Global Climate Change: Turning Knowledge into Action

The science of climate change is a complex subject that balances the physical record and scientific fact with politics, policy, and ethics—and is of particular importance to the geosciences. This thoughtfully crafted new text and accompanying media encourage non-science majors to practice critical thinking, analysis, and discourse about climate change themes. Taking a cross-disciplinary approach, acclaimed educator and researcher, David Kitchen, examines not only the physical science, but the social, economic, political, energy, and environmental issues surrounding climate change. His goal: to turn knowledge into action, equipping students with the knowledge and critical skills to make informed decisions, separate facts from fiction, and participate in the public debate.https://scholarship.richmond.edu/bookshelf/1033/thumbnail.jp

Bringing in the Green: Pharma Stands to Win Hearts, Minds, and Tax Credits by Launching an Eco Bandwagon

A green mind-set can lead to a black bottom line. Becoming nvironmentally friendly can help boost brand image and ROi -- and pharma can get there with a few easy steps. First, with about 90,000 sales representatives on the road, the industry could lead a revolution in transportation if it bought hybrid cars. By replacing the current fleet, the benefits would be substantial. Each hybrid is cheaper to maintain, more fuel-efficient, and leaves a far smaller greenhouse-gas footprint on the environment. Imagine extrapolating these benefits to thousands of ca rs: That\u27s an environmentally friendly signature that shows leadership in the onearmosphere world we live in

An Uncharged Amine in the Transition State of the Ribosomal Peptidyl Transfer Reaction

The ribosome has an active site comprised of RNA that catalyzes peptide bond formation. To understand how RNA promotes this reaction requires a detailed understanding of the chemical transition state. Here, we report the Brønsted coefficient of the α-amino nucleophile with a series of puromycin derivatives. Both 50S subunit- and 70S ribosome-catalyzed reactions displayed linear free-energy relationships with slopes close to zero under conditions where chemistry is rate limiting. These results indicate that, at the transition state, the nucleophile is neutral in the ribosome-catalyzed reaction, in contrast to the substantial positive charge reported for typical uncatalyzed aminolysis reactions. This suggests that the ribosomal transition state involves deprotonation to a degree commensurate with nitrogen-carbon bond formation. Such a transition state is significantly different from that of uncatalyzed aminolysis reactions in solution

Human aquaporins: regulators of transcellular water flow

Background: Emerging evidence supports the view that (AQP) aquaporin water channels are regulators of transcellular water flow. Consistentwith their expression in most tissues, AQPs are associatedwith diverse physiological and pathophysiological processes. Scope of review: AQP knockout studies suggest that the regulatory role of AQPs, rather than their action as passive channels, is their critical function. Transport through all AQPs occurs by a common passive mechanism, but their regulation and cellular distribution varies significantly depending on cell and tissue type; the role of AQPs in cell volumeregulation (CVR) is particularly notable. This reviewexamines the regulatory role of AQPs in transcellular water flow, especially in CVR.We focus on key systems of the human body, encompassing processes as diverse as urine concentration in the kidney to clearance of brain oedema. Major conclusions: AQPs are crucial for the regulation of water homeostasis, providing selective pores for the rapidmovement ofwater across diverse cellmembranes and playing regulatory roles in CVR. Gatingmechanisms have been proposed for human AQPs, but have only been reported for plant andmicrobial AQPs. Consequently, it is likely that the distribution and abundance of AQPs in a particular membrane is the determinant of membrane water permeability and a regulator of transcellular water flow. General significance: Elucidating the mechanisms that regulate transcellular water flow will improve our understanding of the human body in health and disease. The central role of specific AQPs in regulating water homeostasis will provide routes to a range of novel therapies. This article is part of a Special Issue entitled Aquaporins

Tissue of origin determines cancer-associated CpG island promoter hypermethylation patterns

ABSTRACT: BACKGROUND: Aberrant CpG island promoter DNA hypermethylation is frequently observed in cancer and is believed to contribute to tumor progression by silencing the expression of tumor suppressor genes. Previously, we observed that promoter hypermethylation in breast cancer reflects cell lineage rather than tumor progression and occurs at genes that are already repressed in a lineage-specific manner. To investigate the generality of our observation we analyzed the methylation profiles of 1,154 cancers from 7 different tissue types. RESULTS: We find that 1,009 genes are prone to hypermethylation in these 7 types of cancer. Nearly half of these genes varied in their susceptibility to hypermethylation between different cancer types. We show that the expression status of hypermethylation prone genes in the originator tissue determines their propensity to become hypermethylated in cancer; specifically, genes that are normally repressed in a tissue are prone to hypermethylation in cancers derived from that tissue. We also show that the promoter regions of hypermethylation-prone genes are depleted of repetitive elements and that DNA sequence around the same promoters is evolutionarily conserved. We propose that these two characteristics reflect tissue-specific gene promoter architecture regulating the expression of these hypermethylation prone genes in normal tissues. CONCLUSIONS: As aberrantly hypermethylated genes are already repressed in pre-cancerous tissue, we suggest that their hypermethylation does not directly contribute to cancer development via silencing. Instead aberrant hypermethylation reflects developmental history and the perturbation of epigenetic mechanisms maintaining these repressed promoters in a hypomethylated state in normal cells.Publisher PDFPeer reviewe

