De Novo Duplication in the CHD7 Gene Associated With Severe CHARGE Syndrome.

CHARGE syndrome is an autosomal dominant developmental disorder associated with a constellation of traits involving almost every organ and sensory system, in particular congenital anomalies, including choanal atresia and malformations of the heart, inner ear, and retina. Variants in CHD7 have been shown to cause CHARGE syndrome. Here, we report the identification of a novel de novo p.Asp2119_Pro2120ins6 duplication variant in a conserved region of CHD7 in a severely affected boy presenting with 3 and 5 of the CHARGE cardinal major and minor signs, respectively, combined with congenital umbilical hernia, congenital hernia at the linea alba, mildly hypoplastic inferior vermis, slight dilatation of the lateral ventricles, prominent metopic ridge, and hypoglycemic episodes

CliCrop: a Crop Water-Stress and Irrigation Demand Model for an Integrated Global Assessment Model Approach

http://globalchange.mit.edu/research/publications/2264This paper describes the use of the CliCrop model in the context of climate change general assessment modeling. The MIT Integrated Global System Model (IGSM) framework is a global integrated assessment modeling framework that uses emission predictions and economic outputs from the MIT Emission Prediction and Policy Analysis (EPPA) model and earth system modeling predictions from the IGSM to drive a land system component, a crop model (CliCrop) and a Water Resource System (WRS) model. The global Agriculture and Water System are dependant upon and interlinked with the global climate system. As irrigated agriculture provides 60% of grains and 40% of all crop production on 20% of global crop lands and accounts for 80% of global water consumption, it is crucial that the agricultural-water linkage be properly modeled. Crop models are used to predict future yields, irrigation demand and to understand the effect of crop and soil type on food productivity and soil fertility. In the context of an integrated global assessment, a crop water-stress and irrigation demand model must meet certain specifications that are different for other crop models; it needs to be global, fast and generic with a minimal set of inputs. This paper describes how CliCrop models the physical and biological processes of crop growth and yield production and its use within the MIT Integrated Global System Model (IGSM) framework, including the data inputs. This paper discusses the global data bases used as input to CliCrop and provides a comparison of the accuracy of CliCrop with the detailed biological-based crop model DSSAT as well as with measured crop yields over the U.S. at the country level using reanalyzed weather data. In both cases CliCrop performed well and the analysis validated its use for climate change impact assessment. We then show why correctly modeling the soil is important for irrigation demand calculation, especially in temperate areas. Finally, we discuss a method to estimate actual water withdrawal from modeled physical crop requirements using U.S. historical data.The initial funding for CliCrop was provided by USAID under a program on climate change adaptation in Niger. Further funding was provided by UN University World Institute for Development Economics Research for the Application and Development of CliCrop in Africa, the authors would like to particularly thank Prof. Finn Tarp, Prof. Channing Arndt and Dr. James Thurlow for their support. The authors also would like to thank Dr. Jawoo Koo of IFPRI for his review and contributions to the software development. The authors also gratefully acknowledge additional financial support for this work provided by the MIT Joint Program on the Science and Policy of Global Change through a consortium of industrial sponsors and Federal grants. Development of the IGSM applied in this research was supported by the U.S. Department of Energy, Office of Science (DE-FG02-94ER61937); the U.S. Environmental Protection Agency, EPRI, and other U.S. government agencies and a consortium of 40 industrial and foundation sponsors

