PLCγ1 Participates in Protein Transport and Diacylglycerol Production Triggered by cargo Arrival at the Golgi

Diacylglycerol (DAG) is required for membrane traffic and structural organization at the Golgi. DAG is a lipid metabolite of several enzymatic reactions present at this organelle, but the mechanisms by which they are regulated are still unknown. Here, we show that cargo arrival at the Golgi increases the recruitment of the DAG‐sensing constructs C1‐PKCθ‐GFP and the PKD‐wt‐GFP. The recruitment of both constructs was reduced by PLCγ1 silencing. Post‐Golgi trafficking of transmembrane and soluble proteins was impaired in PLCγ1‐silenced cells. Under basal conditions, PLCγ1 contributed to the maintenance of the pool of DAG associated with the Golgi and to the structural organization of the organelle. Finally, we show that cytosolic phospholipase C (PLC) can hydrolyse phosphatidylinositol 4‐phosphate in isolated Golgi membranes. Our results indicate that PLCγ1 is part of the molecular mechanism that couples cargo arrival at the Golgi with DAG production to co‐ordinate the formation of transport carriers for post‐Golgi traffic.      

Size-dependent predation risk in cryptic prey

Journal of Ethology - Visual crypsis of prey is determined by the interaction between an individual’s physical appearance to their predators and visual aspects of their environment. Physical...     

The electrical property of matter,the trigger mechanism controlling cell growth

Summary It has been shown that many of the so-called unknown causes in biological reactions can be explained through the basic laws of physics, namely that all matter is electrical and that the life principle is due to this electrical state; that the electron shift which continues automatically and ceaselessly in every particle of matter is the factor which releases the energy, as it is attracted or repulsed by the positive or negative charges of the atom, thereby producing the biochemical formations of metabolism.The two underlying organizers in all forms of matter are polarity-consisting of a positive charge at one end and a negative charge at the other in every atom, groups of atoms or molecules and organs; and secondly, oxidation-reduction potential which regulates the electromotive force for the definite level of energy production at the appropriate instant.This principle has been applied in the case of various experiments designated as unknown causes in the literature. They include the organizer principle in Biology, why eggs become fertilized, tissue culturesin vitro andvivo and reconstitution of sponge cells from dissociated cells, the basic causes of abnormal growth of cells including cancer cells, and finally some conclusions concerning DNA and RNA.     

Population genetics of Tuberolachnus salignus,an obligate parthenogenetic aphid

• 1 This study reports the results obtained in an investigation of the putatively parthenogenetic aphid species Tuberolachnus salignus Gmelin. Tuberolachnus salignus is one of the largest aphid species in the world but where and how it overwinters is not known. It has recently become noteworthy because it is increasingly found on commercially grown willows used in bioenergy production.
• 2 Seven newly‐developed polymorphic microsatellite markers were used to investigate the genetic diversity of the species, and also to confirm its reproduction strategy.
• 3 Tuberolachnus salignus shows very low clonal diversity; only 16 genotypes were found in 660 specimens from 27 populations in five countries.
• 4 There was limited geographical structuring in the samples, although the two most common genotypes, which comprised more than half of the specimens collected, had a very wide distribution.
• 5 Furthermore, we determined that these aphids, which live in very dense colonies, can consist of more than one genotype, suggesting aggregation of colonizing T. salignus. These results confirm the parthenogenetic nature of T. salignus and demonstrate the presence of common genotypes that are widespread in time and space.

     

Ctenophore population recruits entirely through larval reproduction in the central Baltic Sea

The comb jelly Mertensia ovum, widely distributed in Arctic regions, has recently been discovered in the northern Baltic Sea. We show that M. ovum also exists in the central Baltic but that the population consists solely of small-sized larvae (less than 1.6 mm). Despite the absence of adults, eggs were abundant. Experiments revealed that the larvae were reproductively active. Egg production and anticipated mortality rates suggest a self-sustaining population. This is the first account of a ctenophore population entirely recruiting through larval reproduction (paedogenesis). We hypothesize that early reproduction is favoured over growth to compensate for high predation pressure.     

Targeted overexpression of osteoactivin in cells of osteoclastic lineage promotes osteoclastic resorption and bone loss in mice

This study sought to test whether targeted overexpression of osteoactivin (OA) in cells of osteoclastic lineage, using the tartrate-resistant acid phosphase (TRAP) exon 1B/C promoter to drive OA expression, would increase bone resorption and bone loss in vivo. OA transgenic osteoclasts showed ～2-fold increases in OA mRNA and proteins compared wild-type (WT) osteoclasts. However, the OA expression in transgenic osteoblasts was not different. At 4, 8, and 15.3 week-old, transgenic mice showed significant bone loss determined by pQCT and confirmed by μ-CT. In vitro, transgenic osteoclasts were twice as large, had twice as much TRAP activity, resorbed twice as much bone matrix, and expressed twice as much osteoclastic genes (MMP9, calciton receptor, and ADAM12), as WT osteoclasts. The siRNA-mediated suppression of OA expression in RAW264.7-derived osteoclasts reduced cell size and osteoclastic gene expression. Bone histomorphometry revealed that transgenic mice had more osteoclasts and osteoclast surface. Plasma c-telopeptide (a resorption biomarker) measurements confirmed an increase in bone resorption in transgenic mice in vivo. In contrast, histomorphometric bone formation parameters and plasma levels of bone formation biomarkers (osteocalcin and pro-collagen type I N-terminal peptide) were not different between transgenic mice and WT littermates, indicating the lack of bone formation effects. In conclusion, this study provides compelling in vivo evidence that osteoclast-derived OA is a novel stimulator of osteoclast activity and bone resorption.     

Crystal Structures of Three Classes of Non-Steroidal Anti-Inflammatory Drugs in Complex with Aldo-Keto Reductase 1C3

Aldo-keto reductase 1C3 (AKR1C3) catalyses the NADPH dependent reduction of carbonyl groups in a number of important steroid and prostanoid molecules. The enzyme is also over-expressed in prostate and breast cancer and its expression is correlated with the aggressiveness of the disease. The steroid products of AKR1C3 catalysis are important in proliferative signalling of hormone-responsive cells, while the prostanoid products promote prostaglandin-dependent proliferative pathways. In these ways, AKR1C3 contributes to tumour development and maintenance, and suggest that inhibition of AKR1C3 activity is an attractive target for the development of new anti-cancer therapies. Non-steroidal anti-inflammatory drugs (NSAIDs) are one well-known class of compounds that inhibits AKR1C3, yet crystal structures have only been determined for this enzyme with flufenamic acid, indomethacin, and closely related analogues bound. While the flufenamic acid and indomethacin structures have been used to design novel inhibitors, they provide only limited coverage of the NSAIDs that inhibit AKR1C3 and that may be used for the development of new AKR1C3 targeted drugs. To understand how other NSAIDs bind to AKR1C3, we have determined ten crystal structures of AKR1C3 complexes that cover three different classes of NSAID, N-phenylanthranilic acids (meclofenamic acid, mefenamic acid), arylpropionic acids (flurbiprofen, ibuprofen, naproxen), and indomethacin analogues (indomethacin, sulindac, zomepirac). The N-phenylanthranilic and arylpropionic acids bind to common sites including the enzyme catalytic centre and a constitutive active site pocket, with the arylpropionic acids probing the constitutive pocket more effectively. By contrast, indomethacin and the indomethacin analogues sulindac and zomepirac, display three distinctly different binding modes that explain their relative inhibition of the AKR1C family members. This new data from ten crystal structures greatly broadens the base of structures available for future structure-guided drug discovery efforts.