United States Midwest Soil and Weather Conditions Influence Anaerobic Potentially Mineralizable Nitrogen

Nitrogen provided to crops through mineralization is an important factor in N management guidelines. Understanding of the interactive effects of soil and weather conditions on N mineralization needs to be improved. Relationships between anaerobic potentially mineralizable N (PMNan) and soil and weather conditions were evaluated under the contrasting climates of eight US Midwestern states. Soil was sampled (0–30 cm) for PMNan analysis before pre-plant N application (PP0N) and at the V5 development stage from the pre-plant 0 (V50N) and 180 kg N ha−1 (V5180N) rates and incubated for 7, 14, and 28 d. Even distribution of precipitation and warmer temperatures before soil sampling and greater soil organic matter (SOM) increased PMNan. Soil properties, including total C, SOM, and total N, had the strongest relationships with PMNan (R2 ≤ 0.40), followed by temperature (R2 ≤ 0.20) and precipitation (R2 ≤ 0.18) variables. The strength of the relationships between soil properties and PMNan from PP0N, V50N, and V5180N varied by ≤10%. Including soil and weather in the model greatly increased PMNan predictability (R2 ≤ 0.69), demonstrating the interactive effect of soil and weather on N mineralization at different times during the growing season regardless of N fertilization. Delayed soil sampling (V50N) and sampling after fertilization (V5180N) reduced PMNan predictability. However, longer PMNan incubations improved PMNan predictability from both V5 soil samplings closer to the PMNan predictability from PP0N, indicating the potential of PMNan from longer incubations to provide improved estimates of N mineralization when N fertilizer is applied

Soil sample timing, nitrogen fertilization, and incubation length influence anaerobic potentially mineralizable nitrogen

Understanding the variables that affect the anaerobic potentially mineralizable N (PMNan) test should lead to a standard procedure of sample collection and incubation length, improving PMNan as a tool in corn (Zea mays L.) N management. We evaluated the effect of soil sample timing (preplant and V5 corn development stage [V5]), N fertilization (0 and 180 kg ha−1) and incubation length (7, 14, and 28 d) on PMNan (0–30 cm) across a range of soil properties and weather conditions. Soil sample timing, N fertilization, and incubation length affected PMNan differently based on soil and weather conditions. Preplant vs. V5 PMNan tended to be greater at sites that received \u3c 183 mm of precipitation or \u3c 359 growing degree-days (GDD) between preplant and V5, or had soil C/N ratios \u3e 9.7:1; otherwise, V5 PMNan tended to be greater than preplant PMNan. The PMNan tended to be greater in unfertilized vs. fertilized soil in sites with clay content \u3e 9.5%, total C \u3c 24.2 g kg−1, soil organic matter (SOM) \u3c 3.9 g kg−1, or C to N ratios \u3c 11.0:1; otherwise, PMNan tended to be greater in fertilized vs. unfertilized soil. Longer incubation lengths increased PMNan at all sites regardless of sampling methods. Since PMNan is sensitive to many factors (sample timing, N fertilization, incubation length, soil properties, and weather conditions), it is important to follow a consistent protocol to compare PMNan among sites and potentially use PMNan to improve corn N management

The clock gene <i>Bmal1</i> inhibits macrophage motility, phagocytosis, and impairs defense against pneumonia

The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. Infected mice show both reduced weight loss and lower bacterial burden in circulating blood. In vivo studies of macrophage phagocytosis reveal increased bacterial ingestion following Bmal1 deletion, which was also seen in vitro. BMAL1−/− macrophages exhibited marked differences in actin cytoskeletal organization, a phosphoproteome enriched for cytoskeletal changes, with reduced phosphocofilin and increased active RhoA. Further analysis of the BMAL1−/− macrophages identified altered cell morphology and increased motility. Mechanistically, BMAL1 regulated a network of cell movement genes, 148 of which were within 100 kb of high-confidence BMAL1 binding sites. Links to RhoA function were identified, with 29 genes impacting RhoA expression or activation. RhoA inhibition restored the phagocytic phenotype to that seen in control macrophages. In summary, we identify a surprising gain of antibacterial function due to loss of BMAL1 in macrophages, associated with a RhoA-dependent cytoskeletal change, an increase in cell motility, and gain of phagocytic function