Epithelial N-cadherin and nuclear β-catenin are up-regulated during early development of human lung

Background  

The aim of this study was to analyze the cell-specific expression of E- and N-cadherin and β-catenin in developing human lung tissues from 12 to 40 weeks of gestation.     

The progress and potential of proteomic biomarkers for type 1 diabetes in children

Introduction: Although it is possible to identify the genetic risk for type 1 diabetes (T1D), it is not possible to predict who will develop the disease. New biomarkers are needed that would help understand the mechanisms of disease onset and when to administer targeted therapies and interventions.

Areas covered: An overview is presented of international study efforts towards understanding the cause of T1D, including the collection of several extensive temporal sample series that follow the development of T1D in at risk children. The results of the proteomics analysis of these materials are presented, which have included bodily fluids, such as serum or plasma and urine, as well as tissue samples from the pancreas.

Expert commentary: Promising recent reports have indicated detection of early proteomic changes in the serum of patients prior to diagnosis, potentially providing new measures for risk assessment. Similarly, there has been evidence that post-translational modification (PTM) may result in the recognition of islet cell proteins as autoantigens; modified proteins could thus be used as targets for immunomodulation to overcome the threat of the autoimmune response.     

Cardiac Repolarization and Autonomic Regulation during Short-Term Cold Exposure in Hypertensive Men: An Experimental Study

Objectives

The aim of our study was to assess the effect of short-term cold exposure, typical in subarctic climate, on cardiac electrical function among untreated middle-aged hypertensive men.

Methods

We conducted a population-based recruitment of 51 hypertensive men and a control group of 32 men without hypertension (age 55–65 years) who underwent whole-body cold exposure (15 min exposure to temperature −10°C, wind 3 m/s, winter clothes). Conduction times and amplitudes, vectorcardiography, arrhythmias, and heart rate variability (autonomic nervous function) were assessed.

Results

Short-term cold exposure increased T-peak to T-end interval from 67 to 72 ms (p<0.001) and 71 to 75 ms (p<0.001) and T-wave amplitude from 0.12 to 0.14 mV (p<0.001) and from 0.17 to 0.21 mV (p<0.001), while QTc interval was shortened from 408 to 398 ms (p<0.001) and from 410 to 401 ms (p<0.001) among hypertensive men and controls, respectively. Cold exposure increased both low (from 390 to 630 ms² (p<0.001) and 380 to 700 ms² (p<0.001), respectively) and high frequency heart rate variability (from 90 to 190 ms² (p<0.001) and 150 to 300 ms² (p<0.001), respectively), while low-to-high frequency-ratio was reduced. In addition, the frequency of ventricular ectopic beats increased slightly during cold exposure. The cold induced changes were similar between untreated hypertensive men and controls.

Conclusions

Short-term cold exposure with moderate facial and mild whole body cooling resulted in prolongation of T-peak to T-end interval and higher T-wave amplitude while QTc interval was shortened. These changes of ventricular repolarization may have resulted from altered cardiac autonomic regulation and were unaffected by untreated hypertension.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02007031","term_id":"NCT02007031"}}NCT02007031     

New separation-free assay technique for SNPs using two-photon excitation fluorometry

A new separation-free method for detection of single nucleotide polymorphisms (SNPs) is described. The method is based on the single base extension principle, fluorescently labeled dideoxy nucleotides and two-photon fluorescence excitation technology, known as ArcDia™ TPX technology. In this assay technique, template-directed single base extension is carried out for primers which have been immobilized on polymer microparticles. Depending on the sequence of the template DNA, the primers are extended either with a labeled or with a non-labeled nucleotide. The genotype of the sample is determined on the basis of two-photon excited fluorescence of individual microparticles. The effect of various assay condition parameters on the performance of the assay method is studied. The performance of the new assay method is demonstrated by genotyping the SNPs of human individuals using double-stranded PCR amplicons as samples. The results show that the new SNP assay method provides sensitivity and reliability comparable to the state-of-the-art SNaPshot™ assay method. Applicability of the new method in routine laboratory use is discussed with respect to alternative assay techniques.     

Higher Free Fatty Acid Uptake in Visceral Than in Abdominal Subcutaneous Fat Tissue in Men

Visceral adipose tissue has been shown to have high lipolytic activity. The aim of this study was to examine whether free fatty acid (FFA) uptake into visceral adipose tissue is enhanced compared to abdominal subcutaneous tissue in vivo. Abdominal adipose tissue FFA uptake was measured using positron emission tomography (PET) and [¹⁸F]‐labeled 6‐thia‐hepta‐decanoic acid ([¹⁸F]FTHA) and fat masses using magnetic resonance imaging (MRI) in 18 healthy young adult males. We found that FFA uptake was 30% higher in visceral compared to subcutaneous adipose tissue (0.0025 ± 0.0018 vs. 0.0020 ± 0.0016 µmol/g/min, P = 0.005). Visceral and subcutaneous adipose tissue FFA uptakes were strongly associated with each other (P < 0.001). When tissue FFA uptake per gram of fat was multiplied by the total tissue mass, total FFA uptake was almost 1.5 times higher in abdominal subcutaneous than in visceral adipose tissue. In conclusion, we observed enhanced FFA uptake in visceral compared to abdominal subcutaneous adipose tissue and, simultaneously, these metabolic rates were strongly associated with each other. The higher total tissue FFA uptake in subcutaneous than in visceral adipose tissue indicates that although visceral fat is active in extracting FFA, its overall contribution to systemic metabolism is limited in healthy lean males. Our results indicate that subcutaneous, rather than visceral fat storage plays a more direct role in systemic FFA availability. The recognized relationship between abdominal visceral fat mass and metabolic complications may be explained by direct effects of visceral fat on the liver.     

