Deep 230-470 MHz VLA observations of the mini-halo in the Perseus cluster

© 2017 The Authors. We present a low-frequency view of the Perseus cluster with new observations from the Karl G. Jansky Very Large Array (JVLA) at 230-470 MHz. The data reveal a multitude of new structures associated with the mini-halo. The mini-halo seems to be influenced both by the AGN activity and the sloshing motion of the cool core cluster's gas. In addition, it has a filamentary structure similar to that seen in radio relics found in merging clusters. We present a detailed description of the data reduction and imaging process of the dataset. The depth and resolution of the observations allow us to conduct for the first time a detailed comparison of the mini-halo structure with the X-ray structure as seen in the Chandra X-ray images. The resulting image very clearly shows that the mini-halo emission is mostly contained behind the western cold front, similar to that predicted by simulations of gas sloshing in galaxy clusters, but fainter emission is also seen beyond, as if particles are leaking out. However, due to the proximity of the Perseus cluster, as well as the quality of the data at low radio frequencies and at X-ray wavelengths, we also find evidence of fine structure. This structure includes several radial radio filaments extending in different directions, a concave radio structure associated with the southern X-ray bay and sharp radio edges that correlate with X-ray edges. Minihaloes are therefore not simply diffuse, uniform radio sources, but rather have a rich variety of complex structures. These results illustrate the high-quality images that can be obtained with the new JVLA at low radio frequencies, as well as the necessity to obtain deeper, higher fidelity radio images of mini-haloes in clusters to further understand their origin

Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions.

Journal ArticleThe Hox genes encode transcription factors which mediate the formation of the mammalian body plan along the anteroposterior and appendicular axes. Paralogous Hox genes within the separate linkage groups are closely related with respect to DNA sequence and expression, suggesting that they could have at least partially redundant functions. We showed previously that mice homozygous for independent targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 had no defects in common. But our current analysis of double mutants has revealed strong, dosage-dependent interactions between these genes. We report here that in hoxd-3- homozygotes the first cervical vertebra, the atlas, is homeotically transformed to the adjacent anterior structure. Unexpectedly, in double mutants, rather than observing a more extensive homeotic transformation, the entire atlas is deleted. These observations are interpreted in terms of a model in which these Hox genes differentially regulate the proliferation rates of the appropriate sets of precursor cells

Improving Tree-Thinking One Learnable Skill at a Time

Introducerande artikel inom Läslyftsmodulen Från Vardagsspråk till ÄmnesspråkIntroduction to language sensitive teaching a s part of a Skolverket professional development module in the program Reading Boost

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Closest Star Seen Orbiting the Supermassive Black Hole at the Centre of the Milky Way

Measurements of stellar velocities and variable X-ray emission near the centre of the Milky Way have provided the strongest evidence so far that the dark mass concentrations seen in many galactic nuclei are likely supermassive black holes, but have not yet excluded several alternative configurations. Here we report ten years of high resolution astrometric imaging that allow us to trace two thirds of the orbit of the star currently closest to the compact radio source and massive black hole candidate SgrA*. In particular, we have observed both peri- and apocentre passages. Our observations show that the star is on a bound, highly elliptical Keplerian orbit around SgrA*, with an orbital period of 15.2 years and a peri-centre distance of only 17 light hours. The orbital elements require an enclosed point mass of 3.7+-1.5x10^6 solar masses. The data exclude with high confidence that the central dark mass consists of a cluster of astrophysical objects or massive, degenerate fermions, and strongly constrain the central density structure.Comment: 13 pages, 3 figures, scheduled for publication in Nature on 17 Oct 200

Thriving under Stress: Selective Translation of HIV-1 Structural Protein mRNA during Vpr-Mediated Impairment of eIF4E Translation Activity

