104 research outputs found
Recommended from our members
Observations on drought and vegetation: A global approach and local study of the Congo Basin
Current research suggests that climate change and continued anthropogenic forcing of the climate system may increase the occurrence of extreme events such as droughts in the near future. Prolonged droughts are potentially destructive because of widespread impacts and difficulty in prediction. In addition, droughts interact in complex ways with vegetation systems, inducing abrupt rather than gradual changes in vegetation. Using satellite and station rainfall data, this research seeks to identify patterns in drought and vegetation change on a global scale and in the tropics (15ºN to 35ºS), where precipitation is the predominant determinant of climate. It is observed that long drought occurs in regions of variability in vegetation. Additionally, long drought is observed in regions on the fringe between dominant vegetation types of desert, grassland, and forest. These results suggest that prolonged drought may be a significant contributor to abrupt vegetation changes. The other part of this study is a regional investigation of vegetation change and drought in the Congo Basin. The correlation between drought and forest loss in the Congo is not clear. Preliminary studies of the atmospheric mechanisms governing drought in the Congo are presented. The results of this work as a whole will provide a better understanding of drought patterns and vegetation responses to drought, ultimately to provide better adaptation to a more extreme future climate.Geological SciencesPhysic
Recommended from our members
Regulation of splicing networks in neurodevelopment
Alternative splicing of pre-mRNA is a critical mechanism for enabling genetic diversity, and is a carefully regulated process in neuronal differentiation. RNA binding proteins (RBPs) are developmentally expressed and physically interact with RNA to drive specific splicing changes. This work tests the hypothesis that RBP-RNA interactions are critical for regulating timed and coordinated alternative splicing changes during neurodevelopment and that these splicing changes are in turn part of major regulatory mechanisms that underlie morphological and functional maturation of neurons. I describe our efforts to identify functional RBP-RNA interactions, including the identification of previously unobserved splicing events, and explore the combinatorial roles of multiple brain-specific RBPs during development. Using integrative modeling that combines multiple sources of data, we find hundreds of regulated splicing events for each of RBFOX, NOVA, PTBP, and MBNL. In the neurodevelopmental context, we find that the proteins control different sets of exons, with RBFOX, NOVA, and PTBP regulating early splicing changes and MBNL largely regulating later splicing changes. These findings additionally led to the observation that CNS and sensory neurons express a variety of different RBP programs, with many sensory neurons expressing a less mature splicing pattern than CNS neurons. We also establish a foundation for further exploration of neurodevelopmental splicing, by investigating the regulation of previously unobserved splicing events
Recommended from our members
Dynamic curves and poetic lyricism in selected chansons of Jacques Brel
In this thesis, I analyze eight of Belgian singer-songwriter Jacques Brel's chansons, chosen not for their popularity or Brel's preference, but for their particularities in dynamicism and poetic rhetoric. I open with Brel's first global success, Quand on n'a que l'amour, and then discuss the extensive influence of classical music on Brel, especially striking in Les Désespérés. Following my examination of text painting in Les Désespérés, I proceed with Les F..., La Dame patronnesse, Quand maman reviendra, Mon enfance, and Amsterdam, with the intent of formulating the groundwork for the dynamic highpoint. Each of these titles builds upon characteristics that punctuate the concept of a single dynamic highpoint through musically motivated narrative properties and dynamic curves. It is only upon arriving at Brel's Ces gens-là that I formulate the more complex, less intuitive but more intrinsic principle of the double dynamic highpoint. The concepts of narrative trajectory and musical agent presented throughout this report are based upon the work of Byron Almén and Robert Hatten. Combining Hatten's gestural theories and Almén's rhetorical patterning opens the door to explaining the narrative properties hidden within the musical discourse and the poetic text. I conclude my report by assessing that most of Brel's chansons follow the dynamic curve with the intent of capitalizing on the poetic meaning of the text.Musi
Recommended from our members
Precise temporal regulation of alternative splicing during neural development
Alternative splicing (AS) is one crucial step of gene expression that must be tightly regulated during neurodevelopment. However, the precise timing of developmental splicing switches and the underlying regulatory mechanisms are poorly understood. Here we systematically analyze the temporal regulation of AS in a large number of transcriptome profiles of developing mouse cortices, in vivo purified neuronal subtypes, and neurons differentiated in vitro. Our analysis reveals early-switch and late-switch exons in genes with distinct functions, and these switches accurately define neuronal maturation stages. Integrative modeling suggests that these switches are under direct and combinatorial regulation by distinct sets of neuronal RNA-binding proteins including Nova, Rbfox, Mbnl, and Ptbp. Surprisingly, various neuronal subtypes in the sensory systems lack Nova and/or Rbfox expression. These neurons retain the “immature” splicing program in early-switch exons, affecting numerous synaptic genes. These results provide new insights into the organization and regulation of the neurodevelopmental transcriptome
Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.
