Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
3,638
result(s) for
"Phillips, Kevin"
Sort by:
The emerging Republican majority : with a new preface by the author
\"One of the most important and controversial books in modern American politics, The Emerging Republican Majority (1969) explained how Richard Nixon won the White House in 1968--and why the Republicans would go on to dominate presidential politics for the next quarter century. Rightly or wrongly, the book has widely been seen as a blueprint for how Republicans, using the so-called Southern Strategy, could build a durable winning coalition in presidential elections. Certainly, Nixon's election marked the end of a \"New Deal Democratic hegemony\" and the beginning of a conservative realignment encompassing historically Democratic voters from the South and the Florida-to-California \"Sun Belt,\" in the book's enduring coinage. In accounting for that shift, Kevin Phillips showed how two decades and more of social and political changes had created enormous opportunities for a resurgent conservative Republican Party. For this new edition, Phillips has written a preface describing his view of the book, its reception, and how its analysis was borne out in subsequent elections.A work whose legacy and influence are still fiercely debated, The Emerging Republican Majority is essential reading for anyone interested in American politics or history. \"-- Provided by publisher.
Book
Asprosin is a centrally acting orexigenic hormone
Asprosin, a recently identified secreted hormone from adipose tissue, acts centrally to promote food intake.
Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood–brain barrier and directly activates orexigenic AgRP
+
neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight. In humans, a genetic deficiency in asprosin causes a syndrome characterized by low appetite and extreme leanness; this is phenocopied by mice carrying similar mutations and can be fully rescued by asprosin. Furthermore, we found that obese humans and mice had pathologically elevated concentrations of circulating asprosin, and neutralization of asprosin in the blood with a monoclonal antibody reduced appetite and body weight in obese mice, in addition to improving their glycemic profile. Thus, in addition to performing a glucogenic function, asprosin is a centrally acting orexigenic hormone that is a potential therapeutic target in the treatment of both obesity and diabetes.
Journal Article
Beige Fat, Adaptive Thermogenesis, and Its Regulation by Exercise and Thyroid Hormone
While it is now understood that the proper expansion of adipose tissue is critically important for metabolic homeostasis, it is also appreciated that adipose tissues perform far more functions than simply maintaining energy balance. Adipose tissue performs endocrine functions, secreting hormones or adipokines that affect the regulation of extra-adipose tissues, and, under certain conditions, can also be major contributors to energy expenditure and the systemic metabolic rate via the activation of thermogenesis. Adipose thermogenesis takes place in brown and beige adipocytes. While brown adipocytes have been relatively well studied, the study of beige adipocytes has only recently become an area of considerable exploration. Numerous suggestions have been made that beige adipocytes can elicit beneficial metabolic effects on body weight, insulin sensitivity, and lipid levels. However, the potential impact of beige adipocyte thermogenesis on systemic metabolism is not yet clear and an understanding of beige adipocyte development and regulation is also limited. This review will highlight our current understanding of beige adipocytes and select factors that have been reported to elicit the development and activation of thermogenesis in beige cells, with a focus on factors that may represent a link between exercise and ‘beiging’, as well as the role that thyroid hormone signaling plays in beige adipocyte regulation.
Journal Article
The Amelioration of Hepatic Steatosis by Thyroid Hormone Receptor Agonists Is Insufficient to Restore Insulin Sensitivity in Ob/Ob Mice
Thyroid hormone receptor (TR) agonists have been proposed as therapeutic agents to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride levels and ameliorated hepatic steatosis. However, the amelioration of fatty liver was not sufficient to improve insulin sensitivity in these mice and reductions in hepatic triglycerides did not correlate with improvements in insulin sensitivity or glycemic control. Instead, the effects of TR activation on glycemia varied widely and were found to depend upon the time of treatment as well as the compound and dosage used. Lower doses of GC-1 were found to further impair glycemic control, while a higher dose of the same compound resulted in substantially improved glucose tolerance and insulin sensitivity, despite all doses being equally effective at reducing hepatic triglyceride levels. Improvements in glycemic control and insulin sensitivity were observed only in treatments that also increased body temperature, suggesting that the induction of thermogenesis may play a role in mediating these beneficial effects. These data illustrate that the relationship between TR activation and insulin sensitivity is complex and suggests that although TR agonists may have value in treating NAFLD, their effect on insulin sensitivity must also be considered.
