This article investigates the effects of both soil contamination and nitrogen application on the red edge–chlorophyll concentration relationship for a vegetation canopy. Field based canopy ...reflectance and chlorophyll concentration data were collected at a grassland field site affected by soil contamination and a winter wheat field site affected by different levels of nitrogen fertilisation. The correlation between red edge position (REP) and canopy chlorophyll concentration was
r=0.84 and 0.80 for the grassland and winter wheat field sites, respectively. Airborne imaging spectrometry was used to generate REP images (units, nm) of the grassland and winter wheat field sites. Strong correlations were observed between REP and canopy chlorophyll concentration at both field sites. Predictive regression equations were developed to map canopy chlorophyll concentration across the field sites. The rms error of estimated chlorophyll concentration was 0.42 mg g
−1 (±12.69% of mean) and 2.09 mg g
−1(±16.4% of mean) at the grassland and winter wheat field sites respectively. Results demonstrated the use of remotely sensed estimates of the REP from both field and airborne spectrometers for estimating chlorophyll concentration and indicated the potential of this technique for inferring both land contamination and grain yield.
We recently reported that mutations in HERG, a potassium channel gene, cause long QT syndrome. Heterologous expression of HERG in Xenopus oocytes revealed that this channel had biophysical properties ...nearly identical to a cardiac delayed rectifier K+ current I(Kr), but had dissimilar pharmacological properties. Class III antiarrhythmic drugs such as E-4031 and MK-499 are potent and specific blockers of I (Kr) in cardiac myocytes. Our initial studies indicated that these compounds did not block HERG at a concentration of 1 micromol/L. In the present study, we used standard two-microelectrode voltage-clamp techniques to further characterize the effects of these drugs on HERG channels expressed in oocytes. Consistent with initial findings, 1 micromol/L MK-499 and E-4031 had not effect on HERG when oocytes were voltage clamped at a negative potential and not pulsed during equilibration with the drug. However, MK-499 did block HERG current if oocytes were repetitively pulsed, or clamped at a voltage positive to the threshold potential for channel activation. This finding is in contrast to previous studies that showed significant block of I(Kr) in isolated myocytes by similar drugs, even in the absence of pulsing. This apparent discrepancy may be due to differences in channel characteristics (HERG versus guinea pig and mouse I (Kr)), tissue (oocytes versus myocytes), or specific drugs. Under steady state conditions, block of HERG by MK-499 was half maximal at 123 +/- 12 nmol/L at a test potential of -20 mV. MK-499 (150 nmol/L) did not affect the voltage dependence of activation and rectification nor the kinetics of activation and deactivation of HERG. These data indicate that MK-499 preferentially blocks open HERG channels and further support the conclusion that HERG subunits form I(Kr) channels in cardiac myocytes.
We have previously identified polymorphisms in the serotonin transporter gene promoter region and in intron 2 that were more common among sudden infant death syndrome (SIDS) cases compared with ...control subjects. To elucidate further the genetic profile that might increase an infant's vulnerability to SIDS, we focused on the recognized relationship between autonomic nervous system (ANS) dysregulation and SIDS. We therefore studied genes pertinent to early embryologic development of the ANS, including MASH1, BMP2, PHOX2a, PHOX2b, RET, ECE1, EDN1, TLX3, and EN1 in 92 probands with SIDS and 92 gender- and ethnicity-matched control subjects. Eleven protein-changing rare mutations were identified in 14 of 92 SIDS cases among the PHOX2a, RET, ECE1, TLX3, and EN1 genes. Only 1 of these mutations (TLX3) was identified in 2 of 92 control subjects. Black infants accounted for 10 of these mutations in SIDS cases and 2 control subjects. Four protein-changing common polymorphisms were identified in BMP2, RET, ECE1, and EDN1, but the allele frequency did not differ between SIDS cases and control subjects. However, among SIDS cases, the allele frequency for the BMP2 common polymorphism demonstrated ethnic differences; among control subjects, the allele frequency for the BMP2 and the ECE1 common polymorphisms also demonstrated ethnic differences. These data represent further refinement of the genetic profile that might place an infant at risk for SIDS.
Background
Despite evidence that low-dose irradiation of 2 Mrad (20 kGy) is not virucidal for patellar tendon allografts and reduces tissue strength, many tissue bank protocols include low-dose ...irradiation.
Hypothesis
Maintaining tissue mechanical integrity may be particularly relevant toward accelerated rehabilitation of the injured knee, where the cyclic function of patellar tendon allografts is critical.
Study Design
Controlled laboratory study.
Methods
The cyclic and failure mechanical properties of paired bone-patellar tendon-bone allografts, with and without current low-dose irradiation of 20 kGy, were evaluated. Specimens were loaded from 50 N to 250 N for 1000 cycles at 0.5 Hz and subsequently loaded to failure at a strain rate of 100% per second.
Results
After 1000 cycles, grafts elongated 27% more when irradiated than when not (4.4 ± 1.5 mm vs 3.4 ± 1.0 mm; P = .03). Failure load averaged 1965 ± 512 N for irradiated grafts and 2457 ± 647 N for nonirradiated grafts (P = .007).
Conclusions
The diminished strength of irradiated grafts may contribute to overt anterior cruciate ligament graft failure, and the increase in cyclic elongation may also be detrimental to graft function.
Clinical Relevance
These results suggest that one should consider the use of nonirradiated allografts as an alternative to irradiated grafts in anterior cruciate ligament reconstruction.
