Stuart Maudsley

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..In this overview, we shall attempt to assist the navigation into this new field of cell signaling and highlight several methodologies and technologies to appreciate this exciting new age of signal transduction...

..Euglycemic agents targeting hypothalamic and energy regulation dysfunction in HD could potentially alter disease progression and improve quality of life in HD...

..Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD...

..We used VIP knockout mice to investigate VIP's specific role in taste perception and connection to energy regulation...

..EX-4-Tf proved to be as effective as EX-4 but had longer lived effects on blood glucose and food intake. This novel transferrin fusion technology could improve the pharmacology of various peptides...

..We have investigated transcriptional activation of pathways related to cognitive function in the cortex of the aged mouse by analyzing gene expression following water maze training...

..Our paradigm indicates how cellular physiology can subtly change in different contexts and potentially aid the appreciation of stress response adaptations...

..Our findings should aid LTQ users who desire to explore iTRAQ quantitative proteomics but have limited access to the more costly Orbitrap or other instruments...

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..These results suggest that the enhancement of cognitive function by lifelong exercise is associated with an altered transcriptional profile following learning...

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..Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact...

..It is likely that in the near future, therapeutics with combinatorial neuroprotective and 'eumetabolic' activities may possess superior efficacies compared to less pluripotent remedies...

..Based on our results, we suggest that SILAC experiments should be designed to incorporate label-swap replications for enhanced reliability in expression ratios...

..Our study aims to establish a plasma biomarker analysis workflow, with fewer fractionation steps, for enhanced identification of plasma biomarkers by precursor ion exclusion (PIE)...

..This study highlights the potential for such a program in fields such as pharmacology, genomics, and bioinformatics...

..We have therefore summarized the evidence supporting a central direct role of GnRH ligands and receptors in controlling central nervous physiology and pathophysiology...

..We undertook the current study to investigate if intraislet endogenous cannabinoids (ECs) regulate β-cell proliferation and if they influence insulin action...

..These results indicate that amitriptyline has significant beneficial actions in aged and damaged AD brains and that it shows promise as a tolerable novel therapeutic for the treatment of AD...

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..While not a classical drug target, even with minimal levels of beneficial modulation, its multifactorial efficacy may amplify small effects resulting in significant therapeutic efficacy...

..Our data indicates that components of peroxide-induced ERK1/2 cascades are differentially affected by repeated exposures, indicating that oxidative signaling may be contextually variable...

..Together, these findings suggest a novel paracrine mechanism for the hormonal modulation of taste function in mammals...

..Currently, Class II-based drugs include synthesized analogs of vasoactive intestinal peptide for type 2 diabetes or parathyroid hormone for osteoporosis...

..The development of our understanding of the role of the tachykinin receptor-ligand system in higher order central functions is likely to allow the creation of more specific and selective tachykinin-related neurotherapeutics...

..We will also discuss the potential pharmacotherapeutic role of GSH-R1a-mediated ghrelin signaling for the treatment of complex neuroendocrine disorders...

..Together, our findings contribute to furthering the understanding of the relationships between plasma BDNF, structural brain integrity and cognition. Potential mechanisms mediating these relationships merit further investigation...

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..Therefore treatment of both the peripheral and central pathophysiologies of HD could form the basis of a more effective HD therapeutic strategy...

..Similarly to Huntington's disease patients, mice expressing the mutated human huntingtin protein also exhibit neurodegenerative changes, motor dysfunction, perturbed energy metabolism, and elevated blood glucose levels...

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..The functional interaction of these transcriptional 'programs' may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity...

..Textrous!, therefore, is able to facilitate the output of quantitatively significant and easily appreciable semantic words and phrases linked to both individual gene and batch genomic data...

..Our Pancreas++ analysis was significantly faster than other methods, while still retaining low error rates and a high degree of result correlation with the manually generated reference standard...

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..AT(1A)R-deficient mice live longer and have lower levels of oxidative stress than wild-type mice (Benigni et al., 2009), suggesting a role for AT(1A)R signaling in the aging process...

..Our results indicate that miR-519 promotes DNA damage, alters Ca(2+) homeostasis, and enhances energy production; together, these processes elevate the expression level of p21, promoting growth inhibition and cell survival...

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..In this respect, physical activity may promote neuronal resilience by reducing inflammation...

..g., phosphopeptides). The higher energy fragmentation pathway of PQD on peptide fragmentation was further compared to those of CID and the quadrupole-type activation in parallel experiments...

..It is clear even from the relatively sparse experimental RTK BRET evidence that there is tremendous potential for this technological application for the functional investigation of RTK biology...

..These findings show a neuroprotective role for Sirt1 in mammalian Huntington's disease models and open new avenues for the development of neuroprotective strategies in Huntington's disease...

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..Behavioral and pharmacological manipulations that enhance 5-HT and BDNF signaling could help promote healthy brain aging...

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..As a more comprehensive understanding of the complexity of GPCR signaling is developed, the rational design of ligands possessing increased specific efficacy and attenuated side effects may become the standard mode of drug development...

..Therefore, despite acute and selective ablation of FSH expression the gonadotrophs were able to recover in adulthood, suggesting that perinatal estrogenic exposure was only temporarily deleterious...

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..LSI has been used successfully to formulate new hypotheses, generate novel connections from existing data, and validate empirical data...

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..However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues...

..Our results show that there are significant alterations in numerous receptor/cell signaling proteins in cortical lipid rafts isolated from 3xTgAD mice...

..A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders...

..Gaining a greater appreciation of how flavor perception is linked to peripheral metabolism could lead to novel therapeutic strategies for obesity and lifestyle-related diseases...

..As a more comprehensive understanding of the complexity of GPCR signaling is developed, the rational design of ligands possessing increased specific efficacy and attenuated side effects may become the standard mode of drug development...

..A modest increase in citric acid taste sensitivity in these knockout mice suggests GLP-1 signaling may modulate sour taste, as well. Together, these findings suggest a novel paracrine mechanism for the regulation of taste function...

..Understanding the positioning of the EGFR within the neurometabolic domain will enhance our appreciation of the ability of this receptor system to underpin highly complex physiological paradigms such as aging and neurodegeneration...

..The impaired glucose tolerance was reversible and was not associated with alterations in the levels of adipokines or BDNF...

..Gaining a greater understanding of how bone health is affected in individuals with D/ID could lead to better customized treatments for these specific populations...

..These results indicate that SDF1α, sFRP1, and VEGFD are major components of SDIA and suggest the potential use of these defined factors to elicit DA differentiation of pluripotent human stem cells for therapeutic intervention in PD...

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..In conclusion, the A(2A)R is increased across different iron-insufficient conditions. The relation between A(2A)R and cellular iron status may be an important pathway by which adenosine may alter the function of the dopaminergic system...

..A better understanding of the cellular and molecular mechanisms by which class II GPCRs signaling modulates neuronal survival and plasticity will likely lead to novel therapeutic interventions for neurodegenerative disorders...

..Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminate novel therapeutic avenues for the treatment of AD and other neurodegenerative disorders...

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..These results suggest that the GIP-R is ubiquitated, resulting in downregulation of the actions of GIP...