bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms
Authors: Robinson Jennifer , Manseau Frédéric , Ducharme Guillaume , Amilhon Bénédicte , Vigneault Erika , El Mestikawy Salah , Williams Sylvain 
Published: March 2016

The medial septum and diagonal band of Broca (MS-DBB) has an essential role for theta rhythm generation in the hippocampus and is critical for learning and memory. The MS-DBB contains cholinergic, GABAergic, and recently described glutamatergic neurons, but their specific contribution to theta generation is poorly understood. Here, we examined the role of MS-DBB glutamatergic neurons in theta rhythm using optogenetic activation and electrophysiological recordings performed inin vitropreparations and in freely behaving mice. The experiments in slices suggest that MS-DBB glutamatergic neurons provide prominent excitatory inputs to a majority of local GABAergic and a minority of septal cholinergic neurons. In contrast, activation of MS-DBB glutamatergic fiber terminals in hippocampal slices elicited weak postsynaptic responses in hippocampal neurons. In thein vitrosepto-hippocampal preparation, activation of MS-DBB glutamatergic neurons did increase the rhythmicity of hippocampal theta oscillations, whereas stimulation of septo-hippocampal glutamatergic fibers in the fornix did not have an effect. In freely behaving mice, activation of these neurons in the MS-DBB strongly synchronized hippocampal theta rhythms over a wide range of frequencies, whereas activation of their projections to the hippocampus through fornix stimulations had no effect on theta rhythms, suggesting that MS-DBB glutamatergic neurons played a role in theta generation through local modulation of septal neurons. Together, these results provide the first evidence that MS-DBB glutamatergic neurons modulate local septal circuits, which in turn contribute to theta rhythms in the hippocampus.SIGNIFICANCE STATEMENTThe current paper explores the functional role of septal glutamatergic neurons, a recently identified population, in theta rhythm generation in the hippocampus. Using optogenetics and electrophysiology, we have explored the functional connectivity of these neuronsin vitro, as well as their influence on theta rhythms bothin vitroandin vivo, and show that this neuronal population can powerfully drive theta rhythms through intraseptal connections. These results strongly suggest a role of glutamatergic neurons in theta rhythm generation and may therefore be important for learning and memory.
The Activators of Cyclin-Dependent Kinase 5 p35 and p39 Are Essential for Oligodendrocyte Maturation, Process Formation, and Myelination
Authors: Luo Fucheng , Zhang Jessie , Burke Kathryn , Miller Robert H. , Yang Yan 
Published: March 2016

The regulation of oligodendrocyte development and myelin formation in the CNS is poorly defined. Multiple signals influence the rate and extent of CNS myelination, including the noncanonical cyclin-dependent kinase 5 (Cdk5) whose functions are regulated by its activators p35 and p39. Here we show that selective loss of either p35 or p39 perturbed specific aspects of oligodendrocyte development, whereas loss of both p35 and p39 completely inhibited the development of mature oligodendrocytes and myelination. In the absence of p35, oligodendrocyte differentiation was delayed, process outgrowth was truncatedin vitro, and the patterning and extent of myelination were perturbed in the CNS ofp35−/−mice. In the absence of p39, oligodendrocyte maturation was transiently affected bothin vitroandin vivo. However, loss of both p35 and p39 in oligodendrocyte lineage cells completely inhibited oligodendrocyte progenitor cell differentiation and myelination bothin vitroand after transplantation intoshivererslice cultures. Loss of p35 and p39 had a more profound effect on oligodendrocyte development than simply the loss of Cdk5 and could not be rescued by Cdk5 overexpression. These data suggest p35 and p39 have specific and overlapping roles in oligodendrocyte development, some of which may be independent of Cdk5 activation.SIGNIFICANCE STATEMENTThe development of oligodendrocytes and myelination is essential for normal CNS function and cyclin-dependent kinase 5 (Cdk5) activity is critical for oligodendrocyte maturation, but how Cdk5 activity is controlled is unclear. Here we show that the coactivators of Cdk5, p35 and p39, regulate distinct stages of oligodendrocyte development and myelination. Loss of p35 perturbs oligodendrocyte progenitor cell differentiation, whereas loss of p39 delays oligodendrocyte maturation. Loss of both completely inhibits oligodendrogenesis and myelination. Disruption of oligodendrocyte development was more pronounced inp35−/−;p39shRNA cells than loss of Cdk5 alone and could not be rescued by Cdk5 overexpression, suggesting that p35 and p39 have Cdk5-independent roles during oligodendrocyte development. These studies provide novel targets for therapeutic intervention in conditions in which myelination is perturbed.
Independence of Movement Preparation and Movement Initiation
Authors: Haith Adrian M. , Pakpoor Jina , Krakauer John W. 
Published: March 2016