One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis
m^6A RNA methylation promotes XIST-mediated transcriptional repression
The long non-coding RNA X-inactive specific transcript (XIST) mediates the transcriptional silencing of genes on the X chromosome. Here we show that, in human cells, XIST is highly methylated with at least 78 N^6-methyladenosine (m^6A) residues—a reversible base modification of unknown function in long non-coding RNAs. We show that m^6A formation in XIST, as well as in cellular mRNAs, is mediated by RNA-binding motif protein 15 (RBM15) and its paralogue RBM15B, which bind the m^6A-methylation complex and recruit it to specific sites in RNA. This results in the methylation of adenosine nucleotides in adjacent m^6A consensus motifs. Furthermore, we show that knockdown of RBM15 and RBM15B, or knockdown of methyltransferase like 3 (METTL3), an m^6A methyltransferase, impairs XIST-mediated gene silencing. A systematic comparison of m^6A-binding proteins shows that YTH domain containing 1 (YTHDC1) preferentially recognizes m^6A residues on XIST and is required for XIST function. Additionally, artificial tethering of YTHDC1 to XIST rescues XIST-mediated silencing upon loss of m^6A. These data reveal a pathway of m^6A formation and recognition required for XIST-mediated transcriptional repression
Insights into the design and interpretation of iCLIP experiments
Abstract
Background
Ultraviolet (UV) crosslinking and immunoprecipitation (CLIP) identifies the sites on RNAs that are in direct contact with RNA-binding proteins (RBPs). Several variants of CLIP exist, which require different computational approaches for analysis. This variety of approaches can create challenges for a novice user and can hamper insights from multi-study comparisons. Here, we produce data with multiple variants of CLIP and evaluate the data with various computational methods to better understand their suitability.
Results
We perform experiments for PTBP1 and eIF4A3 using individual-nucleotide resolution CLIP (iCLIP), employing either UV-C or photoactivatable 4-thiouridine (4SU) combined with UV-A crosslinking and compare the results with published data. As previously noted, the positions of complementary DNA (cDNA)-starts depend on cDNA length in several iCLIP experiments and we now find that this is caused by constrained cDNA-ends, which can result from the sequence and structure constraints of RNA fragmentation. These constraints are overcome when fragmentation by RNase I is efficient and when a broad cDNA size range is obtained. Our study also shows that if RNase does not efficiently cut within the binding sites, the original CLIP method is less capable of identifying the longer binding sites of RBPs. In contrast, we show that a broad size range of cDNAs in iCLIP allows the cDNA-starts to efficiently delineate the complete RNA-binding sites.
Conclusions
We demonstrate the advantage of iCLIP and related methods that can amplify cDNAs that truncate at crosslink sites and we show that computational analyses based on cDNAs-starts are appropriate for such methods
Genetic identification of brain cell types underlying schizophrenia
With few exceptions, the marked advances in knowledge about the genetic basis of schizophrenia have not converged on findings that can be confidently used for precise experimental modeling. Applying knowledge of the cellular taxonomy of the brain from single-cell RNA-sequencing, we evaluated whether the genomic loci implicated in schizophrenia map onto specific brain cell types. We found that the common variant genomic results consistently mapped to pyramidal cells, medium spiny neurons, and certain interneurons but far less consistently to embryonic, progenitor, or glial cells. These enrichments were due to sets of genes specifically expressed in each of these cell types. We also found that many of the diverse gene sets previously associated with schizophrenia (synaptic genes, FMRP interactors, antipsychotic targets, etc.) generally implicate the same brain cell types. Our results suggest a parsimonious explanation: the common-variant genetic results for schizophrenia point at a limited set of neurons, and the gene sets point to the same cells. The genetic risk associated with medium spiny neurons did not overlap with that of glutamatergic pyramidal cells and interneurons, suggesting that different cell types have biologically distinct roles in schizophrenia
Recommended from our members
The INIA Texas Gene Expression Database: An online tool for alcohol genomics
Alcoholism is a serious condition that affects millions of people and costs billions of
dollars each year in treatment, damages, and lost income. In addition, it carries a
tremendous emotional burden. Alcoholism is caused by a combination of genetic
and environmental factors, which have yet to be fully identified. Fortunately,
alcoholism research, as well as research into other diseases with a genetic
component, has greatly benefited from recent rapid developments in
high-throughput genomic technologies and the development of relevant model
organisms. This has been highly productive for progress in the field, but effective
methods for identifying relevant data and for performing cross-dataset analyses
have not been developed at the same pace.
To help fulfill this need, I have developed the INIA (Integrative Neuroscience
Initiative on Alcoholism) Texas Gene Expression Database (IT-GED), which is freely
available at http://inia.icmb.utexas.edu. IT-GED is a web-based database which
contains a compilation of the significantly expressed genes from each of several
microarray datasets investigating the role of gene expression in the brain's
regulation of alcohol consumption. The studies were performed both in model
organisms (mouse and rat) and post-mortem humans. The data is presented via a
user-friendly interface which provides advanced searching abilities for identifying
genes of interest and tools for analysis of the data. These tools provide the ability to
compare user data to every dataset in IT-GED in order to assess the significance of
a group of genes across multiple datasets and the ability to generate visual
networks of those genes in order to identify the ones that are likely the most
functionally significant in the response to high alcohol consumption.
IT-GED thus provides a means by which alcohol researchers can combine multiple
sources of data to generate novel hypotheses concerning the genetic causes of
alcoholism. The goal of IT-GED is to provide support for comparing and integrating
results across gene expression studies of alcohol consumption and for generating
novel hypotheses based on individual genes and gene-gene interactions by
simplifying data access, providing various tools for analysis, and presenting users
with an easy-to-use interface.BiochemistryWaggoner Center for Alcohol and Addiction Researc
- …