Global isoform-specific transcript alterations and deregulated networks in clear cell renal cell carcinoma.

Extensive genome-wide analyses of deregulated gene expression have now been performed for many types of cancer. However, most studies have focused on deregulation at the gene-level, which may overlook the alterations of specific transcripts for a given gene. Clear cell renal cell carcinoma (ccRCC) is one of the best-characterized and most pervasive renal cancers, and ccRCCs are well-documented to have aberrant RNA processing. In the present study, we examine the extent of aberrant isoform-specific RNA expression by reporting a comprehensive transcript-level analysis, using the new kallisto-sleuth-RATs pipeline, investigating coding and non-coding differential transcript expression in ccRCC. We analyzed 50 ccRCC tumors and their matched normal samples from The Cancer Genome Altas datasets. We identified 7,339 differentially expressed transcripts and 94 genes exhibiting differential transcript isoform usage in ccRCC. Additionally, transcript-level coexpression network analyses identified vasculature development and the tricarboxylic acid cycle as the most significantly deregulated networks correlating with ccRCC progression. These analyses uncovered several uncharacterized transcripts, including lncRNAs FGD5-AS1 and AL035661.1, as potential regulators of the tricarboxylic acid cycle associated with ccRCC progression. As ccRCC still presents treatment challenges, our results provide a new resource of potential therapeutics targets and highlight the importance of exploring alternative methodologies in transcriptome-wide studies

Quantifying temporal and spatial variations in sediment, nitrogen and phosphorus transport in stream inflows to a large eutrophic lake

High-frequency sampling of two major stream inflows to a large eutrophic lake (Lake Rotorua, New Zealand) was conducted to measure inputs of total suspended sediment (TSS), and fractions of nitrogen and phosphorus (P). A total of 17 rain events were sampled, including three during which both streams were simultaneously monitored to quantify how concentration–discharge (Q) relationships varied between catchments during similar hydrological conditions. Dissolved inorganic nitrogen (DIN) concentrations declined slightly during events, reflecting dilution of groundwater inputs by rainfall, whereas dissolved inorganic P (PO₄–P) concentrations were variable and unrelated to Q, suggesting dynamic sorptive behaviour. Event loads of total nitrogen (TN) were predominantly DIN, which is available for immediate uptake by primary producers, whereas total phosphorus (TP) loads predominantly comprised particulate P (less labile). Positive correlations between Q and concentrations of TP (and to a lesser extent TN) reflected increased particulate nutrient concentrations at high flows. Consequently, load estimates based on hourly Q during storm events and concentrations of routine monthly samples (mostly base flow) under-estimated TN and TP loads by an average of 19% and 40% respectively. Hysteresis with Q was commonly observed and inclusion of hydrological variables that reflect Q history in regression models improved predictions of TN and TP concentrations. Lorenz curves describing the proportions of cumulative load versus cumulative time quantified temporal inequality in loading. In the two study streams, 50% of estimated two-year loads of TN, TP and TSS were transported in 202–207, 76–126 and 1–8 days respectively. This study quantifies how hydrological and landscape factors can interact to influence pollutant flux at the catchment scale and highlights the importance of including storm transfers in lake loading estimates

Cosmic evolution of extragalactic C 1, C 2, and CO luminosity

Carbon is the fourth most abundant element in the Galaxy with an abundance of approximately 4 x 10(exp -4) relative to hydrogen. Of all abundant metals it is the easiest to observe in the interstellar medium (ISM). Carbon can be found in four dominant forms: dust grains, C 2, C 1, and CO. The latter is the most abundant molecule (next to H2) in molecular clouds. All three gas-phase forms produce strong sub-mm wavelength emission lines and are the principal tracers of the warm and dense neutral phases of the ISM. We calculate the gas-phase abundances of neutral carbon (C 1), ionized carbon (C 2), and carbon monoxide (CO) as a function of cosmic time or redshift z in an idealized scenario of galactic evolution

Family-Expressed Emotion, Childhood-Onset Depression, and Childhood-Onset Schizophrenia Spectrum Disorders: Is Expressed Emotion a Nonspecific Correlate of Child Psychopathology or a Specific Risk Factor for Depression?

Expressed emotion (EE) was examined, using the brief Five Minute Speech Sample measure, in families of (1) children with depressive disorders, (2) children with schizophrenia spectrum disorders, and (3) normal controls screened for the absence of psychiatric disorder. Consistent with the hypothesis of some specificity in the association between EE and the form of child disorder, rates of EE were significantly higher among families of depressed children compared to families of normal controls and families of children with schizophrenia spectrum disorders. Within the depressed group, the presence of a comorbid disruptive behavior disorder was associated with high levels of critical EE, underscoring the need to attend to comorbid patterns and subtypes of EE in future research

Use of high-intensity data to define large river management units: A case study on the lower Waikato River, New Zealand

