Expression profile of CREB knockdown in myeloid leukemia cells.

BackgroundThe cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not affect long-term hematopoietic reconstitution.MethodsTo understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line transduced with CREB shRNA.ResultsBy combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA.ConclusionWe have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle

Genome‑wide scan for selection signatures in six cattle breeds in South Africa

BACKGROUND : The detection of selection signatures in breeds of livestock species can contribute to the identification of regions of the genome that are, or have been, functionally important and, as a consequence, have been targeted by selection. METHODS : This study used two approaches to detect signatures of selection within and between six cattle breeds in South Africa, including Afrikaner (n = 44), Nguni (n = 54), Drakensberger (n = 47), Bonsmara (n = 44), Angus (n = 31) and Holstein (n = 29). The first approach was based on the detection of genomic regions in which haplotypes have been driven towards complete fixation within breeds. The second approach identified regions of the genome that had very different allele frequencies between populations (FST). RESULTS AND DISCUSSION : Forty-seven candidate genomic regions were identified as harbouring putative signatures of selection using both methods. Twelve of these candidate selected regions were shared among the breeds and ten were validated by previous studies. Thirty-three of these regions were successfully annotated and candidate genes were identified. Among these genes the keratin genes (KRT222, KRT24, KRT25, KRT26, and KRT27) and one heat shock protein gene (HSPB9) on chromosome 19 between 42,896,570 and 42,897,840 bp were detected for the Nguni breed. These genes were previously associated with adaptation to tropical environments in Zebu cattle. In addition, a number of candidate genes associated with the nervous system (WNT5B, FMOD, PRELP, and ATP2B), immune response (CYM, CDC6, and CDK10), production (MTPN, IGFBP4, TGFB1, and AJAP1) and reproductive performance (ADIPOR2, OVOS2, and RBBP8) were also detected as being under selection. CONCLUSIONS : The results presented here provide a foundation for detecting mutations that underlie genetic variation of traits that have economic importance for cattle breeds in South Africa.Additional file 1: Table S1. Symbols and names for all annotated candidate genes.ARChttp://gsejournal.biomedcentral.com/am2017Animal and Wildlife Science

Tamm Review: Management of mixed-severity fire regime forests in Oregon, Washington, and Northern California

Increasingly, objectives for forests with moderate- or mixed-severity fire regimes are to restore successionally diverse landscapes that are resistant and resilient to current and future stressors. Maintaining native species and characteristic processes requires this successional diversity, but methods to achieve it are poorly explained in the literature. In the Inland Pacific US, large, old, early seral trees were a key historical feature of many young and old forest successional patches, especially where fires frequently occurred. Large, old trees are naturally fire-tolerant, but today are often threatened by dense understory cohorts that create fuel ladders that alter likely post-fire successional pathways. Reducing these understories can contribute to resistance by creating conditions where canopy trees will survive disturbances and climatic stressors; these survivors are important seed sources, soil protectors, and critical habitat elements. Historical timber harvesting has skewed tree size and age class distributions, created hard edges, and altered native patch sizes. Manipulating these altered forests to promote development of larger patches of older, larger, and more widely-spaced trees with diverse understories will increase landscape resistance to severe fires, and enhance wildlife habitat for underrepresented conditions. Closed-canopy, multi-layered patches that develop in hot, dry summer environments are vulnerable to droughts, and they increase landscape vulnerability to insect outbreaks and severe wildfires. These same patches provide habitat for species such as the northern spotted owl, which has benefited from increased habitat area. Regional and local planning will be critical for gauging risks, evaluating trade-offs, and restoring dynamics that can support these and other species. The goal will be to manage for heterogeneous landscapes that include variably-sized patches of (1) young, middle-aged, and old, closed canopy forests growing in upper montane, northerly aspect, and valley bottom settings, (2) a similar diversity of open-canopy, fire-tolerant patches growing on ridgetops, southerly aspects, and lower montane settings, and (3) significant montane chaparral and grassland areas. Tools to achieve this goal include managed wildfire, prescribed burning, and variable density thinning at small to large scales. Specifics on ‘‘how much and where?” will vary according to physiographic, topographic and historical templates, and regulatory requirements, and be determined by means of a socio-ecological process

Tamm Review: Management of mixed-severity fire regime forests in Oregon, Washington, and Northern California

