Brown and beige adipocytes are mitochondria-enriched cells capable of dissipating energy in the form of heat. These thermogenic fat cells were originally considered to function solely in heat ...generation through the action of the mitochondrial protein uncoupling protein 1 (UCP1). In recent years, significant advances have been made in our understanding of the ontogeny, bioenergetics and physiological functions of thermogenic fat. Distinct subtypes of thermogenic adipocytes have been identified with unique developmental origins, which have been increasingly dissected in cellular and molecular detail. Moreover, several UCP1-independent thermogenic mechanisms have been described, expanding the role of these cells in energy homeostasis. Recent studies have also delineated roles for these cells beyond the regulation of thermogenesis, including as dynamic secretory cells and as a metabolic sink. This Review presents our current understanding of thermogenic adipocytes with an emphasis on their development, biological functions and roles in systemic physiology.
Cervical cancer Cohen, Paul A; Jhingran, Anjua; Oaknin, Ana ...
The Lancet (British edition),
01/2019, Letnik:
393, Številka:
10167
Journal Article
Recenzirano
Each year, more than half a million women are diagnosed with cervical cancer and the disease results in over 300 000 deaths worldwide. High-risk subtypes of the human papilloma virus (HPV) are the ...cause of the disease in most cases. The disease is largely preventable. Approximately 90% of cervical cancers occur in low-income and middle-income countries that lack organised screening and HPV vaccination programmes. In high-income countries, cervical cancer incidence and mortality have more than halved over the past 30 years since the introduction of formal screening programmes. Treatment depends on disease extent at diagnosis and locally available resources, and might involve radical hysterectomy or chemoradiation, or a combination of both. Conservative, fertility-preserving surgical procedures have become standard of care for women with low-risk, early-stage disease. Advances in radiotherapy technology, such as intensity-modulated radiotherapy, have resulted in less treatment-related toxicity for women with locally-advanced disease. For women with metastatic or recurrent disease, the overall prognosis remains poor; nevertheless, the incorporation of the anti-VEGF agent bevacizumab has been able to extend overall survival beyond 12 months. Preliminary results of novel immunotherapeutic approaches, similarly to other solid tumours, have shown promising results so far.
Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin resistance, which collectively ...contribute to the development of cardiovascular diseases and resultant morbidity and mortality. Forty-two percent of adults in the United States are obese, and a total of 1.9 billion adults worldwide are overweight or obese. These alarming numbers, which continue to climb, represent a major health and economic burden. Adipose tissue is a highly dynamic organ that can be classified based on the cellular composition of different depots and their distinct anatomical localization. Massive expansion and remodeling of adipose tissue during obesity differentially affects specific adipose tissue depots and significantly contributes to vascular dysfunction and cardiovascular diseases. Visceral adipose tissue accumulation results in increased immune cell infiltration and secretion of vasoconstrictor mediators, whereas expansion of subcutaneous adipose tissue is less harmful. Therefore, fat distribution more than overall body weight is a key determinant of the risk for cardiovascular diseases. Thermogenic brown and beige adipose tissue, in contrast to white adipose tissue, is associated with beneficial effects on the vasculature. The relationship between the type of adipose tissue and its influence on vascular function becomes particularly evident in the context of the heterogenous phenotype of perivascular adipose tissue that is strongly location dependent. In this review, we address the abnormal remodeling of specific adipose tissue depots during obesity and how this critically contributes to the development of hypertension, endothelial dysfunction, and vascular stiffness. We also discuss the local and systemic roles of adipose tissue derived secreted factors and increased systemic inflammation during obesity and highlight their detrimental impact on cardiovascular health.
