Non-Selective Calcium Channel Blocker Bepridil Decreases Secondary Pathology in Mice after Photothrombotic Cortical Lesion

Experimental studies have identified a complex link between neurodegeneration, β-amyloid (Aβ) and calcium homeostasis. Here we asked whether early phase β-amyloid pathology in transgenic hAPP_SL mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPP_SL (n = 33) and non-transgenic (n = 30) male mice (4–5 months) were subjected to unilateral cortical photothrombosis and treated with the non-selective calcium channel blocker bepridil (50 mg/kg, p.o., once a day) or vehicle for 28 days, starting administration 2 days after the operation. Animals were then perfused for histological analysis of infarct size, Aβ and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical Aβ and calcium accumulation in the ipsilateral thalamus. Transgenic mice had significantly smaller infarct volumes than non-transgenic littermates (P<0.05) and ischemia-induced rodent Aβ accumulation in the thalamus was lower in transgenic mice compared to non-transgenic mice (P<0.01). Bepridil decreased calcium load in the thalamus (P<0.01). The present data suggest less pronounced primary and secondary pathology in hAPP_SL transgenic mice after ischemic cortical injury. Bepridil particularly decreased calcium pathology in the thalamus following ischemia.     

The breeding biology of the starling Sturnus vulgaris in northern Finland

The breeding biology of the starling Sturnus vulgaris was studied in three populations in northern Finland, with additional reference localities in nearby areas. Results from a total of 329 nests are presented from years 1962-1976.
The onset of laying in the Oulu area took place on 5 May, the median date being 10 May, about one week later than in southern Finland and 2–3 weeks later than in central Europe. The clutch-size was 5.29 ± 0.05 in the first nests and 5.06 ± 0.26 in later ones. Incubation time was 12.1 ± 0.6 d. An average of 3.31 ± 0.10 fledglings was produced per pair, 3.69 ± 0.08 in succesful clutches, which is significantly less than usually reported from central Europe. Most of the losses were due to starvation of the young.
No second broods were observed in the Oulu area, and repeated nesting was not common, probably because of the general late start of laying.
The reasons for the recent decline in several Finnish starling populations do not lie in the production capacity but must be sought for elsewhere.     

Body Weight and Health Status: Importance of Socioeconomic Position and Working Conditions

Objective: To examine the association between relative body weight and health status and the potential modifying effects of socioeconomic position and working conditions on this association. Research Methods and Procedures: The data were derived from three identical cross‐sectional surveys conducted in 2000, 2001, and 2002. Respondents to postal surveys were middle‐aged employees of the City of Helsinki (7148 women and 1799 men, response rate 67%). BMI was based on self‐reported weight and height. Health status was measured by the Short‐Form 36 subscales and component summaries. Results: Body weight was inversely associated with physical health, but in mental health, differences between BMI categories were small and inconsistent. In women, physical health deteriorated monotonically with increasing BMI, whereas in men, poor physical health was found among the obese only. Socioeconomic position did not modify the association between BMI and health. In women, the association between body weight and physical health became stronger with decreasing job control and increasing physical work load, whereas in men, a similar modifying effect was found for high job demands. Discussion: Body weight was associated with physical health only. Lower levels of relative weight in women than in men may be associated with poor physical health. High body weight combined with adverse working conditions may impose a double burden on physical health.     

Maternal coding variants in complement receptor 1 and spontaneous idiopathic preterm birth

Preterm birth (PTB) is a major global public health concern. However, little is known about the pathophysiology of spontaneous idiopathic PTB. We tested the hypothesis that rare variants in families would target specific genes and pathways that contribute to PTB risk in the general population. Whole-exome sequencing was performed on 10 PTB mothers from densely affected families including two mother–daughter pairs. We identified novel variants shared between the two mother–daughter pairs when compared to a 1000 Genomes Project background exome file and investigated these genes for pathway aggregation using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Genes in enriched pathways were then surveyed in the other six PTB exomes and tested for association in a larger number of nuclear families. The KEGG complement and coagulation cascade was one of the most enriched pathways in our two mother–daughter pairs. When the six genes found in this pathway (CFH, CR1, F13B, F5, CR2, and C4BPA) were examined for novel missense variants, half of all the exomes harbored at least one. Association analysis of variants in these six gene regions in nuclear families from Finland (237 cases and 328 controls) found statistically significant associations after multiple test corrections in three CR1 SNPs; the strongest in an exonic missense SNP, rs6691117, p value = 6.91e?5, OR = 1.71. Our results demonstrate the importance of the complement and coagulation cascades in the pathophysiology of PTB, and suggest potential screening and intervention approaches to prevent prematurity that target this pathway.     

