Genetic Variability of RXRB, PPARA, and PPARG in Wegener's Granulomatosis

A major genomic region involved in Wegener's granulomatosis includes the gene for retinoid receptor beta (RXRB) which forms heterodimers with peroxisome proliferator-activated receptors (PPARs). It is unclear whether this association directly arises from the RXRB allele(s) or via a linked variation. In order to reveal any hitherto unknown and potentially disease-relevant variation of the RXRB gene, we have genotyped four tagging SNPs of this genomic region and have directly sequenced selected WG patients and controls representing disease-associated haplotypes. Additionally, we have genotyped 2 SNPs each in the genes for PPARα and PPARγ (PPARA and PPARG). Hence, we confirmed the strong association of the RXRB locus with WG but could not reveal any novel variation in RXRB. None of the PPARA and PPARG SNPs showed association with WG. Moreover, no epistatic effect was seen between RXRB and PPARA/PPARG alleles. These results do not support an etiopathological role of PPAR in WG. Analyses of further genes functionally linked to RXRB may provide additional data useful to evaluate the RXRB association found in WG

PGC-1alpha as modifier of onset age in Huntington disease

Although there is a strong correlation between CAG repeat length and age at onset (AO) of motor symptoms, individual Huntington disease (HD) patients may differ dramatically in onset age and disease manifestations despite similar CAG repeat lengths. This has led to a search for genetic factors that influence AO. In order to identify such a genetic modifier, we analysed polymorphisms in the PGC-1alpha gene. Recent data indicate inhibition of PGC-1alpha function by mutant Htt supporting a link between transcriptional deregulation and mitochondrial dysfunction in HD. In > 400 HD patients, a polymorphism located within intron 2, a potential recombination hot spot, explains a small, but statistically significant, amount of the variability in AO. Our data suggest that PGC-1alpha has modifying effects on the pathogenic process in HD

ApoE polymorphisms in narcolepsy

BACKGROUND: Narcolepsy is a common neuropsychiatric disorder characterized by increased daytime sleepiness, cataplexy and hypnagogic hallucinations. Deficiency of the hypocretin neurotransmitter system was shown to be involved in the pathogenesis of narcolepsy in animals and men. There are several hints that neurodegeneration of hypocretin producing neurons in the hypothalamus is the pathological correlate of narcolepsy. The ApoE4 allele is a major contributing factor to early-onset neuronal degeneration in Alzheimer disease and other neurodegenerative diseases as well. METHODS: To clarify whether the ApoE4 phenotype predisposes to narcolepsy or associates with an earlier disease onset, we have genotyped the ApoE gene in 103 patients with narcolepsy and 101 healthy controls. RESULTS: The frequency of the E4 allele of the ApoE gene was 11% in the patient and 15% in the control groups. Furthermore, the mean age of onset did not differ between the ApoE4(+) and ApoE4(-) patient groups. CONCLUSION: Our results exclude the ApoE4 allele as a major risk factor for narcolepsy

Biodegradable inkjet-printed electrochromic display for sustainable short-lifecycle electronics

The fabrication of electronics on the basis of biofriendly materials aims to counterbalance the negative trends conveyed by the short life-cycle of electronics. Furthermore, these materials open the possibility to develop optoelectronic technologies which will be in contact with the human body. In this work, we present an electrochromic display fabricated by resource- and energy-efficient digital printing techniques. The biodegradation of the device is certified under the ISO 14855 standard. The display comprises of a poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) electrochromic layer, a gelatin-based electrolyte and Au electrodes deposited on a cellulose di-acetate substrate. We investigate the impact of various naturally sourced ionic species on the ionic conductivity of the electrolyte and the figures of merit of the display. The printed devices show an electrochromic contrast of 32 ± 4% and switching times of 3.0 ± 1.4 s, comparable to the spincoated reference devices. The utilization of inkjet printing enables the fabrication of different device designs with individually addressable pixels. The display can be worn innocuously on the skin without loss of performance thanks to the self-adhesion properties of the gelatin hydrogel. The present work highlights the use of industrial relevant technology for the fabrication of truly ecofriendly optoelectronic systems

Failure to confirm influence of Methyltetrahydrofolate reductase (MTHFR) polymorphisms on age at onset of Huntington disease

