Deuteration as an evolutionary tracer in massive-star formation

Theory predicts, and observations confirm, that the column density ratio of a molecule containing D to its counterpart containing H can be used as an evolutionary tracer in the low-mass star formation process. Since it remains unclear if the high-mass star formation process is a scaled-up version of the low-mass one, we investigated whether the relation between deuteration and evolution can be applied to the high-mass regime. With the IRAM-30m telescope, we observed rotational transitions of N2D+ and N2H+ and derived the deuterated fraction in 27 cores within massive star-forming regions understood to represent different evolutionary stages of the massive-star formation process. Results. Our results clearly indicate that the abundance of N2D+ is higher at the pre-stellar/cluster stage, then drops during the formation of the protostellar object(s) as in the low-mass regime, remaining relatively constant during the ultra-compact HII region phase. The objects with the highest fractional abundance of N2D+ are starless cores with properties very similar to typical pre-stellar cores of lower mass. The abundance of N2D+ is lower in objects with higher gas temperatures as in the low-mass case but does not seem to depend on gas turbulence. Our results indicate that the N2D+-to-N2H+ column density ratio can be used as an evolutionary indicator in both low- and high-mass star formation, and that the physical conditions influencing the abundance of deuterated species likely evolve similarly during the processes that lead to the formation of both low- and high-mass stars.Comment: Accepted by A&AL, 4 pages, 2 figures, 2 appendices (one for Tables, one for additional figures

Initial management of potential occult scaphoid fracture in Australasia

AIM: To characterise current management of adult patients with possible occult scaphoid fracture in Australasian emergency departments. METHODS: Internet-based survey of Directors of Emergency Medicine Training throughout Australasia. Data collected included the most common management used in ED for patients with possible occult scaphoid fracture and whether there was a guideline regarding management of such cases. Data are reported as descriptive statistics. RESULTS: 61 responses were received (response rate 73%). The most common management reported was immobilisation in a backslab (23, 38%) or full cast (19, 32%) with clinical assessment and re-X-ray in 7-10 days. CT scan within 7 days was used by 9 (15%), bone scan within 7 days by 6 (10%) and MRI within 7 days by 3 (5%). Very few sites were using same day/next day CT or MRI. Eighty-three percent of sites reported not having a guideline/protocol for this condition. CONCLUSION: The traditional approach to management of possible occult scaphoid fracture of immobilisation with re-X-ray at 7-10 days remains the most commonly used in Australasia, despite evidence that this is probably over-treatment with significant consequences for patients. The place of advanced imaging for investigation of potential scaphoid fractures requires further research

Non-contrast MR imaging of blood-brain barrier permeability to water

Neuro Imaging Researc

Off-target and a portion of target-specific siRNA mediated mRNA degradation is Ago2 ‘Slicer’ independent and can be mediated by Ago1

It is known that siRNAs are capable of reducing expression of non-target genes due to the interaction of the siRNA guide strand with a partially complementary site on the ‘off-target’ mRNA. In the current study, we show that reduction of cellular Ago2 levels has no effect on off-target reduction of endogenous genes and that off-target degradation of mRNA can occur even in an Ago2 knockout cell line. Using antisense mediated reduction of Ago proteins and chemically modified cleavage- and binding-deficient siRNAs, we demonstrate that siRNA mediated off-target reduction is Ago2 cleavage independent, but does require siRNA interaction with either Ago1 or Ago2 and the RISC-loading complex. We also show that depletion of P-body associated proteins results in a reduction of off-target siRNA-mediated degradation of mRNA. Finally, we present data suggesting that a significant portion of on-target siRNA activity is also Ago2 cleavage independent, however, this activity does not appear to be P-body associated

The Infection of Chicken Tracheal Epithelial Cells with a H6N1 Avian Influenza Virus

