Dystrophic heart failure blocked by membrane sealant poloxamer

Dystrophin deficiency causes Duchenne muscular dystrophy (DMD) in humans, an inherited and progressive disease of striated muscle deterioration that frequently involves pronounced cardiomyopathy(1). Heart failure is the second leading cause of fatalities in DMD1,2. Progress towards defining the molecular basis of disease in DMD has mostly come from studies on skeletal muscle, with comparatively little attention directed to cardiac muscle. The pathophysiological mechanisms involved in cardiac myocytes may differ significantly from skeletal myofibres; this is underscored by the presence of significant cardiac disease in patients with truncated or reduced levels of dystrophin but without skeletal muscle disease(3). Here we show that intact, isolated dystrophin-deficient cardiac myocytes have reduced compliance and increased susceptibility to stretch-mediated calcium overload, leading to cell contracture and death, and that application of the membrane sealant poloxamer 188 corrects these defects in vitro. In vivo administration of poloxamer 188 to dystrophic mice instantly improved ventricular geometry and blocked the development of acute cardiac failure during a dobutamine-mediated stress protocol. Once issues relating to optimal dosing and long-term effects of poloxamer 188 in humans have been resolved, chemical-based membrane sealants could represent a new therapeutic approach for preventing or reversing the progression of cardiomyopathy and heart failure in muscular dystrophy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62706/1/nature03844.pd

δ13C methane source signatures from tropical wetland and rice field emissions

The atmospheric methane (CH4) burden is rising sharply, but the causes are still not well understood. One factor of uncertainty is the importance of tropical CH4 emissions into the global mix. Isotopic signatures of major sources remain poorly constrained, despite their usefulness in constraining the global methane budget. Here, a collection of new δ13CCH4 signatures is presented for a range of tropical wetlands and rice fields determined from air samples collected during campaigns from 2016 to 2020. Long-term monitoring of δ13CCH4 in ambient air has been conducted at the Chacaltaya observatory, Bolivia and Southern Botswana. Both long-term records are dominated by biogenic CH4 sources, with isotopic signatures expected from wetland sources. From the longer-term Bolivian record, a seasonal isotopic shift is observed corresponding to wetland extent suggesting that there is input of relatively isotopically light CH4 to the atmosphere during periods of reduced wetland extent. This new data expands the geographical extent and range of measurements of tropical wetland and rice δ13CCH4 sources and hints at significant seasonal variation in tropical wetland δ13CCH4 signatures which may be important to capture in future global and regional models. This article is part of a discussion meeting issue ‘Rising methane: is warming feeding warming? (part 2)’

ACC/AHA 2002 guideline update for the management of patients with chronic stable angina - Summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina)

"The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or a full revision is needed. This process gives priority to areas in which major changes in text, and particularly recommendations, are merited on the basis of new understanding or evidence. Minor changes in verbiage and references are discouraged. The ACC/AHA/American College of Physicians-American Society of Internal Medicine (ACP-ASIM) Guidelines for the Management of Patients With Chronic Stable Angina, which were published in June 1999, have now been updated. The full-text guideline incorporating the updated material is available on the Internet (www.acc.orgor www.americanheart.org) in both a track-changes version showing the changes in the 1999 guideline in strike-out (deleted text) and highlighting (new text) and a “clean” version that fully incorporates all the changes. This summary article describes the 4 most important areas of change reflected in the update in a format that we hope can be read and understood as a stand-alone document. Interested readers are referred to the full-length version on the Internet to completely understand the location of these changes within the full-length guideline, as well as their proper context. The full-length guideline includes some additional changes that are not reflected in this summary article. All new references appear in bold-faced type; all original references appear in normal type. Although the primary focus of this guideline is on symptomatic patients, asymptomatic patients with known or suspected coronary disease are included in this update and are described in Section V.

