The PLATO Dome A Site-Testing Observatory : instrumentation and first results

The PLATeau Observatory (PLATO) is an automated self-powered astrophysical observatory that was deployed to Dome A, the highest point on the Antarctic plateau, in 2008 January. PLATO consists of a suite of site-testing instruments designed to quantify the benefits of the Dome A site for astronomy, and science instruments designed to take advantage of the unique observing conditions. Instruments include CSTAR, an array of optical telescopes for transient astronomy; Gattini, an instrument to measure the optical sky brightness and cloud cover statistics; DASLE, an experiment to measure the statistics of the meteorological conditions within the near-surface layer; Pre-HEAT, a submillimeter tipping radiometer measuring the atmospheric transmission and water vapor content and performing spectral line imaging of the Galactic plane; and Snodar, an acoustic radar designed to measure turbulence within the near-surface layer. PLATO has run completely unattended and collected data throughout the winter 2008 season. Here we present a detailed description of the PLATO instrument suite and preliminary results obtained from the first season of operation

Diversidad microbiana y componentes tróficos de dos humedales de altura del altiplano chileno

This study examines the limnology and ecology of two high altitude wetlands, Lirima (19°51’24 S; 68°55’02 W; 4000 m asl) and Caya (20°37’21 S; 68°58’28 W; 3700 m asl), located in the Chilean Altiplano. Both wetlands are formed by the evaporitic remnant basins of paleolakes which occupied an extensive area of what today is known as the Altiplano. These systems have a negative hydrological balance, receiving their water from groundwater, snow melt and limited seasonal rains. An ongoing negative water balance and the sediment characteristics in the region have accelerated the salinization process in these systems, as shown by their present physicochemical characteristics. Nutrient values were typical of mesotrophic to eutrophic systems. The ionic content classifies Lirima as a sodium sulfated wetland and Caya as a calcium chloride one. Conductivity values ranged between 778 ?S/cm at Lirima to 2100 ?S/cm at Caya, and were reflected in the differences in biodiversity found in these systems. The Lirima wetland supports a population of the endemic fish Orestias aff. agassii found in several Evolutionary Significant Units (ESU) across the region. Microbial diversity in the water column was characterized by the presence of 5 bacterial phyla and related genera (e.g. Psychrobacter, Bacillus, Eryhtobacter, Halomonas). We present information on several key ecosystem components including macrophytes, plankton, benthos, fish and birds. This descriptive paper highlights the unusual limnological and biological characteristics of high altitude wetlands and highlights the importance of describing their biological communities across levels of organisation (e.g. microbial through to higher vertebrates) as well as their functional role, interactions and sensitivity to changes in water availability.Este estudio examina la limnología y ecología de dos lagos de altura, los humedales de Lirima (19°51’24 S; 68°55’02 W; 4000 m asl) y Caya (20°37’21 S; 68°58’28 W; 3700 m asl) que están ubicados en el Altiplano Chileno, representando cuencas evaporíticas remanentes de antiguos paleolagos los cuales ocuparon una amplia zona en lo que hoy conocemos como Altiplano. Estos sistemas tienen un balance hídrico negativo, recibiendo su agua desde fuentes freáticas, derretimiento de nueves y escasas lluvias estacionales. Las características del suelo junto con la demanda de agua en la región han acelerado el proceso desalinización en estos sistemas siendo reflejado en las características químicas actuales. Los valores de nutrientes fueron típicos de sistemas mesotróficos a eutróficos. El contenido iónico clasifica Lirima como un humedal sodio sulfatado y el humedal de Caya como un humedal de cloruro de calcio. Los valores de conductividad fluctuaron entre 778 ?S/cm en Lirima a 2100 ?S/cm en Caya, reflejándose en las diferencias de biodiversidad encontrada en estos sistemas. El humedal de Lirima conserva el pez endémico Orestias que representa Unidades Evolutivas Significativas (ESU) en la región. La diversidad microbiana en muestras de agua estuvo caracterizada por la presencia de 5 filo bacterianos y géneros relacionados (e.g. Psychrobacter, Bacillus, Eryhtobacter, Halomonas). Los componentes tróficos estudiados incluyeron macrófitas, plancton, bentos, peces, anfibios y aves. Este artículo descriptivo destaca las inusuales características limnológicas y biológicas de los humedales de altura poniendo atención a la importancia de describir comunidades en distintos niveles de organización biológica (desde tapetes microbianos hasta vertebrados superiores), pero también sus funciones, interacciones y sensibilidad a cambios en la disponibilidad de agua

Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood

Background: Hermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder with oculocutaneous albinism, may be caused by mutations in one of at least 10 separate genes. The HPS-2 subtype is distinguished by the presence of neutropenia and knowledge of its pulmonary phenotype in children is scarce. Methods: Six children with genetically proven HPS-2 presented to the chILD-EU register between 2009 and 2017; the data were collected systematically and imaging studies were scored blinded. Results: Pulmonary symptoms including dyspnea, coughing, need for oxygen, and clubbing started 3.3 years before the diagnosis was made at the mean age of 8.83 years (range 2-15). All children had recurrent pulmonary infections, 3 had a spontaneous pneumothorax, and 4 developed scoliosis. The frequency of pulmonary complaints increased over time. The leading radiographic pattern was ground-glass opacities with a rapid increase in reticular pattern and traction bronchiectasis between initial and follow-up Computer tomography (CT) in all subjects. Honeycombing and cysts were newly detectable in 3 patients. Half of the patients received a lung biopsy for diagnosis; histological patterns were cellular non-specific interstitial pneumonia, usual interstitial pneumonia-like, and desquamative interstitial pneumonia. Conclusions: HPS-2 is characterized by a rapidly fibrosing lung disease during early childhood. Effective treatments are required

Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors

Purpose: Sphingosine kinase 1 (SK1) is a protooncogenic enzyme expressed in many human tumours and is associated with chemoresistance and poor prognosis. It is a potent therapy target and its inhibition chemosensitises solid tumours. Despite recent advances in SK1 inhibitors synthesis and validation, their clinical safety and chemosensitising options are not well described. In this study, we have designed, synthesised and tested a new specific SK1 inhibitor with a low toxicity profile. Methods: Field template molecular modelling was used for compound design. Lead compounds were tested in cell and mouse cancer models. Results: Field template analysis of three known SK1 inhibitors, SKI-178, 12aa and SK1-I, was performed and compound screening identified six potential new SK1 inhibitors. SK1 activity assays in both cell-free and in vitro settings showed that two compounds were effective SK1 inhibitors. Compound SK-F has potently decreased cancer cell viability in vitro and sensitised mouse breast tumours to docetaxel (DTX) in vivo, without significant whole-body toxicity. Conclusion: Through field template screening, we have identified a new SK1 inhibitor, SK-F, which demonstrated antitumour activity in vitro and in vivo without overt toxicity when combined with DTX

The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells

INTRODUCTION: Loss of the cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in breast cancer. The decrease in p27 levels is mainly the result of enhanced proteasome-dependent degradation mediated by its specific ubiquitin ligase subunit S phase kinase protein 2 (Skp2). The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer. Rapamycin was found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 expression is unknown. METHODS: The expression of Skp2 mRNA and protein levels were examined in rapamycin-treated breast cancer cell lines. The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1. RESULTS: Rapamycin significantly decreased Skp2 mRNA and protein levels in a dose and time-dependent fashion, depending on the sensitivity of the cell line to rapamycin. The decrease in Skp2 levels in the different cell lines was followed by cell growth arrest at G1. In addition, rapamycin enhanced the degradation rate of Skp2 and down-regulated the expression of the APC\C inhibitor Emi1. CONCLUSION: These results suggest that Skp2, an important oncogene in the development and progression of breast cancer, may be a novel target for rapamycin treatment

Structure of a Wbl protein and implications for NO sensing by M. tuberculosis

Mycobacterium tuberculosis causes pulmonary tuberculosis (TB) and claims ~1.8 million human lives per annum. Host nitric oxide (NO) is important in controlling TB infection. M. tuberculosis WhiB1 is a NO-responsive Wbl protein (actinobacterial iron-sulfur proteins first identified in the 1970s). Until now, the structure of a Wbl protein has not been available. Here a NMR structural model of WhiB1 reveals that Wbl proteins are four-helix bundles with a core of three α-helices held together by a [4Fe-4S] cluster. The iron-sulfur cluster is required for formation of a complex with the major sigma factor (σA) and reaction with NO disassembles this complex. The WhiB1 structure suggests that loss of the iron-sulfur cluster (by nitrosylation) permits positively charged residues in the C-terminal helix to engage in DNA binding, triggering a major reprogramming of gene expression that includes components of the virulence-critical ESX-1 secretion system

RNA localization in neurite morphogenesis and synaptic regulation: current evidence and novel approaches

