Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neuroscience Institute
Total Results:
13363
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2015:112(40). DOI: 10.1073/pnas.1517212112
Erratum: Like cognitive function, decision making across the life span shows profound age-related changes (Proceedings of the National Academy of Sciences of the United States of America (2013) 110 (17143-17148) DOI: 10.1073/pnas.1309909110) [Correction]
SCOPUS:84943373800
ISSN: 0027-8424
CID: 2817412
Angewandte chemie. International edition in English. 2015:54(41):11910-6.DOI: 10.1002/anie.201505507
Richard Willstatter and the 1915 Nobel Prize in chemistry
One hundred years after his Nobel Prize, Richard Willstatter's achievements and the fascinating role he played in 20th century chemistry are discussed in this Essay. Several of his discoveries, such as the anthocyanidins, cyclooctatetraene, the ortho-quinones, and the structure of cocaine, will forever be associated with his name.
PMID: 26291186
ISSN: 1521-3773
CID: 2484352
Somatic mutation in single human neurons tracks developmental and transcriptional history
Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) in the human brain. We identified thousands of somatic SNVs by single-cell sequencing of 36 neurons from the cerebral cortex of three normal individuals. Unlike germline and cancer SNVs, which are often caused by errors in DNA replication, neuronal mutations appear to reflect damage during active transcription. Somatic mutations create nested lineage trees, allowing them to be dated relative to developmental landmarks and revealing a polyclonal architecture of the human cerebral cortex. Thus, somatic mutations in the brain represent a durable and ongoing record of neuronal life history, from development through postmitotic function.
PMID: 26430121
ISSN: 1095-9203
CID: 3332552
Diagnostic Accuracy of Cardiac Magnetic Resonance Imaging in the Evaluation of Newly Diagnosed Heart Failure With Reduced Left Ventricular Ejection Fraction
The aim of this study was to determine the diagnostic value of cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE), cine imaging, and resting first-pass perfusion (FPP) in the evaluation for ischemic (IC) versus nonischemic (NIC) cardiomyopathy in new-onset heart failure with reduced (
PMCID:4567940
PMID: 26251006
ISSN: 1879-1913
CID: 1709282
Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF
PMCID:4755714
PMID: 26367794
ISSN: 1476-4687
CID: 1779142
Adaptive neural coding: from biological to behavioral decision-making
Empirical decision-making in diverse species deviates from the predictions of normative choice theory, but why such suboptimal behavior occurs is unknown. Here, we propose that deviations from optimality arise from biological decision mechanisms that have evolved to maximize choice performance within intrinsic biophysical constraints. Sensory processing utilizes specific computations such as divisive normalization to maximize information coding in constrained neural circuits, and recent evidence suggests that analogous computations operate in decision-related brain areas. These adaptive computations implement a relative value code that may explain the characteristic context-dependent nature of behavioral violations of classical normative theory. Examining decision-making at the computational level thus provides a crucial link between the architecture of biological decision circuits and the form of empirical choice behavior.
PMCID:4692189
PMID: 26722666
ISSN: 2352-1546
CID: 2754672
Holographic fiber bundle system for patterned optogenetic activation of large-scale neuronal networks
Optogenetic perturbation has become a fundamental tool in controlling activity in neurons. Used to control activity in cell cultures, slice preparations, anesthetized and awake behaving animals, optical control of cell-type specific activity enables the interrogation of complex systems. A remaining challenge in developing optical control tools is the ability to produce defined light patterns such that power-efficient, precise control of neuronal populations is obtained. Here, we describe a system for patterned stimulation that enables the generation of structured activity in neurons by transmitting optical patterns from computer-generated holograms through an optical fiber bundle. The system couples the optical system to versatile fiber bundle configurations, including coherent or incoherent bundles composed of hundreds of up to several meters long fibers. We describe the components of the system, a method for calibration, and a detailed power efficiency and spatial specificity quantification. Next, we use the system to precisely control single-cell activity as measured by extracellular electrophysiological recordings in ChR2-expressing cortical cell cultures. The described system complements recent descriptions of optical control systems, presenting a system suitable for high-resolution spatiotemporal optical control of wide-area neural networks in vitro and in vivo, yielding a tool for precise neural system interrogation.
PMCID:4717229
PMID: 26793741
ISSN: 2329-423x
CID: 2959872
Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double-blind, pilot study
The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged >/=7 years and able to walk >/=200 m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain. (c) 2015 Wiley Periodicals, Inc.
PMCID:4744659
PMID: 26069231
ISSN: 1552-4833
CID: 1626662
Oscillometry complements spirometry in evaluation of subjects following toxic inhalation
The World Trade Center (WTC) destruction released dust and fumes into the environment. Although many community members developed respiratory symptoms, screening spirometry was usually normal. We hypothesised that forced oscillation testing would identify functional abnormalities undetected by spirometry and that symptom severity would relate to magnitude of abnormalities measured by oscillometry. A symptomatic cohort (n=848) from the Bellevue Hospital WTC Environmental Health Center was evaluated and compared to an asymptomatic cohort (n=475) from the New York City Department of Health WTC Health Registry. Spirometry and oscillometry were performed. Oscillometry measurements included resistance (R5) and frequency dependence of resistance (R5-20). Spirometry was normal for the majority of subjects (73.2% symptomatic versus 87.6% asymptomatic, p<0.0001). In subjects with normal spirometry, R5 and R5-20 were higher in symptomatic versus asymptomatic subjects (median (interquartile range) R5 0.436 (0.206) versus 0.314 (0.129) kPa.L-1.s-1, p<0.001; R5-20 0.075 (0.085) versus 0.004 (0.042) kPa.L-1.s-1, p<0.0001). In symptomatic subjects, R5 and R5-20 increased with increasing severity and frequency of wheeze (p<0.05). Measurement of R5-20 correlated with the presence and severity of symptoms even when spirometry was within normal limits. These findings are in accord with small airway abnormalities as a potential explanation of the respiratory symptoms.
PMCID:5005120
PMID: 27730155
ISSN: 2312-0541
CID: 2278362
Intrinsic brain indices of verbal working memory capacity in children and adolescents
Working memory (WM) is central to the acquisition of knowledge and skills throughout childhood and adolescence. While numerous behavioral and task-based functional magnetic resonance imaging (fMRI) studies have examined WM development, few have used resting-state fMRI (R-fMRI). Here, we present a systematic R-fMRI examination of age-related differences in the neural indices of verbal WM performance in a cross-sectional pediatric sample (ages: 7-17; n=68), using data-driven approaches. Verbal WM capacity was measured with the digit span task, a commonly used educational and clinical assessment. We found distinct neural indices of digit span forward (DSF) and backward (DSB) performance, reflecting their unique neuropsychological demands. Regardless of age, DSB performance was related to intrinsic properties of brain areas previously implicated in attention and cognitive control, while DSF performance was related to areas less commonly implicated in verbal WM storage (precuneus, lateral visual areas). From a developmental perspective, DSF exhibited more robust age-related differences in brain-behavior relationships than DSB, and implicated a broader range of networks (ventral attention, default, somatomotor, limbic networks) - including a number of regions not commonly associated with verbal WM (angular gyrus, subcallosum). These results highlight the importance of examining the neurodevelopment of verbal WM and of considering regions beyond the "usual suspects".
PMCID:4696540
PMID: 26299314
ISSN: 1878-9307
CID: 1741982