The mechanism of rectification of HERG, the human cardiac delayed rectifier K+ channel, was studied after heterologous expression in Xenopus oocytes. Currents were measured using two-microelectrode ...and macropatch voltage clamp techniques. The fully activated current-voltage (I-V) relationship for HERG inwardly rectified. Rectification was not altered by exposing the cytoplasmic side of a macropatch to a divalent-free solution, indicating this property was not caused by voltage-dependent block of outward current by Mg2+ or other soluble cytosolic molecules. The instantaneous I-V relationship for HERG was linear after removal of fast inactivation by a brief hyperpolarization. The time constants for the onset of and recovery from inactivation were a bell-shaped function of membrane potential. The time constants of inactivation varied from 1.8 ms at +50 mV to 16 ms at -20 mV; recovery from inactivation varied from 4.7 ms at -120 mV to 15 ms at -50 mV. Truncation of the NH2-terminal region of HERG shifted the voltage dependence of activation and inactivation by +20 to +30 mV. In addition, the rate of deactivation of the truncated channel was much faster than wild-type HERG. The mechanism of HERG rectification is voltage-gated fast inactivation. Inactivation of channels proceeds at a much faster rate than activation, such that no outward current is observed upon depolarization to very high membrane potentials. Fast inactivation of HERG and the resulting rectification are partly responsible for the prolonged plateau phase typical of ventricular action potentials.
Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Given the immunologic ...dysregulation in IBD, the human-leukocyte-antigen region on chromosome 6p is of significant interest. Previous association and linkage analysis has provided conflicting evidence as to the existence of an IBD-susceptibility locus in this region. Here we report on a two-stage linkage and association analysis of both a basic population of 353 affected sibling pairs (ASPs) and an extension of this population to 428 white ASPs of northern European extraction. Twenty-eight microsatellite markers on chromosome 6 were genotyped. A peak multipoint LOD score of 4.2 was observed, at D6S461, for the IBD phenotype. A transmission/disequilibrium test (TDT) result of
P=.006 was detected for D6S426 in the basic population and was confirmed in the extended cohort (
P=.004; 97 vs. 56 transmissions). The subphenotypes of Crohn disease, ulcerative colitis, and mixed IBD contributed equally to this linkage, suggesting a general role for the chromosome 6 locus in IBD. Analysis of five single-nucleotide polymorphisms in the TNFA and LTA genes did not reveal evidence for association of these important candidate genes with IBD. In summary, we provide firm linkage evidence for an IBD-susceptibility locus on chromosome 6p and demonstrate that TNFA and LTA are unlikely to be susceptibility loci for IBD.
This study quantified the incidence of arrhythmias during pediatric exercise stress tests (ESTs) and evaluated criteria to identify patients at risk of clinically important arrhythmias.
The incidence ...of clinically important arrhythmias during pediatric ESTs and criteria for identifying high-risk patients are poorly characterized.
A retrospective review of ESTs performed from 2013 to 2015 was studied. Arrhythmias were categorized into 4 classes based on need for test termination and intervention. Risk factors evaluated included having an implantable cardioverter-defibrillator (ICD), cardiomyopathy, severe ventricular dysfunction, complex arrhythmia history, coronary disease with concern for ischemia, pulmonary hypertension, select poorly palliated congenital heart disease (CHD), and concerning symptoms. Negative predictive values (NPVs) were calculated.
During the study period, 5307 ESTs were performed. Median age of the subjects was 16 years (interquartile range: 13 to 24 years); 20% had complex CHD. At least 1 high-risk criterion was present in 507 tests (10%); having an ICD (37%) and cardiomyopathy (36%) were the most common criteria. Some arrhythmias were seen in 46% of tests, but only 33 events (0.6%) required test termination. Three events (0.06%) required cardiopulmonary resuscitation, all with high-risk criteria. Absence of a high-risk criterion had a 99.7% (95% confidence interval CI: 99.5% to 99.8%) NPV for an arrhythmia that required test termination and a 99.96% (95% CI: 99.85% to 99.99%) NPV for an arrhythmia that required intervention beyond test termination.
Although self-terminating arrhythmias are common, dangerous arrhythmias are rare during ESTs in a high-volume pediatric cardiology program. Pre-defined high-risk criteria identified all patients with the most serious events. The absence of any criteria predicted a low risk for arrhythmias that required test termination. These data permitted informed choices regarding supervision of ESTs.
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Abstract Electrical and structural remodeling during the progression of cardiovascular disease is associated with adverse outcomes subjecting affected patients to overt heart failure (HF) and/or ...sudden death. Dysfunction in integral membrane protein trafficking has long been linked with maladaptive electrical remodeling. However, little is known regarding the molecular identity or function of these intracellular targeting pathways in the heart. Eps15 homology domain-containing (EHD) gene products (EHD1–4) are polypeptides linked with endosomal trafficking, membrane protein recycling, and lipid homeostasis in a wide variety of cell types. EHD3 was recently established as a critical mediator of membrane protein trafficking in the heart. Here, we investigate the potential link between EHD3 function and heart disease. Using four different HF models including ischemic rat heart, pressure overloaded mouse heart, chronic pacing-induced canine heart, and non-ischemic failing human myocardium we provide the first evidence that EHD3 levels are consistently increased in HF. Notably, the expression of the Na/Ca exchanger (NCX1), targeted by EHD3 in heart is similarly elevated in HF. Finally, we identify a molecular pathway for EHD3 regulation in heart failure downstream of reactive oxygen species and angiotensin II signaling. Together, our new data identify EHD3 as a previously unrecognized component of the cardiac remodeling pathway.
The cumulative distribution function of the p-values obtained is plotted against the null expected p-values from a normal distribution. The significance of the heritability in the ROIs is listed for ...each cohort and for the meta- and mega-analyses. 1000 permutations for the data in each cohort were also performed to obtain a null distribution on the heritability and significance estimates on the individual cohorts and the mega-analysis.
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