It is now generally accepted that RNA localization in the central nervous system conveys important roles both during development and in the adult brain. Of special interest is protein synthesis located at the synapse, as this potentially confers selective synaptic modification and has been implicated in the establishment of memories. However, the underlying molecular events are largely unknown. In this review, we will first discuss novel findings that highlight the role of RNA localization in neurons. We will focus on the role of RNA localization in neurotrophin signaling, axon outgrowth, dendrite and dendritic spine morphogenesis as well as in synaptic plasticity. Second, we will briefly present recent work on the role of microRNAs in translational control in dendrites and its implications for learning and memory. Finally, we discuss recent approaches to visualize RNAs in living cells and their employment for studying RNA trafficking in neurons

An Intron-Retaining Splice Variant of Human Cyclin A2, Expressed in Adult Differentiated Tissues, Induces a G1/S Cell Cycle Arrest In Vitro

BACKGROUND: Human cyclin A2 is a key regulator of S phase progression and entry into mitosis. Alternative splice variants of the G1 and mitotic cyclins have been shown to interfere with full-length cyclin functions to modulate cell cycle progression and are therefore likely to play a role in differentiation or oncogenesis. The alternative splicing of human cyclin A2 has not yet been studied. METHODOLOGY/PRINCIPAL FINDINGS: Sequence-specific primers were designed to amplify various exon-intron regions of cyclin A2 mRNA in cell lines and human tissues. Intron retaining PCR products were cloned and sequenced and then overexpressed in HeLa cells. The subcellular localization of the splice variants was studied using confocal and time-lapse microscopy, and their impact on the cell cycle by flow cytometry, immunoblotting and histone H1 kinase activity. We found a splice variant of cyclin A2 mRNA called A2V6 that partly retains Intron 6. The gene expression pattern of A2V6 mRNA in human tissues was noticeably different from that of wild-type cyclin A2 (A2WT) mRNA. It was lower in proliferating fetal tissues and stronger in some differentiated adult tissues, especially, heart. In transfected HeLa cells, A2V6 localized exclusively in the cytoplasm whereas A2WT accumulated in the nucleus. We show that A2V6 induced a clear G1/S cell cycle arrest associated with a p21 and p27 upregulation and an inhibition of retinoblastoma protein phosphorylation. Like A2WT, A2V6 bound CDK2, but the A2V6/CDK2 complex did not phosphorylate histone H1. CONCLUSION/SIGNIFICANCE: This study has revealed that some highly differentiated human tissues express an intron-retaining cyclin A2 mRNA that induced a G1/S block in vitro. Contrary to full-length cyclin A2, which regulates cell proliferation, the A2V6 splice variant might play a role in regulating nondividing cell states such as terminal differentiation or senescence

Synergistic inhibition of prostate cancer cell lines by a 19- nor hexafluoride vitamin D3 analogue and anti-activator protein 1 retinoid

The secosteroid hormones, all- trans- and 9- cis -retinoic acid and vitamin D3, have demonstrated significant capacity to control proliferation in itro of many solid tumour cell lines. Cooperative synergistic effects by these two ligands have been reported, and it is, therefore, possible that greater therapeutic effects could be achieved if these compounds were administered together. The role of retinoid-dependent anti-activator protein 1 (anti-AP-1) effects in controlling cancer cell proliferation appears significant. We have utilized an anti- AP-1 retinoid [2-(4,4-dimethyl-3,4-dihydro-2H-1 benzopyran-6-yl)carbonyl-2-(4-carboxyphenyl)-1,3,-dithiane; SR11238], which does not transactivate through a retinoic acid response element (RARE), and a potent vitamin D3analogue [1α,25(OH)2-16-ene-23-yne-26,27-F6-19-nor -D3, code name LH] together at low, physiologically safer doses against a panel of prostate cancer cell lines that represent progressively more transformed phenotypes. The LNCaP (least transformed) and PC-3 (intermediately transformed) cell lines were synergistically inhibited in their clonal growth by the combination of LH and SR11238, whereas SR11238 alone was essentially inactive. DU-145 cells (most transformed) were completely insensitive to these analogues. LNCaP cells, but neither PC-3 nor DU-145, underwent apoptosis in the presence of LH and SR11238. Transactivation of the human osteocalcin vitamin D response element (VDRE) by LH was not enhanced in the presence of SR11238, although the expression of E-cadherin in these cells was additively up-regulated in the presence of both compounds. These data suggest the anti-AP-1 retinoid and the vitamin D3 analogue may naturally act synergistically to control cell proliferation, a process that is interrupted during transformation, and that this combination may form the basis for treatment of some androgen-independent prostate cancer. © 1999 Cancer Research Campaig

Use of cancer-specific yeast-secreted in vivo biotinylated recombinant antibodies for serum biomarker discovery

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens