Internet-Based Biofeedback-Assisted Relaxation Training in the Treatment of Hypertension: A Pilot Study

The effectiveness of biofeedback-assisted behavioral treatment with Internet-based client-therapist contact for hypertension was tested in outpatient settings. A pilot study with a randomized controlled design was adopted with two conditions (treatment versus passive controls), lasting for 8 weeks. There were two assessment time points (pre-treatment and post-treatment) measuring clinic systolic and diastolic blood pressure (SBP and DBP) and administration of a questionnaire collecting demographic and subjective data. Participants included 19 Swedish adults diagnosed with hypertension. The treatment group lowered their SBP 5.9 mm Hg and their DBP 7.6 mm Hg while the control group lowered their SBP 0.8 mm Hg and DBP 3.0 mm Hg. The effect of treatment was significant for DBP but not for SBP. There were no other significant effects of treatment. This pilot study shows encouraging results regarding Internet-based biofeedback treatment for hypertensive adults. However, further research using a larger sample is needed.     

Comparing canopy metrics derived from terrestrial and airborne laser scanning in a Douglas-fir dominated forest stand

Accurate estimates of vegetation structure are important for a large number of applications including ecological modeling and carbon budgets. Light detection and ranging (LiDAR) measures the three-dimensional structure of vegetation using laser beams. Most LiDAR applications today rely on airborne platforms for data acquisitions, which typically record between 1 and 5 “discrete” returns for each outgoing laser pulse. Although airborne LiDAR allows sampling of canopy characteristics at stand and landscape level scales, this method is largely insensitive to below canopy biomass, such as understorey and trunk volumes, as these elements are often occluded by the upper parts of the crown, especially in denser canopies. As a supplement to airborne laser scanning (ALS), a number of recent studies used terrestrial laser scanning (TLS) for the biomass estimation in spatially confined areas. One such instrument is the Echidna^® Validation Instrument (EVI), which is configured to fully digitize the returned energy of an emitted laser pulse to establish a complete profile of the observed vegetation elements. In this study we assess and compare a number of canopy metrics derived from airborne and TLS. Three different experiments were conducted using discrete return ALS data and discrete and full waveform observations derived from the EVI. Although considerable differences were found in the return distribution of both systems, ALS and TLS were both able to accurately determine canopy height (Δ height < 2.5 m) and the vertical distribution of foliage and leaf area (0.86 > r ² > 0.90, p < 0.01). When using more spatially explicit approaches for modeling the biomass and volume throughout the stands, the differences between ALS and TLS observations were more distinct; however, predictable patterns exist based on sensor position and configuration.     

Molecular detection of genomic regions associated with grain yield and yield-related components in an elite bread wheat cross evaluated under irrigated and rainfed conditions

Grain yield and grain weight of wheat are often decreased by water-limitation in the north-eastern cropping belt of Australia. Based on knowledge that CIMMYT lines are well-adapted in this region, a recombinant inbred line (RIL) population between two elite CIMMYT bread wheats (Seri M82 and Babax) was evaluated under water-limited environments. Fourteen productivity traits were evaluated in 192 progeny in up to eight trials. For three aggregations of the environments (all, high yield or low yield), multiple quantitative trait loci (QTL) were detected, each explaining <15% of variation. Co-location of multiple trait QTL was greatest on linkage groups 1B-a, 1D-b, 4A-a, 4D-a, 6A-a, 6B-a, 7A-a and an unassigned linkage group. Two putative QTL (LOD > 3) from Seri (6D-b and UA-d) increased grain yield and co-located with a suggestive (2 < LOD < 3) and a putative QTL for increased stem carbohydrate content (WSC), respectively; the latter QTL also co-located with a putative anthesis QTL for earlier flowering. Both QTL were detected only in high yield (>4t ha⁻¹) environments. A third increased grain yield QTL (7A-a) from Babax co-located with QTL for increased grain number. Six putative QTL increased grain weight and co-located with QTL for harvest index, grains per spike and spike number. Three putative QTL for increased grains per spike co-located with strong QTL for earlier flowering, increased grain weight and fewer spikes. A group of progeny that exceeded the mean grain yield and grain weight of commercial checks had an increased frequency of QTL for high WSC, large grain size, increased harvest index and greater height, but fewer stems, when compared to low yielding (20% less), low grain weight progeny. These findings were consistent with agronomic analyses of the germplasm and demonstrate that there should be opportunities to independently manipulate grain number and grain size which is typically difficult due to strong negative correlations.     

