New Haven, CT, United States
New Haven, CT, United States

Yale University is a private Ivy League research university in New Haven, Connecticut. Founded in 1701 as the "Collegiate School" by a group of Congregationalist ministers and chartered by the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States. In 1718, the school was renamed "Yale College" in recognition of a gift from Elihu Yale, a governor of the British East India Company. Established to train Connecticut ministers in theology and sacred languages, by 1777 the school's curriculum began to incorporate humanities and science. During the 19th century Yale gradually incorporated graduate and professional instruction, awarding the first Ph.D. in the United States in 1861 and organizing as a university in 1887.Yale is organized into twelve constituent schools: the original undergraduate college, the Graduate School of Arts & science, and ten professional schools. While the university is governed by the Yale Corporation, each school's faculty oversees its curriculum and degree programs. In addition to a central campus in downtown New Haven, the University owns athletic facilities in Western New Haven, including the Yale Bowl, a campus in West Haven, Connecticut, and forest and nature preserves throughout New England. The University's assets include an endowment valued at $23.9 billion as of September 27, 2014.Yale College undergraduates follow a liberal arts curriculum with departmental majors and are organized into a system of residential colleges. The Yale University Library, serving all twelve schools, holds more than 15 million volumes and is the third-largest academic library in the United States. Almost all faculty teach undergraduate courses, more than 2,000 of which are offered annually. Students compete intercollegiately as the Yale Bulldogs in the NCAA Division I Ivy League.Yale has graduated many notable alumni, including five U.S. Presidents, 19 U.S. Supreme Court Justices, 13 living billionaires, and many foreign heads of state. In addition, Yale has graduated hundreds of members of Congress and many high-level U.S. diplomats, including former U.S. Secretary of State Hillary Clinton and current Secretary of State John Kerry. Fifty-two Nobel laureates have been affiliated with the University as students, faculty, or staff, and 230 Rhodes Scholars graduated from the University. Wikipedia.

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Higley M.J.,Yale University
Nature Reviews Neuroscience | Year: 2014

Neuronal circuits are defined by synaptic connections between their cellular constituents. In this article, I highlight several recent studies emphasizing the surprising level of precision exhibited by inhibitory GABAergic synapses within the neocortex and hippocampus. Specifically, GABAergic inputs to dendritic shafts and spines of pyramidal cells have a key role in the localized regulation of neuronal Ca2+ signalling. These findings provide important new insights into the cellular mechanisms underlying the contributions of inhibitory transmission to both normal and abnormal brain activity. © 2014 Macmillan Publishers Limited. All rights reserved.

Cannon T.D.,Yale University
Trends in Cognitive Sciences | Year: 2015

Identifying cognitive and neural mechanisms involved in the development of schizophrenia requires longitudinal observation of individuals prior to onset. Here recent studies of prodromal individuals who progress to full psychosis are briefly reviewed in relation to models of schizophrenia pathophysiology. Together, this body of work suggests that disruption in brain connectivity, driven primarily by a progressive reduction in dendritic spines on cortical pyramidal neurons, may represent a key triggering mechanism. The earliest disruptions appear to be in circuits involved in referencing experiences according to time, place, and agency, which may result in a failure to recognize particular cognitions as self-generated or to constrain interpretations of the meaning of events based on prior experiences, providing the scaffolding for faulty reality testing. © 2015 Elsevier Ltd.

Lee D.,Yale University
Neuron | Year: 2013

Adaptive behaviors increase the likelihood of survival and reproduction and improve the quality of life. However, it is often difficult to identify optimal behaviors in real life due to the complexity of the decision maker@s environment and social dynamics. As a result, although many different brain areas and circuits are involved in decision making, evolutionary and learning solutions adopted by individual decision makers sometimes produce suboptimal outcomes. Although these problems are exacerbated in numerous neurological and psychiatric disorders, their underlying neurobiological causes remain incompletely understood. In this review, theoretical frameworks in economics and machine learning and their applications in recent behavioral and neurobiological studies are summarized. Examples of such applications in clinical domains are also discussed for substance abuse, Parkinson@s disease, attention-deficit/hyperactivity disorder, schizophrenia, mood disorders, and autism. Findings from these studies have begun to lay the foundations necessary to improve diagnostics and treatment for various neurological and psychiatric disorders

Koleske A.J.,Yale University
Nature Reviews Neuroscience | Year: 2013

In the developing brain, dendrite branches and dendritic spines form and turn over dynamically. By contrast, most dendrite arbors and dendritic spines in the adult brain are stable for months, years and possibly even decades. Emerging evidence reveals that dendritic spine and dendrite arbor stability have crucial roles in the correct functioning of the adult brain and that loss of stability is associated with psychiatric disorders and neurodegenerative diseases. Recent findings have provided insights into the molecular mechanisms that underlie long-term dendrite stabilization, how these mechanisms differ from those used to mediate structural plasticity and how they are disrupted in disease. © 2013 Macmillan Publishers Limited. All rights reserved.

