-related traits in any of the environments. Neither short-term and long-term heat tolerance shows any consistent relationship with lipid fluorescence polarization and lipid peroxidation across clones or environments. Pervasive positive correlations between fitness-related traits indicate differences in genetic load rather than trade-off based local adaptation or thermal specialization. For heat tolerance such differences may be caused by either relaxation of stabilizing selection due to lower exposure to high temperature extremes, i.e., conditional neutrality, or by small effective population size followed by the recent range expansion.

Breaking free from thermodynamic constraints: thermal acclimation and metabolic compensation in a freshwater zooplankton species.

Respiration rates of ectothermic organisms are affected by environmental temperatures, and sustainable metabolism at high temperatures sometimes limits heat tolerance. Organisms are hypothesized to exhibit acclimatory metabolic compensation effects, decelerating their metabolic processes below Arrhenius expectations based on temperature alone. We tested the hypothesis that either heritable or plastic heat tolerance differences can be explained by metabolic compensation in the eurythermal freshwater zooplankton crustacean Daphnia magna We measured respiration rates in a ramp-up experiment over a range of assay temperatures (5-37°C) in eight genotypes of D. magna representing a range of previously reported acute heat tolerances and, at a narrower range of temperatures (10-35°C), in D. magna with different acclimation history (either 10 or 25°C). We discovered no difference in temperature-specific respiration rates between heat-tolerant and heat-sensitive genotypes. In contrast, we observed acclimation-specific compensatory differences in respiration rates at both extremes of the temperature range studied. Notably, there was a deceleration of oxygen consumption at higher temperature in 25°C-acclimated D. magna relative to their 10°C-acclimated counterparts, observed in active animals, a pattern corroborated by similar changes in filtering rate and, partly, by changes in mitochondrial membrane potential. A recovery experiment indicated that the reduction of respiration was not caused by irreversible damage during exposure to a sublethal temperature. Response time necessary to acquire the respiratory adjustment to high temperature was lower than for low temperature, indicating that metabolic compensation at lower temperatures requires slower, possibly structural changes.

Oxidation of graphene 'bow tie' nanofuses for permanent, write-once-read-many data storage devices.

We have fabricated nanoscale fuses from CVD graphene sheets with a 'bow tie' geometry for write-once-read-many data storage applications. The fuses are programmed using thermal oxidation driven by Joule heating. Fuses that were 250 nm wide with 2.5 µm between contact pads were programmed with average voltages and powers of 4.9 V and 2.1 mW, respectively. The required voltages and powers decrease with decreasing fuse sizes. Graphene shows extreme chemical and electronic stability; fuses require temperatures of about 400 °C for oxidation, indicating that they are excellent candidates for permanent data storage. To further demonstrate this stability, fuses were subjected to applied biases in excess of typical read voltages; stable currents were observed when a voltage of 10 V was applied to the devices in the off state and 1 V in the on state for 90 h each.

Noninfective mitral valve vegetations identified by transesophageal echocardiography as a cause of stroke.

BACKGROUND: Transesophageal echocardiography (TEE) is a useful procedure to evaluate selected stroke patients for cardiac sources of embolism. To date, noninfective valvular vegetations have not been described in large studies using transesophageal echocardiography to detect cardiac sources of embolism. We sought to investigate the frequency of noninfective valvular vegetations in patients with unexplained stroke referred for TEE and to determine the relationship of these vegetations to unrecognized thrombophilic disorders. METHODS: We evaluated 641 consecutive patients referred for TEE as a result of unexplained stroke or transient ischemic attack for the presence of valvular vegetations. Of those with vegetations identified, serial blood cultures were obtained to evaluate for an infectious etiology. Patients also had serum testing for thrombophilic disorders and selected patients underwent cerebral angiography. RESULTS: Thirteen patients (2%) who underwent TEE evaluation for unexplained stroke or transient ischemic attack were found to have noninfective valvular vegetations, all involving the mitral valve; none were identified by transthoracic echocardiography. Antiphospholipid antibodies were identified in 8 of these 13 patients (62%) and a protein C deficiency in 1 patient (8%). CONCLUSIONS: Noninfective valvular vegetations are a potential cardiac source of embolism in patients with unexplained stroke that can be better identified using transesophageal echocardiography. A large percentage of these individuals have a previously unrecognized thrombophilic disorder.