Escherichia coli is a single species consisting of many biotypes, some of which are commensal colonizers of mammals and others that cause disease. Humans are colonized on average with five commensal ...biotypes, and it is widely thought that the commensals serve as a barrier to infection by pathogens. Previous studies showed that a combination of three pre-colonized commensal E. coli strains prevents colonization of E. coli O157:H7 in a mouse model (Leatham, et al., 2010, Infect Immun 77: 2876-7886). The commensal biotypes included E. coli HS, which is known to successfully colonize humans at high doses with no adverse effects, and E. coli Nissle 1917, a human commensal strain that is used in Europe as a preventative of traveler's diarrhea. We hypothesized that commensal biotypes could exert colonization resistance by consuming nutrients needed by E. coli O157:H7 to colonize, thus preventing this first step in infection. Here we report that to colonize streptomycin-treated mice E. coli HS consumes six of the twelve sugars tested and E. coli Nissle 1917 uses a complementary yet divergent set of seven sugars to colonize, thus establishing a nutritional basis for the ability of E. coli HS and Nissle 1917 to occupy distinct niches in the mouse intestine. Together these two commensals use the five sugars previously determined to be most important for colonization of E. coli EDL933, an O157:H7 strain. As predicted, the two commensals prevented E. coli EDL933 colonization. The results support a model in which invading pathogenic E. coli must compete with the gut microbiota to obtain the nutrients needed to colonize and establish infection; accordingly, the outcome of the challenge is determined by the aggregate capacity of the native microbiota to consume the nutrients required by the pathogen.
The epidemic of obesity and type 2 diabetes has increased interest in pathways that affect energy balance in mammalian systems. Brown fat, in all of its dimensions, can increase energy expenditure ...through the dissipation of chemical energy in the form of heat, using mitochondrial uncoupling and perhaps other pathways. We discuss here some of the thermodynamic and cellular aspects of recent progress in brown fat research. This includes studies of developmental lineages of UCP1(+) adipocytes, including the discovery of beige fat cells, a new thermogenic cell type. We also discuss the physiology and transcriptional control of brown and beige cells in rodents and the state of current knowledge about human brown fat.
Available for the first time in English, The Color of the Third Degree uncovers the still-hidden history of police torture in the Jim Crow South. Based on a wide array of previously neglected ...archival sources, Silvan Niedermeier argues that as public lynching decreased, less visible practices of racial subjugation and repression became central to southern white supremacy. In an effort to deter unruly white mobs, as well as oppress black communities, white southern law officers violently extorted confessions and testimony from black suspects and defendants in jail cells and police stations to secure speedy convictions. In response, black citizens and the NAACP fought to expose these brutal practices through individual action, local organizing, and litigation. In spite of these efforts, police torture remained a widespread, powerful form of racial control and suppression well into the late twentieth century. The first historical study of police torture in the American South, Niedermeier draws attention to the willing acceptance of violent coercion by prosecutors, judges, and juries, and brings to light the deep historical roots of police violence against African Americans, one of the most urgent and distressing issues of our time.
Harold Cohen and AARON Cohen, Paul
The AI magazine,
12/2016, Letnik:
37, Številka:
4
Journal Article
Recenzirano
Harold Cohen (1928–2016) was a computer art pioneer and the developer of AARON, one of the most creative AI programs in daily use. This memoriam, written by his son (and AI scientist) Paul, describes ...Harold Cohen's work and contributions to the AI and art communities. — ed.
One of the most promising areas in the therapeutics for metabolic diseases centers around activation of the pathways of energy expenditure. Brown adipose tissue is a particularly appealing target for ...increasing energy expenditure, given its amazing capacity to transform chemical energy into heat. In addition to classical brown adipose tissue, the last few years have seen great advances in our understanding of inducible thermogenic adipose tissue, also referred to as beige fat. A deeper understanding of the molecular processes involved in the development and function of these cell types may lead to new therapeutics for obesity, diabetes, and other metabolic diseases.
Cell biology of fat storage Cohen, Paul; Spiegelman, Bruce M
Molecular biology of the cell,
08/2016, Letnik:
27, Številka:
16
Journal Article
Recenzirano
Odprti dostop
The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in ...the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion. Brown fat, on the other hand, dissipates chemical energy in the form of heat, thereby defending against hypothermia, obesity, and diabetes. It is now appreciated that there are two distinct types of thermogenic fat cells, termed brown and beige adipocytes. In addition to these distinct properties of fat cells, adipocytes exist within adipose tissue, where they are in dynamic communication with immune cells and closely influenced by innervation and blood supply. This review is intended to serve as an introduction to adipose cell biology and to familiarize the reader with how these cell types play a role in metabolic disease and, perhaps, as targets for therapeutic development.
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