Dry demagnetization cryostat for sub-millikelvin helium experiments: Refrigeration and thermometry

We demonstrate successful “dry” refrigeration of quantum fluids down to T = 0.16 mK by using copper nuclear demagnetization stage that is pre-cooled by a pulse-tube-based dilution refrigerator. This type of refrigeration delivers a flexible and simple sub-mK solution to a variety of needs including experiments with superfluid 3He. Our central design principle was to eliminate relative vibrations between the high-field magnet and the nuclear refrigeration stage, which resulted in the minimum heat leak of Q = 4.4 nW obtained in field of 35 mT. For thermometry, we employed a quartz tuning fork immersed into liquid 3He. We show that the fork oscillator can be considered as self-calibrating in superfluid 3He at the crossover point from hydrodynamic into ballistic quasiparticle regime.Peer reviewe

Factors affecting young adults’ willingness to try novel health-enhancing nature-based products

One of the megatrends that affects consumers' preferences is a growing interest in health, well-being and self-care. This study explores consumer perceptions of a health-enhancing nature-based substance. Based on a survey data (N = 944) collected among national and international students in Finland, we examined factors that affect young adults' willingness to try products containing the substance. The results showed a relatively high willingness to try the products, particularly among female and non-Finnish respondents. Relationship to nature and beliefs related to the health benefits or risks of soil microbes influenced willingness to try products. The results highlight the importance of accounting for consumer perceptions in the innovation process.Peer reviewe

Parvovirus nonstructural protein 2 interacts with chromatin-regulating cellular proteins

Autonomous parvoviruses encode at least two nonstructural proteins, NS1 and NS2. While NS1 is linked to important nuclear processes required for viral replication, much less is known about the role of NS2. Specifically, the function of canine parvovirus (CPV) NS2 has remained undefined. Here we have used proximity-dependent biotin identification (BioID) to screen for nuclear proteins that associate with CPV NS2. Many of these associations were seen both in noninfected and infected cells, however, the major type of interacting proteins shifted from nuclear envelope proteins to chromatin-associated proteins in infected cells. BioID interactions revealed a potential role for NS2 in DNA remodeling and damage response. Studies of mutant viral genomes with truncated forms of the NS2 protein suggested a change in host chromatin accessibility. Moreover, further studies with NS2 mutants indicated that NS2 performs functions that affect the quantity and distribution of proteins linked to DNA damage response. Notably, mutation in the splice donor site of the NS2 led to a preferred formation of small viral replication center foci instead of the large coalescent centers seen in wild-type infection. Collectively, our results provide insights into potential roles of CPV NS2 in controlling chromatin remodeling and DNA damage response during parvoviral replication.Peer reviewe

Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer's Disease Patients

Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. Olfactory dysfunction manifests early in several neurodegenerative disorders including Alzheimer's disease, however, disease-related alterations to the olfactory mucosal cells remain poorly described. The aim of this study was to evaluate the olfactory mucosa differences between cognitively healthy individuals and Alzheimer's disease patients. We report increased amyloid-beta secretion in Alzheimer's disease olfactory mucosal cells and detail cell-type-specific gene expression patterns, unveiling 240 differentially expressed disease-associated genes compared to the cognitively healthy controls, and five distinct cell populations. Overall, alterations of RNA and protein metabolism, inflammatory processes, and signal transduction were observed in multiple cell populations, suggesting their role in Alzheimer's disease-related olfactory mucosa pathophysiology. Furthermore, the single-cell RNA-sequencing proposed alterations in gene expression of mitochondrially located genes in AD OM cells, which were verified by functional assays, demonstrating altered mitochondrial respiration and a reduction of ATP production. Our results reveal disease-related changes of olfactory mucosal cells in Alzheimer's disease and demonstrate the utility of single-cell RNA sequencing data for investigating molecular and cellular mechanisms associated with the disease.Peer reviewe

Transcriptional Profiling of Hypoxia-Regulated Non-coding RNAs in Human Primary Endothelial Cells