Effects of ozone on macrophage adhesion in vitro and epithelial and inflammatory responses in vivo: the role of cytokines.

Inhalation exposure to ozone (O3) is known to induce epithelial and inflammatory changes in the lungs, characterized by neutrophilia and changes in epithelial permeability. Several cell types and their soluble mediators, including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), are involved in the evolution of these responses. In this study, we have compared the effects of the combination of anti-IL-1 alpha and anti-TNF-alpha on in vitro and in vivo responses to inhaled O3. Male, Sprague-Dawley rats were exposed, nose-only, to 0.8 ppm O3 for 3 h and the in vitro and in vivo parameters were measured 8-12 h following exposure. The in vitro studies revealed that the adherence of inflammatory cells, primarily macrophages, harvested from the lungs of O3-exposed rats to cultured lung epithelial cells (ARL-14) was significantly greater than the adherence of macrophages from air-exposed controls. Furthermore, this adherence was significantly reduced in antibody-treated cells as compared to cells treated with preimmune rabbit serum. In vivo, elevations were found in the percentage of neutrophils in bronchoalveolar lavage fluid (BALF), transport of 99mTc-diethylenetriaminepentaacetate (DTPA) across the tracheal epithelium, and concentrations of total protein and albumin in BALF following O3 exposure. However, these effects were not significantly altered by treatment with the anti-IL-1 alpha/anti-TNF-alpha combination. Therefore, it was concluded that O3 affects the early stages of the inflammatory response, particularly with respect to macrophage activation and adherence to epithelial cells, and that this early response may be mediated by IL-1 alpha and/or TNF-alpha. The results also suggest that the in vivo effects of O3 are controlled by complex mechanisms involving factors other than IL-1 alpha and TNF-alpha, even though these cytokines are capable of modifying macrophage function as revealed by the in vitro adherence studies.

The morphologic characteristics of flail mitral leaflets by transesophageal echocardiography.

BACKGROUND AND AIMS OF THE STUDY: Mitral valve prolapse due to floppy mitral valve (MVP/FMV) is a common valvular abnormality with a variable clinical course. Flail mitral valve leaflet resulting in severe mitral regurgitation is a complication of MVP/FMV. METHODS: In order to understand the structural correlates of flail mitral valve leaflet in MVP, we reviewed the morphologic characteristics of the mitral valve by transesophageal echocardiography (TEE) in 72 patients (24 normal; 26 mitral valve prolapse; 22 flail mitral valve leaflet). RESULTS: Compared with the normal group, the mitral valve prolapse group had greater anterior and posterior mitral valve leaflet thickness and anterior mitral valve leaflet length. Patients with flail mitral valve leaflets as a complication of FMV had greater anterior and posterior mitral valve leaflet length and posterior mitral valve leaflet thickness compared with MVP patients without flail mitral valve leaflets. Posterior mitral valve leaflet length was the only echocardiographic independent predictor of flail mitral valve leaflet. Older FMV patients with increased mitral valve leaflet length and thickness are predisposed to flail mitral valve leaflets and severe mitral regurgitation. CONCLUSIONS: TEE may identify patients with MVP/FMV with the greatest structural abnormalities who are at risk for complications such as flail mitral valve leaflet(s).

Modification of macrophage adhesion by ozone: role of cytokines and cell adhesion molecules.