Translation is a regulated process and is pivotal to proper cell growth and homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis and thus may be susceptible to its perturbation in response to stress, co-infection, and/or cell cycle arrest. HIV-1 infection arrests the cell cycle in the G2/M phase, potentially disrupting the regulation of host cell translation. In this study, we present evidence that HIV-1 infection downregulates translation in lymphocytes, attributable to the cell cycle arrest induced by the HIV-1 accessory protein Vpr. The molecular basis of the translation suppression is reduced accumulation of the active form of the translation initiation factor 4E (eIF4E). However, synthesis of viral structural proteins is sustained despite the general suppression of protein production. HIV-1 mRNA translation is sustained due to the distinct composition of the HIV-1 ribonucleoprotein complexes. RNA-coimmunoprecipitation assays determined that the HIV-1 unspliced and singly spliced transcripts are predominantly associated with nuclear cap binding protein 80 (CBP80) in contrast to completely-spliced viral and cellular mRNAs that are associated with eIF4E. The active translation of the nuclear cap binding complex (CBC)-bound viral mRNAs is demonstrated by ribosomal RNA profile analyses. Thus, our findings have uncovered that the maintenance of CBC association is a novel mechanism used by HIV-1 to bypass downregulation of eIF4E activity and sustain viral protein synthesis. We speculate that a subset of CBP80-bound cellular mRNAs contribute to recovery from significant cellular stress, including human retrovirus infection

Divergence in transcriptional and regulatory responses to mating in male and female fruitflies

Mating induces extensive physiological, biochemical and behavioural changes in female animals of many taxa. In contrast, the overall phenotypic and transcriptomic consequences of mating for males, hence how they might differ from those of females, are poorly described. Post mating responses in each sex are rapidly initiated, predicting the existence of regulatory mechanisms in addition to transcriptional responses involving de novo gene expression. That post mating responses appear different for each sex also predicts that the genome-wide signatures of mating should show evidence of sex-specific specialisation. In this study, we used high resolution RNA sequencing to provide the first direct comparisons of the transcriptomic responses of male and female Drosophila to mating, and the first comparison of mating-responsive miRNAs in both sexes in any species. As predicted, the results revealed the existence of sex- and body part-specific mRNA and miRNA expression profiles. More genes were differentially expressed in the female head-thorax than the abdomen following mating, whereas the opposite was true in males. Indeed, the transcriptional profile of male head-thorax tissue was largely unaffected by mating, and no differentially expressed genes were detected at the most stringent significance threshold. A subset of ribosomal genes in females were differentially expressed in both body parts, but in opposite directions, consistent with the existence of body part-specific resource allocation switching. Novel, mating-responsive miRNAs in each sex were also identified, and a miRNA-mRNA interactions analysis revealed putative targets among mating-responsive genes. We show that the structure of genome-wide responses by each sex to mating is strongly divergent, and provide new insights into how shared genomes can achieve characteristic distinctiveness

Dynamic purine signaling and metabolism during neutrophil–endothelial interactions

During episodes of hypoxia and inflammation, polymorphonuclear leukocytes (PMN) move into underlying tissues by initially passing between endothelial cells that line the inner surface of blood vessels (transendothelial migration, TEM). TEM creates the potential for disturbances in vascular barrier and concomitant loss of extravascular fluid and resultant edema. Recent studies have demonstrated a crucial role for nucleotide metabolism and nucleoside signaling during inflammation. These studies have implicated multiple adenine nucleotides as endogenous tissue protective mechanisms invivo. Here, we review the functional components of vascular barrier, identify strategies for increasing nucleotide generation and nucleoside signaling, and discuss potential therapeutic targets to regulate the vascular barrier during inflammation

C9orf72-mediated ALS and FTD: multiple pathways to disease

The discovery that repeat expansions in the C9orf72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has revolutionized our understanding of these diseases. Substantial headway has been made in characterizing C9orf72-mediated disease and unravelling its underlying aetiopathogenesis. Three main disease mechanisms have been proposed: loss of function of the C9orf72 protein and toxic gain of function from C9orf72 repeat RNA or from dipeptide repeat proteins produced by repeat-associated non-ATG translation. Several downstream processes across a range of cellular functions have also been implicated. In this article, we review the pathological and mechanistic features of C9orf72-associated FTD and ALS (collectively termed C9FTD/ALS), the model systems used to study these conditions, and the probable initiators of downstream disease mechanisms. We suggest that a combination of upstream mechanisms involving both loss and gain of function and downstream cellular pathways involving both cell-autonomous and non-cell-autonomous effects contributes to disease progression