Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling

Wnt/β-catenin signalling is central to development and its regulation is essential in preventing cancer. Using phosphorylation of Dishevelled as readout of pathway activation, we identified Drosophila Wnk kinase as a new regulator of canonical Wnt/β-catenin signalling. WNK kinases are known for regulating ion co-transporters associated with hypertension disorders. We demonstrate that wnk loss-of-function phenotypes resemble canonical Wnt pathway mutants, while Wnk overexpression causes gain-of-function canonical Wnt-signalling phenotypes. Importantly, knockdown of human WNK1 and WNK2 also results in decreased Wnt signalling in mammalian cell culture, suggesting that Wnk kinases have a conserved function in ensuring peak levels of canonical Wnt signalling.     

Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases

Introduction

Gout is a common arthritis that occurs particularly in patients who frequently have associated comorbidities that limit the use of conventional therapies. The main mechanism of crystal-induced inflammation is interleukin-1 production by activation of the inflammasome. We aimed to evaluate the efficacy and tolerance of anakinra in gouty patients.

Methods

We conducted a multicenter retrospective review of patients receiving anakinra for gouty arthritis. We reviewed the response to treatment, adverse events and relapses.

Results

We examined data for 40 gouty patients (32 men; mean age 60.0 ± 13.9 years) receiving anakinra. Mean disease duration was 8.7 ± 8.7 years. All patients showed contraindications to and/or failure of at least two conventional therapies. Most (36; 90%) demonstrated good response to anakinra. Median pain on a 100-mm visual analog scale was rapidly decreased (73.5 (70.0 to 80.0) to 25.0 (20.0 to 32.5) mm, P <0.0001), as was median C-reactive protein (CRP) level (130.5 (55.8 to 238.8) to 16.0 (5.0 to 29.5) mg/l, P <0.0001). After a median follow-up of 7.0 (2.0 to 13.0) months, relapse occurred in 13 patients after a median delay of 15.0 (10.0 to 70.0) days. Seven infectious events, mainly with long-term use of anakinra, were noted.

Conclusions

Anakinra may be efficient in gouty arthritis, is relatively well tolerated with short-term use, and could be a relevant option in managing gouty arthritis when conventional therapies are ineffective or contraindicated. Its long-term use could be limited by infectious complications.     