BACKGROUND: Huntington disease (HD) is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO) of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Recently, suggestive association has been reported between a single nucleotide polymorphism (SNP; rs1801131, also known as A1298C) in the methyltetrahydrofolate reductase (MTHFR) gene and AO of HD. 5,10-MTHFR is a key enzyme in the folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using part of a previously established study cohort plus additional patients and appropriate statistical methods, we reinvestigated two polymorphisms in the MTHFR gene, C677T and A1298C, as well as their association with AO in 167 HD patients. RESULTS: There was no statistically significant impact on AO for HD patients, neither of MTHFR SNPs nor of the combinations thereof. CONCLUSION: Contrary to previously described evidence the A1298C polymorphism in the MTHFR gene does not appear to modulate AO of HD patients

Time-lagged response of siberian treeline forests revealed by individual-based modelling

Global warming allows arctic vegetation, which is mainly limited by temperatures, to move north. A change from tundra to taiga will cause a decrease of albedo which further fuels the warming through positive feedback mechanisms. This raises several questions of which we want to address here: (1) Will trees move northwards and thereby change vast treeless tundra areas to taiga? (2) And if so, how long does this response lags behind the temperature changes? To answer these questions we built an individual-based and spatially-explicit vegetation simulator model for larches in Siberia (LAVESI). We present the parameterization and validation of the model's incorporated processes which describe the full life-cycle of the simulated larch species Larix gmelinii. Furthermore, we share results of the first regional-scale simulations testing the model's performance at the Taymyr Peninsula, Russia, ranging from 64-80° N and 92-120° E. In a second experiment, we tested the influence of up to 6 °C warmer and cooler climates on simulated populations. Our results show that already the recent temperature rise will allow forests to expand farther north by roughly one degree, when no seed limitation hinders populations to migrate. Furthermore, climate warming caused populations to densify but with a time-lag of decades. We conclude that in the near future expanding taiga after its first establishment in the former tundra will rapidly form dense tree stands, thus ultimatively fueling the feedback loop of global warming. We show that simulation results of the newly-build vegetation model were reliable, and hence the model can be used as a tool to improve our knowledge about individual-based processes that are important to understand past and future treeline migration

Reconstruction of Images from Gabor Graphs with Applications in Facial Image Processing

Graphs labeled with complex-valued Gabor jets are one of the important data formats for face recognition and the classification of facial images into medically relevant classes like genetic syndromes. We here present an interpolation rule and an iterative algorithm for the reconstruction of images from these graphs. This is especially important if graphs have been manipulated for information processing. One such manipulation is averaging the graphs of a single syndrome, another one building a composite face from the features of various individuals. In reconstructions of averaged graphs of genetic syndromes, the patients' identities are suppressed, while the properties of the syndromes are emphasized. These reconstructions from average graphs have a much better quality than averaged images

Spring snow cover duration and tundra greenness in the Lena Delta, Siberia: two decades of MODIS satellite time series (2001–2021)

The Lena Delta in Siberia is the largest delta in the Arctic and as a snow-dominated ecosystem particularly vulnerable to climate change. Using the two decades of MODerate resolution Imaging Spectroradiometer satellite acquisitions, this study investigates interannual and spatial variability of snow-cover duration and summer vegetation vitality in the Lena Delta. We approximated snow by the application of the normalized difference snow index and vegetation greenness by the normalized difference vegetation index (NDVI). We consolidated the analyses by integrating reanalysis products on air temperature from 2001 to 2021, and air temperature, ground temperature, and the date of snow-melt from time-lapse camera (TLC) observations from the Samoylov observatory located in the central delta. We extracted spring snow-cover duration determined by a latitudinal gradient. The ‘regular year’ snow-melt is transgressing from mid-May to late May within a time window of 10 days across the delta. We calculated yearly deviations per grid cell for two defined regions, one for the delta, and one focusing on the central delta. We identified an ensemble of early snow-melt years from 2012 to 2014, with snow-melt already starting in early May, and two late snow-melt years in 2004 and 2017, with snow-melt starting in June. In the times of TLC recording, the years of early and late snow-melt were confirmed. In the three summers after early snow-melt, summer vegetation greenness showed neither positive nor negative deviations. Whereas, vegetation greenness was reduced in 2004 after late snow-melt together with the lowest June monthly air temperature of the time series record. Since 2005, vegetation greenness is rising, with maxima in 2018 and 2021. The NDVI rise since 2018 is preceded by up to 4 °C warmer than average June air temperature. The ongoing operation of satellite missions allows to monitor a wide range of land surface properties and processes that will provide urgently needed data in times when logistical challenges lead to data gaps in land-based observations in the rapidly changing Arctic.GeoXREKLIMBMBFERCPeer Reviewe