Drugs activating 5-hydroxytryptamine 2C receptors (5-HT 2C Rs) potently suppress appetite, but th... more Drugs activating 5-hydroxytryptamine 2C receptors (5-HT 2C Rs) potently suppress appetite, but the underlying mechanisms for these effects are not fully understood. To tackle this issue, we generated mice with global 5-HT 2C R deficiency (2C null) and mice with 5-HT 2C Rs re-expression only in pro-opiomelanocortin (POMC) neurons (2C/POMC mice). We show that 2C null mice predictably developed hyperphagia, hyperactivity, and obesity and showed attenuated responses to anorexigenic 5-HT drugs. Remarkably, all these deficiencies were normalized in 2C/POMC mice. These results demonstrate that 5-HT 2C R expression solely in POMC neurons is sufficient to mediate effects of serotoninergic compounds on food intake. The findings also highlight the physiological relevance of the 5-HT 2C R-melanocortin circuitry in the long-term regulation of energy balance.
AimsStanniocalcin‐2 (STC2) has recently been implicated in human muscle mass variability by genet... more AimsStanniocalcin‐2 (STC2) has recently been implicated in human muscle mass variability by genetic analysis. Biochemically, STC2 inhibits the proteolytic activity of the metalloproteinase PAPP‐A, which promotes muscle growth by upregulating the insulin‐like growth factor (IGF) axis. The aim was to examine if STC2 affects skeletal muscle mass and to assess how the IGF axis mediates muscle hypertrophy induced by functional overload.MethodsWe compared muscle mass and muscle fiber morphology between Stc2−/− (n = 21) and wild‐type (n = 15) mice. We then quantified IGF1, IGF2, IGF binding proteins −4 and −5 (IGFBP‐4, IGFBP‐5), PAPP‐A and STC2 in plantaris muscles of wild‐type mice subjected to 4‐week unilateral overload (n = 14).ResultsStc2−/− mice showed up to 10% larger muscle mass compared with wild‐type mice. This increase was mediated by greater cross‐sectional area of muscle fibers. Overload increased plantaris mass and components of the IGF axis, including quantities of IGF1 (by 2...
F1000 - Post-publication peer review of the biomedical literature, 2010
Hypothalamic circuits regulating energy balance are highly plastic and develop in response to nut... more Hypothalamic circuits regulating energy balance are highly plastic and develop in response to nutrient and hormonal cues. To identify processes that could be susceptible to gestational influences in the mouse, we characterized the ontogeny of proopiomelanocortin (POMC) and neuropeptide Y (NPY) populations, which exert opposing influences on food intake and body weight. These analyses revealed that Pomc is broadly expressed in immature hypothalamic neurons and that half of embryonic Pomc-expressing precursors subsequently adopt a non-POMC fate in the adult. Moreover, nearly one quarter of the mature orexigenic NPY population shares a common progenitor with anorexigenic POMC neurons.
F1000 - Post-publication peer review of the biomedical literature, 2010
Genome-wide association studies have identified SNPs within the human FTO gene that display a str... more Genome-wide association studies have identified SNPs within the human FTO gene that display a strong association with obesity. Individuals homozygous for the at-risk rs9939609 A allele weigh 3kg more. Loss of function and/or expression of FTO in mice leads to increased energy expenditure and a lean phenotype. We show here that ubiquitous overexpression of Fto leads to a dose-dependent increase in body and fat mass, irrespective of whether mice are fed a standard or high fat diet. The increased body mass results primarily from increased food intake. Glucose intolerance develops with increased Fto expression on a high fat diet. This study provides the first direct evidence that increased Fto expression causes obesity in mice. AUTHOR CONTRIBUTIONS CC, RDC and FMA planned the project and wrote the manuscript. CC, LM, and FM carried out the whole animal experiments. PMN, SW and GTB carried out the behavioural and circadian studies. JCB and CG provided overexpression vector design, construction and methods. LT and CC carried out the transgenic work.
