Molecular Gas in the Host Galaxy of a Quasar at Redshift z=6.42

Observations of the molecular gas phase in quasar host galaxies provide fundamental constraints on galaxy evolution at the highest redshifts. Molecular gas is the material out of which stars form; it can be traced by spectral line emission of carbon--monoxide (CO). To date, CO emission has been detected in more than a dozen quasar host galaxies with redshifts (z) larger 2, the record holder being at z=4.69. At these distances the CO lines are shifted to longer wavelengths, enabling their observation with sensitive radio and millimetre interferometers. Here we present the discovery of CO emission toward the quasar SDSS J114816.64+525150.3 (hereafter J1148+5251) at a redshift of z=6.42, when the universe was only 1/16 of its present age. This is the first detection of molecular gas at the end of cosmic reionization. The presence of large amounts of molecular gas (M(H_2)=2.2e10 M_sun) in an object at this time demonstrates that heavy element enriched molecular gas can be generated rapidly in the earliest galaxies.Comment: 12 pages, 2 figures. To appear in Nature, July, 200

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Telomeres and disease

The telomeres of most eukaryotes are characterized by guanine-rich repeats synthesized by the reverse transcriptase telomerase. Complete loss of telomerase is tolerated for several generations in most species, but modestly reduced telomerase levels in human beings are implicated in bone marrow failure, pulmonary fibrosis and a spectrum of other diseases including cancer. Differences in telomerase deficiency phenotypes between species most likely reflect a tumour suppressor function of telomeres in long-lived mammals that does not exist as such in short-lived organisms. Another puzzle provided by current observations is that family members with the same genetic defect, haplo-insufficiency for one of the telomerase genes, can present with widely different diseases. Here, the crucial role of telomeres and telomerase in human (stem cell) biology is discussed from a Darwinian perspective. It is proposed that the variable phenotype and penetrance of heritable human telomerase deficiencies result from additional environmental, genetic and stochastic factors or combinations thereof

Quality of care in elder emergency department patients with pneumonia: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The goals of the study were to assess the relationship between age and processes of care in emergency department (ED) patients admitted with pneumonia and to identify independent predictors of failure to meet recommended quality care measures.</p> <p>Methods</p> <p>This was a prospective cohort study of a pre-existing database undertaken at a university hospital ED in the Midwest. ED patients ≥18 years of age requiring admission for pneumonia, with no documented use of antibiotics in the 24 hours prior to ED presentation were included. Compliance with Pneumonia National Quality Measures was assessed including ED antibiotic administration, antibiotics within 4 hours, oxygenation assessment, and obtaining of blood cultures. Odds ratios were calculated for elders and non-elders. Logistic regression was used to identify independent predictors of process failure.</p> <p>Results</p> <p>One thousand, three hundred seventy patients met inclusion criteria, of which 560 were aged ≥65 years. In multiple variable logistic regression analysis, age ≥65 years was independently associated with receiving antibiotics in the ED (odds ratio [OR] = 2.03, 95% CI 1.28–3.21) and assessment of oxygenation (OR = 2.10, 95% CI, 1.18–3.32). Age had no significant impact on odds of receiving antibiotics within four hours of presentation (OR 1.10, 95% CI 0.84–1.43) or having blood cultures drawn (OR 1.02, 95%CI 0.78–1.32). Certain other patient characteristics were also independently associated with process failure.</p> <p>Conclusion</p> <p>Elderly patients admitted from the ED with pneumonia are more likely to receive antibiotics while in the ED and to have oxygenation assessed in the ED than younger patients. The independent association of certain patient characteristics with process failure provides an opportunity to further increase compliance with recommended quality measures in admitted patients diagnosed with pneumonia.</p

Role of supplemental foods and habitat structural complexity in persistence and coexistence of generalist predatory mites

Variation in the strength of intraguild predation (IGP) may be related to habitat structural complexity and to additional resources outside the narrow predator-prey relationship. We studied the food web interactions on grape, which involves two generalist predatory mites. We evaluated the effects of grape powdery mildew (GPM) as supplemental food, and habitat structural complexity provided by domatia. Our findings suggest that structural and nutritional diversity/complexity promote predatory mite abundance and can help to maintain the beneficial mites - plants association. The effect of these factors on coexistence between predators is influenced by the supplemental food quality and relative differences in body size of interacting species

Remote Electrical Stimulation by Means of Implanted Rectifiers

Miniaturization of active implantable medical devices is currently compromised by the available means for electrically powering them. Most common energy supply techniques for implants – batteries and inductive couplers – comprise bulky parts which, in most cases, are significantly larger than the circuitry they feed. Here, for overcoming such miniaturization bottleneck in the case of implants for electrical stimulation, it is proposed to make those implants act as rectifiers of high frequency bursts supplied by remote electrodes. In this way, low frequency currents will be generated locally around the implant and these low frequency currents will perform stimulation of excitable tissues whereas the high frequency currents will cause only innocuous heating. The present study numerically demonstrates that low frequency currents capable of stimulation can be produced by a miniature device behaving as a diode when high frequency currents, neither capable of thermal damage nor of stimulation, flow through the tissue where the device is implanted. Moreover, experimental evidence is provided by an in vivo proof of concept model consisting of an anesthetized earthworm in which a commercial diode was implanted. With currently available microelectronic techniques, very thin stimulation capsules (diameter <500 µm) deliverable by injection are easily conceivable