The inflammatory response in the lungs following an inhalation exposure of animals and humans to ozone (O3) is associated with macrophage stimulation, release of chemotactic agents, and neutrophilia. This study investigated the adhesive behavior of the alveolar macrophages and its relevance to the inflammatory processes in the lung. Macrophages recovered by BAL from rats exposed to purified air or 0.8 ppm O3 were studied in vitro for their adhesion to epithelial cells derived from ARL-14. The macrophages from O3-exposed animals displayed greater adhesion to the epithelial cells than the macrophages from control rats exposed to purified air. The O3-induced adhesion was attenuated in the macrophages treated with a combination of interleukin-1 alpha and tumor necrosis factor-alpha antibodies (anti-IL-1+anti-TNF). The cell adhesion stimulated by O3 exposure was also attenuated when the macrophages were incubated in the presence of antibodies to leukocyte adhesion molecules, CD11b, or epithelial cell adhesion molecules, ICAM-1. A marginal increase in the surface expression of CD11b was noticed in macrophages from the rats exposed to O3. A similar change in the ICAM-1 expression was, however, not observed. The results suggest that the O3-induced modifications of macrophages are mediated by IL-1 and TNF, and that these modifications are accompanied by a minimal change in the expression of the cell-adhesion molecules.

Vascular hypertrophy is an early finding in essential hypertension and is related to arterial pressure waveform contour.

The effects of hypertension on the arterial vasculature were examined in a study group of 20 patients with newly diagnosed essential hypertension, 18 patients with chronic essential hypertension, and 32 control subjects with normal blood pressure. Left ventricular mass was determined echocardiographically. Carotid artery intimal-medial thickness was measured by means of B-mode ultrasound imaging, and carotid arterial waveforms were obtained by applanation tonometry. Compared with that in control subjects, carotid intimal-medial thickness was increased in patients with chronic hypertension (0.74 +/- 0.17 mm vs 0.61 +/- 0.15 mm in control subjects; p < 0.01) and in patients with newly diagnosed hypertension (0.66 +/- 0.12 mm vs 0.61 +/- 0.15 mm in control subjects; p < 0.05). Left ventricular mass was also higher in patients with chronic hypertension than in control subjects but was very similar between control subjects and those with newly diagnosed hypertension. Both the group with early hypertension and the group with chronic hypertension had an increased incidence of early waveform reflection evident on carotid arterial waveform examination. By multiple regression analysis, independent predictors of increased carotid intimal-medial thickness were age, systolic arterial pressure, and Murgo class of arterial waveform. Conduit arterial wall thickening precedes left ventricular remodeling in essential hypertension and is significantly related to the degree of pressure elevation and the arterial waveform contour.

Mitral valve strands in patients with focal cerebral ischemia.

BACKGROUND AND PURPOSE: Filamentous strands attached to the mitral valve are a recently described finding in occasional patients undergoing transesophageal echocardiography (TEE), but the frequency and clinical significance of these strands remain poorly defined. The purpose of the present study was to review the prevalence of mitral valve strands in patients undergoing TEE examination and to explore the relation of these strands to cardioembolic cerebral ischemia. METHODS: All patients with native mitral valves referred for clinically indicated TEE over a 2-year period at our institution were evaluated for the presence of mitral valve strands (defined as highly mobile filamentous masses <1 mm thick attached to the atrial surface of mitral leaflets). RESULTS: Of 968 study patients, mitral valve strands were identified in 22 individuals (2.3%). Mitral valve strands were significantly more common in patients referred for TEE as a result of a recent ischemic cerebrovascular event compared with patients referred for other study indications (6.3% versus 0.3%, respectively; P<.00001). Among patients < or = 50 years of age with likely cardioembolic stroke or transient ischemic attack, 16% were found to have mitral valve strands on TEE examination. In 9% of these young patients, no other TEE finding associated with cardioembolic risk was present. CONCLUSIONS: Filamentous strands attached to the mitral valve appear to represent another risk factor for embolic cerebral ischemia, particularly in patients < or = 50 years of age.