The genera in the second catalogue (1833–1836) of?Dejean’s Coleoptera collection

All genus-group names listed in the second edition of the catalogue (1833-1836) of Dejean’s beetle collection are recorded. For each new genus-group name the originally included available species are listed and for generic names with at least one available species, the type species and the current status are given. Names available prior to the publication of Dejean’s second catalogue (1833-1836) are listed in an appendix.The following new synonymies are proposed: Cyclonotum Dejean, 1833 (= Dactylosternum Wollaston, 1854) [Hydrophilidae], Hyporhiza Dejean, 1833 (= Rhinaspis Perty, 1830) [Scarabaeidae], Aethales Dejean, 1834 (= Epitragus Latreille, 1802) [Tenebrionidae], Arctylus Dejean, 1834 (= Praocis Eschscholtz, 1829) [Tenebrionidae], Euphron Dejean, 1834 (= Derosphaerus Thomson, 1858) [Tenebrionidae], Hipomelus Dejean, 1834 (= Trachynotus Latreille, 1828) [Tenebrionidae], Pezodontus Dejean, 1834 (= Odontopezus Alluaud, 1889) [Tenebrionidae], Zygocera Dejean, 1835 (= Disternopsis Breuning, 1939) [Cerambycidae], and Physonota Chevrolat, 1836 (= Anacassis Spaeth, 1913) [Chrysomelidae]. Heterogaster pilicornis Dejean, 1835 [Cerambycidae] and Labidomera trimaculata Chevrolat, 1836 [Chrysomelidae] are placed for the first time in synonymy with Anisogaster flavicans Deyrolle, 1862 and Chrysomela clivicollis Kirby, 1837 respectively. Type species of the following genus-group taxa are proposed: Sphaeromorphus Dejean, 1833 (Sphaeromorphus humeralis Erichson, 1843) [Scarabaeidae], Adelphus Dejean, 1834 (Helops marginatus Fabricius, 1792) [Tenebrionidae], Cyrtoderes Dejean, 1834 (Tenebrio cristatus DeGeer, 1778) [Tenebrionidae], Selenepistoma Dejean, 1834 (Opatrum acutum Wiedemann, 1823) [Tenebrionidae], Charactus Dejean, 1833 (Lycus limbatus Fabricius, 1801) [Lycidae], Corynomalus Chevrolat, 1836 (Eumorphus limbatus Olivier, 1808) [Endomychidae], Hebecerus Dejean, 1835 (Acanthocinus marginicollis Boisduval, 1835) [Cerambycidae], Pterostenus Dejean, 1835 (Cerambyx abbreviatus Fabricius, 1801) [Cerambycidae], Psalicerus Dejean, 1833 (Lucanus femoratus Fabricius, 1775) [Lucanidae], and Pygolampis Dejean, 1833 (Lampyris glauca Olivier, 1790) [Lampyridae]. A new name, Neoeutrapela Bousquet and Bouchard [Tenebrionidae], is proposed for Eutrapela Dejean, 1834 (junior homonym of Eutrapela Hübner, 1809).The following generic names, made available in Dejean’s catalogue, were found to be older than currently accepted valid names: Catoxantha Dejean, 1833 over Catoxantha Solier, 1833 [Buprestidae], Pristiptera Dejean, 1833 over Pelecopselaphus Solier, 1833 [Buprestidae], Charactus Dejean, 1833 over Calopteron Laporte, 1836 [Lycidae], Cyclonotum Dejean, 1833 over Dactylosternum Wollaston, 1854 [Hydrophilidae], Ancylonycha Dejean, 1833 over Holotrichia Hope, 1837 [Scarabaeidae], Aulacium Dejean, 1833 over Mentophilus Laporte, 1840 [Scarabaeidae], Sciuropus Dejean, 1833 over Ancistrosoma Curtis, 1835 [Scarabaeidae], Sphaeromorphus Dejean, 1833 over Ceratocanthus White, 1842 [Scarabaeidae], Psalicerus Dejean, 1833 over Leptinopterus Hope, 1838 [Lucanidae], Adelphus Dejean, 1834 over Praeugena Laporte, 1840 [Tenebrionidae], Amatodes Dejean, 1834 over Oncosoma Westwood, 1843 [Tenebrionidae], Cyrtoderes Dejean, 1834 over Phligra Laporte, 1840 [Tenebrionidae], Euphron Dejean, 1834 over Derosphaerus Thomson, 1858 [Tenebrionidae], Pezodontus Dejean, 1834 over Odontopezus Alluaud, 1889 [Tenebrionidae], Anoplosthaeta Dejean, 1835 over Prosopocera Blanchard, 1845 [Cerambycidae], Closteromerus Dejean, 1835 over Hylomela Gahan, 1904 [Cerambycidae], Hebecerus Dejean, 1835 over Ancita Thomson, 1864 [Cerambycidae], Mastigocera Dejean, 1835over Mallonia Thomson, 1857 [Cerambycidae], Zygocera Dejean, 1835 over Disternopsis Breuning, 1939 [Cerambycidae], Australica Chevrolat, 1836 over Calomela Hope, 1840 [Chrysomelidae], Edusa Chevrolat, 1836 over Edusella Chapuis, 1874 [Chrysomelidae], Litosonycha Chevrolat, 1836 over Asphaera Duponchel and Chevrolat, 1842 [Chrysomelidae], and Pleuraulaca Chevrolat, 1836 over Iphimeis Baly, 1864 [Chrysomelidae]. In each of these cases, Reversal of Precedence (ICZN 1999: 23.9) or an applicationto the International Commission on Zoological Nomenclature will be necessary to retain usage of the younger synonyms.     

Do Red Deer Stags (Cervus elaphus) Use Roar Fundamental Frequency (F0) to Assess Rivals?

It is well established that in humans, male voices are disproportionately lower pitched than female voices, and recent studies suggest that this dimorphism in fundamental frequency (F0) results from both intrasexual (male competition) and intersexual (female mate choice) selection for lower pitched voices in men. However, comparative investigations indicate that sexual dimorphism in F0 is not universal in terrestrial mammals. In the highly polygynous and sexually dimorphic Scottish red deer Cervus elaphus scoticus, more successful males give sexually-selected calls (roars) with higher minimum F0s, suggesting that high, rather than low F0s advertise quality in this subspecies. While playback experiments demonstrated that oestrous females prefer higher pitched roars, the potential role of roar F0 in male competition remains untested. Here we examined the response of rutting red deer stags to playbacks of re-synthesized male roars with different median F0s. Our results show that stags’ responses (latencies and durations of attention, vocal and approach responses) were not affected by the F0 of the roar. This suggests that intrasexual selection is unlikely to strongly influence the evolution of roar F0 in Scottish red deer stags, and illustrates how the F0 of terrestrial mammal vocal sexual signals may be subject to different selection pressures across species. Further investigations on species characterized by different F0 profiles are needed to provide a comparative background for evolutionary interpretations of sex differences in mammalian vocalizations.     