Singlet Oxygen-induced Attenuation of Growth Factor Signaling: Possible Role of Ceramides

Singlet oxygen, an electronically excited form of molecular oxygen, is a primary mediator of the activation of stress-activated protein kinases elicited by ultraviolet A (UVA; 320–400?nm). Here, the effects of singlet oxygen (¹O²) on the extracellular signal-regulated kinase (ERK) 1/2 and Akt/protein kinase B pathways were analyzed in human dermal fibroblasts. While basal ERK 1/2 phosphorylation was lowered in cells exposed to either ¹O², UVA or photodynamic treatment, Akt was moderately activated by photochemically generated ¹O² in a phosphoinositide 3-kinase (PI3K)-dependent fashion, resulting in the phosphorylation of glycogen synthase kinase-3 (GSK3). The activation of ERK 1/2 and Akt as induced by stimulation with epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) was inhibited by ¹O² generated intracellularly upon photoexcitation of rose Bengal (RB). Photodynamic therapy (PDT)-induced apoptosis is known to be associated with increased formation of ceramides. Likewise, both ¹O² and UVA induced ceramide generation in human skin fibroblasts. The attenuation of EGF- and PDGF-induced activation of ERK 1/2 and Akt by ¹O² was mimicked by stimulation of fibroblasts with the cell-permeable C²-ceramide. Interestingly, EGF-induced tyrosine phosphorylation of the EGF receptor was strongly attenuated by ¹O² but unimpaired by C²-ceramide, implying that, although ceramide formation may mediate the above attenuation of ERK and Akt phosphorylation induced by ¹O², mechanisms beyond ceramide formation exist that mediate impairment of growth factor signaling by singlet oxygen. In summary, these data point to a novel mechanism of ¹O² toxicity: the known ¹O²-induced activation of proapoptotic kinases such as JNK and p38 is paralleled by the prevention of activation of growth factor receptor-dependent signaling and of anti-apoptotic kinases, thus shifting the balance towards apoptosis.     

Insertion of green fluorescent protein into nonstructural protein 5A allows direct visualization of functional hepatitis C virus replication complexes

Hepatitis C virus (HCV) replicates its genome in a membrane-associated replication complex, composed of viral proteins, replicating RNA and altered cellular membranes. We describe here HCV replicons that allow the direct visualization of functional HCV replication complexes. Viable replicons selected from a library of Tn7-mediated random insertions in the coding sequence of nonstructural protein 5A (NS5A) allowed the identification of two sites near the NS5A C terminus that tolerated insertion of heterologous sequences. Replicons encoding green fluorescent protein (GFP) at these locations were only moderately impaired for HCV RNA replication. Expression of the NS5A-GFP fusion protein could be demonstrated by immunoblot, indicating that the GFP was retained during RNA replication and did not interfere with HCV polyprotein processing. More importantly, expression levels were robust enough to allow direct visualization of the fusion protein by fluorescence microscopy. NS5A-GFP appeared as brightly fluorescing dot-like structures in the cytoplasm. By confocal laser scanning microscopy, NS5A-GFP colocalized with other HCV nonstructural proteins and nascent viral RNA, indicating that the dot-like structures, identified as membranous webs by electron microscopy, represent functional HCV replication complexes. These findings reveal an unexpected flexibility of the C-terminal domain of NS5A and provide tools for studying the formation and turnover of HCV replication complexes in living cells.     