Spectrum of structural abnormalities in floppy mitral valve echocardiographic evaluation.

Posterior displacement of the mitral valve with billowing into the left atrium has been the major echocardiographic criterion used for the diagnosis of mitral valve prolapse (MVP). However, the current criteria are limited by the influence of hemodynamic factors on the degree of prolapse, whereas complications such as mitral regurgitation, endocarditis, and need for surgery have been associated with redundancy or thickening of the leaflets. Sixty-eight normal subjects (mean age, 40 years; range, 18 to 76 years) were compared with 58 patients with MVP (mean age, 37 years, range, 18 to 83 years). Leaflet displacement across the annular plane in the parasternal long-axis view was mandatory for the diagnosis of MVP. Transthoracic echocardiographic measurements of anterior and posterior leaflet thickness, leaflet length, and chordal length were made from the parasternal long-axis view and the mitral annular diameter, from the apical four-chamber and two-chamber views. The MVP group had greater anterior thickness (4.1 +/- 0.4 mm vs 5.3 +/- 0.7 mm; p = 0.0001), posterior thickness (3.2 +/- 0.4 mm vs 4.7 +/- 0.9 mm; p = 0.0001), anterior length (22.8 +/- 2.0 mm vs 25.7 +/- 1.7 mm; p = 0.0001), posterior length (12.8 +/- 1.0 mm vs 15.7 +/- 2.5 mm; p = 0.0001), chordal length (25.6 +/- 2.7 mm vs 28.0 +/- 2.5 mm; p = 0.0001), and annular diameter (29.1 +/- 1.5 mm vs 31.3 +/- 2.6 mm; p = 0.0001). Of the MVP group, >80% had at least one abnormality identified and >50% had at least two abnormalities. In addition, patients with MVP with significant regurgitation had greater anterior thickness (5.2 +/- 0.7 mm vs 5.8 +/- 0.8 mm; p = 0.015), posterior thickness (4.5 +/- 0.9 mm vs 5.3 +/- 0.7 mm; p = 0.024), posterior length (15.1 +/- 1.6 mm vs 17.9 +/- 4.2 mm; p = 0.004), and annular diameter (36.0 +/- 2.0 mm vs 33.3 +/- 2.1 mm; p = 0.0001). The majority of patients with floppy mitral valves resulting in MVP have structural abnormalities that may be defined by echocardiography. A spectrum of floppy valve structure is demonstrated by echocardiography, with mitral regurgitation occurring more frequently in patients with multiple and more severe anatomic abnormalities. In addition to the presence of prolapse and regurgitation, the assessment of leaflet thickness, leaflet length, annular diameter, and chordal length is fundamental to the definition and stratification of patients with MVP associated with the floppy mitral valve.

Comparison of thickness and distensibility in the carotid artery and descending thoracic aorta: in vivo ultrasound assessment.

Early atherosclerotic changes in the carotid artery and thoracic aorta have been examined by high-frequency ultrasound measuring of intimal-medial thickness and stiffness. Whether changes in stiffness and thickness occur in parallel and whether the determinants of stiffness and thickness in the two vessels are similar is unknown. To examine the relation between ultrasonographic measures of atherosclerosis in the carotid and the thoracic aorta, 146 patients aged 20 to 84 years (mean 54 years) were studied by both transesophageal echocardiography (TEE) and carotid duplex scanning. From two-dimensionally derived M-mode recordings of the thoracic aorta and high-frequency B-mode imaging of the common carotid, the intimal-medial thickness was measured along with diastolic and systolic diameters for calculation of stiffness. Interobserver and intraobserver variability of carotid and aortic intimal-medial thickness and diameter were low. There was a good relation between carotid and aortic intimal-medial thickness (r = 0.69; p=0.0001). Age was the major independent determinant of thickness in both vessels. Carotid and aortic stiffness, as measured by Peterson's elastic modulus, were less closely related (r=0.51; p=0.0001). Age was the only independent predictor of stiffness in both vessels. In conclusion, structural ultrasonographic manifestations of early atherosclerosis in the carotid artery and thoracic aorta are closely related. Large population studies measuring only carotid intimal-medial two-thickness may reflect atherosclerotic changes occurring throughout the vascular bed.