The MultiBac Protein Complex Production Platform at the EMBL

Proteomics research revealed the impressive complexity of eukaryotic proteomes in unprecedented detail. It is now a commonly accepted notion that proteins in cells mostly exist not as isolated entities but exert their biological activity in association with many other proteins, in humans ten or more, forming assembly lines in the cell for most if not all vital functions.^1,2 Knowledge of the function and architecture of these multiprotein assemblies requires their provision in superior quality and sufficient quantity for detailed analysis. The paucity of many protein complexes in cells, in particular in eukaryotes, prohibits their extraction from native sources, and necessitates recombinant production. The baculovirus expression vector system (BEVS) has proven to be particularly useful for producing eukaryotic proteins, the activity of which often relies on post-translational processing that other commonly used expression systems often cannot support.³ BEVS use a recombinant baculovirus into which the gene of interest was inserted to infect insect cell cultures which in turn produce the protein of choice. MultiBac is a BEVS that has been particularly tailored for the production of eukaryotic protein complexes that contain many subunits.⁴ A vital prerequisite for efficient production of proteins and their complexes are robust protocols for all steps involved in an expression experiment that ideally can be implemented as standard operating procedures (SOPs) and followed also by non-specialist users with comparative ease. The MultiBac platform at the European Molecular Biology Laboratory (EMBL) uses SOPs for all steps involved in a multiprotein complex expression experiment, starting from insertion of the genes into an engineered baculoviral genome optimized for heterologous protein production properties to small-scale analysis of the protein specimens produced.^5-8 The platform is installed in an open-access mode at EMBL Grenoble and has supported many scientists from academia and industry to accelerate protein complex research projects.     

The Xer/dif site-specific recombination system of Campylobacter jejuni

Chromosome dimers, which form during the bacterial life cycle, represent a problem that must be solved by the bacterial cell machinery so that chromosome segregation can occur effectively. The Xer/dif site-specific recombination system, utilized by most bacteria, resolves chromosome dimers into monomers using two tyrosine recombinases, XerC and XerD, to perform the recombination reaction at the dif site which consists of 28–30 bp. However, single Xer recombinase systems have been recently discovered in several bacterial species. In Streptococci and Lactococci a single recombinase, XerS, is capable of completing the monomerisation reaction by acting at an atypical dif site called dif _SL (31 bp). It was recently shown that a subgroup of ε-proteobacteria including Campylobacter spp. and Helicobacter spp. had a phylogenetically distinct Xer/dif recombination system with only one recombinase (XerH) and an atypical dif motif (difH). In order to biochemically characterize this system in greater detail, Campylobacter jejuni XerH was purified and its DNA-binding activity was characterized. The protein showed specific binding to the complete difH site and to both halves separately. It was also shown to form covalent complexes with difH suicide substrates. In addition, XerH was able to catalyse recombination between two difH sites located on a plasmid in Escherichia coli in vivo. This indicates that this XerH protein performs a similar function as the related XerS protein, but shows significantly different binding characteristics.     

Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases

Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk for chronic diseases, and one promising mechanism for fetal metabolic programming is epigenetics. Therefore, we postulated that GDM exposure impacts the offspring’s methylome and used an epigenomic approach to explore this hypothesis. Placenta and cord blood samples were obtained from 44 newborns, including 30 exposed to GDM. Women were recruited at first trimester of pregnancy and followed until delivery. GDM was assessed after a 75-g oral glucose tolerance test at 24–28 weeks of pregnancy. DNA methylation was measured at > 485,000 CpG sites (Infinium HumanMethylation450 BeadChips). Ingenuity Pathway Analysis was conducted to identify metabolic pathways epigenetically affected by GDM. Our results showed that 3,271 and 3,758 genes in placenta and cord blood, respectively, were potentially differentially methylated between samples exposed or not to GDM (p-values down to 1 × 10⁻⁰⁶; none reached the genome-wide significance levels), with more than 25% (n = 1,029) being common to both tissues. Mean DNA methylation differences between groups were 5.7 ± 3.2% and 3.4 ± 1.9% for placenta and cord blood, respectively. These genes were likely involved in the metabolic diseases pathway (up to 115 genes (11%), p-values for pathways = 1.9 × 10⁻¹³ < p < 4.0 × 10⁻⁰³; including diabetes mellitus p = 4.3 × 10⁻¹¹). Among the differentially methylated genes, 326 in placenta and 117 in cord blood were also associated with newborn weight. Our results therefore suggest that GDM has epigenetic effects on genes preferentially involved in the metabolic diseases pathway, with consequences on fetal growth and development, and provide supportive evidence that DNA methylation is involved in fetal metabolic programming.     

Expression pattern of the homeotic gene Bapx1 during early chick gastrointestinal tract development

Regulation of the Bone Morphogenetic Protein (BMP) signaling pathway is essential for the normal development of vertebrate gastrointestinal (GI) tract, but also for the differentiation of the digestive mesenchymal layer into smooth muscles and submucosal layer. Different studies demonstrated that Bapx1 (for bagpipe homeobox homolog 1) negatively regulates the BMP pathway, but its precise expression pattern during the development and the differentiation of the GI tract mesenchyme actually remains to be examined. Here, we present the spatio-temporal expression profile of Bapx1 in the chick GI tract. We show that Bapx1 is first expressed in the undifferentiated mesenchyme of the gizzard and the colon. After the differentiation of the digestive mesenchyme, we found Bapx1 strongly expressed in the gizzard smooth muscle and in the submucosa layer of the colon. This expression pattern provides new insights into the roles of Bapx1 during the regionalization of the GI tract and the differentiation of the digestive mesenchyme of the colon and the stomach.