Previous research has suggested that chronic intake of palatable foods and fluids enhances the ac... more Previous research has suggested that chronic intake of palatable foods and fluids enhances the activity of the endogenous opioid system. To examine this suggestion, the effect of naltrexone on food intake was examined in male Long-Evans rats with or without prior exposure to palatable solutions. In Experiment 1, rats were fed laboratory chow alone or laboratory chow and a 32% sucrose solution, and in Experiment 2, were fed chow alone, chow and a 32% Polycose solution, or chow and a 0.15% saccharin solution for three weeks. The sucrose, Polycose, and saccharin solutions were removed 18 h prior to drug administration. Rats then received injections of naltrexone hydrochloride (0.0, 0.3 or 3.0 mg/kg. sc) and chow intakes were measured during the subsequent 1, 2, 4, 6 and 24 h. Naltrexone injections had minimal effects on intakes of animals which previously had consumed only chow. In contrast, naltrexone led to significant dose-related decreases in chow intakes in rats which had previously consumed the sucrose, Polycose, or saccharin solutions. These results provide confirmation for the suggestion that chronic intake of palatable solutions alters the activity of the endogenous opioid system.
Reduction of fat and protein intakes, but not carbohydrate intake following acute and chronic flu... more Reduction of fat and protein intakes, but not carbohydrate intake following acute and chronic fluoxetine in female rats. PHARMACOL BIOCHEM BEHAV 63 (3) 377-385, 1999.-Fluoxetine hydrochloride, a selective serotonin reuptake inhibitor, leads to reductions in food intake and body weight and is under investigation as a possible treatment for obesity. Additionally, it has been suggested that fluoxetine administration could lead to a selective suppression in carbohydrate consumption. Because women more often than men seek weight reduction treatment, the present study examined the acute and chronic effects of fluoxetine on food intake, macronutrient selection, body weight, estrous cycle, and motor activity in female rats. Female Long-Evans rats were provided with separate sources of protein, fat and carbohydrate, and nutrient intakes were recorded following single (5.0, 10.0, and 20.0 mg/kg, IP) and chronic daily (10 mg/kg for 28 days) injections of fluoxetine. Acute and chronic administration of fluoxetine significantly reduced total caloric intake when compared to vehicle treatment. Moreover, fluoxetine significantly suppressed fat and protein intakes, but not carbohydrate intake following both acute and chronic drug administration. Animals chronically treated with fluoxetine gained significantly less weight than animals treated with vehicle. Chronic fluoxetine treatment did not significantly alter estrous cycle. However, in both fluoxetine-and vehicle-treated animals, total caloric intake, and carbohydrate and protein intakes were reduced and fat intake was increased when estrogen levels were high. Fluoxetine significantly reduced motor activity up to 4 h postinjection, and increased motor activity 24 h postinjection.
The central serotonin (5-hydroxytryptamine, 5-HT) system is an established modulator of energy ba... more The central serotonin (5-hydroxytryptamine, 5-HT) system is an established modulator of energy balance. Therefore, it is unsurprising that former (eg D-fenfluramine), current (eg sibutramine), and drug discovery (eg lorcaserin) obesity treatments target serotonin ...