Systolic anterior motion of the mitral chordae tendineae: prevalence and clinical and Doppler-echocardiographic features.

The objective of this investigation was to determine the prevalence and clinical associations of systolic anterior motion (SAM) of the mitral chordae (chordal SAM) in patients without evidence of hypertrophic cardiomyopathy. Although SAM of the mitral valve is thought to be a specific marker of hypertrophic obstructive cardiomyopathy, little is known about the clinical significance of chordal SAM either as an isolated echocardiographic finding (ICSAM) or in patients with mitral valve prolapse (MVP). A retrospective search of the clinical echocardiographic database was made to identify studies demonstrating chordal SAM with no other echocardiographic features of hypertrophic cardiomyopathy. The prevalence of chordal SAM was also ascertained in a group of 97 normal control subjects. Clinical, demographic, and two-dimensional and Doppler echocardiographic characteristics were compared between patients with and without MVP. Chordal SAM was identified in 3.9 percent of clinical studies but was rarely seen in normal volunteers (1 percent). Of the 57 patients with chordal SAM, 21 had systemic or cardiovascular conditions other than MVP associated with SAM (including 7 with aortic insufficiency and 8 with secondary concentric left ventricular hypertrophy), 18 (32 percent) had MVP, and 19 (33 percent) had no associated cardiovascular or systemic condition. These 19 patients with ICSAM were similar to patients with MVP and SAM with respect to age (44 +/- 8 vs 41 +/- 17 years), blood pressure, left ventricular wall thickness, ejection fraction, left atrial size, degree of mitral insufficiency, and left ventricular outflow tract velocity. Indications for the echocardiographic studies were similar between the two groups (chest pain, syncope, arrhythmia, cardiac source of embolus, and suspected MVP), but more patients in the ICSAM group were men (16 of 19 vs 8 of 18; p < 0.05). In conclusion, patients with ICSAM and CSAM associated with MVP are virtually indistinguishable by clinical, demographic, or Doppler-echocardiographic features. The syndrome of ICSAM deserves further study as a potentially clinically significant echocardiographic variant of the floppy mitral valve/MVP syndrome.

Detection of prosthetic valve strands by transesophageal echocardiography: clinical significance in patients with suspected cardiac source of embolism.

OBJECTIVES: The purpose of this study was to determine how frequently prosthetic valve strands are associated with prosthetic mitral and aortic valves, as detected by transesophageal echocardiography, and to assess their significance in relation to clinical cardioembolic events. BACKGROUND: Strands attached to prosthetic mitral valves are a recently described finding of uncertain clinical significance. There are no reports of strands attached to aortic valve prostheses, and data are limited concerning the relation of valvular strands to cardioembolic events. METHODS: We identified all transesophageal echocardiographic studies performed during a 5-year period at our institution for evaluation of valve dysfunction or a suspected cardioembolic event in patients with a valve prosthesis. All studies were reviewed. The presence of strands was noted and the prevalence compared between patients evaluated for a suspected cardioembolic event and those evaluated for valve dysfunction. In patients with no strands detected, the presence of other potential cardiac sources of embolism was noted. RESULTS: Strands were detected in 56 (26%) of 214 studies. There was a significant difference (p = 0.0001) in the prevalence of strands between studies performed for a suspected cardioembolic event (34 [53%] of 64) versus those performed for suspected valve dysfunction (22 [15%] of 150). Strands were more prevalent on mitral than on aortic valves (32% vs. 13%, p = 0.0004) and were more frequently detected on mechanical than on bioprosthetic valves (27% vs. 8%, p = 0.003). Among patients with a suspected cardioembolic event and normal valves, other potential cardiac sources of embolism were detected in 67%. CONCLUSIONS: Prosthetic valve strands are frequently detected by transesophageal echocardiography. They are more commonly detected in patients being evaluated for a suspected cardioembolic event and thus represent a potential cardiac source of embolism. In patients with apparently normal valves, other potential sources of embolism are frequently detected. Thus, transesophageal echo-cardiography may have a significant impact on the management of these patients.

