Strong rapid dipolarizations in Saturn's magnetotail: In situ evidence of reconnection

The oppositely directed magnetic field in the kronian magnetic tail is expected eventually to reconnect across the current sheet, allowing plasma to escape in an anti-solar direction down the tail. This reconnection process accelerates ions and electrons both toward and away from the planet, allowing the magnetotail to relax to a more dipolar configuration. Previous missions to Saturn shed no light on the possible presence of this critical process in the kronian magnetosphere. Recent Cassini measurements of the magnetic field in the magnetotail, reported herein, reveal strong, rapid dipolarizations between 40 and 50 Saturn radii (R-S) downtail, signalling the episodic release of energy to the magnetosphere and ions to the solar wind

Survival of immature Anopheles arabiensis (Diptera: Culicidae) in aquatic habitats in Mwea rice irrigation scheme, central Kenya

BACKGROUND: The survivorship and distribution of Anopheles arabiensis larvae and pupae was examined in a rice agro-ecosystem in Mwea Irrigation Scheme, central Kenya, from August 2005 to April 2006, prior to implementation of larval control programme. METHODS: Horizontal life tables were constructed for immatures in semi-field condition. The time spent in the various immature stages was determined and survival established. Vertical life tables were obtained from five paddies sampled by standard dipping technique. RESULTS: Pre-adult developmental time for An. arabiensis in the trays in the experimental set up in the screen house was 11.85 days from eclosion to emergence. The mean duration of each instar stage was estimated to be 1.40 days for first instars, 2.90 days for second instars, 1.85 days for third instars, 3.80 days for fourth instars and 1.90 days for pupae. A total of 590 individuals emerged into adults, giving an overall survivorship from L1 to adult emergence of 69.4%. A total of 4,956 An. arabiensis immatures were collected in 1,400 dips throughout the sampling period. Of these, 55.9% were collected during the tillering stage, 42.5% during the transplanting period and 1.6% during the land preparation stage. There was a significant difference in the An. arabiensis larval densities among the five stages. Also there was significant variation in immature stage composition for each day's collection in each paddy. These results indicate that the survival of the immatures was higher in some paddies than others. The mortality rate during the transplanting was 99.9% and at tillering was 96.6%, while the overall mortality was 98.3%. CONCLUSION: The survival of An. arabiensis immatures was better during the tillering stage of rice growth. Further the survival of immatures in rice fields is influenced by the rice agronomic activities including addition of nitrogenous fertilizers and pesticides. For effective integrated vector management, the application of larvicides should target An. arabiensis larvae at the tillering stage (early vegetative stage of rice) when their survival in the aquatic habitats is high to significantly reduce them and the larvicides should be long-lasting to have a significant impact on the malaria vector productivity on the habitats

Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

Cannabidiol (CBD) is the most abundant cannabinoid in Cannabis sativa that has no psychoactive properties. CBD has been approved to treat inflammation, pain and spasticity associated with multiple sclerosis (MS), of which demyelination and oligodendrocyte loss are hallmarks. Thus, we investigated the protective effects of CBD against the damage to oligodendrocyte progenitor cells (OPCs) mediated by the immune system. Doses of 1 μM CBD protect OPCs from oxidative stress by decreasing the production of reactive oxygen species. CBD also protects OPCs from apoptosis induced by LPS/IFNγ through the decrease of caspase 3 induction via mechanisms that do not involve CB1, CB2, TRPV1 or PPARγ receptors. Tunicamycin-induced OPC death was attenuated by CBD, suggesting a role of endoplasmic reticulum (ER) stress in the mode of action of CBD. This protection against ER stress-induced apoptosis was associated with reduced phosphorylation of eiF2α, one of the initiators of the ER stress pathway. Indeed, CBD diminished the phosphorylation of PKR and eiF2α induced by LPS/IFNγ. The pro-survival effects of CBD in OPCs were accompanied by decreases in the expression of ER apoptotic effectors (CHOP, Bax and caspase 12), and increased expression of the anti-apoptotic Bcl-2. These findings suggest that attenuation of the ER stress pathway is involved in the ‘oligoprotective' effects of CBD during inflammation

Comparison of Life History Characteristics of the Genetically Modified OX513A Line and a Wild Type Strain of Aedes aegypti

The idea of implementing genetics-based insect control strategies modelled on the traditional SIT (Sterile Insect Technique), such as RIDL (Release of Insects carrying a Dominant Lethal), is becoming increasingly popular. In this paper, we compare a genetically modified line of Aedes aegypti carrying a tetracycline repressible, lethal positive feedback system (OX513A) with a genetically similar, unmodified counterpart and their respective responses to increasing larval rearing density using a constant amount of food per larva. The parameters that we examined were larval mortality, developmental rate (i.e., time to pupation), adult size and longevity

Myelin Proteomics: Molecular Anatomy of an Insulating Sheath

Fast-transmitting vertebrate axons are electrically insulated with multiple layers of nonconductive plasma membrane of glial cell origin, termed myelin. The myelin membrane is dominated by lipids, and its protein composition has historically been viewed to be of very low complexity. In this review, we discuss an updated reference compendium of 342 proteins associated with central nervous system myelin that represents a valuable resource for analyzing myelin biogenesis and white matter homeostasis. Cataloging the myelin proteome has been made possible by technical advances in the separation and mass spectrometric detection of proteins, also referred to as proteomics. This led to the identification of a large number of novel myelin-associated proteins, many of which represent low abundant components involved in catalytic activities, the cytoskeleton, vesicular trafficking, or cell adhesion. By mass spectrometry-based quantification, proteolipid protein and myelin basic protein constitute 17% and 8% of total myelin protein, respectively, suggesting that their abundance was previously overestimated. As the biochemical profile of myelin-associated proteins is highly reproducible, differential proteome analyses can be applied to material isolated from patients or animal models of myelin-related diseases such as multiple sclerosis and leukodystrophies

Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

​Leucine-rich repeat kinase 2 (​LRRK2) mutations are the most common genetic cause of Parkinson’s disease. ​LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules. Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson’s disease, but whether ​LRRK2 mutations affect this process to mediate pathogenesis is not known. Here we find that ​LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila, causing locomotor deficits in vivo. In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase ​αTAT1 prevents association of mutant ​LRRK2 with microtubules, and the deacetylase inhibitor ​trichostatin A (​TSA) restores axonal transport. In vivo knockdown of the deacetylases ​HDAC6 and ​Sirt2, or administration of ​TSA rescues both axonal transport and locomotor behavior. Thus, this study reveals a pathogenic mechanism and a potential intervention for Parkinson’s disease

Resolving early mesoderm diversification through single-cell expression profiling.

In mammals, specification of the three major germ layers occurs during gastrulation, when cells ingressing through the primitive streak differentiate into the precursor cells of major organ systems. However, the molecular mechanisms underlying this process remain unclear, as numbers of gastrulating cells are very limited. In the mouse embryo at embryonic day 6.5, cells located at the junction between the extra-embryonic region and the epiblast on the posterior side of the embryo undergo an epithelial-to-mesenchymal transition and ingress through the primitive streak. Subsequently, cells migrate, either surrounding the prospective ectoderm contributing to the embryo proper, or into the extra-embryonic region to form the yolk sac, umbilical cord and placenta. Fate mapping has shown that mature tissues such as blood and heart originate from specific regions of the pre-gastrula epiblast, but the plasticity of cells within the embryo and the function of key cell-type-specific transcription factors remain unclear. Here we analyse 1,205 cells from the epiblast and nascent Flk1(+) mesoderm of gastrulating mouse embryos using single-cell RNA sequencing, representing the first transcriptome-wide in vivo view of early mesoderm formation during mammalian gastrulation. Additionally, using knockout mice, we study the function of Tal1, a key haematopoietic transcription factor, and demonstrate, contrary to previous studies performed using retrospective assays, that Tal1 knockout does not immediately bias precursor cells towards a cardiac fate.We thank M. de Bruijn, A. Martinez-Arias, J. Nichols and C. Mulas for discussion, the Cambridge Institute for Medical Research Flow Cytometry facility for their expertise in single-cell index sorting, and S. Lorenz from the Sanger Single Cell Genomics Core for supervising purification of Tal1−/− sequencing libraries. ChIP-seq reads were processed by R. Hannah. Research in the authors’ laboratories is supported by the Medical Research Council, Cancer Research UK, the Biotechnology and Biological Sciences Research Council, Bloodwise, the Leukemia and Lymphoma Society, and the Sanger-EBI Single Cell Centre, and by core support grants from the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute and by core funding from Cancer Research UK and the European Molecular Biology Laboratory. Y.T. was supported by a fellowship from the Japan Society for the Promotion of Science. W.J. is a Wellcome Trust Clinical Research Fellow. A.S. is supported by the Sanger-EBI Single Cell Centre. This work was funded as part of Wellcome Trust Strategic Award 105031/D/14/Z ‘Tracing early mammalian lineage decisions by single-cell genomics’ awarded to W. Reik, S. Teichmann, J. Nichols, B. Simons, T. Voet, S. Srinivas, L. Vallier, B. Göttgens and J. Marioni.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1863

Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states

Fastloc-GPS reveals daytime departure and arrival during long-distance migration and the use of different resting strategies in sea turtles

Determining the time of day that animals initiate and end migration, as well as variation in diel movement patterns during migration, provides insights into the types of strategy used to maximise energy efficiency and ensure successful completion of migration. However, obtaining this level of detail has been difficult for long-distance migratory marine species. Thus, we investigated whether the large volume of highly accurate locations obtained by Argos-linked Fastloc-GPS transmitters could be used to identify the time of day that adult green (n = 8 turtles, 9487 locations) and loggerhead (n = 46 turtles, 47,588 locations) sea turtles initiate and end migration, along with potential resting strategies during migration. We found that departure from and arrival at breeding, stopover and foraging sites consistently occurred during the daytime, which is consistent with previous findings suggesting that turtles might use solar visual cues for orientation. Only seven turtles made stopovers (of up to 6 days and all located close to the start or end of migration) during migration, possibly to rest and/or refuel; however, observations of day versus night speed of travel indicated that turtles might use other mechanisms to rest. For instance, turtles travelled 31% slower at night compared to day during their oceanic crossings. Furthermore, within the first 24 h of entering waters shallower than 100 m towards the end of migration, some individuals travelled 72% slower at night, repeating this behaviour intermittently (each time for a one-night duration at 3–6 day intervals) until reaching the foraging grounds. Thus, access to data-rich, highly accurate Argos-linked Fastloc-GPS provided information about differences in day versus night activity at different stages in migration, allowing us, for the first time, to compare the strategies used by a marine vertebrate with terrestrial land-based and flying species