Initiating a movement in response to a visual stimulus takes significantly longer than might be expected on the basis of neural transmission delays, but it is unclear why. In a visually guided reaching task, we forced human participants to move at lower-than-normal reaction times to test whether normal reaction times are strictly necessary for accurate movement. We found that participants were, in fact, capable of moving accurately ∼80 ms earlier than their reaction times would suggest. Reaction times thus include a seemingly unnecessary delay that accounts for approximately one-third of their duration. Close examination of participants' behavior in conventional reaction-time conditions revealed that they generated occasional, spontaneous errors in trials in which their reaction time was unusually short. The pattern of these errors could be well accounted for by a simple model in which the timing of movement initiation is independent of the timing of movement preparation. This independence provides an explanation for why reaction times are usually so sluggish: delaying the mean time of movement initiation relative to preparation reduces the risk that a movement will be initiated before it has been appropriately prepared. Our results suggest that preparation and initiation of movement are mechanistically independent and may have a distinct neural basis. The results also demonstrate that, even in strongly stimulus-driven tasks, presentation of a stimulus does not directly trigger a movement. Rather, the stimulus appears to trigger an internal decision whether to make a movement, reflecting a volitional rather than reactive mode of control.SIGNIFICANCE STATEMENTThe reaction time, i.e., how quickly we can initiate a movement in response to a stimulus, is important for daily activities such as driving and is also a critical tool in neuroscience, used to probe a multitude of cognitive functions. However, there remains a surprising lack of basic understanding about exactly what determines reaction times, even for simple movements such as reaching to a target. We show that the reaction time for a reaching movement does not reflect the moment that the movement becomes ready to execute. Instead, the reaction time is determined by a separate initiation process. These findings suggest a distinct neural basis for preparation and initiation of movement and provide an explanation for the sluggishness of typical reaction times.
Feeding and Reward Are Differentially Induced by Activating GABAergic Lateral Hypothalamic Projections to VTA
Authors: Barbano M. Flavia , Wang Hui-Ling , Morales Marisela , Wise Roy A. 
Published: March 2016

Electrical stimulation of the lateral hypothalamus (LH) has two motivational effects: long trains of stimulation induce drive-like effects such as eating, and short trains are rewarding. It has not been clear whether a single set of activated fibers subserves the two effects. Previous optogenetic stimulation studies have confirmed that reinforcement and induction of feeding can each be induced by selective stimulation of GABAergic fibers originating in the bed nucleus of the LH and projecting to the ventral tegmental area (VTA). In the present study we determined the optimal stimulation parameters for each of the two optogenetically induced effects in food-sated mice. Stimulation-induced eating was strongest with 5 Hz and progressively weaker with 10 and 20 Hz. Stimulation-induced reward was strongest with 40 Hz and progressively weaker with lower or higher frequencies. Mean preferred duration for continuous 40 Hz stimulation was 61.6 s in a “real-time” place preference task; mean preferred duration for 5 Hz stimulation was 45.6 s. The differential effects of high- and low-frequency stimulation of this pathway seem most likely to be due to differential effects on downstream targets.SIGNIFICANCE STATEMENTOur study reports that the eating and the reward induced by optogenetic stimulation of a previously identified GABAergic projection from the lateral hypothalamus to the ventral tegmental area are differentially affected by low- and high-frequency stimulation, respectively. This suggests a way that stimulation of the same pathway can have very different motivational effects on behavior, inducing a drive state (usually thought to be aversive) under one condition and inducing the rewarding state under another. This offers an insight into what has been called the “drive-reward paradox”: why would an animal work for stimulation that established an apparent drive state?
Intermolecular Interaction between Anchoring Subunits Specify Subcellular Targeting and Function of RGS Proteins in Retina ON-Bipolar Neurons
Authors: Sarria Ignacio , Orlandi Cesare , McCall Maureen A. , Gregg Ronald G. , Martemyanov Kirill A. 
Published: March 2016

