Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.     

Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome

3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome.     

Asynchronous reproduction in three species of crocodilians in south-eastern Amazonia

We studied reproduction of three species of crocodilians, Paleosuchus trigonatus, Caiman crocodilus and Melanosuchus niger, in the Xingu River, near the Belo Monte hydroelectric dam. The periods of laying and hatching of eggs were estimated for each nest before (2013–2014) and after (2016–2017) the river was dammed and the reservoir was formed. Nesting of the three species occurred between August and December, but was largely asynchronous; nest construction peaked in September for P. trigonatus, October for M. niger and November for C. crocodilus. Reservoir filling had little effect on the laying period of any of the species. Nests of P. trigonatus and M. niger were always within 0–12 m of the bank, whereas nests of C. crocodilus, which nests later in the season when flooding is more likely, were up to 100 m from the nearest water body. There was no relationship between distance from water and the number of eggs in nests, suggesting that larger and presumably more experienced females do not lay at different distances from the bank in any of the species.     

Natural history of the Lined Seedeater Sporophila lineola (Aves: Thraupidae) in southeastern Brazil

The Lined Seedeater (Sporophila lineola) is a migratory species that inhabits a variety of open habitats in South America. We studied the breeding biology and territorial behaviour of a colour-banded population of the species in the Universidade Federal de Viçosa, Campus Florestal (1–19,8808ºS, –44,4136ºW), during two breeding seasons (2014/2015 and 2015/2016), which spans from December to April. We monitored 74 nests of this species. The nest is a low cup supported between a fork. Nests are mainly built with grass stems and rootlets, with spider-web used to hold the material together and to bind the nest to its supporting plant. Females are solely responsible for nest building and incubation, which is synchronic, and also for feeding nestlings to a large extent. Males are responsible for defending the territory, which corresponds to a small portion of the home range restricted to the nest environs, and also feed the nestlings. Mean clutch size is two eggs (78% of nests monitored), with clutches of three (20.3%) and four (1.7%) eggs also observed. Eggs are whitish, covered with dark brown blotches and spots to a variable extent. Mean incubation period, considered as the period between the onset of incubation and hatching of the first egg, is 11 days. Nestling period, considered as the period between hatching of the first egg and fledging of the last young, is 10 days. During the first breeding season, the simple percentage of successful nests was 34.1%, while the Mayfield success was 29.8%, with slightly higher values observed during the second breeding season, with 39.4% and 35.7%, respectively. We recorded, for the first time, three cases of polygamy in the species. We also recorded breeding site fidelity for the first time in the species, with males returning to the same territory owned in a previous breeding season.     

Can We Predict the Financial Markets Based on Google's Search Queries?

We look into the interaction of Google's search queries and several aspects of international equity markets. Using a novel methodology for selecting words and a vector autoregressive modeling approach, we study whether the search queries of finance‐related words can have an impact on returns, volatility of returns and traded volume in four different English‐speaking countries. We identify several words whose search frequency is associated with changes in the dependent variables. In particular, we find that increases in search queries including the word stock predict increased volatility and decreased index returns over the next week. On top of that, we investigate the performance of a market‐timing strategy based on the search frequency of this word and benchmark it against random words from the Word‐Net database and a naive buy‐and‐hold strategy. The results of this empirical application are positive and particularly stronger during the global crisis of 2009. Copyright © 2016 John Wiley & Sons, Ltd.     

Proliferation status defines functional properties of endothelial cells

Homeostasis of solid tissue is characterized by a low proliferative activity of differentiated cells while special conditions like tissue damage induce regeneration and proliferation. For some cell types it has been shown that various tissue-specific functions are missing in the proliferating state, raising the possibility that their proliferation is not compatible with a fully differentiated state. While endothelial cells are important players in regenerating tissue as well as in the vascularization of tumors, the impact of proliferation on their features remains elusive. To examine cell features in dependence of proliferation, we established human endothelial cell lines in which proliferation is tightly controlled by a doxycycline-dependent, synthetic regulatory unit. We observed that uptake of macromolecules and establishment of cell–cell contacts was more pronounced in the growth-arrested state. Tube-like structures were formed in vitro in both proliferating and non-proliferating conditions. However, functional vessel formation upon transplantation into immune-compromised mice was restricted to the proliferative state. Kaposi’s sarcoma-associated herpes virus (KSHV) infection resulted in reduced expression of endothelial markers. Upon transplantation of infected cells, drastic differences were observed: proliferation arrested cells acquired a high migratory activity while the proliferating counterparts established a tumor-like phenotype, similar to Kaposi Sarcoma lesions. The study gives evidence that proliferation governs endothelial functions. This suggests that several endothelial functions are differentially expressed during angiogenesis. Moreover, since proliferation defines the functional properties of cells upon infection with KSHV, this process crucially affects the fate of virus-infected cells.     

Assembly and regulation of ASC specks

The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function. In several inflammatory diseases, ASC specks can be found in the extracellular space and its presence correlates with poor prognosis. Here, we review the role of ASC in inflammation, and focus on the structural mechanisms that lead to ASC speck formation, the regulation of ASC function during inflammasome assembly, and the importance of ASC specks in disease.     

Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A

Red blood cells (RBC) have emerged as a novel regulatory cell type endowed with bioactivities toward activated human T cells. Herein we show that the RBC bioactivities act on intracellular pathways initiated by T cell receptor (TCR)-dependent and -independent stimuli, including IL-2, IL-15, and the mixture of phorbol dibutyrate and ionomycin. The RBC bioactivities preserve the antioxidant status and are capable of rescuing activated T cells from cell death induced by serum deprivation. They are not mediated by glycosylphosphatidylinositol-linked receptors or sialic acids, and kinetic studies revealed that they hasten the entrance into the cell cycle. By using cyclosporine A (CsA) and rapamycin (Rapa) we show that the RBC bioactivities are calcineurin-dependent. Thus, treatment of T cells with CsA, but not Rapa, impaired RBC bioactivities, and preincubation of RBC with CsA completely abolished their bioactivities. We have demonstrated that RBC carry out bioactivities that are sensitive to CsA.