Curtis J. Mello
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View article: A shared DNA-repeat toxicity threshold, reached somatically at cell-type-specific rates, unites cortical and striatal neurodegeneration in Huntington’s disease
A shared DNA-repeat toxicity threshold, reached somatically at cell-type-specific rates, unites cortical and striatal neurodegeneration in Huntington’s disease Open
Huntington’s disease (HD) affects two major brain areas – the striatum and cerebral cortex – in ways that differ in timing, severity, and gene-expression changes. For these reasons, and because many cortical neurons project axons to the af…
View article: A partially automated method for DNA extraction from marmoset hair follicles to avoid blood chimerism
A partially automated method for DNA extraction from marmoset hair follicles to avoid blood chimerism Open
Marmosets are valuable non-human primate models, however their unique reproduction results in high levels of blood chimerism, making blood unreliable for DNA sequencing. Hair follicles have lower levels of chimerism however DNA extraction …
View article: Nuclei Isolation from Fresh Frozen Human Brain “Villages” v1
Nuclei Isolation from Fresh Frozen Human Brain “Villages” v1 Open
This protocol describes nuclei isolation from fresh frozen human brain tissue, using anywhere from 1 brain donor to ~20-25 brain donors in one prep.
View article: Human genetic variation shapes the response of neurons to interferons
Human genetic variation shapes the response of neurons to interferons Open
Inflammation is increasingly recognized as important to neuropathology, including more classic neuroimmune disease as well as neurodegenerative and neuropsychiatric disorders. Interferons (IFN) are important mediators of central nervous sy…
View article: Sibling chimerism among microglia in marmosets
Sibling chimerism among microglia in marmosets Open
Chimerism happens rarely among most mammals but is common in marmosets and tamarins, a result of fraternal twin or triplet birth patterns in which in utero connected circulatory systems (through which stem cells transit) lead to persistent…
View article: Sibling chimerism among microglia in marmosets
Sibling chimerism among microglia in marmosets Open
Chimerism happens rarely among most mammals but is common in marmosets and tamarins, a result of fraternal twin or triplet birth patterns in which in utero connected circulatory systems (through which stem cells transit) lead to persistent…
View article: Sibling chimerism among microglia in marmosets
Sibling chimerism among microglia in marmosets Open
Chimerism happens rarely among most mammals but is common in marmosets and tamarins, a result of fraternal twin or triplet birth patterns in which in utero connected circulatory systems (through which stem cells transit) lead to persistent…
View article: Natural variation in gene expression and viral susceptibility revealed by neural progenitor cell villages
Natural variation in gene expression and viral susceptibility revealed by neural progenitor cell villages Open
Human genome variation contributes to diversity in neurodevelopmental outcomes and vulnerabilities; recognizing the underlying molecular and cellular mechanisms will require scalable approaches. Here, we describe a "cell village" experimen…
View article: Efficient generation of lower induced motor neurons by coupling Ngn2 expression with developmental cues
Efficient generation of lower induced motor neurons by coupling Ngn2 expression with developmental cues Open
View article: Chromosomal phase improves aneuploidy detection in non-invasive prenatal testing at low fetal DNA fractions
Chromosomal phase improves aneuploidy detection in non-invasive prenatal testing at low fetal DNA fractions Open
Non-invasive prenatal testing (NIPT) to detect fetal aneuploidy by sequencing the cell-free DNA (cfDNA) in maternal plasma is being broadly adopted. To detect fetal aneuploidies from maternal plasma, where fetal DNA is mixed with far-large…
View article: Efficient generation of lower induced Motor Neurons by coupling <i>Ngn2</i> expression with developmental cues
Efficient generation of lower induced Motor Neurons by coupling <i>Ngn2</i> expression with developmental cues Open
SUMMARY Human pluripotent stem cells (hPSCs) are a powerful tool for disease modelling and drug discovery, especially when access to primary tissue is limited, such as in the brain. Current neuronal differentiation approaches use either sm…
View article: Natural variation in gene expression and Zika virus susceptibility revealed by villages of neural progenitor cells
Natural variation in gene expression and Zika virus susceptibility revealed by villages of neural progenitor cells Open
