Local temperatures inferred from plant communities suggest strong spatial buffering of climate warming across Northern Europe

Recent studies from mountainous areas of small spatial extent (<2500 km²) suggest that fine‐grained thermal variability over tens or hundreds of metres exceeds much of the climate warming expected for the coming decades. Such variability in temperature provides buffering to mitigate climate‐change impacts. Is this local spatial buffering restricted to topographically complex terrains? To answer this, we here study fine‐grained thermal variability across a 2500‐km wide latitudinal gradient in Northern Europe encompassing a large array of topographic complexities. We first combined plant community data, Ellenberg temperature indicator values, locally measured temperatures (LmT) and globally interpolated temperatures (GiT) in a modelling framework to infer biologically relevant temperature conditions from plant assemblages within <1000‐m² units (community‐inferred temperatures: CiT). We then assessed: (1) CiT range (thermal variability) within 1‐km² units; (2) the relationship between CiT range and topographically and geographically derived predictors at 1‐km resolution; and (3) whether spatial turnover in CiT is greater than spatial turnover in GiT within 100‐km² units. Ellenberg temperature indicator values in combination with plant assemblages explained 46–72% of variation in LmT and 92–96% of variation in GiT during the growing season (June, July, August). Growing‐season CiT range within 1‐km² units peaked at 60–65°N and increased with terrain roughness, averaging 1.97 °C (SD = 0.84 °C) and 2.68 °C (SD = 1.26 °C) within the flattest and roughest units respectively. Complex interactions between topography‐related variables and latitude explained 35% of variation in growing‐season CiT range when accounting for sampling effort and residual spatial autocorrelation. Spatial turnover in growing‐season CiT within 100‐km² units was, on average, 1.8 times greater (0.32 °C km^?1) than spatial turnover in growing‐season GiT (0.18 °C km^?1). We conclude that thermal variability within 1‐km² units strongly increases local spatial buffering of future climate warming across Northern Europe, even in the flattest terrains.     

Characterization of Novel CSF Tau and ptau Biomarkers for Alzheimer’s Disease

Cerebral spinal fluid (CSF) Aβ42, tau and p181tau are widely accepted biomarkers of Alzheimer’s disease (AD). Numerous studies show that CSF tau and p181tau levels are elevated in mild-to-moderate AD compared to age-matched controls. In addition, these increases might predict preclinical AD in cognitively normal elderly. Despite their importance as biomarkers, the molecular nature of CSF tau and ptau is not known. In the current study, reverse-phase high performance liquid chromatography was used to enrich and concentrate tau prior to western-blot analysis. Multiple N-terminal and mid-domain fragments of tau were detected in pooled CSF with apparent sizes ranging from <20 kDa to ~40 kDa. The pattern of tau fragments in AD and control samples were similar. In contrast, full-length tau and C-terminal-containing fragments were not detected. To quantify levels, five tau ELISAs and three ptau ELISAs were developed to detect different overlapping regions of the protein. The discriminatory potential of each assay was determined using 20 AD and 20 age-matched control CSF samples. Of the tau ELISAs, the two assays specific for tau containing N-terminal sequences, amino acids 9-198 (numbering based on tau 441) and 9-163, exhibited the most significant differences between AD and control samples. In contrast, CSF tau was not detected with an ELISA specific for a more C-terminal region (amino acids 159-335). Significant discrimination was also observed with ptau assays measuring amino acids 159-p181 and 159-p231. Interestingly, the discriminatory potential of p181 was reduced when measured in the context of tau species containing amino acids 9-p181. Taken together, these results demonstrate that tau in CSF occurs as a series of fragments and that discrimination of AD from control is dependent on the subset of tau species measured. These assays provide novel tools to investigate CSF tau and ptau as biomarkers for other neurodegenerative diseases.     

Temperament and Character in the Child and Adolescent Twin Study in Sweden (CATSS): Comparison to the General Population,and Genetic Structure Analysis

Background

The Child and Adolescent Twin Study in Sweden (CATSS) is an on-going, large population-based longitudinal twin study. We aimed (1) to investigate the reliability of two different versions (125-items and 238-items) of Cloninger''s Temperament and Character Inventory (TCI) used in the CATSS and the validity of extracting the short version from the long version, (2) to compare these personality dimensions between twins and adolescents from the general population, and (3) to investigate the genetic structure of Cloninger''s model.

Method

Reliability and correlation analyses were conducted for both TCI versions, 2,714 CATSS-twins were compared to 631 adolescents from the general population, and the genetic structure was investigated through univariate genetic analyses, using a model-fitting approach with structural equation-modeling techniques based on same-sex twin pairs from the CATSS (423 monozygotic and 408 dizygotic pairs).

