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Full-Text Articles in Life Sciences

Use Of Hidden Markov Models For Qtl Mapping, Karl W. Broman Dec 2006

Use Of Hidden Markov Models For Qtl Mapping, Karl W. Broman

Johns Hopkins University, Dept. of Biostatistics Working Papers

An important aspect of the QTL mapping problem is the treatment of missing genotype data. If complete genotype data were available, QTL mapping would reduce to the problem of model selection in linear regression. However, in the consideration of loci in the intervals between the available genetic markers, genotype data is inherently missing. Even at the typed genetic markers, genotype data is seldom complete, as a result of failures in the genotyping assays or for the sake of economy (for example, in the case of selective genotyping, where only individuals with extreme phenotypes are genotyped). We discuss the use of ...


Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh Nov 2006

Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh

Harvard University Biostatistics Working Paper Series

No abstract provided.


Limited Functional Redundancy And Oscillation Of Cyclins In Multinucleated Ashbya Gossypii Fungal Cells, A. Katrin Hungerbuehler, Peter Philippsen, Amy S. Gladfelter Nov 2006

Limited Functional Redundancy And Oscillation Of Cyclins In Multinucleated Ashbya Gossypii Fungal Cells, A. Katrin Hungerbuehler, Peter Philippsen, Amy S. Gladfelter

Open Dartmouth: Faculty Open Access Scholarship

Cyclin protein behavior has not been systematically investigated in multinucleated cells with asynchronous mitoses. Cyclins are canonical oscillating cell cycle proteins, but it is unclear how fluctuating protein gradients can be established in multinucleated cells where nuclei in different stages of the division cycle share the cytoplasm. Previous work in A. gossypii, a filamentous fungus in which nuclei divide asynchronously in a common cytoplasm, demonstrated that one G1 and one B-type cyclin do not fluctuate in abundance across the division cycle. We have undertaken a comprehensive analysis of all G1 and B-type cyclins in A. gossypii to determine whether any ...


The Allantois And Chorion, When Isolated Before Circulation Or Chorio-Allantoic Fusion, Have Hematopoietic Potential, Brandon M. Zeigler, Daisuke Sugiyama, Michael Chen, Yalin Guo, K. M. Downs, N. A. Speck Nov 2006

The Allantois And Chorion, When Isolated Before Circulation Or Chorio-Allantoic Fusion, Have Hematopoietic Potential, Brandon M. Zeigler, Daisuke Sugiyama, Michael Chen, Yalin Guo, K. M. Downs, N. A. Speck

Open Dartmouth: Faculty Open Access Scholarship

The chorio-allantoic placenta forms through the fusion of the allantois (progenitor tissue of the umbilical cord), with the chorionic plate. The murine placenta contains high levels of hematopoietic stem cells, and is therefore a stem cell niche. However, it is not known whether the placenta is a site of hematopoietic cell emergence, or whether hematopoietic cells originate from other sites in the conceptus and then colonize the placenta. Here, we show that the allantois and chorion, isolated prior to the establishment of circulation, have the potential to give rise to myeloid and definitive erythroid cells following explant culture. We further ...


A Unifying Approach For Haplotype Analysis Of Quantitative Traits In Family-Based Association Studies: Testing And Estimating Gene-Environment Interactions With Complex Exposure Variables, Stijn Vansteelandt, Christoph Lange Sep 2006

A Unifying Approach For Haplotype Analysis Of Quantitative Traits In Family-Based Association Studies: Testing And Estimating Gene-Environment Interactions With Complex Exposure Variables, Stijn Vansteelandt, Christoph Lange

COBRA Preprint Series

We propose robust and e±cient tests and estimators for gene-environment/gene-drug interactions in family-based association studies. The methodology is designed for studies in which haplotypes, quantitative pheno- types and complex exposure/treatment variables are analyzed. Using causal inference methodology, we derive family-based association tests and estimators for the genetic main effects and the interactions. The tests and estimators are robust against population admixture and strati¯cation without requiring adjustment for confounding variables. We illustrate the practical relevance of our approach by an application to a COPD study. The data analysis suggests a gene-environment interaction between a SNP in the ...


Structural Inference In Transition Measurement Error Models For Longitudinal Data, Wenqin Pan, Xihong Lin, Donglin Zeng Aug 2006

Structural Inference In Transition Measurement Error Models For Longitudinal Data, Wenqin Pan, Xihong Lin, Donglin Zeng

Harvard University Biostatistics Working Paper Series

No abstract provided.


Nonparametric Regression Using Local Kernel Estimating Equations For Correlated Failure Time Data, Zhangsheng Yu, Xihong Lin Aug 2006

Nonparametric Regression Using Local Kernel Estimating Equations For Correlated Failure Time Data, Zhangsheng Yu, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.


Causal Inference In Hybrid Intervention Trials Involving Treatment Choice, Qi Long, Rod Little, Xihong Lin Aug 2006

Causal Inference In Hybrid Intervention Trials Involving Treatment Choice, Qi Long, Rod Little, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.


A Comparison Of Methods For Estimating The Causal Effect Of A Treatment In Randomized Clinical Trials Subject To Noncompliance, Rod Little, Qi Long, Xihong Lin Aug 2006

A Comparison Of Methods For Estimating The Causal Effect Of A Treatment In Randomized Clinical Trials Subject To Noncompliance, Rod Little, Qi Long, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.


Chironomid Hemoglobin Genetic Diversity As An Indicator Of The New Jersey Hackensack Meadowlands Wetland Health, Lene Marie De Coursin Jacobs Aug 2006

Chironomid Hemoglobin Genetic Diversity As An Indicator Of The New Jersey Hackensack Meadowlands Wetland Health, Lene Marie De Coursin Jacobs

Seton Hall University Dissertations and Theses (ETDs)

Kearny Marsh located within the Hackensack Meadowlands is a freshwater wetland impacted by multiple environmental stressors from human activity. The marsh is located in the northeastern New Jersey metropolitan area. Chironomid larvae, aquatic larvae of midge fly, were analyzed from two Kearny Marsh sample sites, W9 and W22. A previous sediment analysis and toxicity study characterized heavy metal contaminants the marsh. The data results were applied in this thesis study to determine the correlation between environmental stressors and chironomid genetic diversity. Site W9 sediment was impacted by severe levels of total heavy metal contamination, whereas site W22 had just below ...


A Subset Of Arabidopsis Ap2 Transcription Factors Mediates Cytokinin Responses In Concert With A Two-Component Pathway, Aaron M. Rashotte, Michael G. Mason, Claire E. Hutchison, Fernando J. Ferreira, G. Eric Schaller, Joseph J. Kieber Jul 2006

A Subset Of Arabidopsis Ap2 Transcription Factors Mediates Cytokinin Responses In Concert With A Two-Component Pathway, Aaron M. Rashotte, Michael G. Mason, Claire E. Hutchison, Fernando J. Ferreira, G. Eric Schaller, Joseph J. Kieber

Open Dartmouth: Faculty Open Access Scholarship

The plant hormone cytokinin regulates numerous growth and developmental processes. A signal transduction pathway for cytokinin has been elucidated that is similar to bacterial two-component phosphorelays. In Arabidopsis, this pathway is comprised of receptors that are similar to sensor histidine kinases, histidine-containing phosphotransfer proteins, and response regulators (ARRs). There are two classes of response regulators, the type-A ARRs, which act as negative regulators of cytokinin responses, and the type-B ARRs, which are transcription factors that play a positive role in mediating cytokinin-regulated gene expression. Here we show that several closely related members of the Arabidopsis AP2 gene family of unknown ...