In vertebrate retina, light responses generated by the rod photoreceptors are transmitted to the second-order neurons, the ON-bipolar cells (ON-BC), and this communication is indispensible for vision in dim light. In ON-BCs, synaptic transmission is initiated by the metabotropic glutamate receptor, mGluR6, that signals via the G-protein Go to control opening of the effector ion channel, TRPM1. A key role in this process belongs to the GTPase Activating Protein (GAP) complex that catalyzes Go inactivation upon light-induced suppression of glutamate release in rod photoreceptors, thereby driving ON-BC depolarization to changes in synaptic input. The GAP complex has a striking molecular complexity. It contains two Regulator of G-protein Signaling (RGS) proteins RGS7 and RGS11 that directly act on Go and two adaptor subunits: RGS Anchor Protein (R9AP) and the orphan receptor, GPR179. Here we examined the organizational principles of the GAP complex in ON-BCs. Biochemical experiments revealed that RGS7 binds to a conserved site in GPR179 and that RGS11in vivoforms a complex only with R9AP. R9AP and GPR179 are further integrated via direct protein–protein interactions involving their cytoplasmic domains. Elimination of GPR179 prevents postsynaptic accumulation of R9AP. Furthermore, concurrent knock-out of both R9AP and RGS7 does not reconfigure the GAP complex and completely abolishes synaptic transmission, resulting in a novel mouse model of night blindness. Based on these results, we propose a model of hierarchical assembly and function of the GAP complex that supports ON-BCs visual signaling.SIGNIFICANCE STATEMENTThe ability of photoreceptors to transmit signals to the downstream ON-bipolar neurons in the retina is indispensible for vision. In this study, we delineate the molecular organization of the central regulatory complex, the GTPase Activating Protein (GAP) complex, that drives postsynaptic responses in ON-bipolar cells. Here, we identify an unexpected complexity and interdependence between multiple subunits of the GAP complex. We propose a model for its supramolecular assembly, where individual components hierarchically control expression and intracellular targeting of the GAP complex. Broad interest results from the crucial role of similarly organized GAP complexes throughout the nervous system, where they control a wide range of fundamental neuronal processes, including learning and memory, reward, and movement coordination.
A comparison of two forms of the continuity equation in the Trifecta bovine pericardial aortic valve
Authors: Chambers John B. , Parkin Denise , Roxburgh James , Bapat Vinayak , Young Christopher 
Published: March 2016

Abstract
Aim: To compare the classical and simplified form of the continuity equation in small Trifecta valves.
Methods: This is a retrospective analysis of post-operative echocardiograms performed for clinical reasons after implantation of Trifecta bioprosthetic valves.
Results: There were 60 patients aged 74 (range 38–89) years. For the valves of size 19, 21 and 23mm, the mean gradient was 11.3, 10.7 and 9.7mmHg, respectively. The effective orifice areas by the classical form of the continuity equation were 1.4, 1.7 and 1.9cm2, respectively. There was a good correlation between the two forms of the continuity equation, but they were significantly different using a t-test (P<0.00001). Results using the classical form were a mean 0.11 (s.d. 0.18)cm2 larger than those using the simple formula.
Conclusion: Haemodynamic function of the Trifecta valve in the small aortic root is good. There are significant differences between the classical and simplified forms of the continuity equation.
Poverty and Child Health in the United States
Authors:   COUNCIL ON COMMUNITY PEDIATRICS, Gitterman Benjamin A. , Flanagan Patricia J. , Cotton William H. , Dilley Kimberley J. , Duffee James H. , Green Andrea E. , Keane Virginia A. , Krugman Scott D. , Linton Julie M. , McKelvey Carla D. , Nelson Jacqueline L. 
Published: March 2016