Journal Article
Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity
The bacterial metalloregulator IscR possesses the unusual ability to direct differential gene expression via specific recognition of two distinct operator motifs in an Fe-S–dependent manner. New work shows that Fe-S binding displaces a residue required for sequence discrimination at the DNA binding interface, revealing a conditional, ligand-mediated mechanism regulating sequence-specific recognition.
IscR from
Escherichia coli
is an unusual metalloregulator in that both apo and iron sulfur (Fe-S)-IscR regulate transcription and exhibit different DNA binding specificities. Here, we report structural and biochemical studies of IscR suggesting that remodeling of the protein-DNA interface upon Fe-S ligation broadens the DNA binding specificity of IscR from binding the type 2 motif only to both type 1 and type 2 motifs. Analysis of an apo-IscR variant with relaxed target-site discrimination identified a key residue in wild-type apo-IscR that, we propose, makes unfavorable interactions with a type 1 motif. Upon Fe-S binding, these interactions are apparently removed, thereby allowing holo-IscR to bind both type 1 and type 2 motifs. These data suggest a unique mechanism of ligand-mediated DNA site recognition, whereby metallocluster ligation relocates a protein-specificity determinant to expand DNA target-site selection, allowing a broader transcriptomic response by holo-IscR.
Journal Article
Wonder Woman
\"From his co-creation, with Marv Wolfman, of THE NEW TEEN TITANS in the 80s and his work on CRISIS ON INFINITE EARTHS and WONDER WOMAN to his mega-successful JLA/AVENGERS, Pérez's work has thrilled comics fans for over three decades. Wonder Woman's first assignment in this new series takes her to Man's World, to teach humanity the ways of the goddess Gaea--no matter who objects. This omnibus collects the start of Perez's acclaimed run on Wonder Woman, presenting a thrilling new vision of the Amazon Warrior\"-- Provided by publisher.
Book
Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy
Intravesical therapy (IVT) is the standard of care to decrease risk of recurrence and progression for high‐grade nonmuscle‐invasive bladder cancer. However, post‐IVT recurrence remains common and the ability to risk‐stratify patients before or after IVT is limited. In this prospectively designed and accrued cohort study, we examine the utility of urinary comprehensive genomic profiling (uCGP) for predicting recurrence risk following transurethral resection of bladder tumor (TURBT) and evaluating longitudinal IVT response. Urine was collected before and after IVT instillation and uCGP testing was done using the UroAmp™ platform. Baseline uCGP following TURBT identified patients with high (61%) and low (39%) recurrence risk. At 24 months, recurrence‐free survival (RFS) was 100% for low‐risk and 45% for high‐risk patients with a hazard ratio (HR) of 9.3. Longitudinal uCGP classified patients as minimal residual disease (MRD) Negative, IVT Responder, or IVT Refractory with 24‐month RFS of 100%, 50%, and 32%, respectively. Compared with MRD Negative patients, IVT Refractory patients had a HR of 10.5. Collectively, uCGP enables noninvasive risk assessment of patients following TURBT and induction IVT. uCGP could inform surveillance cystoscopy schedules and identify high‐risk patients in need of additional therapy. This study used genomic profiling to detect mutations associated with urothelial carcinoma in patient urine samples collected before and after intravesical therapy. Genomic profiles informed an algorithmic assessment of minimal residual disease, which accurately predicted recurrence risk after surgery and quantified molecular response to therapy. These findings demonstrate the utility of genomics to inform personalized risk stratification.
Journal Article