Saccharomyces Cerevisiae-Based Molecular Tool Kit For Manipulation Of Genes From Gram-Negative Bacteria, Robert M. Q. Shanks, Nicky C. Caiazza, Shannon M. Hinsa, Christine M. Toutain, George A. O'Toole Jul 2006

Saccharomyces Cerevisiae-Based Molecular Tool Kit For Manipulation Of Genes From Gram-Negative Bacteria, Robert M. Q. Shanks, Nicky C. Caiazza, Shannon M. Hinsa, Christine M. Toutain, George A. O'Toole

Open Dartmouth: Faculty Open Access Scholarship

A tool kit of vectors was designed to manipulate and express genes from a wide range of gram-negative species by using in vivo recombination. Saccharomyces cerevisiae can use its native recombination proteins to combine several amplicons in a single transformation step with high efficiency. We show that this technology is particularly useful for vector design. Shuttle, suicide, and expression vectors useful in a diverse group of bacteria are described and utilized. This report describes the use of these vectors to mutate clpX and clpP of the opportunistic pathogen Pseudomonas aeruginosa and to explore their roles in biofilm formation and surface ...


A Faster Circular Binary Segmentation Algorithm For The Analysis Of Array Cgh Data, E S. Venkatraman, Adam Olshen Jun 2006

A Faster Circular Binary Segmentation Algorithm For The Analysis Of Array Cgh Data, E S. Venkatraman, Adam Olshen

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

Motivation: Array CGH technologies enable the simultaneous measurement of DNA copy number for thousands of sites on a genome. We developed the circular binary segmentation (CBS) algorithm to divide the genome into regions of equal copy number (Olshen {\it et~al}, 2004). The algorithm tests for change-points using a maximal $t$-statistic with a permutation reference distribution to obtain the corresponding $p$-value. The number of computations required for the maximal test statistic is $O(N^2),$ where $N$ is the number of markers. This makes the full permutation approach computationally prohibitive for the newer arrays that contain tens of ...


Bounded Search For De Novo Identification Of Degenerate Cis-Regulatory Elements, Jonathan M. Carlson, Arijit Chakravarty, Radhika S. Khetani, Robert H. Gross May 2006

Bounded Search For De Novo Identification Of Degenerate Cis-Regulatory Elements, Jonathan M. Carlson, Arijit Chakravarty, Radhika S. Khetani, Robert H. Gross

Open Dartmouth: Faculty Open Access Scholarship

The identification of statistically overrepresented sequences in the upstream regions of coregulated genes should theoretically permit the identification of potential cis-regulatory elements. However, in practice many cis-regulatory elements are highly degenerate, precluding the use of an exhaustive word-counting strategy for their identification. While numerous methods exist for inferring base distributions using a position weight matrix, recent studies suggest that the independence assumptions inherent in the model, as well as the inability to reach a global optimum, limit this approach.


A Role For Cetp Taqib Polymorphism In Determining Susceptibility To Atrial Fibrillation: A Nested Case Control Study, Folkert W. Asselbergs, Jason H. Moore, Maarten P. Van Den Berg, Eric B. Rimm Apr 2006

A Role For Cetp Taqib Polymorphism In Determining Susceptibility To Atrial Fibrillation: A Nested Case Control Study, Folkert W. Asselbergs, Jason H. Moore, Maarten P. Van Den Berg, Eric B. Rimm

Open Dartmouth: Faculty Open Access Scholarship

Studies investigating the genetic and environmental characteristics of atrial fibrillation (AF) may provide new insights in the complex development of AF. We aimed to investigate the association between several environmental factors and loci of candidate genes, which might be related to the presence of AF. A nested case-control study within the PREVEND cohort was conducted. Standard 12 lead electrocardiograms were recorded and AF was defined according to Minnesota codes. For every case, an age and gender matched control was selected from the same population (n = 194). In addition to logistic regression analyses, the multifactor-dimensionality reduction (MDR) method and interaction entropy ...


Ewe And Wether Trials - Tools For Benchmarking Your Sheep Genetics, Lock Butler Apr 2006

Ewe And Wether Trials - Tools For Benchmarking Your Sheep Genetics, Lock Butler

Bulletins 4000 -

Research and sheep productivity trial results demonstrate a huge variability in genetic productivity between flocks. For example a range of up to 2 kg clean fleece weight, 5 microns, 55 percentage points in lambing percentage and 20 kg live weight, can lead to big differences in gross margin between flocks.