Increasingly, objectives for forests with moderate- or mixed-severity fire regimes are to restore successionally diverse landscapes that are resistant and resilient to current and future stressors. Maintaining native species and characteristic processes requires this successional diversity, but methods to achieve it are poorly explained in the literature. In the Inland Pacific US, large, old, early seral trees were a key historical feature of many young and old forest successional patches, especially where fires frequently occurred. Large, old trees are naturally fire-tolerant, but today are often threatened by dense understory cohorts that create fuel ladders that alter likely post-fire successional pathways. Reducing these understories can contribute to resistance by creating conditions where canopy trees will survive disturbances and climatic stressors; these survivors are important seed sources, soil protectors, and critical habitat elements. Historical timber harvesting has skewed tree size and age class distributions, created hard edges, and altered native patch sizes. Manipulating these altered forests to promote development of larger patches of older, larger, and more widely-spaced trees with diverse understories will increase landscape resistance to severe fires, and enhance wildlife habitat for underrepresented conditions. Closed-canopy, multi-layered patches that develop in hot, dry summer environments are vulnerable to droughts, and they increase landscape vulnerability to insect outbreaks and severe wildfires. These same patches provide habitat for species such as the northern spotted owl, which has benefited from increased habitat area. Regional and local planning will be critical for gauging risks, evaluating trade-offs, and restoring dynamics that can support these and other species. The goal will be to manage for heterogeneous landscapes that include variably-sized patches of (1) young, middle-aged, and old, closed canopy forests growing in upper montane, northerly aspect, and valley bottom settings, (2) a similar diversity of open-canopy, fire-tolerant patches growing on ridgetops, southerly aspects, and lower montane settings, and (3) significant montane chaparral and grassland areas. Tools to achieve this goal include managed wildfire, prescribed burning, and variable density thinning at small to large scales. Specifics on ‘‘how much and where?” will vary according to physiographic, topographic and historical templates, and regulatory requirements, and be determined by means of a socio-ecological process

Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy

Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Lower export production during glacial periods in the equatorial Pacific derived from (231Pa/230Th)xs,0 measurements in deep-sea sediments

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 19 (2004): PA4023, doi:10.1029/2003PA000994.The (231Pa/230Th)xs,0 records obtained from two cores from the western (MD97-2138; 1°25′S, 146°24′E, 1900 m) and eastern (Ocean Drilling Program Leg 138 Site 849, 0°11.59′N, 110°31.18′W, 3851 m) equatorial Pacific display similar variability over the last 85,000 years, i.e., from isotopic stages 1 to 5a, with systematically higher values during the Holocene, isotopic stage 3, and isotopic stage 5a, and lower values, approaching the production rate ratio of the two isotopes (0.093), during the colder periods corresponding to isotopic stages 2 and 4. We have also measured the 230Th-normalized biogenic preserved and terrigenous fluxes, as well as major and trace elements concentrations, in both cores. The (231Pa/230Th)xs,0 results combined with the changes in preserved carbonate and opal fluxes at the eastern site indicate lower productivity in the eastern equatorial Pacific during glacial periods. The (231Pa/230Th)xs,0 variations in the western equatorial Pacific also seem to be controlled by productivity (carbonate and/or opal). The generally high (231Pa/230Th)xs,0 ratios (>0.093) of the profile could be due to opal and/or MnO2 in the sinking particles. The profiles of (231Pa/230Th)xs,0 and 230Th-normalized fluxes indicate a decrease in exported carbonate, and possibly opal, during isotopic stages 2 and 4 in MD97-2138. Using 230Th-normalized flux, we also show that sediments from the two cores were strongly affected by sediment redistribution by bottom currents suggesting a control of mass accumulation rates by sediment focusing variability.SP funding for this research was provided by grants from the French Minister of Research and a EURODOC grant of the Re´gion Rhoˆne-Alpes (SAFIR-980065327). SP also gratefully acknowledges the financial support of the WHOI Geology and Geophysics Dept. This work was also supported by a CNRS-NSF grant (SP and KWWS). The contribution of JFM to this study was supported in part by the US NSF and by WHOI OCCI and Mellon awards

Identification, characterization, and gene expression analysis of nucleotide binding site (NB)-type resistance gene homologues in switchgrass

