19 research outputs found
Not your father's pension plan: the rise of 401K and other defined contribution plans
The number of workers with a 401(k) plan grew from 7.1 million in 1983 to 38.9 million by 1993. The rapid diffusion of 401(k) and other portable defined contribution plans and the decline in defined benefit pensions represent a major change in pension structure. Old-style defined benefit pensions were designed to give a fixed income after retirement, but only for workers who stayed in a job for 20 or 30 years; workers who left early ended up with little or nothing. Resulting changes in portability, access to pension wealth, and riskiness are altering incentives for job tenure and worker mobility, retirement, and saving both before and after retirement.Pensions ; Retirement
D2R signaling in striatal spiny neurons modulates L-DOPA induced dyskinesia
Degeneration of dopaminergic neurons leads to Parkinson's disease (PD), characterized by reduced levels of striatal dopamine (DA) and impaired voluntary movements. DA replacement is achieved by levodopa treatment which in long-term causes involuntary movements or dyskinesia. Dyskinesia is linked to the pulsatile activation of D1 receptors of the striatal medium spiny neurons (MSNs) forming the direct output pathway (dMSNs). The contribution of DA stimulation of D2R in MSNs of the indirect pathway (iMSNs) is less clear. Using the 6-hydroxydopamine model of PD, here we show that loss of DA-mediated inhibition of these neurons intensifies levodopa-induced dyskinesia (LID) leading to reprogramming of striatal gene expression. We propose that the motor impairments characteristic of PD and of its therapy are critically dependent on D2R-mediated iMSNs activity. D2R signaling not only filters inputs to the striatum but also indirectly regulates dMSNs mediated responses
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Progress Towards a Formal Enantiospecific Total Synthesis of Potent Antimalarial (-)-7-Isocyano-11(20),14-epiamphilectadiene and Preliminary Investigations of Carbene [2,3]-Wittig Reactions and Epoxypolyene Polycyclizations
Total synthesis and methodology are two large fields of study in synthetic organic chemistry which serve to expand available reactions and strategies with the overarching goal of revealing unique and concise solutions to complex chemical problems. Achievements in these fields are crucial for current and future reasonable syntheses of bioactive compounds of interest in order to evaluate potentially useful materials. Our efforts to contribute to these endeavors included the attempted formal synthesis of an antimalarial isocyanoterpene (ICT) and the investigation into the expansion of the carbene [2,3]-Wittig and polycyclization methodologies. Malaria currently causes millions of infections yearly, and the drugs that are commonly used to treat it are losing efficacy. ICTs are a class of compounds that show great potential for becoming the basis of a new class of antimalarials that are believed to act via traditional and non-traditional routes to eliminate the malaria parasite. To improve upon the synthesis of one of the most potent ICTs, reported by Shenvi, we chose to pursue an enantiospecific formal synthesis of (-)-7-Isocyano-11(20),14-epiamphilectadiene. In the course of our investigations into two separate methodologies, we gained insight into the [2,3]-Wittig rearrangement of various carbenes and the polycyclization of 2,2-disubstituted epoxides and established reliable routes to substrates for the latter. It is our hope that this progress—in addition to future contributions from our lab—aids in the development of expedient and concise syntheses of useful bioactive compounds
D2R signaling in striatal spiny neurons modulates L-DOPA induced dyskinesia
Degeneration of dopaminergic neurons leads to Parkinson's disease (PD), characterized by reduced levels of striatal dopamine (DA) and impaired voluntary movements. DA replacement is achieved by levodopa treatment which in long-term causes involuntary movements or dyskinesia. Dyskinesia is linked to the pulsatile activation of D1 receptors of the striatal medium spiny neurons (MSNs) forming the direct output pathway (dMSNs). The contribution of DA stimulation of D2R in MSNs of the indirect pathway (iMSNs) is less clear. Using the 6-hydroxydopamine model of PD, here we show that loss of DA-mediated inhibition of these neurons intensifies levodopa-induced dyskinesia (LID) leading to reprogramming of striatal gene expression. We propose that the motor impairments characteristic of PD and of its therapy are critically dependent on D2R-mediated iMSNs activity. D2R signaling not only filters inputs to the striatum but also indirectly regulates dMSNs mediated responses
Heteroleptic Nickel Complexes for the Markovnikov-Selective Hydroboration of Styrenes
First-row
transition metal catalysis offers a cheaper, more environmentally
sustainable alternative to second- and third-row transition metal
catalysts. Nickel has shown great promise as a tool for the borylation
of unsaturated compounds to yield boronic esters, but Markovnikov-selective
hydroborations of simple styrenes have not been well-explored. Herein,
we report the synthesis of benzyl boronic esters via nickel-catalyzed
hydroboration of styrenes using a heteroleptic N-heterocyclic carbene
(NHC)–phosphine nickel complex, IMesÂ(Cy<sub>3</sub>P)ÂNiCl<sub>2</sub>. The IMesÂ(Cy<sub>3</sub>P)ÂNiCl<sub>2</sub> complex displays
a broad substrate scope and maintains the integrity of yield and regioselectivity
when challenged with substrates bearing increased steric hindrance.
The heteroleptic complexes also tolerate both electron-withdrawing
and -donating groups, in contrast to traditional bis-phosphine and
Ni(0) complexes