There is an opportunity for genetic improvement, depending on your current ram source or sires performance. For example, Western Australian (WA) Wether Trial results suggest half the WA flocks could improve clean fleece weight per head by half a kilogram or more. The trial results suggest that this could occur ...


Poor Performance Of Bootstrap Confidence Intervals For The Location Of A Quantitative Trait Loucs, Ani Manichaikul, Josee Dupuis, Saunak Sen, Karl W. Broman Mar 2006

Poor Performance Of Bootstrap Confidence Intervals For The Location Of A Quantitative Trait Loucs, Ani Manichaikul, Josee Dupuis, Saunak Sen, Karl W. Broman

Johns Hopkins University, Dept. of Biostatistics Working Papers

The aim of many genetic studies is to locate the genomic regions (called quantitative trait loci, QTLs) that contribute to variation in a quantitative trait (such as body weight). Confidence intervals for the locations of QTLs are particularly important for the design of further experiments to identify the gene or genes responsible for the effect. Likelihood support intervals are the most widely used method to obtain confidence intervals for QTL location, but the non-parametric bootstrap has also been recommended. Through extensive computer simulation, we show that bootstrap confidence intervals are poorly behaved and so should not be used in this ...


Multiple Tests Of Association With Biological Annotation Metadata, Sandrine Dudoit, Sunduz Keles, Mark J. Van Der Laan Mar 2006

Multiple Tests Of Association With Biological Annotation Metadata, Sandrine Dudoit, Sunduz Keles, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a general and formal statistical framework for the multiple tests of associations between known fixed features of a genome and unknown parameters of the distribution of variable features of this genome in a population of interest. The known fixed gene-annotation profiles, corresponding to the fixed features of the genome, may concern Gene Ontology (GO) annotation, pathway membership, regulation by particular transcription factors, nucleotide sequences, or protein sequences. The unknown gene-parameter profiles, corresponding to the variable features of the genome, may be, for example, regression coefficients relating genome-wide transcript levels or DNA copy numbers to possibly censored biological and ...


The Scarlet Gene: Behavioral Genetics, Criminal Law, And Racial And Ethnic Stigma, Karen H. Rothenberg, Alice Wang Mar 2006

The Scarlet Gene: Behavioral Genetics, Criminal Law, And Racial And Ethnic Stigma, Karen H. Rothenberg, Alice Wang

Faculty Scholarship

Imagine that a scientist from the state university asks you and your family to participate in a study on a particular gene variant associated with alcoholism. The project focuses on your ethnic group, the Tracy Islanders, who have a higher incidence of alcoholism, as well as a higher incidence of the gene variant, than the general population. You will not be informed whether you have the gene variant, but your participation in the study might help scientists develop drugs to help individuals control their addiction to alcohol. You have a family history of alcoholism, and you are concerned that your ...


Gpnn: Power Studies And Applications Of A Neural Network Method For Detecting Gene-Gene Interactions In Studies Of Human Disease, Alison A. Motsinger, Stephen L. Lee, George Mellick, Marylyn D. Ritchie Jan 2006

Gpnn: Power Studies And Applications Of A Neural Network Method For Detecting Gene-Gene Interactions In Studies Of Human Disease, Alison A. Motsinger, Stephen L. Lee, George Mellick, Marylyn D. Ritchie

Open Dartmouth: Faculty Open Access Scholarship

The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease.


Isolation And Characterization Of High Persistence Mutants Of Salmonella Enterica Serotype Typhimurium, Andrew Richard Slattery Jan 2006

Isolation And Characterization Of High Persistence Mutants Of Salmonella Enterica Serotype Typhimurium, Andrew Richard Slattery

Retrospective Theses and Dissertations

A small fraction of bacterial populations consist of "persistent" cells that are phenotypically distinct from the majority of cells by their ability to avoid killing by a variety of antimicrobial challenges. Persistence is distinct from resistance in that persistent cells are unable to grow in the presence of the antimicrobial agent or treatment, but resume growth after the selection has been removed. Presently, little is known about the genetic or physiological basis of persistence. In this study we demonstrate that Salmonella enterica serovar Typhimurium (S. typhimurium) displays the persistence phenotype. To better understand persistence in this important food-borne pathogen, we ...