Membrane filtering properties of the bumblebee (Bombus terrestris) photoreceptors across three spectral classes

Filtering properties of the membrane form an integral part of the mechanisms producing the light-induced electrical signal in insect photoreceptors. Insect photoreceptors vary in response speed between different species, but recently it has also been shown that different spectral photoreceptor classes within a species possess diverse response characteristics. However, it has not been quantified what roles phototransduction and membrane properties play in such diversity. Here, we use electrophysiological methods in combination with system analysis to study whether the membrane properties could create the variation of the response speed found in the bumblebee (Bombus terrestris) photoreceptors. We recorded intracellular responses from each photoreceptor class to white noise-modulated current stimuli and defined their input resistance and linear filtering properties. We found that green sensitive cells exhibit smaller input resistance and membrane impedance than other cell classes. Since green sensitive cells are the fastest photoreceptor class in the bumblebee retina, our results suggest that the membrane filtering properties are correlated with the speed of light responses across the spectral classes. In general, our results provide a compelling example of filtering at the sensory cell level where the biophysical properties of the membrane are matched to the performance requirements set by visual ecology.     

Multi‐generational long‐distance migration of insects: studying the painted lady butterfly in the Western Palaearctic

Long‐range, seasonal migration is a widespread phenomenon among insects, allowing them to track and exploit abundant but ephemeral resources over vast geographical areas. However, the basic patterns of how species shift across multiple locations and seasons are unknown in most cases, even though migrant species comprise an important component of the temperate‐zone biota. The painted lady butterfly Vanessa cardui is such an example; a cosmopolitan continuously‐brooded species which migrates each year between Africa and Europe, sometimes in enormous numbers. The migration of 2009 was one of the most impressive recorded, and thousands of observations were collected through citizen science programmes and systematic entomological surveys, such as high altitude insect‐monitoring radar and ground‐based butterfly monitoring schemes. Here we use V. cardui as a model species to better understand insect migration in the Western Palaearctic, and we capitalise on the complementary data sources available for this iconic butterfly. The migratory cycle in this species involves six generations, encompassing a latitudinal shift of thousands of kilometres (up to 60 degrees of latitude). The cycle comprises an annual poleward advance of the populations in spring followed by an equatorward return movement in autumn, with returning individuals potentially flying thousands of kilometres. We show that many long‐distance migrants take advantage of favourable winds, moving downwind at high elevation (from some tens of metres from the ground to altitudes over 1000 m), pointing at strong similarities in the flight strategies used by V. cardui and other migrant Lepidoptera. Our results reveal the highly successful strategy that has evolved in these insects, and provide a useful framework for a better understanding of long‐distance seasonal migration in the temperate regions worldwide.     

Genetic Loci Associated with Alzheimer’s Disease and Cerebrospinal Fluid Biomarkers in a Finnish Case-Control Cohort

Objectives

To understand the relation between risk genes for Alzheimer’s disease (AD) and their influence on biomarkers for AD, we examined the association of AD in the Finnish cohort with single nucleotide polymorphisms (SNPs) from top AlzGene loci, genome-wide association studies (GWAS), and candidate gene studies; and tested the correlation between these SNPs and AD markers Aβ_1–42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF).

Methods

We tested 25 SNPs for genetic association with clinical AD in our cohort comprised of 890 AD patients and 701-age matched healthy controls using logistic regression. For the correlational study with biomarkers, we tested 36 SNPs in a subset of 222 AD patients with available CSF using mixed models. Statistical analyses were adjusted for age, gender and APOE status. False discovery rate for multiple testing was applied. All participants were from academic hospital and research institutions in Finland.

Results

APOE-ε4, CLU rs11136000, and MS4A4A rs2304933 correlated with significantly decreased Aβ_1–42 (corrected p<0.05). At an uncorrected p<0.05, PPP3R1 rs1868402 and MAPT rs2435211 were related with increased t-tau; while SORL1 rs73595277 and MAPT rs16940758, with increased p-tau. Only TOMM40 rs2075650 showed association with clinical AD after adjusting for APOE-ε4 (p = 0.007), but not after multiple test correction (p>0.05).

Conclusions

We provide evidence that APOE-ε4, CLU and MS4A4A, which have been identified in GWAS to be associated with AD, also significantly reduced CSF Aβ_1–42 in AD. None of the other AlzGene and GWAS loci showed significant effects on CSF tau. The effects of other SNPs on CSF biomarkers and clinical AD diagnosis did not reach statistical significance. Our findings suggest that APOE-ε4, CLU and MS4A4A influence both AD risk and CSF Aβ_1–42.