The Metastasis Suppressor,N-myc Downstream-regulated Gene 1 (NDRG1), Inhibits Stress-induced Autophagy in Cancer Cells

N-myc downstream regulated gene 1 (NDRG1) is a potent metastasis suppressor with an undefined role in the stress response. Autophagy is a pro-survival pathway and can be regulated via the protein kinase-like endoplasmic reticulum kinase (PERK)/eIF2α-mediated endoplasmic reticulum (ER) stress pathway. Hence, we investigated the role of NDRG1 in stress-induced autophagy as a mechanism of inhibiting metastasis via the induction of apoptosis. As thiosemicarbazone chelators induce stress and up-regulate NDRG1 to inhibit metastasis, we studied their effects on the ER stress response and autophagy. This was important to assess, as little is understood regarding the role of the stress induced by iron depletion and its role in autophagy. We observed that the chelator, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), which forms redox-active iron and copper complexes, effectively induced ER stress as shown by activation of the PERK/eIF2α pathway. Dp44mT also increased the expression of the autophagic marker, LC3-II, and this was dependent on activation of the PERK/eIF2α axis, as silencing PERK prevented LC3-II accumulation. The effect of Dp44mT on LC3-II expression was at least partially due to iron-depletion, as this effect was also demonstrated with the classical iron chelator, desferrioxamine (DFO), and was not observed for the DFO-iron complex. NDRG1 overexpression also inhibited basal autophagic initiation and the ER stress-mediated autophagic pathway via suppression of the PERK/eIF2α axis. Moreover, NDRG1-mediated suppression of the pro-survival autophagic pathway probably plays a role in its anti-metastatic effects by inducing apoptosis. In fact, multiple pro-apoptotic markers were increased, whereas anti-apoptotic Bcl-2 was decreased upon NDRG1 overexpression. This study demonstrates the role of NDRG1 as an autophagic inhibitor that is important for understanding its mechanism of action.     

Contrast‐enhanced optical coherence tomography for melanoma detection: An in vitro study

Optical coherence tomography (OCT), with a high‐spatial resolution (<10 microns), intermediate penetration depth (~1.5 mm) and volumetric imaging capability is a great candidate to be used as a diagnostic‐assistant modality in dermatology. At this time, the accuracy of OCT for melanoma detection is lower than anticipated. In this letter, we studied for the first time, the use of a novel contrast agent consist of ultra‐small nanoparticles conjugated to a melanoma biomarker to improve the accuracy of OCT for differentiation of melanoma cells from nonmelanoma cells, in vitro. We call this approach SMall nanoparticle Aggregation‐enhanced Radiomics of Tumor (SMART)‐OCT imaging. This initial proof of concept study is the first step toward the broad utilization of this method for high accuracy all types of tumor detection applications.     

Fiber attenuated total reflection infrared spectroscopy of kidney tissue during live surgery

More than 90% of solid kidney tumors are cancerous and have to be treated by surgical resection where surgical outcomes and patient prognosis are dependent on the tumor discrimination. The development of alternative approaches based on a new generation of fiber attenuated total reflection (ATR) probes could aid tumor identification even under intrasurgical conditions. Herein, fiber ATR IR spectroscopy is employed to distinguish normal and cancerous kidney tissues. Freshly resected tissue samples from 34 patients are investigated under nearly native conditions. Spectral marker bands that allow a reliable discrimination between tumor and normal tissue are identified by a supervised classification algorithm. The absorbance values of the bands at 1025, 1155 and 1240 cm^?1 assigned to glycogen and fructose 1,6‐bisphosphatase are used as the clearest markers for the tissue discrimination. Absorbance threshold values for tumor and normal tissue are determined by discriminant analysis. This new approach allows the surgeon to make a clinical diagnosis.