Analysis of U.S. Water Resources under Climate Change

The MIT Integrated Global System Model (IGSM) framework, extended to include a Water Resource System (WRS) component, is applied to an integrated assessment of effects of alternative climate policy scenarios on U.S. water systems. Climate results are downscaled to yield estimates of surface runoff at 99 river basins of the continental U.S., with an exploration of climate patterns that are relatively wet and dry over the region. These estimates are combined with estimated groundwater supplies. An 11-region economic model (USREP) sets conditions driving water requirements estimated for five use sectors, with detailed sub-models employed for analysis of irrigation and electric power. The water system of the interconnected basins is operated to minimize water stress. Results suggest that, with or without climate change, U.S. average annual water stress is expected to increase over the period 2041 to 2050, primarily because of an increase in water requirements, with the largest water stresses projected in the South West. Policy to lower atmospheric greenhouse gas concentrations has a beneficial effect, reducing water stress intensity and variability in the concerned basins.The Joint Program on the Science and Policy of Global Change is funded by the U.S. Department of Energy, Office of Science under grants DE-FG02-94ER61937, DE-FG02- 93ER61677, DEFG02-08ER64597, and DE-FG02-06ER64320; the U.S. Environmental Protection Agency under grants XA-83344601-0, XA-83240101, XA-83042801-0, PI-83412601- 0, RD-83096001, and RD-83427901-0; the U.S. National Science Foundation under grants SES- 0825915, EFRI-0835414, ATM-0120468, BCS-0410344, ATM-0329759, and DMS-0426845; the U.S. National Aeronautics and Space Administration under grants NNX07AI49G, NNX08AY59A, NNX06AC30A, NNX09AK26G, NNX08AL73G, NNX09AI26G, NNG04GJ80G, NNG04GP30G, and NNA06CN09A; the U.S. National Oceanic and Atmospheric Administration under grants DG1330-05-CN-1308, NA070AR4310050, and NA16GP2290; the U.S. Federal Aviation Administration under grant 06-C-NE-MIT; the Electric Power Research Institute under grant EPP32616/C15124; and a consortium of 40 industrial and foundation sponsors (for the complete list see http://globalchange.mit.edu/sponsors/current.html

Modeling Water Resource Systems under Climate Change: IGSM-WRS

Through the integration of a Water Resource System (WRS) component, the MIT Integrated Global System Model (IGSM) framework has been enhanced to study the effects of climate change on managed water-resource systems. Development of the WRS involves the downscaling of temperature and precipitation from the zonal representation of the IGSM to regional (latitude-longitude) scale, and the translation of the resulting surface hydrology to runoff at the scale of river basins, referred to as Assessment Sub-Regions (ASRs). The model of water supply is combined with analysis of water use in agricultural and non-agricultural sectors and with a model of water system management that allocates water among uses and over time and routes water among ASRs. Results of the IGSM-WRS framework include measures of water adequacy and ways it is influenced by climate change. Here we document the design of WRS and its linkage to other components of the IGSM, and present tests of consistency of model simulations with the historical record.The Joint Program on the Science and Policy of Global Change is funded by the U.S. Department of Energy, Office of Science under grants DE-FG02-94ER61937, DE-FG02-93ER61677, DEFG02- 08ER64597, and DE-FG02-06ER64320; the U.S. Environmental Protection Agency under grants XA-83344601-0, XA-83240101, XA-83042801-0, PI-83412601-0, RD-83096001, and RD- 83427901-0; the U.S. National Science Foundation under grants SES-0825915, EFRI-0835414, ATM-0120468, BCS-0410344, ATM-0329759, and DMS-0426845; the U.S. National Aeronautics and Space Administration under grants NNX07AI49G, NNX08AY59A, NNX06AC30A, NNX09AK26G, NNX08AL73G, NNX09AI26G, NNG04GJ80G, NNG04GP30G, and NNA06CN09A; the U.S. National Oceanic and Atmospheric Administration under grants DG1330-05-CN-1308, NA070AR4310050, and NA16GP2290; the U.S. Federal Aviation Administration under grant 06-C-NE-MIT; the Electric Power Research Institute under grant EPP32616/ C15124; and a consortium of 40 industrial and foundation sponsors (for the complete list see http://globalchange.mit.edu/sponsors/current.html)

Climate change adaptation in agriculture: Ex ante analysis of promising and alternative crop technologies using DSSAT and IMPACT

Achieving and maintaining global food security is challenged by changes in population, income, and climate, among other drivers. Assessing these challenges and possible solutions over the coming decades requires a rigorous multidisciplinary approach. To answer this challenge, the International Food Policy Research Institute (IFPRI) has developed a system of linked simulation models of global agriculture to do long-run scenario analysis of the effects of climate change and various adaptation strategies. This system includes the core International Model for Policy Analysis of Agricultural Commodities and Trade (IMPACT), which is linked to water models (global hydrology, water basin management, and water stress on crops) and crop simulation models. The Global Futures and Strategic Foresight program, a CGIAR initiative led by IFPRI in collaboration with other CGIAR research centers, is working to improve these tools and conducting ex ante assessments of promising technologies, investments, and policies under alternative global futures. Baseline projections from IMPACT set the foundation with the latest outlook on long-term trends in food demand and agricultural production based on projected changes in population, income, technology, and climate. On top of the baseline, scenarios are developed for assessing the impacts of promising climate-adapted technologies for maize, wheat, rice, potatoes, sorghum, groundnut, and cassava on yields, area, production, trade, and prices in 2050 at a variety of scales. Yield gains from adoption of the selected technologies vary by technology and region, but are found to be generally comparable in scale to (and thus able to offset) the adverse effects of climate change under a high-emissions representative concentration pathway (RCP 8.5). Even more important in this long-term climate change scenario are effects of growth in population, income, and investments in overall technological change, highlighting the importance of linked assessment of biophysical and socioeconomic drivers to better understand climate impacts and responses. For all crops in the selected countries, climate change impacts are negative with the baseline technology. All new technologies have beneficial effects on yields under climate change, with combined traits (drought and heat tolerance) showing the greatest benefi

Mycobacterium tuberculosis ClpP Proteases Are Co-transcribed but Exhibit Different Substrate Specificities

PMCID: PMC3613350This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The Diversification of the LIM Superclass at the Base of the Metazoa Increased Subcellular Complexity and Promoted Multicellular Specialization

Background: Throughout evolution, the LIM domain has been deployed in many different domain configurations, which has led to the formation of a large and distinct group of proteins. LIM proteins are involved in relaying stimuli received at the cell surface to the nucleus in order to regulate cell structure, motility, and division. Despite their fundamental roles in cellular processes and human disease, little is known about the evolution of the LIM superclass. Results: We have identified and characterized all known LIM domain-containing proteins in six metazoans and three nonmetazoans. In addition, we performed a phylogenetic analysis on all LIM domains and, in the process, have identified a number of novel non-LIM domains and motifs in each of these proteins. Based on these results, we have formalized a classification system for LIM proteins, provided reasonable timing for class and family origin events; and identified lineagespecific loss events. Our analysis is the first detailed description of the full set of LIM proteins from the non-bilaterian species examined in this study. Conclusion: Six of the 14 LIM classes originated in the stem lineage of the Metazoa. The expansion of the LIM superclass at the base of the Metazoa undoubtedly contributed to the increase in subcellular complexity required for the transition from a unicellular to multicellular lifestyle and, as such, was a critically important event in the history of animal multicellularity

Immunohistochemistry on a Panel of Emery-Dreifuss Muscular Dystrophy Samples Reveals Nuclear Envelope Proteins as Inconsistent Markers for Pathology

Reports of aberrant distribution for some nuclear envelope proteins in cells expressing a few Emery–Dreifuss muscular dystrophy mutations raised the possibility that such protein redistribution could underlie pathology and/or be diagnostic. However, this disorder is linked to 8 different genes encoding nuclear envelope proteins, raising the question of whether a particular protein is most relevant. Therefore, myoblast/fibroblast cultures from biopsy and tissue sections from a panel of nine Emery–Dreifuss muscular dystrophy patients (4 male, 5 female) including those carrying emerin and FHL1 (X-linked) and several lamin A (autosomal dominant) mutations were stained for the proteins linked to the disorder. As tissue-specific nuclear envelope proteins have been postulated to mediate the tissue-specific pathologies of different nuclear envelopathies, patient samples were also stained for several muscle-specific nuclear membrane proteins. Although linked proteins nesprin 1 and SUN2 and muscle-specific proteins NET5/Samp1 and Tmem214 yielded aberrant distributions in individual patient cells, none exhibited defects through the larger patient panel. Muscle-specific Tmem38A normally appeared in both the nuclear envelope and sarcoplasmic reticulum, but most patient samples exhibited a moderate redistribution favouring the sarcoplasmic reticulum. The absence of striking uniform defects in nuclear envelope protein distribution indicates that such staining will be unavailing for general diagnostics, though it remains possible that specific mutations exhibiting protein distribution defects might reflect a particular clinical variant. These findings further argue that multiple pathways can lead to the generally similar pathologies of this disorder while at the same time the different cellular phenotypes observed possibly may help explain the considerable clinical variation of EDMD