Objective: Obesity is one of the primary healthcare challenges of the 21st century. Signals relay... more Objective: Obesity is one of the primary healthcare challenges of the 21st century. Signals relaying information regarding energy needs are integrated within the brain to influence body weight. Central among these integration nodes are the brain pro-opiomelanocortin (POMC) peptides, perturbations of which disrupt energy balance and promote severe obesity. However, POMC neurons are neurochemically diverse and the crucial source of POMC peptides that regulate energy homeostasis and body weight remains to be fully clarified. Methods: Given that a 5-hydroxytryptamine 2c receptor (5-HT 2C R) agonist is a current obesity medication and 5-HT 2C R agonist's effects on appetite are primarily mediated via POMC neurons, we hypothesized that a critical source of POMC regulating food intake and body weight is specifically synthesized in cells containing 5-HT 2C Rs. To exclusively manipulate Pomc synthesis only within 5-HT 2C R containing cells, we generated a novel 5-HT 2C R CRE mouse line and intercrossed it with Cre recombinase-dependent and hypothalamic specific reactivatable Pomc NEO mice to restrict Pomc synthesis to the subset of hypothalamic cells containing 5-HT 2C Rs. This provided a means to clarify the specific contribution of a defined subgroup of POMC peptides in energy balance and body weight. Results: Here we transform genetically programed obese and hyperinsulinemic male mice lacking hypothalamic Pomc with increased appetite, reduced physical activity and compromised brown adipose tissue (BAT) into lean, healthy mice via targeted restoration of Pomc function only within 5-HT 2C R expressing cells. Remarkably, the same metabolic transformation does not occur in females, who despite corrected feeding behavior and normalized insulin levels remain physically inactive, have lower energy expenditure, compromised BAT and develop obesity. Conclusions: These data provide support for the functional heterogeneity of hypothalamic POMC neurons, revealing that Pomc expression within 5-HT 2C R expressing neurons is sufficient to regulate energy intake and insulin sensitivity in male and female mice. However, an unexpected sex difference in the function of this subset of POMC neurons was identified with regard to energy expenditure. We reveal that a large sex difference in physical activity, energy expenditure and the development of obesity is driven by this subpopulation, which constitutes approximately 40% of all POMC neurons in the hypothalamic arcuate nucleus. This may have broad implications for strategies utilized to combat obesity, which at present largely ignore the sex of the obese individual.
Highlights d Selective 5-HT 2C R NTS neuron activation significantly reduces food intake d 5-HT 2... more Highlights d Selective 5-HT 2C R NTS neuron activation significantly reduces food intake d 5-HT 2C R NTS are sufficient for obesity medication acute appetite suppression d 5-HT 2C R NTS are co-expressed with POMC NTS ; lorcaserin activates POMC NTS cells
<p>Radioactive in situ hybridisation histochemistry analysis of <i>Bscl2</i> mR... more <p>Radioactive in situ hybridisation histochemistry analysis of <i>Bscl2</i> mRNA distribution in coronal section across the rostral-caudal extent of adult mouse brain. Endogenous <i>Bscl2</i> expression was detected throughout the brain, for full characterisation see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045790#pone-0045790-t001" target="_blank">Table 1</a>. (<b>A–O</b>) <sup>35</sup>S-labelled <i>Bscl2</i> expression was detected in the piriform cortex (Pir), olfactory tubercle (Tu), islands of Calleja (ICj), caudate putamen (CP) lateral septal nucleus intermediate part (LSI), medial septal nucleus (MS), nucleus of the vertical limb of the diagonal band (VDB), lateral septal nucleus ventral part (LSV), nucleus of the horizontal limb of the diagonal band (HDB), magnocellular preoptic nucleus (MCPO), ventromedial preoptic nucleus (VMPO), median preoptic nucleus (MnPO), medial preoptic nucleus medial part (MPOM), paraventricular thalamic nucleus (PVA), lateral globus pallidus (LGP), supraoptic nucleus (SO), suprachiasmatic nucleus (SCh), subfornical organ (SFO), paraventricular nucleus of the hypothalamus (PVN), zona incerta (ZI), dorsomedial nucleus of the hypothalamus (DMH), ventromedial nucleus of the hypothalamus (VMH), arcuate nucleus of the hypothalamus (ARC), basomedial amygdaloid nucleus (BMA), medial amygdaloid nucleus (MeA), medial habenular (MHb), pyramidal cell layer of the hippocampus (py), granular layer of the dentate gyrus (GrDG), posterior hypothalamus (PH), supramammilliary nucleus medial part (SuMM), premammillary nucleus ventral part (PMV), nucleus of Darkschewitsch (Dk), Edinger-Westphal nucleus (EW), ventral tegmental area (VTA), dorsal raphe nucleus (DRN), periaqueductal grey (PAG), median raphe nucleus (MnR), lateral parabrachial nucleus (LPBN), dorsal tegmental nucleus (DTg), laterodorsal tegmental nucleus (LDTg), locus coeruleus (LC), Barrington’s nucleus (Bar), medial vestibular nucleus (MVe), ambiguous nucleus (Amb), dorsal vagal complex (DVC), hypoglossal nucleus (12N). Scale bar in (A) represents 1 mm and applies to all other images.</p
Where will the extra compensation come from? Many PIs, especially young ones, are struggling with... more Where will the extra compensation come from? Many PIs, especially young ones, are struggling with obtaining funding. Requiring them to pay more to postdocs would really put the squeeze on them, especially since postdoc minimum salaries were already raised last year. Would it come from the department? Should the NIH give out larger grants? powabiatch Brian: This is a really important question that unfortunately does not have a simple answer that covers everything. Firstly, I want to clarify that the NIH NRSA guidelines ended up not being a part of the Fair Labor Standards Act (FLSA), although several universities (including the UW) increased the salaries for postdocs anyway (although, the increased rates are not guaranteed for postdocs hired since then). When this happened, the Office of the Provost said they would provide funding for PIs who could not afford it given their current grants, demonstrating that the university can step in to help smaller groups.
Chronic disorders of consciousness (DOC) include the vegetative state and the minimally conscious... more Chronic disorders of consciousness (DOC) include the vegetative state and the minimally consciousness state. The DOC diagnosis mainly relies on the evaluation of clinical behavioral scales, electrophysiological testing, and neuroimaging examinations. No specifically effective neurorestorative methods for chronic DOC currently exist. Any valuable exploration therapies of being able to repair functions and/or structures in the consciousness loop (e.g., drugs, hyperbaric medicines, noninvasive neurostimulation, sensory and environmental stimulation, invasive neuromodulation therapy, and cell transplantation) may become effective neurorestorative strategies for chronic DOC. In the viewpoint of Neurorestoratology, this guideline proposes the diagnostic and neurorestorative therapeutic suggestions and future exploration direction for this disease following the review of the existing treatment exploration achievements for chronic DOC.
Drugs activating 5-hydroxytryptamine 2C receptors (5-HT 2C Rs) potently suppress appetite, but th... more Drugs activating 5-hydroxytryptamine 2C receptors (5-HT 2C Rs) potently suppress appetite, but the underlying mechanisms for these effects are not fully understood. To tackle this issue, we generated mice with global 5-HT 2C R deficiency (2C null) and mice with 5-HT 2C Rs re-expression only in pro-opiomelanocortin (POMC) neurons (2C/POMC mice). We show that 2C null mice predictably developed hyperphagia, hyperactivity, and obesity and showed attenuated responses to anorexigenic 5-HT drugs. Remarkably, all these deficiencies were normalized in 2C/POMC mice. These results demonstrate that 5-HT 2C R expression solely in POMC neurons is sufficient to mediate effects of serotoninergic compounds on food intake. The findings also highlight the physiological relevance of the 5-HT 2C R-melanocortin circuitry in the long-term regulation of energy balance.
AimsStanniocalcin‐2 (STC2) has recently been implicated in human muscle mass variability by genet... more AimsStanniocalcin‐2 (STC2) has recently been implicated in human muscle mass variability by genetic analysis. Biochemically, STC2 inhibits the proteolytic activity of the metalloproteinase PAPP‐A, which promotes muscle growth by upregulating the insulin‐like growth factor (IGF) axis. The aim was to examine if STC2 affects skeletal muscle mass and to assess how the IGF axis mediates muscle hypertrophy induced by functional overload.MethodsWe compared muscle mass and muscle fiber morphology between Stc2−/− (n = 21) and wild‐type (n = 15) mice. We then quantified IGF1, IGF2, IGF binding proteins −4 and −5 (IGFBP‐4, IGFBP‐5), PAPP‐A and STC2 in plantaris muscles of wild‐type mice subjected to 4‐week unilateral overload (n = 14).ResultsStc2−/− mice showed up to 10% larger muscle mass compared with wild‐type mice. This increase was mediated by greater cross‐sectional area of muscle fibers. Overload increased plantaris mass and components of the IGF axis, including quantities of IGF1 (by 2...