Hypoxia occurs in human atherosclerotic lesions and has multiple adverse effects on endothelial cell metabolism. Recently, key roles of long non-coding RNAs (lncRNAs) in the development of atherosclerosis have begun to emerge. In this study, we investigate the lncRNA profiles of human umbilical vein endothelial cells subjected to hypoxia using global run-on sequencing (GRO-Seq). We demonstrate that hypoxia regulates the nascent transcription of ~1800 lncRNAs. Interestingly, we uncover evidence that promoter-associated lncRNAs are more likely to be induced by hypoxia compared to enhancer-associated lncRNAs, which exhibit an equal distribution of up- and downregulated transcripts. We also demonstrate that hypoxia leads to a significant induction in the activity of super-enhancers next to transcription factors and other genes implicated in angiogenesis, cell survival and adhesion, whereas super-enhancers near several negative regulators of angiogenesis were repressed. Despite the majority of lncRNAs exhibiting low detection in RNA-Seq, a subset of lncRNAs were expressed at comparable levels to mRNAs. Among these, MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia

Reference values of whole-blood fatty acids by age and sex from European children aged 3-8 years

OBJECTIVES: To establish reference values for fatty acids (FA) especially for n-3 and n-6 long-chain polyunsaturated FAs (LC PUFA) in whole-blood samples from apparently healthy 3-8-year-old European children. The whole-blood FA composition was analysed and the age-and sex-specific distribution of FA was determined. DESIGN AND SUBJECTS: Blood samples for FA analysis were taken from 2661 children of the IDEFICS (identification and prevention of dietary-and lifestyle-induced health effects in children and infants) study cohort. Children with obesity (n = 454) and other diseases that are known to alter the FA composition (n = 450) were excluded leaving 1653 participants in the reference population. MEASUREMENTS: The FA composition of whole blood was analysed from blood drops by a rapid, validated gas chromatographic method. RESULTS: Pearson correlation coefficients showed an age-dependent increase of C18:2n-6 and a decrease of C18:1n-9 in a subsample of normal weight boys and girls. Other significant correlations with age were weak and only seen either in boys or in girls, whereas most of the FA did not show any age dependence. For age-dependent n-3 and n-6 PUFA as well as for other FA that are correlated with age (16:0, C18:0 and C18:1n-9) percentiles analysed with the general additive model for location scale and shape are presented. A higher median in boys than in girls was observed for C20:3n-6, C20:4n-6 and C22:4n-6. CONCLUSIONS: Given the reported associations between FA status and health-related outcome, the provision of FA reference ranges may be useful for the interpretation of the FA status of children in epidemiological and clinical studies

Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans

Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.Peer reviewe

Six-week high-intensity exercise program for middle-aged patients with knee osteoarthritis: a randomized controlled trial [ISRCTN20244858]

BACKGROUND: Studies on exercise in knee osteoarthritis (OA) have focused on elderly subjects. Subjects in this study were middle-aged with symptomatic and definite radiographic knee osteoarthritis. The aim was to test the effects of a short-term, high-intensity exercise program on self-reported pain, function and quality of life. METHODS: Patients aged 36–65, with OA grade III (Kellgren & Lawrence) were recruited. They had been referred for radiographic examination due to knee pain and had no history of major knee injury. They were randomized to a twice weekly supervised one hour exercise intervention for six weeks, or to a non-intervention control group. Exercise was performed at ≥ 60% of maximum heart rate (HR max). The primary outcome measure was the Knee injury and Osteoarthritis Outcome Score (KOOS). Follow-up occurred at 6 weeks and 6 months. RESULTS: Sixty-one subjects (mean age 56 (SD 6), 51 % women, mean BMI 29.5 (SD 4.8)) were randomly assigned to intervention (n = 30) or control group (n = 31). No significant differences in the KOOS subscales assessing pain, other symptoms, or function in daily life or in sport and recreation were seen at any time point between exercisers and controls. In the exercise group, an improvement was seen at 6 weeks in the KOOS subscale quality of life compared to the control group (mean change 4.0 vs. -0.7, p = 0.05). The difference between groups was still persistent at 6 months (p = 0.02). CONCLUSION: A six-week high-intensive exercise program had no effect on pain or function in middle-aged patients with moderate to severe radiographic knee OA. Some effect was seen on quality of life in the exercise group compared to the control group