This Policy Statement was reaffirmed April 2021.
Almost half of young children in the United States live in poverty or near poverty. The American Academy of Pediatrics is committed to reducing and ultimately eliminating child poverty in the United States. Poverty and related social determinants of health can lead to adverse health outcomes in childhood and across the life course, negatively affecting physical health, socioemotional development, and educational achievement. The American Academy of Pediatrics advocates for programs and policies that have been shown to improve the quality of life and health outcomes for children and families living in poverty. With an awareness and understanding of the effects of poverty on children, pediatricians and other pediatric health practitioners in a family-centered medical home can assess the financial stability of families, link families to resources, and coordinate care with community partners. Further research, advocacy, and continuing education will improve the ability of pediatricians to address the social determinants of health when caring for children who live in poverty. Accompanying this policy statement is a technical report that describes current knowledge on child poverty and the mechanisms by which poverty influences the health and well-being of children.
Mediators and Adverse Effects of Child Poverty in the United States
Authors: Pascoe John M. , Wood David L. , Duffee James H. , Kuo Alice ,   COMMITTEE ON PSYCHOSOCIAL ASPECTS OF CHILD AND FAMILY HEALTH,   COUNCIL ON COMMUNITY PEDIATRICS, Yogman Michael , Bauer Nerissa , Gambon Thresia B , Lavin Arthur , Lemmon Keith M. , Mattson Gerri , Rafferty Jason Richard , Wissow Lawrence Sagin , Gitterman Benjamin A. , Flanagan Patricia J. , Cotton William H. , Dilley Kimberley J. , Green Andrea E. , Keane Virginia A. , Krugman Scott D. , Linton Julie M. , McKelvey Carla D. , Nelson Jacqueline L. 
Published: March 2016

This Technical Report was reaffirmed April 2021.
The link between poverty and children’s health is well recognized. Even temporary poverty may have an adverse effect on children’s health, and data consistently support the observation that poverty in childhood continues to have a negative effect on health into adulthood. In addition to childhood morbidity being related to child poverty, epidemiologic studies have documented a mortality gradient for children aged 1 to 15 years (and adults), with poor children experiencing a higher mortality rate than children from higher-income families. The global great recession is only now very slowly abating for millions of America’s children and their families. At this difficult time in the history of our nation’s families and immediately after the 50th anniversary year of President Lyndon Johnson’s War on Poverty, it is particularly germane for the American Academy of Pediatrics, which is “dedicated to the health of all children,” to publish a research-supported technical report that examines the mediators associated with the long-recognized adverse effects of child poverty on children and their families. This technical report draws on research from a number of disciplines, including physiology, sociology, psychology, economics, and epidemiology, to describe the present state of knowledge regarding poverty’s negative impact on children’s health and development. Children inherit not only their parents’ genes but also the family ecology and its social milieu. Thus, parenting skills, housing, neighborhood, schools, and other factors (eg, medical care) all have complex relations to each other and influence how each child’s genetic canvas is expressed. Accompanying this technical report is a policy statement that describes specific actions that pediatricians and other child advocates can take to attenuate the negative effects of the mediators identified in this technical report and improve the well-being of our nation’s children and their families.
How Long Should An Individual At Full Retirement Age Delay Receiving Social Security Benefits?
Authors: Hebein Fred 
Published: March 2016