F1000 - Post-publication peer review of the biomedical literature, 2010
Hypothalamic circuits regulating energy balance are highly plastic and develop in response to nut... more Hypothalamic circuits regulating energy balance are highly plastic and develop in response to nutrient and hormonal cues. To identify processes that could be susceptible to gestational influences in the mouse, we characterized the ontogeny of proopiomelanocortin (POMC) and neuropeptide Y (NPY) populations, which exert opposing influences on food intake and body weight. These analyses revealed that Pomc is broadly expressed in immature hypothalamic neurons and that half of embryonic Pomc-expressing precursors subsequently adopt a non-POMC fate in the adult. Moreover, nearly one quarter of the mature orexigenic NPY population shares a common progenitor with anorexigenic POMC neurons.
F1000 - Post-publication peer review of the biomedical literature, 2010
Genome-wide association studies have identified SNPs within the human FTO gene that display a str... more Genome-wide association studies have identified SNPs within the human FTO gene that display a strong association with obesity. Individuals homozygous for the at-risk rs9939609 A allele weigh 3kg more. Loss of function and/or expression of FTO in mice leads to increased energy expenditure and a lean phenotype. We show here that ubiquitous overexpression of Fto leads to a dose-dependent increase in body and fat mass, irrespective of whether mice are fed a standard or high fat diet. The increased body mass results primarily from increased food intake. Glucose intolerance develops with increased Fto expression on a high fat diet. This study provides the first direct evidence that increased Fto expression causes obesity in mice. AUTHOR CONTRIBUTIONS CC, RDC and FMA planned the project and wrote the manuscript. CC, LM, and FM carried out the whole animal experiments. PMN, SW and GTB carried out the behavioural and circadian studies. JCB and CG provided overexpression vector design, construction and methods. LT and CC carried out the transgenic work.
Previous research has suggested that chronic intake of palatable foods and fluids enhances the ac... more Previous research has suggested that chronic intake of palatable foods and fluids enhances the activity of the endogenous opioid system. To examine this suggestion, the effect of naltrexone on food intake was examined in male Long-Evans rats with or without prior exposure to palatable solutions. In Experiment 1, rats were fed laboratory chow alone or laboratory chow and a 32% sucrose solution, and in Experiment 2, were fed chow alone, chow and a 32% Polycose solution, or chow and a 0.15% saccharin solution for three weeks. The sucrose, Polycose, and saccharin solutions were removed 18 h prior to drug administration. Rats then received injections of naltrexone hydrochloride (0.0, 0.3 or 3.0 mg/kg. sc) and chow intakes were measured during the subsequent 1, 2, 4, 6 and 24 h. Naltrexone injections had minimal effects on intakes of animals which previously had consumed only chow. In contrast, naltrexone led to significant dose-related decreases in chow intakes in rats which had previously consumed the sucrose, Polycose, or saccharin solutions. These results provide confirmation for the suggestion that chronic intake of palatable solutions alters the activity of the endogenous opioid system.
Reduction of fat and protein intakes, but not carbohydrate intake following acute and chronic flu... more Reduction of fat and protein intakes, but not carbohydrate intake following acute and chronic fluoxetine in female rats. PHARMACOL BIOCHEM BEHAV 63 (3) 377-385, 1999.-Fluoxetine hydrochloride, a selective serotonin reuptake inhibitor, leads to reductions in food intake and body weight and is under investigation as a possible treatment for obesity. Additionally, it has been suggested that fluoxetine administration could lead to a selective suppression in carbohydrate consumption. Because women more often than men seek weight reduction treatment, the present study examined the acute and chronic effects of fluoxetine on food intake, macronutrient selection, body weight, estrous cycle, and motor activity in female rats. Female Long-Evans rats were provided with separate sources of protein, fat and carbohydrate, and nutrient intakes were recorded following single (5.0, 10.0, and 20.0 mg/kg, IP) and chronic daily (10 mg/kg for 28 days) injections of fluoxetine. Acute and chronic administration of fluoxetine significantly reduced total caloric intake when compared to vehicle treatment. Moreover, fluoxetine significantly suppressed fat and protein intakes, but not carbohydrate intake following both acute and chronic drug administration. Animals chronically treated with fluoxetine gained significantly less weight than animals treated with vehicle. Chronic fluoxetine treatment did not significantly alter estrous cycle. However, in both fluoxetine-and vehicle-treated animals, total caloric intake, and carbohydrate and protein intakes were reduced and fat intake was increased when estrogen levels were high. Fluoxetine significantly reduced motor activity up to 4 h postinjection, and increased motor activity 24 h postinjection.