Bloom P.,Yale University
Trends in Cognitive Sciences | Year: 2017

What role does the experience of feeling what you think others are feeling – often known as ‘empathy’ – have in moral deliberation and moral action? Empathy has many fans and there is abundant evidence that it can motivate prosocial behavior. However, empathy is narrow in its focus, rendering it innumerate and subject to bias. It can motivate cruelty and aggression and lead to burnout and exhaustion. Compassion is distinct from empathy in its neural instantiation and its behavioral consequences and is a better prod to moral action, particularly in the modern world we live in. © 2016 Elsevier Ltd

van den Pol A.,Yale University
Neuron | Year: 2012

Neuropeptides are found in many mammalian CNS neurons where they play key roles in modulating neuronal activity. In contrast to amino acid transmitter release at the synapse, neuropeptide release is not restricted to the synaptic specialization, and after release, a neuropeptide may diffuse some distance to exert its action through a G protein-coupled receptor. Some neuropeptides such as hypocretin/orexin are synthesized only in single regions of the brain, and the neurons releasing these peptides probably have similar functional roles. Other peptides such as neuropeptide Y (NPY) are synthesized throughout the brain, and neurons that synthesize the peptide in one region have no anatomical or functional connection with NPY neurons in other brain regions. Here, I review converging data revealing a complex interaction between slow-acting neuromodulator peptides and fast-acting amino acid transmitters in the control of energy homeostasis, drug addiction, mood and motivation, sleep-wake states, and neuroendocrine regulation.

Romberg N.,Yale University
Nature Genetics | Year: 2014

Upon detection of pathogen-associated molecular patterns, innate immune receptors initiate inflammatory responses. These receptors include cytoplasmic NOD-like receptors (NLRs) whose stimulation recruits and proteolytically activates caspase-1 within the inflammasome, a multiprotein complex. Caspase-1 mediates the production of interleukin-1 family cytokines (IL1FCs), leading to fever and inflammatory cell death (pyroptosis). Mutations that constitutively activate these pathways underlie several autoinflammatory diseases with diverse clinical features. We describe a family with a previously unreported syndrome featuring neonatal-onset enterocolitis, periodic fever, and fatal or near-fatal episodes of autoinflammation. We show that the disease is caused by a de novo gain-of-function mutation in NLRC4 encoding a p.Val341Ala substitution in the HD1 domain of the protein that cosegregates with disease. Mutant NLRC4 causes constitutive IL1FC production and macrophage cell death. Infected macrophages from affected individuals are polarized toward pyroptosis and exhibit abnormal staining for inflammasome components. These findings identify and describe the cause of a life-threatening but treatable autoinflammatory disease that underscores the divergent roles of the NLRC4 inflammasome. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Humphrey J.D.,Yale University
Nature Reviews Molecular Cell Biology | Year: 2014

Soft connective tissues at steady state are dynamic; resident cells continually read environmental cues and respond to them to promote homeostasis, including maintenance of the mechanical properties of the extracellular matrix (ECM) that are fundamental to cellular and tissue health. The mechanosensing process involves assessment of the mechanics of the ECM by the cells through integrins and the actomyosin cytoskeleton, and is followed by a mechanoregulation process, which includes the deposition, rearrangement or removal of the ECM to maintain overall form and function. Progress towards understanding the molecular, cellular and tissue-level effects that promote mechanical homeostasis has helped to identify key questions for future research. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Bogan J.S.,Yale University
Annual Review of Biochemistry | Year: 2012

To enhance glucose uptake into muscle and fat cells, insulin stimulates the translocation of GLUT4 glucose transporters from intracellular membranes to the cell surface. This response requires the intersection of insulin signaling and vesicle trafficking pathways, and it is compromised in the setting of overnutrition to cause insulin resistance. Insulin signals through AS160Tbc1D4 and Tbc1D1 to modulate Rab GTPases and through the Rho GTPase TC10α to act on other targets. In unstimulated cells, GLUT4 is incorporated into specialized storage vesicles containing IRAP, LRP1, sortilin, and VAMP2, which are sequestered by TUG, Ubc9, and other proteins. Insulin mobilizes these vesicles directly to the plasma membrane, and it modulates the trafficking itinerary so that cargo recycles from endosomes during ongoing insulin exposure. Knowledge of how signaling and trafficking pathways are coordinated will be essential to understanding the pathogenesis of diabetes and the metabolic syndrome and may also inform a wide range of other physiologies. © 2012 by Annual Reviews. All rights reserved.

Work done in the field of resolving heterogeneity problems and impurity artifacts in operationally homogeneous transition metal catalysts are discussed. Unintended heterotopy with loss of all the ligands initially present in the precatalyst are found to nullify the effect of sophisticated ligand design such as in the multifunctional ligands. Narayanan et al. have shown that nanoparticle shape and size can strongly affect activity. Finke and co-workers have now modified their conclusions for the Maitlis catalyst and find in operando X-ray absorption fine structure (XAFS), kinetic, and kinetic poisoning evidence for the predominant species and active catalyst being subnanometer Rh 4 clusters. Conlon and co-workers studied the Suzuki-Miyaura reaction catalyzed by Pd/C by estimating the solution levels of Pd by hot filtration followed by high-performance liquid chromatography (HPLC) analysis for the organics and inductively coupled plasma-mass spectrometry (ICP-MS) analysis for the palladium.

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