Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
1,355
result(s) for
"Wall, Jeff"
Sort by:
Transcriptomic and epigenomic characterization of the developing bat wing
Nadav Ahituv, Nicola Illing, Jeff Wall and colleagues sequence the genome of the bat
Miniopterus natalensis
and perform RNA-seq and ChIP-seq (H3K27ac and H3K27me3) analyses on its developing forelimb and hindlimb autopods at sequential embryonic stages. Their analyses identify genomic regions that may contribute to bat wing formation.
Bats are the only mammals capable of powered flight, but little is known about the genetic determinants that shape their wings. Here we generated a genome for
Miniopterus natalensis
and performed RNA-seq and ChIP-seq (H3K27ac and H3K27me3) analyses on its developing forelimb and hindlimb autopods at sequential embryonic stages to decipher the molecular events that underlie bat wing development. Over 7,000 genes and several long noncoding RNAs, including Tbx5-as1 and Hottip, were differentially expressed between forelimb and hindlimb, and across different stages. ChIP-seq analysis identified thousands of regions that are differentially modified in forelimb and hindlimb. Comparative genomics found 2,796 bat-accelerated regions within H3K27ac peaks, several of which cluster near limb-associated genes. Pathway analyses highlighted multiple ribosomal proteins and known limb patterning signaling pathways as differentially regulated and implicated increased forelimb mesenchymal condensation in differential growth. In combination, our work outlines multiple genetic components that likely contribute to bat wing formation, providing insights into this morphological innovation.
Journal Article
Examining Phylogenetic Relationships Among Gibbon Genera Using Whole Genome Sequence Data Using an Approximate Bayesian Computation Approach
Gibbons are believed to have diverged from the larger great apes ∼16.8 MYA and today reside in the rainforests of Southeast Asia. Based on their diploid chromosome number, the family Hylobatidae is divided into four genera, Nomascus, Symphalangus, Hoolock, and Hylobates. Genetic studies attempting to elucidate the phylogenetic relationships among gibbons using karyotypes, mitochondrial DNA (mtDNA), the Y chromosome, and short autosomal sequences have been inconclusive . To examine the relationships among gibbon genera in more depth, we performed second-generation whole genome sequencing (WGS) to a mean of ∼15× coverage in two individuals from each genus. We developed a coalescent-based approximate Bayesian computation (ABC) method incorporating a model of sequencing error generated by high coverage exome validation to infer the branching order, divergence times, and effective population sizes of gibbon taxa. Although Hoolock and Symphalangus are likely sister taxa, we could not confidently resolve a single bifurcating tree despite the large amount of data analyzed. Instead, our results support the hypothesis that all four gibbon genera diverged at approximately the same time. Assuming an autosomal mutation rate of 1 × 10−9/site/year this speciation process occurred ∼5 MYA during a period in the Early Pliocene characterized by climatic shifts and fragmentation of the Sunda shelf forests. Whole genome sequencing of additional individuals will be vital for inferring the extent of gene flow among species after the separation of the gibbon genera.
Journal Article
Analysis of a deeply-phenotyped familial hypercholesterolemia cohort from Mexico shows a role for both rare and common alleles across known dyslipidemia genes and reveals structural variation in a novel locus
Familial hypercholesterolemia (FH) is a genetic disorder driven in part by mutations in three genes that encode components of the cholesterol pathway:
LDLR, APOB,
and
PCSK9
. However, the majority of FH genetics has been performed in individuals of European descent. Here, we leveraged a cohort of 300 patients from the Mexican FH registry to understand how rare, high liability alleles and common variants might contribute to shaping individual risk. Using a combination of whole exome and of short- and long-read whole genome sequencing, we report three key findings. First, we observed that rare pathogenic point mutations and structural variants in all known FH genes, together with variants in
APOE, CREB3L3,
and
PLIN1
, contribute to a molecular FH diagnosis in 67% of families, including novel gene-disruptive copy number variants (CNVs) which arose in a native American background. Second, ancestry-adjusted polygenic risk score analysis identified a significant liability for coronary artery disease, hypertension, LDL, HDL, and Type 2 Diabetes. The polygenic signal for LDL was present in patients with rare, pathogenic FH mutations and was more prominent in individuals bereft of a molecular FH diagnosis. Finally, we report both a whole-gene duplication and common, non-coding variants in a novel locus,
PDZK1
, which contribute to the genetic burden of FH, a finding we replicated in the UK Biobank (UKB). Together, our analyses illustrate the value of genetic studies in non-European populations and reinforce the notion that individual risk to disease can arise from both rare, large effect alleles (alone or in combination across genes) and common variants that increase the mutational burden of a biological system.