The central serotonin (5-hydroxytryptamine, 5-HT) system is an established modulator of energy ba... more The central serotonin (5-hydroxytryptamine, 5-HT) system is an established modulator of energy balance. Therefore, it is unsurprising that former (eg D-fenfluramine), current (eg sibutramine), and drug discovery (eg lorcaserin) obesity treatments target serotonin ...
Objective: Obesity is one of the primary healthcare challenges of the 21st century. Signals relay... more Objective: Obesity is one of the primary healthcare challenges of the 21st century. Signals relaying information regarding energy needs are integrated within the brain to influence body weight. Central among these integration nodes are the brain pro-opiomelanocortin (POMC) peptides, perturbations of which disrupt energy balance and promote severe obesity. However, POMC neurons are neurochemically diverse and the crucial source of POMC peptides that regulate energy homeostasis and body weight remains to be fully clarified. Methods: Given that a 5-hydroxytryptamine 2c receptor (5-HT 2C R) agonist is a current obesity medication and 5-HT 2C R agonist's effects on appetite are primarily mediated via POMC neurons, we hypothesized that a critical source of POMC regulating food intake and body weight is specifically synthesized in cells containing 5-HT 2C Rs. To exclusively manipulate Pomc synthesis only within 5-HT 2C R containing cells, we generated a novel 5-HT 2C R CRE mouse line and intercrossed it with Cre recombinase-dependent and hypothalamic specific reactivatable Pomc NEO mice to restrict Pomc synthesis to the subset of hypothalamic cells containing 5-HT 2C Rs. This provided a means to clarify the specific contribution of a defined subgroup of POMC peptides in energy balance and body weight. Results: Here we transform genetically programed obese and hyperinsulinemic male mice lacking hypothalamic Pomc with increased appetite, reduced physical activity and compromised brown adipose tissue (BAT) into lean, healthy mice via targeted restoration of Pomc function only within 5-HT 2C R expressing cells. Remarkably, the same metabolic transformation does not occur in females, who despite corrected feeding behavior and normalized insulin levels remain physically inactive, have lower energy expenditure, compromised BAT and develop obesity. Conclusions: These data provide support for the functional heterogeneity of hypothalamic POMC neurons, revealing that Pomc expression within 5-HT 2C R expressing neurons is sufficient to regulate energy intake and insulin sensitivity in male and female mice. However, an unexpected sex difference in the function of this subset of POMC neurons was identified with regard to energy expenditure. We reveal that a large sex difference in physical activity, energy expenditure and the development of obesity is driven by this subpopulation, which constitutes approximately 40% of all POMC neurons in the hypothalamic arcuate nucleus. This may have broad implications for strategies utilized to combat obesity, which at present largely ignore the sex of the obese individual.
