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"Birnbaum, Molly"
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Taking scent for granted
The recent warning from the Food and Drug Administration (FDA) that a widely used homeopathic cold remedy, Zicam, can destroy one's sense of smell has alarmed many consumers who have used the product. At least 130 Zicam users, according to the FDA, have reported a loss of smell after using the zinc-based nasal gel or swabs produced by Matrixx Initiatives Inc. The company, which has defended the safety of its medication, has begun a recall.
Newspaper Article
Finally The Scent of the City
I MOVED to New York on a cold February morning in 2006. When I stepped off the train at Penn Station, lugging two suitcases and a good deal of anxiety, I didn't smell the garbage overflowing in a bin next to the tracks. I didn't smell the piping hot coffee in the terminal kiosks as 1 walked...
Newspaper Article
Finally, the Scent of the City
[...] most of my sense of smell had vanished six months earlier, when, on a drizzly August morning while jogging near my family's home in Boston, I had been hit by a Honda Civic and shattered its windshield with the back of my skull. While my fractured pelvis and torn knee ligaments eventually healed, milk remained a viscous liquid, steak a slimy rubber, and ice cream was little more than freezing.
Newspaper Article
An Aspiring Chef Loses Her Sense Of Smell
I decided to bake because baking seemed to rely on measurement rather than improvisation, and butter cookies seemed a simple enough choice. I decided to add chocolate, to see if I could taste it. And a pinch of cayenne because at least that I knew I'd be able to feel. Before the accident, I had been training to be a chef and was only months away from my starting date at the Culinary Institute of America, but the kitchen felt strange and unfamiliar in that first crutch-bound day. I didn't know how to operate without my sense of smell. For the first month of my recovery, when my bones healed but my nose stayed blank and mute, I wondered what I could do if I couldn't taste. Could I cook? Would I want to? As it was, I could barely eat, subsisting on a diet that consisted largely of cottage cheese with salsa, because I loved the texture of the dairy and could feel the spicy tingle of the salsa's heat from the trigeminal nerve, which wraps around the face and into the mouth.
Newspaper Article
The mutational constraint spectrum quantified from variation in 141,456 humans
Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes
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. Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve the power of gene discovery for both common and rare diseases.
A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.
Journal Article
Hit-and-run transcriptional control by bZIP1 mediates rapid nutrient signaling in Arabidopsis
The dynamic nature of gene regulatory networks allows cells to rapidly respond to environmental change. However, the underlying temporal connections are missed, even in kinetic studies, as transcription factor (TF) binding within at least one time point is required to identify primary targets. The TF-regulated but unbound genes are dismissed as secondary targets. Instead, we report that these genes comprise transient TF-target interactions most relevant to rapid signal transduction. We temporally perturbed a master TF (Basic Leucine Zipper 1, bZIP1) and the nitrogen (N) signal it transduces and integrated TF regulation and binding data from the same cell samples. Our enabling approach could identify primary TF targets based solely on gene regulation, in the absence of TF binding. We uncovered three classes of primary TF targets: (i) poised (TF-bound but not TF-regulated), (ii) stable (TF-bound and TF-regulated), and (iii) transient (TF-regulated but not TF-bound), the largest class. Unexpectedly, the transient bZIP1 targets are uniquely relevant to rapid N signaling in planta, enriched in dynamic N-responsive genes, and regulated by TF and N signal interactions. These transient targets include early N responders nitrate transporter 2.1 and NIN-like protein 3, bound by bZIP1 at 1-5 min, but not at later time points following TF perturbation. Moreover, promoters of these transient targets are uniquely enriched with cis-regulatory motifs coinherited with bZIP1 binding sites, suggesting a recruitment role for bZIP1. This transient mode of TF action supports a classic, but forgotten, \"hit-and-run\" transcription model, which enables a \"catalyst TF\" to activate a large set of targets within minutes of signal perturbation.
Journal Article
Flow Diversion for Endovascular Treatment of Intracranial Aneurysms: Past, Present, and Future Directions
Flow diversion for intracranial aneurysms emerged as an efficacious and durable treatment option over the last two decades. In a paradigm shift from intrasaccular aneurysm embolization to parent vessel remodeling as the mechanism of action, the proliferation of flow-diverting devices has enabled the treatment of many aneurysms previously considered untreatable. In this review, we review the history and development of flow diverters, highlight the pivotal clinical trials leading to their regulatory approval, review current devices including endoluminal and intrasaccular flow diverters, and discuss current and expanding indications for their use. Areas of clinical equipoise, including ruptured aneurysms and wide-neck bifurcation aneurysms, are summarized with a focus on flow diverters for these pathologies. Finally, we discuss future directions in flow diversion technology including bioresorbable flow diverters, transcriptomics and radiogenomics, and machine learning and artificial intelligence.
Journal Article