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 SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis

Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis.     

Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.     

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.     

Microhabitat selection in the sand recluse spider (Sicarius thomisoides): the effect of rock size and temperature

In spiders, temperature is considered an important environmental variable for microhabitat selection. In this study, we evaluated the effect of temperature and rock size on the presence of the sand recluse spider Sicarius thomisoides and the degree of selectivity in different locations. This species is a large spider that lives under rocks in desert and semi-desert climates and is particularly active during the summer. In Chile, these spiders can be found at both coastal and inland locations under different thermal conditions, where usually the temperatures are lower near the coast. If large-scale climatic conditions are important for this species, they may be expected to select lower rock temperatures on the coast than at inland locations. In addition, we would expect that the spiders would choose larger rocks in inland compared to coast locations, which reduce the effect of high temperatures. We found that the probability of finding individuals of this species increased according to rock temperature and rock size in the field. Our results suggest that S. thomisoides prefers larger and warmer rocks to shelter under during the day, this selectivity being similar at both coastal and inland locations. Thus, this species tends to select rocks with the same thermal and structural conditions, independent of the climatic conditions.     

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.     

A new parasitoid (Hymenoptera: Braconidae: Aphidiinae) of the invasive bamboo aphids Takecallis spp. (Hemiptera: Aphididae) from Western Europe

A long-term survey of tritrophic (plant–aphid–parasitoid) associations in the urban ecosystems of Lleida (Catalonia) and Paris (France) resulted in the detection of associations of two bamboo aphids, Takecallis arundinariae (Essig) and Takecallis taiwanus (Takahashi), respectively, with a new aphid parasitoid species. Trioxys remaudierei Starý & Rakhshani sp. nov. is described and illustrated as a unique parasitoid of Takecallis aphids outside the area of their origin. The new species is easily distinguishable from its congeners in having the ventral prongs of the abdomen fused over two-thirds of their length, then bifurcated towards the tip. The only morphologically similar species is Trioxys betulae (Marshall), which exhibits a clearly different prong shape (and has a different host range, Symydobius Mordvilko and Clethrobius Mordvilko). The new species is compared with allied taxa associated with bamboo aphids. The occurrence of Takecallis taiwanus on bamboo is recorded in France for the first time.

www.zoobank.org/urn:lsid:zoobank.org:pub:ED15BA16-E8A9-4CEA-BDA7-FBAB02FEB091     

Immunoregulatory properties of the cytokine IL-34

Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more complex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Until now, studies have demonstrated that this cytokine is released by some tissues that differ to those where CSF-1 is expressed and is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation. The involvement of IL-34 has been shown in areas as diverse as neuronal protection, autoimmune diseases, infection, cancer, and transplantation. Our recent work has demonstrated a new and possible therapeutic role for IL-34 as a Foxp3⁺ Treg-secreted cytokine mediator of transplant tolerance. In this review, we recapitulate most recent findings on IL-34 and its controversial effects on immune responses and address its immunoregulatory properties and the potential of targeting this cytokine in human.