Volatile emissions and phenolic compound concentrations along a vertical profile of <Emphasis Type="Italic">Populus nigra</Emphasis> leaves exposed to realistic ozone concentrations

Plants are exposed to increasing levels of tropospheric ozone concentrations. This pollutant penetrates in leaves through stomata and quickly reacts inside leaves, thus making plants valuable ozone sinks, but at the same time triggers oxidation processes which lead to leaf injuries. To counteract these negative effects, plants produce an array of antioxidants which react with ozone and reactive molecules which ozone generates in the leaf tissues. In this study, we measured the effect of an ozone concentration which is likely to be attained in many areas of the world in the near future (80 ppb) on leaves of the vertical profile of the widespread agroforestry species Populus nigra. Changes in (1) physiological parameters (photosynthesis and stomatal conductance), (2) ozone uptake, (3) emission of volatile organic compounds (VOCs, i.e. isoprene, methanol and other oxygenated compounds), (4) concentration of antioxidant surface compounds, and (5) concentration of phenolic compounds were assessed. The aim was to assess whether the defensive pathways leading to isoprenoids and phenolics formation were induced when a moderate and chronic increment of ozone is not able to damage photosynthesis. No visual injuries and minor changes in physiology and ozone uptake were observed. The emission of isoprene and oxygenated six-carbon (C6) volatiles were inhibited by ozone, whereas methanol emission was increased, especially in developing leaves. We interpret these results as suggesting an ontogenetic shift in ozone-treated leaves, leading to a slower development and a faster senescence. Most surface and phenolic compounds showed a declining trend in concentration from the youngest to the fully expanded leaves. Ozone reduced the concentrations of chlorogenic acid derivatives at the leaf surface, whereas in total leaf extracts a metabolic shift towards few phenolics with higher antioxidant capacity was observed.     

Effect of climate change on bud phenology of young aspen plants (Populus tremula. L)

Boreal tree species are excellent tools for studying tolerance to climate change. Bud phenology is a trait, which is highly sensitive to environmental fluctuations and thus useful for climate change investigations. However, experimental studies of bud phenology under simulated climate change outdoors are deficient. We conducted a multifactorial field experiment with single (T, UVA, UVB) and combined treatments (UVA+T, UVB+T) of elevated temperature (T, +2°C) and ultraviolet‐B radiation (+30% UVB) in order to examine their impact on both male and female genotypes of aspen (Populus tremula L.). This study focuses on the effect of the treatments in years 2 and 3 after planting (2013, 2014) and follows how bud phenology is adapting in year 4 (2015), when the treatments were discontinued. Moreover, the effect of bud removal was recorded. We found that elevated temperature played a key role in delaying bud set and forcing bud break in intact individuals, as well as slightly delaying bud break in bud‐removed individuals. UVB delayed the bud break in bud‐removed males. In addition, both UVA and UVB interacted with temperature in year 3 and even in year 4, when the treatments were off, but only in male individuals. Axillary bud removal forced both bud break and bud set under combined treatments (UVA+T, UVB+T) and delayed both under individual treatments (T, UVB). In conclusion, male aspens were more responsive to the treatments than females and that effect of elevated temperature and UV radiation on bud set and bud break of aspen is not disappearing over 4‐year study period.     

Amyloid-beta 1-42 induced endocytosis and clusterin/apoJ protein accumulation in cultured human astrocytes

Recent studies indicate that astrocytes may be the primary target of secreted amyloid-beta 1-42 peptides, with the neurotoxicity representing a secondary response to astrocytic stress. Our purpose was to clarify the astrocytic stress response induced by amyloid-beta peptides in human and rat astrocytes. Human amyloid-beta 1-42 peptides and fibrils induced the appearance of cytoplasmic vacuoles in normal human astrocytes (NHA) and CCFsttg1 astrocytoma cells. Vacuoles appeared 9-12h after the amyloid-beta exposure and remained present for several days. Rat primary neonatal astrocytes showed similar but less prominent vacuolar response. Human amyloid-beta peptides 1-16, 1-28, 10-20, 17-21 and 25-35 did not cause vacuole formation. Electron microscopic observations revealed large endocytic vacuoles containing fibrillar amyloid material. Stress marker analysis did not show any increase in protein levels of HSP70, HSP90, GRP78 and GRP94. However, the protein level of clusterin/apoJ, a secreted chaperone, was strongly increased both in NHA and CCFsttg1 astrocytes. Endocytic response associated with the accumulation of clusterin/apoJ protein suggests that clusterin/apoJ has a role in the clearance of amyloid-beta peptides.