Plant Genome Informatics: Evaluation And Analysis Of Genomic Dna Features Involved In The Transcriptional Processing Of Protein Coding Genes , Shannon Dwayne Schlueter Jan 2006

Plant Genome Informatics: Evaluation And Analysis Of Genomic Dna Features Involved In The Transcriptional Processing Of Protein Coding Genes , Shannon Dwayne Schlueter

Retrospective Theses and Dissertations

As biological data collection methods have become more cost effective and less time consuming, the necessity for computational tools to store, manage, and analyze this data has led to the creation of a broad field of research. Bioinformatics, while firmly rooted in the technology of information management, is now a mainstream component in the majority of scientific investigations. With the vast majority of effort in bioinformatics being applied to research on vertebrate species, researchers in the plant sciences have often been left with less than satisfactory tools. The research presented in this dissertation was done in an effort to advance ...


Genomics And Molecular Biology Approaches To Plant-Parasitic Nematode Biology And Parasitism , Axel Armin Elling Jan 2006

Genomics And Molecular Biology Approaches To Plant-Parasitic Nematode Biology And Parasitism , Axel Armin Elling

Retrospective Theses and Dissertations

The plant-parasitic nematodes Pratylenchus penetrans and Heterodera glycines are of major economic importance worldwide. Here, we present a survey of over 1,900 expressed sequence tags (ESTs) for P. penetrans and of almost 22,000 ESTs for H. glycines. Furthermore, we conducted microarray expression profiling for over 6,800 H. glycines genes throughout the life cycle. We identified over 600 H. glycines genes that encode secretory proteins and provide microarray data for all known H. glycines parasitism genes as well as for H. glycines genes with similarity to known plant and microbe sequences. In order to extend these studies, we ...


Controlled Integration Of The Ty5 Retrotransposon In Saccharomyces Ceverisiae [I.E. Cerevisiae] , Junbiao Dai Jan 2006

Controlled Integration Of The Ty5 Retrotransposon In Saccharomyces Ceverisiae [I.E. Cerevisiae] , Junbiao Dai

Retrospective Theses and Dissertations

One essential step in the life cycle of retroelements is the stable integration of a copy of retroelement cDNA into the host genome. Random integration is potentially hazardous and could have deleterious genetic effects to the host. Therefore, elements and their hosts have coevolved mechanisms to regulate retroelement integration. In the budding yeast Saccharomyces cerevisiae, the Ty5 retrotransposon preferentially integrates into domains of heterochromatin. Targeting to these locations is determined by interactions between an amino acid sequence motif at the C-terminus of Ty5 integrase (the targeting domain) and the heterochromatin protein Sir4p. New Ty5 integration hotspots are created when Sir4p ...


Characterization And Interactions Of Tbx2 , Christian Nephi Paxton Jan 2006

Characterization And Interactions Of Tbx2 , Christian Nephi Paxton

Retrospective Theses and Dissertations

T-box (Tbx) proteins are dynamically expressed throughout embryogenesis and appear to have significant roles in a number of developmental processes. The T-box family is characterized by a highly conserved DNA binding domain. Over twenty mammalian T-box proteins have been identified, many of which have the demonstrated ability to regulate transcription. Both activators and repressors of gene transcription have been described within this family, but how their functions are performed is largely unknown;Tbx2 is a powerful transcriptional repressor with functional roles identified in cardiogenesis and limb development. However the functional domain(s) of Tbx2 are poorly characterized. Tbx2 contains a ...


Functional Characterization Of The Rad51 Genes In Zea Mays And Their Roles In Mu Transposition , Jin Li Jan 2006

Functional Characterization Of The Rad51 Genes In Zea Mays And Their Roles In Mu Transposition , Jin Li

Retrospective Theses and Dissertations

In Saccharomyces cerevisiae, Rad51p plays a central role in homologous recombination and DNA repair. Double mutants of the two Zea mays L. rad51 homologs are viable, but male sterile and have ~22% of normal seed set. Light microscopic analyses of male meiosis in these plants reveal: many chromosomes are unpaired at diakinesis and over 33% of quartets carry cells that either lack a nucleolus or have two nucleoli, indicating that non-disjunction occurs at both meiotic divisions. FISH analysis shows that 70% pachytene cells have paired 5S rDNA loci. Thus, maize RAD51 is required for efficient chromosome pairing and proper chromosome ...


Recognition And Signal Transduction In The Expression Of Phytophthora Resistance In Soybean [Glycine Max (L) Merr] , Hongyu Gao Jan 2006

Recognition And Signal Transduction In The Expression Of Phytophthora Resistance In Soybean [Glycine Max (L) Merr] , Hongyu Gao

Retrospective Theses and Dissertations

Phytophthora sojae, a hemibiotrophic oomycete, is the causal pathogen of stem and root rot disease of soybean (Glycine max [L.] Merr). The annual soybean yield loss suffered from this disease is valued at about 300 million dollars. A series of single Rps genes protect soybean from the root and stem rot disease. In the last two decades Rps1-k has been the most stable and widely used Phytophthora resistance gene in the major soybean-producing regions of the United States;Two classes of CC-NB-LRR-type Rps1-k genes were isolated from the Rps1-k locus. Representative members from each gene class were expressed in transgenic ...


Use Of Qtl Identified In Breed Crosses For Genetic Improvement In Pigs, Napapan Piyasatian Jan 2006

Use Of Qtl Identified In Breed Crosses For Genetic Improvement In Pigs, Napapan Piyasatian

Retrospective Theses and Dissertations

Strategies for the exploitation of multiple QTL identified in breed crosses for genetic improvement of livestock were examined through marker-assisted introgression (MAI) and marker-assisted selection (MAS). Evaluation of the effectiveness of alternate strategies for MAI and MAS were carried out using stochastic computer simulation. In general, introgression of multiple QTL and maintaining the frequency of the donor's allele at 50% requires large population sizes that are not feasible in livestock. An alternate selection approach for MAI of multiple QTL was developed for a breeding program of limited size, without requiring the selected candidates to be heterozygous at all loci ...


The Paleopolyploid Nature Of The Soybean Genome: Duplicate Gene Identification, Regional Sequence Characterization And Expression Studies , Jessica Ann Schlueter Jan 2006

The Paleopolyploid Nature Of The Soybean Genome: Duplicate Gene Identification, Regional Sequence Characterization And Expression Studies , Jessica Ann Schlueter

Retrospective Theses and Dissertations

The paleopolyploid nature of the soybean genome was investigated through bioinformatic analysis of ESTs, sequencing of homeologous BAC clones and functional analysis of retained duplicate genes. From ESTs, 294 soybean contig pairs were identified representing retained transcribed duplicate genes. Clustering of synonymous distances between each gene pair identified two mixtures of normal distributions corresponding to two rounds of genome duplication approximately 14.5 and 45 million years ago. Ratios of nonsynonymous to synonymous distances showed that most duplicate gene pairs are under purifying selection. Pearson correlation coefficients of EST-based expression patterns between duplicate pairs illustrated both retain expression and uncorrelated ...


Studies Of Hypoxia Response And Regulation Of Hypoxia-Inducible Factor Hif-1 In Caenorhabditis Elegans , Chuan Shen Jan 2006

Studies Of Hypoxia Response And Regulation Of Hypoxia-Inducible Factor Hif-1 In Caenorhabditis Elegans , Chuan Shen

Retrospective Theses and Dissertations

All aerobic organisms require molecular oxygen to generate metabolic energy for normal growth and survival. During evolution, multi-cellular organisms have developed and refined complex networks for adaptation to hypoxic environments at both systemic and cellular levels. Adaptation to hypoxia largely results from changes in the activity and expression of key proteins. These include proteins involved in increasing oxygen delivery to hypoxic tissues and proteins that facilitate glycolysis for anaerobic metabolism. The mammalian transcription factor hypoxia-inducible factor (HIF) is a master regulator of oxygen homeostasis. More than 100 target genes of HIF mediate broad systemic and local responses to hypoxia, including ...