Results

The TCI scores from the short and long versions showed comparable reliability coefficients and were strongly correlated. Twins scored about half a standard deviation higher in the character scales. Three of the four temperament dimensions (Novelty Seeking, Harm Avoidance, and Persistence) had strong genetic and non-shared environmental effects, while Reward Dependence and the three character dimensions had moderate genetic effects, and both shared and non-shared environmental effects.

Conclusions

Twins showed higher scores in character dimensions compared to adolescents from the general population. At least among adolescents there is a shared environmental influence for all of the character dimensions, but only for one of the temperament dimensions (i.e., Reward Dependence). This specific finding regarding the existence of shared environmental factors behind the character dimensions in adolescence, together with earlier findings showing a small shared environmental effects on character among young adults and no shared environmental effects on character among adults, suggest that there is a shift in type of environmental influence from adolescence to adulthood regarding character.     

Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions

Microfibrillar-associated protein 4 (MFAP4) is located in the extracellular matrix (ECM). We sought to identify tissues with high levels of MFAP4 mRNA and MFAP4 protein expression. Moreover, we aimed to evaluate the significance of MFAP4 as a marker of cardiovascular disease (CVD) and to correlate MFAP4 with other known ECM markers, such as fibulin-1, osteoprotegerin (OPG), and osteopontin (OPN). Quantitative real-time PCR demonstrated that MFAP4 mRNA was more highly expressed in the heart, lung, and intestine than in other elastic tissues. Immunohistochemical studies demonstrated high levels of MFAP4 protein mainly at sites rich in elastic fibers and within blood vessels in all tissues investigated. The AlphaLISA technique was used to determine serum MFAP4 levels in a clinical cohort of 172 patients consisting of 5 matched groups with varying degrees of CVD: 1: patients with ST elevation myocardial infarction (STEMI), 2: patients with non-STEMI, 3: patients destined for vascular surgery because of various atherosclerotic diseases (stable atherosclerotic disease), 4: apparently healthy individuals with documented coronary artery calcification (CAC-positive), and 5: apparently healthy individuals without signs of coronary artery calcification (CAC-negative). Serum MFAP4 levels were significantly lower in patients with stable atherosclerotic disease than CAC-negative individuals (p<0.05). Furthermore, lower serum MFAP4 levels were present in patients with stable atherosclerotic disease compared with STEMI and non-STEMI patients (p<0.05). In patients with stable atherosclerotic disease, positive correlations between MFAP4 and both fibulin-1 (ρ = 0.50; p = 0.0244) and OPG (ρ = 0.62; p = 0.0014) were found. Together, these results indicate that MFAP4 is mainly located in elastic fibers and is highly expressed in blood vessels. The present study suggests that serum MFAP4 varies in groups of patients with different cardiovascular conditions. Further studies are warranted to describe the role of serum MFAP4 as a biomarker of stable atherosclerotic disease.     

Molecular Weight Dependence of Exciton Diffusion in Poly(3‐hexylthiophene)

A joint experimental and theoretical study of singlet exciton diffusion in spin‐coated poly(3‐hexylthiophene) (P3HT) films and its dependence on molecular weight is presented. The results show that exciton diffusion is fast along the co‐facial π–π aggregates of polymer chromophores and about 100 times slower in the lateral direction between aggregates. Exciton hopping between aggregates is found to show a subtle dependence on interchain coupling, aggregate size, and Boltzmann statistics. Additionally, a clear correlation is observed between the effective exciton diffusion coefficient, the degree of aggregation of chromophores, and exciton delocalization along the polymer chain, which suggests that exciton diffusion length can be enhanced by tailored synthesis and processing conditions.     

Semi-automated 3D Leaf Reconstruction and Analysis of Trichome Patterning from Light Microscopic Images

Trichomes are leaf hairs that are formed by single cells on the leaf surface. They are known to be involved in pathogen resistance. Their patterning is considered to emerge from a field of initially equivalent cells through the action of a gene regulatory network involving trichome fate promoting and inhibiting factors. For a quantitative analysis of single and double mutants or the phenotypic variation of patterns in different ecotypes, it is imperative to statistically evaluate the pattern reliably on a large number of leaves. Here we present a method that enables the analysis of trichome patterns at early developmental leaf stages and the automatic analysis of various spatial parameters. We focus on the most challenging young leaf stages that require the analysis in three dimensions, as the leaves are typically not flat. Our software TrichEratops reconstructs 3D surface models from 2D stacks of conventional light-microscope pictures. It allows the GUI-based annotation of different stages of trichome development, which can be analyzed with respect to their spatial distribution to capture trichome patterning events. We show that 3D modeling removes biases of simpler 2D models and that novel trichome patterning features increase the sensitivity for inter-accession comparisons.     