The importance of environmental heterogeneity in lotic ecosystems is well recognised in river management, and continues to underpin studies of hierarchical patch dynamics, geomorphology and landscape ecology. We evaluated how physical characteristics and water chemistry measurements at high spatiotemporal resolution define channel units of potential ecological importance along 134 km of the lower Waikato River in North Island, New Zealand. We used multivariate hierarchical clustering to classify river reaches in an a priori unstructured manner based on (i) high-frequency, along-river water quality measurements collected in four seasons and (ii) river channel morphology data resolved from aerial photos for 1-km long reaches. Patterns of channel character were shaped by the depth and lateral complexity of constituent river reaches, while water quality patterns were represented by differences in clarity, chlorophyll fluorescence and specific conductance driven by tributary inflows in the mid-section of the river and tidal cycles in the lower section. Management units defined by physical characteristics or water quality did not necessarily align with boundaries typically reflecting clinal processes (e.g. tidal influence) or geomorphic, network or anthropogenic discontinuities. The results highlight the dynamic spatial and temporal properties of large rivers and the need to define clear objectives when deriving spatial units for management and research. Given that actions and targets for physical channel and water quality management may differ, the spatial extent identified for each of these does not necessarily need to directly coincide, although both should be considered in decision making and experimental design

Forest views: Northeast Oregon survey looks at community and environment

This brief reports on a survey conducted in fall 2011 as one component of the ongoing Communities and Forests in Oregon (CAFOR) project. The CAFOR project focuses on the people and landscapes of three counties in northeast Oregon (Baker, Union, and Wallowa), where landscapes and communities are changing in interconnected ways

Capturing the distributional impacts of long-term low-carbon transitions

Major policy proposals often require a distributional impact assessment, focusing on differential financial and other impacts across population segments. Such assessments are rare, however, at the multi-decadal scale addressed in long-term (e.g. to 2050) low carbon transition modelling. There is therefore a risk of socially inequitable outcomes, which in turn presents a socio-political risk for decision-makers driving transitions. This paper uses a literature review and expert interviews to identify mechanisms by which low carbon transitions could differentially impact population sub-groups. As well as impacts of policy costs on bills, this includes factors such as ability to connect to heat networks or install onsite generation or storage. An approach to exploring distributional impacts across a range of long term scenarios from a United Kingdom energy model (ESME), is proposed. This sets out how bill changes and other costs associated with low carbon transition could impact different income quintiles in the UK

Determination of the Baryon Density from Large Scale Galaxy Redshift Surveys

We estimate the degree to which the baryon density, $\Omega_{b}$, can be determined from the galaxy power spectrum measured from large scale galaxy redshift surveys, and in particular, the Sloan Digital Sky Survey. A high baryon density will cause wiggles to appear in the power spectrum, which should be observable at the current epoch. We assume linear theory on scales $\geq 20h^{-1}Mpc$ and do not include the effects of redshift distortions, evolution, or biasing. With an optimum estimate of $P(k)$ to $k\sim 2\pi/(20 h^{-1} Mpc)$, the $1 \sigma$ uncertainties in $\Omega_{b}$ are roughly 0.07 and 0.016 in flat and open ($\Omega_{0}=0.3$) cosmological models, respectively. This result suggests that it should be possible to test for consistency with big bang nucleosynthesis estimates of $\Omega_{b}$ if we live in an open universe.Comment: 23 Pages, 10 Postscript figure

Cost and U.S. public policy for new coal power plants with carbon capture and sequestration

This paper provides a financial analysis for new supercritical pulverized coal plants with carbon capture and sequestration (CCS) that compares the effects of two relevant climate policies. First, an updated cost estimate is presented for new supercritical pulverized coal plants, both with and without CCS. The capital cost escalation of recent years can be attributed to rising materials, plant supply, and plant contractor constraints. This estimate is then compared with recent estimates from public sources. Second, several current and proposed public policies relevant to CCS are presented. Finally, a financial analysis is performed to evaluate the effectiveness of two likely US carbon regulations on deploying Nth-plant CCS technology. The major conclusion is that the leading US carbon cap-and-trade bills will likely not be sufficient to deploy CCS technology in a manner consistent with a 550 ppm CO[subscript 2] stabilization scenario. A more aggressive carbon policy including CCS research, development, and demonstration must be considered to achieve this goal with significant CCS deployment.Massachusetts Institute of Technology. Carbon Sequestration InitiativeMIT Industrial Performance Cente

Genes of the serotonergic and dopaminergic pathways and their interaction affect the expression of Behavioural and Psychological Symptoms in Dementia (BPSD).

Although there is evidence for the involvement of genes of serotonergic and dopaminergic systems in the manifestation of the Behavioural and Psychological Symptoms in Dementia (BPSD), genetic association studies are contradictory. We used 1008 probable AD patients from the UK and applied a Multiple Indicators Multiple Causes (MIMIC) approach to investigate the effect of 11 polymorphisms in the serotonergic and dopaminergic systems, on four behavioural sub-phenotypes, namely "psychosis"," moods", "agitation" and "behavioural dyscontrol", as well as on 12 NPI items. Significant findings included the association of DRD1 A48G with "psychosis" (p=0.037), the association of DAT1 VNTR with "agitation" (p=0.006) and the association of DRD4 with "moods" sub-phenotype (p=0.008). In addition, associations were identified between DRD1 A48G and DAT1 VNTR with aberrant motor behaviour (AMB) symptoms (p=0.001 and p=0.015 respectively), between DRD4 and sleep disturbances (p=0.018) and between 5HTTLPR and apathy (p=0.033). Finally, significant interactions were observed between COMT Val158Met and 5HTTLPR with "psychosis" (p=0.026), between HTTLPR and STin2 with "psychosis" (p=0.005), between DAT1 3'UTR VNTR and COMT Val158Met with "agitation" (p=0.0001) and between DAT1 3'UTR VNTR and 5HTTLPR with the "moods" factor (p=0.0027). The complexity of the interrelations between genetic variation, behavioural symptoms and clinical variables was efficiently captured by this MIMIC model