Acute hospital admissions among nursing home residents: a population-based observational study

<p>Abstract</p> <p>Background</p> <p>Nursing home residents are prone to acute illness due to their high age, underlying illnesses and immobility. We examined the incidence of acute hospital admissions among nursing home residents versus the age-matched community dwelling population in a geographically defined area during a two years period. The hospital stays of the nursing home population are described according to diagnosis, length of stay and mortality. Similar studies have previously not been reported in Scandinavia.</p> <p>Methods</p> <p>The acute hospitalisations of the nursing home residents were identified through ambulance records. These were linked to hospital patient records for inclusion of demographics, diagnosis at discharge, length of stay and mortality. Incidence of hospitalisation was calculated based on patient-time at risk.</p> <p>Results</p> <p>The annual hospital admission incidence was 0.62 admissions per person-year among the nursing home residents and 0.26 among the community dwellers. In the nursing home population we found that dominant diagnoses were respiratory diseases, falls-related and circulatory diseases, accounting for 55% of the cases. The median length of stay was 3 days (interquartile range = 4). The in-hospital mortality rate was 16% and 30 day mortality after discharge 30%.</p> <p>Conclusion</p> <p>Acute hospital admission rate among nursing home residents was high in this Scandinavian setting. The pattern of diagnoses causing the admissions appears to be consistent with previous research. The in-hospital and 30 day mortality rates are high.</p

The c-Myc Target Glycoprotein1bα Links Cytokinesis Failure to Oncogenic Signal Transduction Pathways in Cultured Human Cells

An increase in chromosome number, or polyploidization, is associated with a variety of biological changes including breeding of cereal crops and flowers, terminal differentiation of specialized cells such as megakaryocytes, cellular stress and oncogenic transformation. Yet it remains unclear how cells tolerate the major changes in gene expression, chromatin organization and chromosome segregation that invariably accompany polyploidization. We show here that cancer cells can initiate increases in chromosome number by inhibiting cell division through activation of glycoprotein1b alpha (GpIbα), a component of the c-Myc signaling pathway. We are able to recapitulate cytokinesis failure in primary cells by overexpression of GpIbα in a p53-deficient background. GpIbα was found to localize to the cleavage furrow by microscopy analysis and, when overexpressed, to interfere with assembly of the cellular cortical contraction apparatus and normal division. These results indicate that cytokinesis failure and tetraploidy in cancer cells are directly linked to cellular hyperproliferation via c-Myc induced overexpression of GpIbα

Robust evidence for reversal of the trend in aerosol effective climate forcing

Anthropogenic aerosols exert a cooling influence that offsets part of the greenhouse gas warming. Due to their short tropospheric lifetime of only several days, the aerosol forcing responds quickly to emissions. Here, we present and discuss the evolution of the aerosol forcing since 2000. There are multiple lines of evidence that allow us to robustly conclude that the anthropogenic aerosol effective radiative forcing (ERF) – both aerosol–radiation interactions (ERFari) and aerosol–cloud interactions (ERFaci) – has become less negative globally, i.e. the trend in aerosol effective radiative forcing changed sign from negative to positive. Bottom-up inventories show that anthropogenic primary aerosol and aerosol precursor emissions declined in most regions of the world; observations related to aerosol burden show declining trends, in particular of the fine-mode particles that make up most of the anthropogenic aerosols; satellite retrievals of cloud droplet numbers show trends in regions with aerosol declines that are consistent with these in sign, as do observations of top-of-atmosphere radiation. Climate model results, including a revised set that is constrained by observations of the ocean heat content evolution show a consistent sign and magnitude for a positive forcing relative to the year 2000 due to reduced aerosol effects. This reduction leads to an acceleration of the forcing of climate change, i.e. an increase in forcing by 0.1 to 0.3 W m−2, up to 12 % of the total climate forcing in 2019 compared to 1750 according to the Intergovernmental Panel on Climate Change (IPCC)

Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression

Colorectal adenomas form a biologically and clinically distinct intermediate stage in development of colorectal cancer (CRC) from normal colon epithelium. Only 5% of adenomas progress into adenocarcinomas, indicating that malignant transformation requires other biological alterations than those involved in adenoma formation. The present study aimed to explore which cancer-related biological processes are affected during colorectal adenoma-to-carcinoma progression and to identify key genes within these pathways that can serve as tumor markers for malignant transformation. The activity of 12 cancer-related biological processes was compared between 37 colorectal adenomas and 31 adenocarcinomas, using the pathway analysis tool Gene Set Enrichment Analysis. Expression of six gene sets was significantly increased in CRCs compared to adenomas, representing chromosomal instability, proliferation, differentiation, invasion, stroma activation, and angiogenesis. In addition, 18 key genes were identified for these processes based on their significantly increased expression levels. For AURKA and PDGFRB, increased mRNA expression levels were verified at the protein level by immunohistochemical analysis of a series of adenomas and CRCs. This study revealed cancer-related biological processes whose activities are increased during malignant transformation and identified key genes which may be used as tumor markers to improve molecular characterization of colorectal tumors