Abstract Background Switchgrass (Panicum virgatum L.) is a warm-season perennial grass that can be used as a second generation bioenergy crop. However, foliar fungal pathogens, like switchgrass rust, have the potential to significantly reduce switchgrass biomass yield. Despite its importance as a prominent bioenergy crop, a genome-wide comprehensive analysis of NB-LRR disease resistance genes has yet to be performed in switchgrass. Results In this study, we used a homology-based computational approach to identify 1011 potential NB-LRR resistance gene homologs (RGHs) in the switchgrass genome (v 1.1). In addition, we identified 40 RGHs that potentially contain unique domains including major sperm protein domain, jacalin-like binding domain, calmodulin-like binding, and thioredoxin. RNA-sequencing analysis of leaf tissue from ‘Alamo’, a rust-resistant switchgrass cultivar, and ‘Dacotah’, a rust-susceptible switchgrass cultivar, identified 2634 high quality variants in the RGHs between the two cultivars. RNA-sequencing data from field-grown cultivar ‘Summer’ plants indicated that the expression of some of these RGHs was developmentally regulated. Conclusions Our results provide useful insight into the molecular structure, distribution, and expression patterns of members of the NB-LRR gene family in switchgrass. These results also provide a foundation for future work aimed at elucidating the molecular mechanisms underlying disease resistance in this important bioenergy crop

The biogeochemical impact of glacial meltwater from Southwest Greenland

Biogeochemical cycling in high-latitude regions has a disproportionate impact on global nutrient budgets. Here, we introduce a holistic, multi-disciplinary framework for elucidating the influence of glacial meltwaters, shelf currents, and biological production on biogeochemical cycling in high-latitude continental margins, with a focus on the silica cycle. Our findings highlight the impact of significant glacial discharge on nutrient supply to shelf and slope waters, as well as surface and benthic production in these regions, over a range of timescales from days to thousands of years. Whilst biological uptake in fjords and strong diatom activity in coastal waters maintains low dissolved silicon concentrations in surface waters, we find important but spatially heterogeneous additions of particulates into the system, which are transported rapidly away from the shore. We expect the glacially-derived particles – together with biogenic silica tests – to be cycled rapidly through shallow sediments, resulting in a strong benthic flux of dissolved silicon. Entrainment of this benthic silicon into boundary currents may supply an important source of this key nutrient into the Labrador Sea, and is also likely to recirculate back into the deep fjords inshore. This study illustrates how geochemical and oceanographic analyses can be used together to probe further into modern nutrient cycling in this region, as well as the palaeoclimatological approaches to investigating changes in glacial meltwater discharge through time, especially during periods of rapid climatic change in the Late Quaternary

Breeding progress and preparedness for mass‐scale deployment of perennial lignocellulosic biomass crops switchgrass, miscanthus, willow and poplar

UK: The UK‐led miscanthus research and breeding was mainly supported by the Biotechnology and Biological Sciences Research Council (BBSRC), Department for Environment, Food and Rural Affairs (Defra), the BBSRC CSP strategic funding grant BB/CSP1730/1, Innovate UK/BBSRC “MUST” BB/N016149/1, CERES Inc. and Terravesta Ltd. through the GIANT‐LINK project (LK0863). Genomic selection and genomewide association study activities were supported by BBSRC grant BB/K01711X/1, the BBSRC strategic programme grant on Energy Grasses & Bio‐refining BBS/E/W/10963A01. The UK‐led willow R&D work reported here was supported by BBSRC (BBS/E/C/00005199, BBS/E/C/00005201, BB/G016216/1, BB/E006833/1, BB/G00580X/1 and BBS/E/C/000I0410), Defra (NF0424) and the Department of Trade and Industry (DTI) (B/W6/00599/00/00). IT: The Brain Gain Program (Rientro dei cervelli) of the Italian Ministry of Education, University, and Research supports Antoine Harfouche. US: Contributions by Gerald Tuskan to this manuscript were supported by the Center for Bioenergy Innovation, a US Department of Energy Bioenergy Research Center supported by the Office of Biological and Environmental Research in the DOE Office of Science, under contract number DE‐AC05‐00OR22725. Willow breeding efforts at Cornell University have been supported by grants from the US Department of Agriculture National Institute of Food and Agriculture. Contributions by the University of Illinois were supported primarily by the DOE Office of Science; Office of Biological and Environmental Research (BER); grant nos. DE‐SC0006634, DE‐SC0012379 and DE‐SC0018420 (Center for Advanced Bioenergy and Bioproducts Innovation); and the Energy Biosciences Institute. EU: We would like to further acknowledge contributions from the EU projects “OPTIMISC” FP7‐289159 on miscanthus and “WATBIO” FP7‐311929 on poplar and miscanthus as well as “GRACE” H2020‐EU.3.2.6. Bio‐based Industries Joint Technology Initiative (BBI‐JTI) Project ID 745012 on miscanthus.Peer reviewedPostprintPublisher PD