Journal Article
3q26 Amplification Is an Effective Negative Triage Test for LSIL: A Historical Prospective Study
Women with low grade squamous intraepithelial lesions (LSIL) at cervical cancer screening are currently referred for further diagnostic work up despite 80% having no precancerous lesion. The primary purpose of this study is to measure the test characteristics of 3q26 chromosome gain (3q26 gain) as a host marker of carcinogenesis in women with LSIL. A negative triage test may allow these women to be followed by cytology alone without immediate referral to colposcopy.
A historical prospective study was designed to measure 3q26 gain from the archived liquid cytology specimens diagnosed as LSIL among women attending colposcopy between 2007 and 2009. 3q26 gain was assessed on the index liquid sample; and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were measured at immediate triage and at 6-16 months after colposcopic biopsy. The sensitivity of 3q26 gain measured at immediate triage from automated and manually reviewed tests in 65 non-pregnant unique women was 70% (95% CI: 35, 93) with a NPV of 89% (95% CI: 78, 96). The sensitivity and NPV increased to 80% (95% CI: 28, 99) and 98% (95% CI: 87, 100), respectively, when only the automated method of detecting 3q26 gain was used.
3q26 gain demonstrates high sensitivity and NPV as a negative triage test for women with LSIL, allowing possible guideline changes to routine surveillance instead of immediate colposcopy. Prospective studies are ongoing to establish the sensitivity, specificity, PPV and NPV of 3q26 gain for LSIL over time.
Journal Article
Conceptual, Postconceptual, Nonconceptual: Photography and the Depictive Arts
The model work of conceptual art is a text of indeterminate length that argues successfully for its own status as a work of art under the existing criteria of autonomous art, but that, in succeeding in doing so, passes beyond those criteria, and that of autonomous art as well. A painter can make any number of almost-identical monochrome paintings and justify doing that as his or her response to the need to remind his or her audience, or emphasize to that audience, or berate and hector that audience, about the cultural emergency that is bourgeois art, about the permanent crisis of bourgeois art. In the same vein, the most rigorously logical conceptual artist could present the same text any number of times in any number of exhibitions, situations, or other contexts. Here, Wall implies that photography played some central role in the elaboration of conceptual art, what he's going to call the conceptual reduction of autonomous art.
Journal Article
Vancouver appearing and not appearing in Fred Herzog's photographs
In the 1950s to 1970s, Fred Herzog photographed buildings and scenes in Vancouver, British Columbia. His pieces show a city that has changed; many of the buildings in his photographs have been replaced with others with less character. The development of Vancouver since the 1970s was not based on aesthetics but on financial aspects and familiar building designs.
Journal Article
Depiction, Object, Event
Discusses the expansion of the field of canonic art forms since the 1950s, with reference to the depictive and anti-depictive qualities of modern and modernist art, fine art's engagement from the mid-20th century with the movement arts, and the post-Conceptual claim for a form of art which is not a work of art. Comments on the issue of depiction in art with reference to the Minimalist object, Duchamp's use of the readymade and Conceptual art's substitution of the written text for artwork. Considers the emergence of movement arts in the avant-garde art events of the 1970s, commenting on the blurring of boundaries with mass culture that this effected, noting the role played by Warhol and Pop art. Notes the mimetic, hybrid, neo-Situationism of the social forms of art events at 21st century biennials, and suggests that the formlessness of these events signify them as a final new art form. Concludes by discussing the autonomy of art and the question of aesthetic criteria in the context of innovative art's departure from canonic art forms.
Journal Article