ACC/AHA 2002 guideline update for the management of patients with chronic stable angina - Summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina)

"The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or a full revision is needed. This process gives priority to areas in which major changes in text, and particularly recommendations, are merited on the basis of new understanding or evidence. Minor changes in verbiage and references are discouraged. The ACC/AHA/American College of Physicians–American Society of Internal Medicine (ACP-ASIM) Guidelines for the Management of Patients With Chronic Stable Angina, which were published in June 1999, have now been updated. The full-text guideline incorporating the updated material is available on the Internet (www.acc.org or www.americanheart.org) in both a track-changes version showing the changes in the 1999 guideline in strike-out (deleted text) and highlighting (new text) and a “clean” version that fully incorporates all the changes. This summary article describes the 4 most important areas of change reflected in the update in a format that we hope can be read and understood as a stand-alone document. Interested readers are referred to the full-length version on the Internet to completely understand the location of these changes within the full-length guideline, as well as their proper context. The full-length guideline includes some additional changes that are not reflected in this summary article. All new references appear in bold-faced type; all original references appear in normal type. Although the primary focus of this guideline is on symptomatic patients, asymptomatic patients with known or suspected coronary disease are included in this update and are described in Section V.

Large Methane Emission Fluxes Observed From Tropical Wetlands in Zambia

Methane (CH4) is a potent greenhouse gas with a warming potential 84 times that of carbon dioxide (CO2) over a 20-year period. Atmospheric CH4 concentrations have been rising since the nineteenth century but the cause of large increases post-2007 is disputed. Tropical wetlands are thought to account for ∼20% of global CH4 emissions, but African tropical wetlands are understudied and their contribution is uncertain. In this work, we use the first airborne measurements of CH4 sampled over three wetland areas in Zambia to derive emission fluxes. Three independent approaches to flux quantification from airborne measurements were used: Airborne mass balance, airborne eddy-covariance, and an atmospheric inversion. Measured emissions (ranging from 5 to 28 mg m−2 hr−1) were found to be an order of magnitude greater than those simulated by land surface models (ranging from 0.6 to 3.9 mg m−2 hr−1), suggesting much greater emissions from tropical wetlands than currently accounted for. The prevalence of such underestimated CH4 sources may necessitate additional reductions in anthropogenic greenhouse gas emissions to keep global warming below a threshold of 2°C above preindustrial levels

A Single Molecule Scaffold for the Maize Genome

About 85% of the maize genome consists of highly repetitive sequences that are interspersed by low-copy, gene-coding sequences. The maize community has dealt with this genomic complexity by the construction of an integrated genetic and physical map (iMap), but this resource alone was not sufficient for ensuring the quality of the current sequence build. For this purpose, we constructed a genome-wide, high-resolution optical map of the maize inbred line B73 genome containing >91,000 restriction sites (averaging 1 site/∼23 kb) accrued from mapping genomic DNA molecules. Our optical map comprises 66 contigs, averaging 31.88 Mb in size and spanning 91.5% (2,103.93 Mb/∼2,300 Mb) of the maize genome. A new algorithm was created that considered both optical map and unfinished BAC sequence data for placing 60/66 (2,032.42 Mb) optical map contigs onto the maize iMap. The alignment of optical maps against numerous data sources yielded comprehensive results that proved revealing and productive. For example, gaps were uncovered and characterized within the iMap, the FPC (fingerprinted contigs) map, and the chromosome-wide pseudomolecules. Such alignments also suggested amended placements of FPC contigs on the maize genetic map and proactively guided the assembly of chromosome-wide pseudomolecules, especially within complex genomic regions. Lastly, we think that the full integration of B73 optical maps with the maize iMap would greatly facilitate maize sequence finishing efforts that would make it a valuable reference for comparative studies among cereals, or other maize inbred lines and cultivars

Detailed Analysis of a Contiguous 22-Mb Region of the Maize Genome

Most of our understanding of plant genome structure and evolution has come from the careful annotation of small (e.g., 100 kb) sequenced genomic regions or from automated annotation of complete genome sequences. Here, we sequenced and carefully annotated a contiguous 22 Mb region of maize chromosome 4 using an improved pseudomolecule for annotation. The sequence segment was comprehensively ordered, oriented, and confirmed using the maize optical map. Nearly 84% of the sequence is composed of transposable elements (TEs) that are mostly nested within each other, of which most families are low-copy. We identified 544 gene models using multiple levels of evidence, as well as five miRNA genes. Gene fragments, many captured by TEs, are prevalent within this region. Elimination of gene redundancy from a tetraploid maize ancestor that originated a few million years ago is responsible in this region for most disruptions of synteny with sorghum and rice. Consistent with other sub-genomic analyses in maize, small RNA mapping showed that many small RNAs match TEs and that most TEs match small RNAs. These results, performed on ∼1% of the maize genome, demonstrate the feasibility of refining the B73 RefGen_v1 genome assembly by incorporating optical map, high-resolution genetic map, and comparative genomic data sets. Such improvements, along with those of gene and repeat annotation, will serve to promote future functional genomic and phylogenomic research in maize and other grasses

Isotopic signatures of methane emissions from tropical fires, agriculture and wetlands: the MOYA and ZWAMPS flights.