Highlights d Selective 5-HT 2C R NTS neuron activation significantly reduces food intake d 5-HT 2... more Highlights d Selective 5-HT 2C R NTS neuron activation significantly reduces food intake d 5-HT 2C R NTS are sufficient for obesity medication acute appetite suppression d 5-HT 2C R NTS are co-expressed with POMC NTS ; lorcaserin activates POMC NTS cells
<p>Radioactive in situ hybridisation histochemistry analysis of <i>Bscl2</i> mR... more <p>Radioactive in situ hybridisation histochemistry analysis of <i>Bscl2</i> mRNA distribution in coronal section across the rostral-caudal extent of adult mouse brain. Endogenous <i>Bscl2</i> expression was detected throughout the brain, for full characterisation see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045790#pone-0045790-t001" target="_blank">Table 1</a>. (<b>A–O</b>) <sup>35</sup>S-labelled <i>Bscl2</i> expression was detected in the piriform cortex (Pir), olfactory tubercle (Tu), islands of Calleja (ICj), caudate putamen (CP) lateral septal nucleus intermediate part (LSI), medial septal nucleus (MS), nucleus of the vertical limb of the diagonal band (VDB), lateral septal nucleus ventral part (LSV), nucleus of the horizontal limb of the diagonal band (HDB), magnocellular preoptic nucleus (MCPO), ventromedial preoptic nucleus (VMPO), median preoptic nucleus (MnPO), medial preoptic nucleus medial part (MPOM), paraventricular thalamic nucleus (PVA), lateral globus pallidus (LGP), supraoptic nucleus (SO), suprachiasmatic nucleus (SCh), subfornical organ (SFO), paraventricular nucleus of the hypothalamus (PVN), zona incerta (ZI), dorsomedial nucleus of the hypothalamus (DMH), ventromedial nucleus of the hypothalamus (VMH), arcuate nucleus of the hypothalamus (ARC), basomedial amygdaloid nucleus (BMA), medial amygdaloid nucleus (MeA), medial habenular (MHb), pyramidal cell layer of the hippocampus (py), granular layer of the dentate gyrus (GrDG), posterior hypothalamus (PH), supramammilliary nucleus medial part (SuMM), premammillary nucleus ventral part (PMV), nucleus of Darkschewitsch (Dk), Edinger-Westphal nucleus (EW), ventral tegmental area (VTA), dorsal raphe nucleus (DRN), periaqueductal grey (PAG), median raphe nucleus (MnR), lateral parabrachial nucleus (LPBN), dorsal tegmental nucleus (DTg), laterodorsal tegmental nucleus (LDTg), locus coeruleus (LC), Barrington’s nucleus (Bar), medial vestibular nucleus (MVe), ambiguous nucleus (Amb), dorsal vagal complex (DVC), hypoglossal nucleus (12N). Scale bar in (A) represents 1 mm and applies to all other images.</p
Where will the extra compensation come from? Many PIs, especially young ones, are struggling with... more Where will the extra compensation come from? Many PIs, especially young ones, are struggling with obtaining funding. Requiring them to pay more to postdocs would really put the squeeze on them, especially since postdoc minimum salaries were already raised last year. Would it come from the department? Should the NIH give out larger grants? powabiatch Brian: This is a really important question that unfortunately does not have a simple answer that covers everything. Firstly, I want to clarify that the NIH NRSA guidelines ended up not being a part of the Fair Labor Standards Act (FLSA), although several universities (including the UW) increased the salaries for postdocs anyway (although, the increased rates are not guaranteed for postdocs hired since then). When this happened, the Office of the Provost said they would provide funding for PIs who could not afford it given their current grants, demonstrating that the university can step in to help smaller groups.
Chronic disorders of consciousness (DOC) include the vegetative state and the minimally conscious... more Chronic disorders of consciousness (DOC) include the vegetative state and the minimally consciousness state. The DOC diagnosis mainly relies on the evaluation of clinical behavioral scales, electrophysiological testing, and neuroimaging examinations. No specifically effective neurorestorative methods for chronic DOC currently exist. Any valuable exploration therapies of being able to repair functions and/or structures in the consciousness loop (e.g., drugs, hyperbaric medicines, noninvasive neurostimulation, sensory and environmental stimulation, invasive neuromodulation therapy, and cell transplantation) may become effective neurorestorative strategies for chronic DOC. In the viewpoint of Neurorestoratology, this guideline proposes the diagnostic and neurorestorative therapeutic suggestions and future exploration direction for this disease following the review of the existing treatment exploration achievements for chronic DOC.
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