Rural America's fiscal challenge

Fiscal challenges at state and local governments are a potential threat to the economic recovery in rural America. Rural communities depend heavily on intergovernmental transfers from the states to provide local services. Many people in rural communities rely on the state or local government for their jobs and on Medicaid as part of their income. Thus, rural economies are highly susceptible to state budget shortfalls. As state governments cut spending in response to looming budget deficits in coming years, rural America's fiscal problems may also deepen.

Investigating the dynamics of resilience and greenhouse gas performance of pastoral cattle systems in southern Ethiopia

Context: Pastoral and agro-pastoral (PAP) systems in East Africa face a range of challenges including increased climate variability. Various measures have been proposed to improve the resilience of pastoral/agro-pastoral (PAP) systems to drought. However, identifying the most effective measure for a given system and location is complicated, and tools are required to appraise measures on a consistent basis.Objective: This paper develops a model of a PAP system and uses it to assess the effects of four measures (Index-based livestock insurance, IBLI; Commercial destocking with an early warning system, EWS; Rangeland restoration, RR; Fodder planting, FP) on the resilience of the PAP system. It also quantifies the greenhouse gas (GHG) effects of the measures, thereby identifying potential trade-offs and synergies between the policy objectives of resilience and climate smart agriculture (CSA).Methods: A dynamic model of the Borena pastoral cattle system was developed to undertake the analysis. At its core is a herd model that calculates the changes in cattle population over time. Feed availability and drought occurrence affect fertility and mortality rates, which in turn determine the population and (meat and milk) production. A suite of indicators covering the three dimensions of CSA (increasing productivity, enhancing resilience and reducing GHG emissions) were developed, and used to compare the situation with and without measures.Results and discussions: Destocking with an early warning system provides the biggest increases (relative to the no measure situation) in production and profit, due to the way it changes the herd size and structure. It maintains a larger herd than any of the other measures, and a greater proportion of the herd are adult females. Fodder planting and rangeland restoration provide moderate increases in production and profit. Index-based livestock insurance provides a moderate increase in protein production, but has no effect on profit, as it is designed to reduce risk rather than increase productivity or profit, at least in the short term.All of the measures increase the total emissions relative to the no measure scenario. In terms of the three dimensions of climate-smart agriculture, IBLI leads to some improvements in productivity and resilience but leads to large increases in total emissions, and modest increases in emissions intensity (EI). EWS leads to large increases in productivity and resilience. However, it also leads to large increases in total emissions and a mixed effect on EI. FP and RR improve productivity and increase total emissions, while having little effect on EI or resilience.Significance: This paper illustrates the way in which systems dynamic model can be used to appraise measures designed to improve resilience. The result identify potential synergies and tensions between the goals of resilience and climate smart agriculture, and raises the question of whether fully climate-smart goals are viable in these systems

Extended HI Rotation Curve and Mass Distribution of M31

New HI observations of Messier 31 (M31) obtained with the Effelsberg and Green Bank 100-m telescopes make it possible to measure the rotation curve of that galaxy out to ~35 kpc. Between 20 and 35 kpc, the rotation curve is nearly flat at a velocity of ~226 km/s. A model of the mass distribution shows that at the last observed velocity point, the minimum dark-to-luminous mass ratio is \~0.5 for a total mass of 3.4 10^11 Msol at R < 35 kpc. This can be compared to the estimated MW mass of 4.9 10^11 Msol for R < 50 kpc.Comment: 4 pages, 2 figures, accepted for publication in ApJ Letter

Global proteomics analysis of the response to starvation in <i>C. elegans</i>

Periodic starvation of animals induces large shifts in metabolism but may also influence many other cellular systems and can lead to adaption to prolonged starvation conditions. To date, there is limited understanding of how starvation affects gene expression, particularly at the protein level. Here, we have used mass-spectrometry-based quantitative proteomics to identify global changes in the Caenorhabditis elegans proteome due to acute starvation of young adult animals. Measuring changes in the abundance of over 5,000 proteins, we show that acute starvation rapidly alters the levels of hundreds of proteins, many involved in central metabolic pathways, highlighting key regulatory responses. Surprisingly, we also detect changes in the abundance of chromatin-associated proteins, including specific linker histones, histone variants, and histone posttranslational modifications associated with the epigenetic control of gene expression. To maximize community access to these data, they are presented in an online searchable database, the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/)

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p &lt; 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth

The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is unknown. We show that pericyte FAK regulates tumour growth and angiogenesis in multiple mouse models of melanoma, lung carcinoma and pancreatic B-cell insulinoma and provide evidence that loss of pericyte FAK enhances Gas6-stimulated phosphorylation of the receptor tyrosine kinase, Axl with an upregulation of Cyr61, driving enhanced tumour growth. We further show that pericyte derived Cyr61 instructs tumour cells to elevate expression of the proangiogenic/protumourigenic transmembrane receptor Tissue Factor. Finally, in human melanoma we show that when 50% or more tumour blood vessels are pericyte-FAK negative, melanoma patients are stratified into those with increased tumour size, enhanced blood vessel density and metastasis. Overall our data uncover a previously unknown mechanism of tumour growth by pericytes that is controlled by pericyte FAK

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN