Johnathon Walls - Academia.edu (original) (raw)

Papers by Johnathon Walls

Research paper thumbnail of Comparison of transcriptional differences between IL-4Ra and IL-5 blockade in a mouse model of asthma

Molecular pathology and functional genomics

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Research paper thumbnail of Genome-wide association study of liver fat, iron, and extracellular fluid fraction in the UK Biobank

Abdominal magnetic resonance imaging (MRI) represents a non-invasive approach allowing the extrac... more Abdominal magnetic resonance imaging (MRI) represents a non-invasive approach allowing the extraction of clinically informative phenotypes. We developed an automated pipeline to segment liver pixels from abdominal MRI images and apply published models to approximate fat fraction, extracellular fluid fraction and iron content in 40,058 MRIs from the UK Biobank. We then conducted a genome-wide association of these traits using imputed variants (N=37,250 individuals, 11,914,698 variants) and exome sequence data (N=35,274 individuals, 8,287,315 variants). For liver fat we identified 8 novel loci in or near genes MARC1, GCKR, ADH1B, MTTP, TRIB1, GPAM, PNPLA2 and APOH. For liver iron we identified 1 novel locus between the genes ASNSD1 and SLC40A1, an iron transporter involved in hemochromatosis. For extracellular fluid fraction we identified 6 novel loci in or near genes AGMAT, NAT2, MRPL4-S1PR2, FADS1, ABO and HFE, with almost all having prior associations to obesity, liver, iron, or li...

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Research paper thumbnail of Functional biology of the Steel syndrome founder allele and evidence for clan genomics derivation of COL27A1 pathogenic alleles worldwide

European Journal of Human Genetics

Previously we reported the identification of a homozygous COL27A1 (c.2089G>C; p.Gly697Arg) mis... more Previously we reported the identification of a homozygous COL27A1 (c.2089G>C; p.Gly697Arg) missense variant and proposed it as a founder allele in Puerto Rico segregating with Steel syndrome (STLS, MIM #615155); a rare osteochondrodysplasia characterized by short stature, congenital bilateral hip dysplasia, carpal coalitions, and scoliosis. We now report segregation of this variant in five probands from the initial clinical report defining the syndrome and an additional family of Puerto Rican descent with multiple affected adult individuals. We modeled the orthologous variant in murine Col27a1 and found it recapitulates some of the major Steel syndrome associated skeletal features including reduced body length, scoliosis, and a more rounded skull shape. Characterization of the in vivo murine model shows abnormal collagen deposition in the extracellular matrix and disorganization of the proliferative zone of the growth plate. We report additional COL27A1 pathogenic variant alleles...

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Research paper thumbnail of Deletion of Adam6 in Mus musculus leads to male subfertility and deficits in sperm ascent into the oviduct

Biology of Reproduction

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Research paper thumbnail of Axial molecular-beam mid-infrared diode laser spectrometer

SPIE Proceedings, 2002

A novel molecular beam spectrometer for the purpose of trace gas sensing is described. Sensitivit... more A novel molecular beam spectrometer for the purpose of trace gas sensing is described. Sensitivity is greatly enhanced and absorption interference by atmospheric H2O and CO2 is greatly reduced by using a molecular expansion. The expansion results in rotational cooling and population enhancement of low-lying energy levels. The instrument employs a tunable mid-infrared lead salt diode, which operates in single mode from 2348.5 to 2351.1 cm-1, and a 36 m Herriott multipass cell. The sample gas is injected axially through a coupling hole in one of the spherical mirrors. The result is an increase of the residence time of the molecular beam in the sampling region. Pulsed operation of the nozzle allows background subtracted spectra to be acquired. The spectrometer can either be operated in fast scan mode, in which the laser frequency is rapidly scanned over the absorption feature of interest, or in frequency modulation mode with 2f-detection. A special adaptation of frequency modulation to the axial sampling system is described. Sample data of CO2 are presented.

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Research paper thumbnail of Design and Implementation of a Custom Built Optical Projection Tomography System

PLoS ONE, 2013

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Research paper thumbnail of An axial molecular-beam diode laser spectrometer

Review of Scientific Instruments, 2004

A mid-infrared tunable diode laser molecular-beam spectrometer for the purpose of trace gas sensi... more A mid-infrared tunable diode laser molecular-beam spectrometer for the purpose of trace gas sensing and the study of van der Waals complexes is described. The spectrometer employs a Herriott multipass cell with up to 72 passes. The sample gas is injected parallel to the optical axis through a hole at the center of the far mirror. The molecular absorption is Doppler split, resulting from the laser beam propagating parallel and antiparallel to the molecular-beam expansion. The axial expansion leads to narrower line widths and increased sensitivity, compared to the traditional vertical injection method, as a result of selective sampling of the central part of the molecular expansion with reduced Doppler broadening and longer residence time of the molecular sample in the laser beam. The molecular expansion leads also to selective signal enhancement of low-J transitions, as demonstrated for the nu3 antisymmetric stretch vibration of CO2. A microwave horn antenna was implemented into the spectrometer to enable microwave-infrared double-resonance experiments. The spectrometer performance was evaluated by recording spectra of the CO2-Ar, (CO2)2, CO2-He, and CO2-SO2 van der Waals complexes near the R(0) transition of the nu3 band of CO2 around 2349 cm-1. The feasibility of using a pulsed molecular expansion for trace gas sensing is explored.

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Research paper thumbnail of Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptor

Proceedings of the National Academy of Sciences, 2011

The vasculature of the CNS is structurally and functionally distinct from that of other organ sys... more The vasculature of the CNS is structurally and functionally distinct from that of other organ systems and is particularly prone to developmental abnormalities and hemorrhage. Although other embryonic tissues undergo primary vascularization, the developing nervous system is unique in that it is secondarily vascularized by sprouting angiogenesis from a surrounding perineural plexus. This sprouting angiogenesis requires the TGF-β and Wnt pathways because ablation of these pathways results in aberrant sprouting and hemorrhage. We have genetically deleted Gpr124, a member of the large family of long N-terminal group B G protein-coupled receptors, few members of which have identified ligands or well-defined biologic functions in mammals. We show that, in the developing CNS, Gpr124 is specifically expressed in the vasculature and is absolutely required for proper angiogenic sprouting into the developing neural tube. Embryos lacking Gpr124 exhibit vascular defects characterized by delayed v...

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Research paper thumbnail of Three-Dimensional Analysis of Vascular Development in the Mouse Embryo

PLoS ONE, 2008

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Research paper thumbnail of Correction of artefacts in optical projection tomography

Physics in Medicine and Biology, 2005

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Research paper thumbnail of Resolution improvement in emission optical projection tomography

Physics in Medicine and Biology, 2007

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Research paper thumbnail of Baf60c is essential for function of BAF chromatin remodelling complexes in heart development

Nature, 2004

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Research paper thumbnail of In parallel' interconnectivity of the dorsal longitudinal anastomotic vessels requires both VEGF signaling and circulatory flow

Journal of Cell Science, 2012

Blood vessels deliver oxygen, nutrients, hormones and immunity factors throughout the body. To pe... more Blood vessels deliver oxygen, nutrients, hormones and immunity factors throughout the body. To perform these vital functions, vascular cords branch, lumenize and interconnect. Yet, little is known about the cellular, molecular and physiological mechanisms that control how circulatory networks form and interconnect. Specifically, how circulatory networks merge by interconnecting in parallel along their boundaries remains unexplored. To examine this process we studied the formation and functional maturation of the plexus that forms between the Dorsal Longitudinal Anastomotic Vessels (DLAVs) in the zebrafish. We find that the migration and proliferation of endothelial cells within the DLAVs and their Segmental (Se) vessel precursors drives DLAV plexus formation. Remarkably, the presence of Se vessels containing only endothelial cells of the arterial lineage is sufficient for DLAV plexus morphogenesis, suggesting that endothelial cells from the venous lineage make a dispensable or null ...

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Research paper thumbnail of Embryonic and Neonatal Phenotyping of Genetically Engineered Mice

ILAR Journal, 2006

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Research paper thumbnail of Measurement of isotope shifts, fine and hyperfine structure splittings of the lithium D lines

The European Physical Journal D, 2003

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Research paper thumbnail of Foxh1 Is Essential for Development of the Anterior Heart Field

Developmental Cell, 2004

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Research paper thumbnail of A novel 3D mouse embryo atlas based on micro-CT

Development, 2012

The goal of the International Mouse Phenotyping Consortium (IMPC) is to phenotype targeted knocko... more The goal of the International Mouse Phenotyping Consortium (IMPC) is to phenotype targeted knockout mouse strains throughout the whole mouse genome (23,000 genes) by 2021. A significant percentage of the generated mice will be embryonic lethal; therefore, phenotyping methods tuned to the mouse embryo are needed. Methods that are robust, quantitative, automated and high-throughput are attractive owing to the numbers of mice involved. Three-dimensional (3D) imaging is a useful method for characterizing morphological phenotypes. However, tools to automatically quantify morphological information of mouse embryos from 3D imaging have not been fully developed. We present a representative mouse embryo average 3D atlas comprising micro-CT images of 35 individual C57BL/6J mouse embryos at 15.5 days post-coitum. The 35 micro-CT images were registered into a consensus average image with our automated image registration software and 48 anatomical structures were segmented manually. We report th...

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Research paper thumbnail of Imaging for Mouse Phenotyping

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Research paper thumbnail of Design and Implementation of a Custom Built Optical Projection Tomography System

PLoS ONE, 2013

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Research paper thumbnail of Comparison of transcriptional differences between IL-4Ra and IL-5 blockade in a mouse model of asthma

Molecular pathology and functional genomics

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Research paper thumbnail of Genome-wide association study of liver fat, iron, and extracellular fluid fraction in the UK Biobank

Abdominal magnetic resonance imaging (MRI) represents a non-invasive approach allowing the extrac... more Abdominal magnetic resonance imaging (MRI) represents a non-invasive approach allowing the extraction of clinically informative phenotypes. We developed an automated pipeline to segment liver pixels from abdominal MRI images and apply published models to approximate fat fraction, extracellular fluid fraction and iron content in 40,058 MRIs from the UK Biobank. We then conducted a genome-wide association of these traits using imputed variants (N=37,250 individuals, 11,914,698 variants) and exome sequence data (N=35,274 individuals, 8,287,315 variants). For liver fat we identified 8 novel loci in or near genes MARC1, GCKR, ADH1B, MTTP, TRIB1, GPAM, PNPLA2 and APOH. For liver iron we identified 1 novel locus between the genes ASNSD1 and SLC40A1, an iron transporter involved in hemochromatosis. For extracellular fluid fraction we identified 6 novel loci in or near genes AGMAT, NAT2, MRPL4-S1PR2, FADS1, ABO and HFE, with almost all having prior associations to obesity, liver, iron, or li...

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Research paper thumbnail of Functional biology of the Steel syndrome founder allele and evidence for clan genomics derivation of COL27A1 pathogenic alleles worldwide

European Journal of Human Genetics

Previously we reported the identification of a homozygous COL27A1 (c.2089G>C; p.Gly697Arg) mis... more Previously we reported the identification of a homozygous COL27A1 (c.2089G>C; p.Gly697Arg) missense variant and proposed it as a founder allele in Puerto Rico segregating with Steel syndrome (STLS, MIM #615155); a rare osteochondrodysplasia characterized by short stature, congenital bilateral hip dysplasia, carpal coalitions, and scoliosis. We now report segregation of this variant in five probands from the initial clinical report defining the syndrome and an additional family of Puerto Rican descent with multiple affected adult individuals. We modeled the orthologous variant in murine Col27a1 and found it recapitulates some of the major Steel syndrome associated skeletal features including reduced body length, scoliosis, and a more rounded skull shape. Characterization of the in vivo murine model shows abnormal collagen deposition in the extracellular matrix and disorganization of the proliferative zone of the growth plate. We report additional COL27A1 pathogenic variant alleles...

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Research paper thumbnail of Deletion of Adam6 in Mus musculus leads to male subfertility and deficits in sperm ascent into the oviduct

Biology of Reproduction

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Research paper thumbnail of Axial molecular-beam mid-infrared diode laser spectrometer

SPIE Proceedings, 2002

A novel molecular beam spectrometer for the purpose of trace gas sensing is described. Sensitivit... more A novel molecular beam spectrometer for the purpose of trace gas sensing is described. Sensitivity is greatly enhanced and absorption interference by atmospheric H2O and CO2 is greatly reduced by using a molecular expansion. The expansion results in rotational cooling and population enhancement of low-lying energy levels. The instrument employs a tunable mid-infrared lead salt diode, which operates in single mode from 2348.5 to 2351.1 cm-1, and a 36 m Herriott multipass cell. The sample gas is injected axially through a coupling hole in one of the spherical mirrors. The result is an increase of the residence time of the molecular beam in the sampling region. Pulsed operation of the nozzle allows background subtracted spectra to be acquired. The spectrometer can either be operated in fast scan mode, in which the laser frequency is rapidly scanned over the absorption feature of interest, or in frequency modulation mode with 2f-detection. A special adaptation of frequency modulation to the axial sampling system is described. Sample data of CO2 are presented.

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Research paper thumbnail of Design and Implementation of a Custom Built Optical Projection Tomography System

PLoS ONE, 2013

Bookmarks Related papers MentionsView impact

Research paper thumbnail of An axial molecular-beam diode laser spectrometer

Review of Scientific Instruments, 2004

A mid-infrared tunable diode laser molecular-beam spectrometer for the purpose of trace gas sensi... more A mid-infrared tunable diode laser molecular-beam spectrometer for the purpose of trace gas sensing and the study of van der Waals complexes is described. The spectrometer employs a Herriott multipass cell with up to 72 passes. The sample gas is injected parallel to the optical axis through a hole at the center of the far mirror. The molecular absorption is Doppler split, resulting from the laser beam propagating parallel and antiparallel to the molecular-beam expansion. The axial expansion leads to narrower line widths and increased sensitivity, compared to the traditional vertical injection method, as a result of selective sampling of the central part of the molecular expansion with reduced Doppler broadening and longer residence time of the molecular sample in the laser beam. The molecular expansion leads also to selective signal enhancement of low-J transitions, as demonstrated for the nu3 antisymmetric stretch vibration of CO2. A microwave horn antenna was implemented into the spectrometer to enable microwave-infrared double-resonance experiments. The spectrometer performance was evaluated by recording spectra of the CO2-Ar, (CO2)2, CO2-He, and CO2-SO2 van der Waals complexes near the R(0) transition of the nu3 band of CO2 around 2349 cm-1. The feasibility of using a pulsed molecular expansion for trace gas sensing is explored.

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Research paper thumbnail of Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptor

Proceedings of the National Academy of Sciences, 2011

The vasculature of the CNS is structurally and functionally distinct from that of other organ sys... more The vasculature of the CNS is structurally and functionally distinct from that of other organ systems and is particularly prone to developmental abnormalities and hemorrhage. Although other embryonic tissues undergo primary vascularization, the developing nervous system is unique in that it is secondarily vascularized by sprouting angiogenesis from a surrounding perineural plexus. This sprouting angiogenesis requires the TGF-β and Wnt pathways because ablation of these pathways results in aberrant sprouting and hemorrhage. We have genetically deleted Gpr124, a member of the large family of long N-terminal group B G protein-coupled receptors, few members of which have identified ligands or well-defined biologic functions in mammals. We show that, in the developing CNS, Gpr124 is specifically expressed in the vasculature and is absolutely required for proper angiogenic sprouting into the developing neural tube. Embryos lacking Gpr124 exhibit vascular defects characterized by delayed v...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Three-Dimensional Analysis of Vascular Development in the Mouse Embryo

PLoS ONE, 2008

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Research paper thumbnail of Correction of artefacts in optical projection tomography

Physics in Medicine and Biology, 2005

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Research paper thumbnail of Resolution improvement in emission optical projection tomography

Physics in Medicine and Biology, 2007

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Research paper thumbnail of Baf60c is essential for function of BAF chromatin remodelling complexes in heart development

Nature, 2004

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Research paper thumbnail of In parallel' interconnectivity of the dorsal longitudinal anastomotic vessels requires both VEGF signaling and circulatory flow

Journal of Cell Science, 2012

Blood vessels deliver oxygen, nutrients, hormones and immunity factors throughout the body. To pe... more Blood vessels deliver oxygen, nutrients, hormones and immunity factors throughout the body. To perform these vital functions, vascular cords branch, lumenize and interconnect. Yet, little is known about the cellular, molecular and physiological mechanisms that control how circulatory networks form and interconnect. Specifically, how circulatory networks merge by interconnecting in parallel along their boundaries remains unexplored. To examine this process we studied the formation and functional maturation of the plexus that forms between the Dorsal Longitudinal Anastomotic Vessels (DLAVs) in the zebrafish. We find that the migration and proliferation of endothelial cells within the DLAVs and their Segmental (Se) vessel precursors drives DLAV plexus formation. Remarkably, the presence of Se vessels containing only endothelial cells of the arterial lineage is sufficient for DLAV plexus morphogenesis, suggesting that endothelial cells from the venous lineage make a dispensable or null ...

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Research paper thumbnail of Embryonic and Neonatal Phenotyping of Genetically Engineered Mice

ILAR Journal, 2006

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Measurement of isotope shifts, fine and hyperfine structure splittings of the lithium D lines

The European Physical Journal D, 2003

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Foxh1 Is Essential for Development of the Anterior Heart Field

Developmental Cell, 2004

Bookmarks Related papers MentionsView impact

Research paper thumbnail of A novel 3D mouse embryo atlas based on micro-CT

Development, 2012

The goal of the International Mouse Phenotyping Consortium (IMPC) is to phenotype targeted knocko... more The goal of the International Mouse Phenotyping Consortium (IMPC) is to phenotype targeted knockout mouse strains throughout the whole mouse genome (23,000 genes) by 2021. A significant percentage of the generated mice will be embryonic lethal; therefore, phenotyping methods tuned to the mouse embryo are needed. Methods that are robust, quantitative, automated and high-throughput are attractive owing to the numbers of mice involved. Three-dimensional (3D) imaging is a useful method for characterizing morphological phenotypes. However, tools to automatically quantify morphological information of mouse embryos from 3D imaging have not been fully developed. We present a representative mouse embryo average 3D atlas comprising micro-CT images of 35 individual C57BL/6J mouse embryos at 15.5 days post-coitum. The 35 micro-CT images were registered into a consensus average image with our automated image registration software and 48 anatomical structures were segmented manually. We report th...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Imaging for Mouse Phenotyping

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Design and Implementation of a Custom Built Optical Projection Tomography System

PLoS ONE, 2013

Bookmarks Related papers MentionsView impact