We report methane isotopologue data from aircraft and ground measurements in Africa and South America. Aircraft campaigns sampled strong methane fluxes over tropical papyrus wetlands in the Nile, Congo and Zambezi basins, herbaceous wetlands in Bolivian southern Amazonia, and over fires in African woodland, cropland and savannah grassland. Measured methane δ13CCH4 isotopic signatures were in the range -55 to -49‰ for emissions from equatorial Nile wetlands and agricultural areas, but widely -60 ± 1‰ from Upper Congo and Zambezi wetlands. Very similar δ13CCH4 signatures were measured over the Amazonian wetlands of NE Bolivia (around -59‰) and the overall δ13CCH4 signature from outer tropical wetlands in the southern Upper Congo and Upper Amazon drainage plotted together was -59 ± 2‰. These results were more negative than expected. For African cattle, δ13CCH4 values were around -60 to -50‰. Isotopic ratios in methane emitted by tropical fires depended on the C3 : C4 ratio of the biomass fuel. In smoke from tropical C3 dry forest fires in Senegal, δ13CCH4 values were around -28‰. By contrast, African C4 tropical grass fire δ13CCH4 values were -16 to -12‰. Methane from urban landfills in Zambia and Zimbabwe, which have frequent waste fires, had δ13CCH4 around -37 to -36‰. These new isotopic values help improve isotopic constraints on global methane budget models because atmospheric δ13CCH4 values predicted by global atmospheric models are highly sensitive to the δ13CCH4 isotopic signatures applied to tropical wetland emissions. Field and aircraft campaigns also observed widespread regional smoke pollution over Africa, in both the wet and dry seasons, and large urban pollution plumes. The work highlights the need to understand tropical greenhouse gas emissions in order to meet the goals of the UNFCCC Paris Agreement, and to help reduce air pollution over wide regions of Africa. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'

Isotopic signatures of methane emissions from tropical fires, agriculture and wetlands: the MOYA and ZWAMPS flights

We report methane isotopologue data from aircraft and ground measurements in Africa and South America. Aircraft campaigns sampled strong methane fluxes over tropical papyrus wetlands in the Nile, Congo and Zambezi basins, herbaceous wetlands in Bolivian southern Amazonia, and over fires in African woodland, cropland and savannah grassland. Measured methane δ13CCH4 isotopic signatures were in the range −55 to −49‰ for emissions from equatorial Nile wetlands and agricultural areas, but widely −60 ± 1‰ from Upper Congo and Zambezi wetlands. Very similar δ13CCH4 signatures were measured over the Amazonian wetlands of NE Bolivia (around −59‰) and the overall δ13CCH4 signature from outer tropical wetlands in the southern Upper Congo and Upper Amazon drainage plotted together was −59 ± 2‰. These results were more negative than expected. For African cattle, δ13CCH4 values were around −60 to −50‰. Isotopic ratios in methane emitted by tropical fires depended on the C3 : C4 ratio of the biomass fuel. In smoke from tropical C3 dry forest fires in Senegal, δ13CCH4 values were around −28‰. By contrast, African C4 tropical grass fire δ13CCH4 values were −16 to −12‰. Methane from urban landfills in Zambia and Zimbabwe, which have frequent waste fires, had δ13CCH4 around −37 to −36‰. These new isotopic values help improve isotopic constraints on global methane budget models because atmospheric δ13CCH4 values predicted by global atmospheric models are highly sensitive to the δ13CCH4 isotopic signatures applied to tropical wetland emissions. Field and aircraft campaigns also observed widespread regional smoke pollution over Africa, in both the wet and dry seasons, and large urban pollution plumes. The work highlights the need to understand tropical greenhouse gas emissions in order to meet the goals of the UNFCCC Paris Agreement, and to help reduce air pollution over wide regions of Africa. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'.Natural Environment Research Council (NERC): NE/S00159X/1; NE/N016238/1; NE/P019641/