n important topic for many individuals approaching 66 in 2011 is whether to start social security benefits at full retirement age (FRA) or to delay the benefits in order to gain greater payouts in the future. In 2009, the bonus for delaying the start of benefits rose to about 8% per year. By delaying benefits for four years (to age 70), it is possible to increase benefits by 38 to 55 percent per month for the remainder of the retirees life. In addition to the higher monthly benefits from delaying start of benefits, there are also substantial benefits for high income retirees in relocating to lower tax states. Also, given that the remaining age to death for most retirees at FRA is clearly finite, one would expect to see some value in discounting future earnings. Our paper evaluates accumulated benefits over a 25 year time horizon to assess retirement decisions post FRA. We consider three examples of accumulated benefits: (1) constant dollar accumulated benefits without discount or taxes; (2) alternative rates of discount of the future stream of earnings without income taxes; and (3) discounted after tax benefits. Each scenario is evaluated to assess whether delaying social security benefits past FRA is a profitable idea. Based upon our analysis, any discount rate in excess of 5% of the available after-tax returns provides no breakeven age within expected life ages. That is, at high discount rates, it is always better to start benefits at FRA or with only short delay once FRA is reached, if the individual wishes to maximize accumulated benefits over the expected life. At discount rates of less than 3%, the accumulated benefits may be increased within the expected life span by delaying the start of benefits. If no discount rate is applied, accumulated benefits are maximized by delayed start since all breakeven ages occur within life expectancy. In addition, we find that the negative impact of taxes on accumulated benefits can be as large as a discount rate of 3% on accumulated benefits. For high income retirees, a strategy of (1) relocating to lower tax states and (2) delaying the start of benefits can provide substantial increases to accumulated benefits. Finally, we note that the retirement decision is not entirely financial, but that many factors including family, spouse, work climate, health, expected life span, and fear of running out of money lead individuals into making decisions that may not optimize the present value of future benefits.
Measuring Internationality Of Board Members via Secondary Data A Comparison Of Methods
Authors: Sommer Lutz 
Published: March 2016

he assessment of the internationality of board members is based on the quality of the assessment of each individual member. In practice, different indices based on secondary data are used to capture the internationality of management boards. The CVs of 213 board members of DAX-listed companies were analyzed with regard to internationally relevant data with the aim to compare the quality of the refined benchmark index InEx NWE+WE P to a selection of indices used in practice in terms of their information value. The results show that the partly very simplistic indices used in practice lead to significant distortions with regard to the assessment of the internationality of individual board members and thus of the management boards as whole. In other words, the simpler indices dont use the information potential of the existing secondary data sufficiently, thus enticing the viewer to partly significant misinterpretations.
Cash Balance Pension Plan Conversions: An Analysis Of Motivations And Pension Costs
Authors: D’Souza Julia , Jacob, (Deceased) John , Lougee Barbara 
Published: March 2016

In recent years, many corporations have replaced their traditional defined benefit (DB) pension plans with cash balance (CB) plans, which share many of the characteristics of defined contribution plans. This study provides empirical evidence on the characteristics of CB converters and the behavior of pension costs and obligations pre- and post-conversion. We find that CB converters are larger than firms that retain traditional DB plans as well as those that terminate DB plans. They are less profitable than the former, but more profitable than the latter. CB conversions are not associated with proxies for greater labor mobility (e.g., firm-specific employee turnover rate). They are associated with a workforce that is closer to retirement, on average, lending credence to the breach of implicit contract rather than the labor market hypothesis as a motivator of CB conversions. Consistent with this intuition, we document that CB converters recognize a reduction of unrecognized prior service costs in the year of conversion, consistent with a negative plan amendment. Unlike pre-conversion, pension costs and obligations are significantly lower for CB firms post-conversion than for a matched sample of firms retaining traditional DB plans. CB conversions are more popular than DB plan terminations among firms with overfunded pension plans in periods when expected return on plan assets is likely to be high, with a consequent positive effect on reported income.