SUMMARY Variation in the human genome contributes to abundant diversity in human traits and vulnerabilities, but the underlying molecular and cellular mechanisms are not yet known, and will need scalable approaches to accelerate their reco…
View article: Single cell analysis of DNA in more than 10,000 individual sperm from men with abnormal reproductive outcomes
Single cell analysis of DNA in more than 10,000 individual sperm from men with abnormal reproductive outcomes Open
View article: Mapping genetic effects on cellular phenotypes with “cell villages”
Mapping genetic effects on cellular phenotypes with “cell villages” Open
Summary Tens of thousands of genetic variants shape human phenotypes, mostly by unknown cellular mechanisms. Here we describe Census-seq, a way to measure cellular phenotypes in cells from many people simultaneously. Analogous to pooled CR…
View article: Absolute quantification and degradation evaluation of SARS-CoV-2 RNA by droplet digital PCR
Absolute quantification and degradation evaluation of SARS-CoV-2 RNA by droplet digital PCR Open
Quantifying SARS-CoV-2 infectivity, formulating well-calibrated public-health policy, and managing the safety of workplaces would all be facilitated by precise measurement of the extent to which SARS-CoV-2 RNA is present in an intact form …
View article: Insights into variation in meiosis from 31,228 human sperm genomes
Insights into variation in meiosis from 31,228 human sperm genomes Open
View article: Sperm-seq wet lab protocol: sperm preparation and droplet-based sequencing library generation
Sperm-seq wet lab protocol: sperm preparation and droplet-based sequencing library generation Open
Sperm-seq is a high-throughput, droplet-based single-sperm sequencing technology capable of generating thousands of cell-barcoded single-sperm sequencing libraries at one time. This protocol describes Sperm-seq library generation, featurin…
View article: Insights about variation in meiosis from 31,228 human sperm genomes
Insights about variation in meiosis from 31,228 human sperm genomes Open
Meiosis, while critical for reproduction, is also highly variable and error prone: crossover rates vary among humans and individual gametes, and chromosome nondisjunction leads to aneuploidy, a leading cause of miscarriage. To study variat…
View article: Recombination and aneuploidy data for: Insights about variation in meiosis from 31,228 human sperm genomes
Recombination and aneuploidy data for: Insights about variation in meiosis from 31,228 human sperm genomes Open
This repository holds crossover and aneuploidy data for 31,228 human sperm genomes sequenced with Sperm-seq. Data are described in the preprint/paper "Insights about variation in meiosis from 31,228 human sperm genomes." Several levels of …
View article: Recombination and aneuploidy data for: Insights about variation in meiosis from 31,228 human sperm genomes
Recombination and aneuploidy data for: Insights about variation in meiosis from 31,228 human sperm genomes Open
This repository holds crossover and aneuploidy data for 31,228 human sperm genomes sequenced with Sperm-seq. Data are described in the preprint/paper "Insights about variation in meiosis from 31,228 human sperm genomes." Several levels of …
View article: Recombination and aneuploidy data for: Insights about variation in meiosis from 31,228 human sperm genomes
Recombination and aneuploidy data for: Insights about variation in meiosis from 31,228 human sperm genomes Open
This repository holds crossover and aneuploidy data for 31,228 human sperm genomes sequenced with Sperm-seq. Data are described in the preprint/paper "Insights about variation in meiosis from 31,228 human sperm genomes." Several levels of …
View article: Analysis scripts for: Insights about variation in meiosis from 31,228 human sperm genomes
Analysis scripts for: Insights about variation in meiosis from 31,228 human sperm genomes Open
This repository holds scripts that call crossovers, determine ploidy, and perform various other analyses for data generated via Sperm-seq. The methods from the preprint/paper ("Insights about variation in meiosis from 31,228 human sperm ge…
View article: Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations
Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations Open
View article: First Stars XVI. HST/STIS Abundances Of Heavy Elements In The Uranium-Rich Metal-Poor Star CS 31082-001
First Stars XVI. HST/STIS Abundances Of Heavy Elements In The Uranium-Rich Metal-Poor Star CS 31082-001 Open
Context. The origin and site(s) of the r-process nucleosynthesis is(are) still not known with certainty, but complete, detailed r-element abundances off er our best clues. The few extremely metal-poor (EMP) stars with large r-element exces…
View article: Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension
Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension Open
After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects o…