Differing autonomic response to dobutamine in the presence and absence of ischemia: implications for the autonomic contribution to positive inotropic intervention.

Although it is well recognized that dobutamine is a powerful positive inotropic agent mediating increased myocardial contractility through direct beta-adrenergic stimulation, the mechanism of its overall circulatory effects appears more complex than that which may be ascribed solely to this direct action on the myocardium. Previous investigations have implied that reflex alterations in autonomic balance may contribute significantly to the response to this agent, but direct evidence describing such a response has not been reported. The objective of this investigation was to assess changes in autonomic tone induced by dobutamine in the presence and absence of ischemia through the measurement of heart rate variability in patients undergoing dobutamine stress echocardiography. Of 25 consecutive patients undergoing dobutamine stress echocardiography, 16 were found to have unequivocal evidence for or against the presence of ischemia during dobutamine infusion. Heart rate data from these 16 patients were submitted for spectral analysis of heart rate variability and quantification of parasympathetically governed high-frequency heart rate variability and sympathetically influenced low-frequency heart rate variability. Of the 16 patients nine were not found to have evidence for ischemia (group 1), and seven were found to have echocardiographic findings consistent with dobutamine-induced ischemia (group 2). The two groups significantly differed (p = 0.04) in the change in parasympathetic tone associated with dobutamine with a significant (p = 0.04) increase in parasympathetic tone in group 1 and a numeric decrease in group 2. A significant (p = 0.04) decrease in sympathetic tone was noted in group 1 as reflected by low-frequency heart rate variability with a numeric increase in this measure in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Left atrial performance indices in chronic mitral valve disease.

Multidimensional left atrial (LA) performance indices have not been extensively studied in chronic mitral valve disease. LA maximal volume, stroke volume (LA volume at atrial systole minus LA minimal volume), LA ejection fraction (stroke volume/volume at atrial systole) and A-wave velocity, were measured in 14 patients with mitral stenosis (mean mitral valve area 1.5 cm2); 14 patients with chronic mitral regurgitation all in sinus rhythm; and were compared to 20 age and sex matched normal control subjects using biplane transthoracic echo and pulsed Doppler. Although LA volumes--maximal and at onset of atrial systole--were greater in mitral regurgitation and mitral stenosis (p < 0.01) compared to normal subjects, LA ejection fraction was not statistically different among the three groups. LA stroke volume was greater in mitral regurgitation and mitral stenosis compared to normal subjects, p < 0.01. LA kinetic energy (LAKE) = 1/2 mv2 (m = LA stroke volume x 1.06, blood's specific gravity, v = A wave velocity) was increased in mitral stenosis and mitral regurgitation compared to normal subjects (p < 0.001). An inverse correlation (r = 0.66, p < 0.01) was present between LAKE and mitral valve area in mitral stenosis. It is concluded that LA function, a complex interplay of multiple factors, requires multidimensional methods of analysis beyond standard measurements of size and volume, which provide additional insight into normal LA function, and better definition of LA function changes involved in the natural history of chronic mitral valve disease.

Is the pulmonary venous-transmitral A-wave duration difference altered by age and hypertension?

We have demonstrated that the pulmonary venous and transmitral atrial duration, and the difference between the 2 are independent of age and not influenced by hypertension, but have a high interobserver variability and range of variability. Enthusiasm for this parameter with the currently available recording techniques must be tempered by the high variability in this measurement.