Frequency Dependence of Signal Power and Spatial Reach of the Local Field Potential

Despite its century-old use, the interpretation of local field potentials (LFPs), the low-frequency part of electrical signals recorded in the brain, is still debated. In cortex the LFP appears to mainly stem from transmembrane neuronal currents following synaptic input, and obvious questions regarding the ‘locality’ of the LFP are: What is the size of the signal-generating region, i.e., the spatial reach, around a recording contact? How far does the LFP signal extend outside a synaptically activated neuronal population? And how do the answers depend on the temporal frequency of the LFP signal? Experimental inquiries have given conflicting results, and we here pursue a modeling approach based on a well-established biophysical forward-modeling scheme incorporating detailed reconstructed neuronal morphologies in precise calculations of population LFPs including thousands of neurons. The two key factors determining the frequency dependence of LFP are the spatial decay of the single-neuron LFP contribution and the conversion of synaptic input correlations into correlations between single-neuron LFP contributions. Both factors are seen to give low-pass filtering of the LFP signal power. For uncorrelated input only the first factor is relevant, and here a modest reduction (<50%) in the spatial reach is observed for higher frequencies (>100 Hz) compared to the near-DC () value of about . Much larger frequency-dependent effects are seen when populations of pyramidal neurons receive correlated and spatially asymmetric inputs: the low-frequency () LFP power can here be an order of magnitude or more larger than at 60 Hz. Moreover, the low-frequency LFP components have larger spatial reach and extend further outside the active population than high-frequency components. Further, the spatial LFP profiles for such populations typically span the full vertical extent of the dendrites of neurons in the population. Our numerical findings are backed up by an intuitive simplified model for the generation of population LFP.     

Carboxylesterase 1 Gene Duplication and mRNA Expression in Adipose Tissue Are Linked to Obesity and Metabolic Function

Context and Aims

Carboxylesterase 1 (CES1) appears to play an important role in the control of the metabolism of triglycerides and cholesterol in adipocytes and other cell types including hepatocytes. Therefore, it is relevant to gain insights into the genetic versus non-genetic mechanisms involved in the control of CES1 mRNA expression. Here, we investigated CES1 mRNA expression level in adipose tissue and its association with measures of adiposity and metabolic function in a population of elderly twins. Furthermore, the heritability of CES1 mRNA expression level in adipose tissue and the effect of CES1 gene duplication were assessed.

Methodology

A total of 295 monozygotic and dizygotic twin subjects (62–83 years) with (n = 48) or without (n = 247) type 2 diabetes mellitus were enrolled in the study. They were subjected to a standard oral glucose tolerance test and excision of abdominal subcutaneous fat biopsies during the fasting state. Levels of CES1 mRNA and copy number of the gene were assessed by quantitative PCR.

Results

CES1 mRNA expression level in adipose tissue was positively associated with body-mass index (P<0.001), homeostasis model assessment-insulin resistance (P = 0.003) and level of fasting glucose (P = 0.002), insulin (P = 0.006), and triglycerides (P = 0.003). The heritability for the expression of CES1 mRNA in adipose tissue was high. CES1 gene duplication was positively associated with insulin sensitivity (P = 0.05) as well as glucose tolerance (P = 0.03) and negatively associated with homeostasis model assessment-insulin resistance (P = 0.02). Duplication of CES1 was not linked to mRNA level of this gene (P = 0.63).

Conclusion

CES1 mRNA in adipose tissue appears to be under strong genetic control and was associated with measures of metabolic function raising the possibility of a potential role of this enzyme in the development of type 2 diabetes mellitus. Further studies are needed to understand the potential effect of CES1 gene duplication on adipocyte and whole-body metabolic functions.     

Global and 3D Spatial Assessment of Neuroinflammation in Rodent Models of Multiple Sclerosis

Multiple Sclerosis (MS) is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS). T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE) animal models for the disease. A technology for quantitative and 3 dimensional (3D) spatial assessment of inflammation in this and other CNS inflammatory conditions is much needed. Here we present a procedure for 3D spatial assessment and global quantification of the development of neuroinflammation based on Optical Projection Tomography (OPT). Applying this approach to the analysis of rodent models of MS, we provide global quantitative data of the major inflammatory component as a function of the clinical course. Our data demonstrates a strong correlation between the development and progression of neuroinflammation and clinical disease in several mouse and a rat model of MS refining the information regarding the spatial dynamics of the inflammatory component in EAE. This method provides a powerful tool to investigate the effect of environmental and genetic forces and for assessing the therapeutic effects of drug therapy in animal models of MS and other neuroinflammatory/neurodegenerative disorders.