Computation,wiring, and plasticity in synaptic clusters

Synaptic clusters on dendrites are extraordinarily compact computational building blocks. They contribute to key local computations through biophysical and biochemical signaling that utilizes convergence in space and time as an organizing principle. However, these computations can only arise in very special contexts. Dendritic cluster computations, their highly organized input connectivity, and the mechanisms for their formation are closely linked, yet these have not been analyzed as parts of a single process. Here, we examine these linkages. The sheer density of axonal and dendritic arborizations means that there are far more potential connections (close enough for a spine to reach an axon) than actual ones. We see how dendritic clusters draw upon electrical, chemical, and mechano–chemical signaling to implement the rules for formation of connections and subsequent computations. Crucially, the same mechanisms that underlie their functions also underlie their formation.     

Natural products as modulators of the nuclear receptors and metabolic sensors LXR,FXR and RXR

Nuclear receptors (NRs) represent attractive targets for the treatment of metabolic syndrome-related diseases. In addition, natural products are an interesting pool of potential ligands since they have been refined under evolutionary pressure to interact with proteins or other biological targets.This review aims to briefly summarize current basic knowledge regarding the liver X (LXR) and farnesoid X receptors (FXR) that form permissive heterodimers with retinoid X receptors (RXR). Natural product-based ligands for these receptors are summarized and the potential of LXR, FXR and RXR as targets in precision medicine is discussed.     

NFκB mediated elevation of KCNJ11 promotes tumor progression of hepatocellular carcinoma through interaction of lactate dehydrogenase A

It has been well documented that changes in ion fluxes across cellular membranes is fundamental in maintaining cellular homeostasis. Dysregulation and/or malfunction of ion channels are critical events in the pathogenesis of diverse diseases, including cancers. In this study, we focused on the study of K⁺ channels in hepatocellular carcinoma (HCC). By data mining TCGA cohort, the expression of 27 K⁺ channels was investigated and KCNJ11 was identified as a key dysregulated K⁺ channels in HCC. KCNJ11 was differentially expressed in HCC and predicted a poor prognosis in HCC patients. Inhibition of NFκB signaling suppressed KCNJ11 expression in HCC cells. Knockdown of KCNJ11 expression inhibited cell proliferation, promoted cell apoptosis, and reduced cell invasive capacity. Mechanistically, we found that KCNJ11 promotes tumor progression through interaction with LDHA and enhancing its enzymatic activity. Pharmacological inhibition of LDHA largely compromised the oncogenic function of KCNJ11 in cell proliferation, cell apoptosis, and cell invasion. Collectively, our data, as a proof of principle, demonstrate that KCNJ11 acts as an oncogene in HCC though forming a complex with LDHA and suggest that targeting KCNJ11 can be developed as a candidate tool to dampen HCC.     

Biochemical characterization of two haloalkane dehalogenases: DccA from Caulobacter crescentus and DsaA from Saccharomonospora azurea

Two putative haloalkane dehalogenases (HLDs) of the HLD‐I subfamily, DccA from Caulobacter crescentus and DsaA from Saccharomonospora azurea, have been identified based on sequence comparisons with functionally characterized HLD enzymes. The two genes were synthesized, functionally expressed in E. coli and shown to have activity toward a panel of haloalkane substrates. DsaA has a moderate activity level and a preference for long (greater than 3 carbons) brominated substrates, but little activity toward chlorinated alkanes. DccA shows high activity with both long brominated and chlorinated alkanes. The structure of DccA was determined by X‐ray crystallography and was refined to 1.5 Å resolution. The enzyme has a large and open binding pocket with two well‐defined access tunnels. A structural alignment of HLD‐I subfamily members suggests a possible basis for substrate specificity is due to access tunnel size.     

A new genus and nine new species of Eugnomini (Coleoptera,Curculionidae) from New Caledonia

The genus Rasilinus gen. n. is described (type species Rasilinus tchambicus sp. n.). Nine new species: Rasilinus bicolor sp. n., Rasilinus bifurcatus sp. n., Rasilinus bimaculatus sp. n., Rasilinus grandidens sp. n., Rasilinus longulus sp. n., Rasilinus subgemellus sp. n., Rasilinus subnodulus sp. n., Rasilinus tchambicus sp. n., Rasilinus virgatus sp. n. are described from New Caledonia. Illustrations of the external morphology, male and female terminalia, dorsal habitus colour photographs of the adults, key to species and distribution map of the new genus Rasilinus are provided.     

A revision of Megalocraerus Lewis, 1902 (Coleoptera,Histeridae: Exosternini)

The formely monotypic Neotropical genus Megalocraerus Lewis is revised to include five species, known from southeastern Brazil to Costa Rica: Megalocraerus rubricatus Lewis, Megalocraerus mandibularis sp. n., Megalocraerus chico sp. n., Megalocraerus madrededios sp. n., and Megalocraerus tiputini sp. n. We describe the species, map their distributions, and provide a key for their identification. Their subcylindrical body form and emarginate mesosternum have previously hindered placement to tribe, although their curent assignment to Exosternini now appears well supported by morphological evidence. Nothing is known of the natural history of the species.     

Six new species of the spider genus Spiricoelotes species (Araneae,Agelenidae) from caves in Jiangxi,China

Six new species of the spider genus Spiricoelotes Wang, 2002 are described, Spiricoelotes anshiensis Chen & Li, sp. n. (♂♀), Spiricoelotes chufengensis Chen & Li, sp. n. (♂♀), Spiricoelotes nansheensis Chen & Li, sp. n. (♂♀), Spiricoelotes taipingensis Chen & Li, sp. n. (♂♀), Spiricoelotes xianheensis Chen & Li, sp. n. (♂♀) and Spiricoelotes xiongxinensis Chen & Li, sp. n. (♀). All new species were collected from caves in Jiangxi Province, China.