Sialic acids (SAs) linked to galactose (Gal) in α2,3- and α2,6-configurations are the receptors for avian and human influenza viruses, respectively. We demonstrate that chicken tracheal ciliated cells express α2,3-linked SA, while goblet cells mainly express α2,6-linked SA. In addition, the plant lectin MAL-II, but not MAA/MAL-I, is bound to the surface of goblet cells, suggesting that SA2,3-linked oligosaccharides with Galβ1–3GalNAc subterminal residues are specifically present on the goblet cells. Moreover, both α2,3- and α2,6-linked SAs are detected on single tracheal basal cells. At a low multiplicity of infection (MOI) avian influenza virus H6N1 is exclusively detected in the ciliated cells, suggesting that the ciliated cell is the major target cell of the H6N1 virus. At a MOI of 1, ciliated, goblet and basal cells are all permissive to the AIV infection. This result clearly elucidates the receptor distribution for the avian influenza virus among chicken tracheal epithelial cells and illustrates a primary cell model for evaluating the cell tropisms of respiratory viruses in poultry

The Induction of MicroRNA Targeting IRS-1 Is Involved in the Development of Insulin Resistance under Conditions of Mitochondrial Dysfunction in Hepatocytes

BACKGROUND: Mitochondrial dysfunction induces insulin resistance in myocytes via a reduction of insulin receptor substrate-1 (IRS-1) expression. However, the effect of mitochondrial dysfunction on insulin sensitivity is not understood well in hepatocytes. Although research has implicated the translational repression of target genes by endogenous non-coding microRNAs (miRNA) in the pathogenesis of various diseases, the identity and role of the miRNAs that are involved in the development of insulin resistance also remain largely unknown. METHODOLOGY: To determine whether mitochondrial dysfunction induced by genetic or metabolic inhibition causes insulin resistance in hepatocytes, we analyzed the expression and insulin-stimulated phosphorylation of insulin signaling intermediates in SK-Hep1 hepatocytes. We used qRT-PCR to measure cellular levels of selected miRNAs that are thought to target IRS-1 3' untranslated regions (3'UTR). Using overexpression of miR-126, we determined whether IRS-1-targeting miRNA causes insulin resistance in hepatocytes. PRINCIPAL FINDINGS: Mitochondrial dysfunction resulting from genetic (mitochondrial DNA depletion) or metabolic inhibition (Rotenone or Antimycin A) induced insulin resistance in hepatocytes via a reduction in the expression of IRS-1 protein. In addition, we observed a significant up-regulation of several miRNAs presumed to target IRS-1 3'UTR in hepatocytes with mitochondrial dysfunction. Using reporter gene assay we confirmed that miR-126 directly targeted to IRS-1 3'UTR. Furthermore, the overexpression of miR-126 in hepatocytes caused a substantial reduction in IRS-1 protein expression, and a consequent impairment in insulin signaling. CONCLUSIONS/SIGNIFICANCE: We demonstrated that miR-126 was actively involved in the development of insulin resistance induced by mitochondrial dysfunction. These data provide novel insights into the molecular basis of insulin resistance, and implicate miRNA in the development of metabolic disease

Non-Coding RNAs : multi-tasking molecules in the cell

Articles in International JournalsIn the last years it has become increasingly clear that the mammalian transcriptome is highly complex and includes a large number of small non-coding RNAs (sncRNAs) and long noncoding RNAs (lncRNAs). Here we review the biogenesis pathways of the three classes of sncRNAs, namely short interfering RNAs (siRNAs), microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs). These ncRNAs have been extensively studied and are involved in pathways leading to specific gene silencing and the protection of genomes against virus and transposons, for example. Also, lncRNAs have emerged as pivotal molecules for the transcriptional and post-transcriptional regulation of gene expression which is supported by their tissue-specific expression patterns, subcellular distribution, and developmental regulation. Therefore, we also focus our attention on their role in differentiation and development. SncRNAs and lncRNAs play critical roles in defining DNA methylation patterns, as well as chromatin remodeling thus having a substantial effect in epigenetics. The identification of some overlaps in their biogenesis pathways and functional roles raises the hypothesis that these molecules play concerted functions in vivo, creating complex regulatory networks where cooperation with regulatory proteins is necessary. We also highlighted the implications of biogenesis and gene expression deregulation of sncRNAs and lncRNAs in human diseases like cancer