The nuclear receptor family of PPARs was named for the ability of the original member to induce hepatic peroxisome proliferation in mice in response to xenobiotic stimuli. However, studies on the action and structure of the 3 human PPAR isotypes (PPARalpha, PPARdelta, and PPARgamma) suggest that these moieties are intimately involved in nutrient sensing and the regulation of carbohydrate and lipid metabolism. PPARalpha and PPARdelta appear primarily to stimulate oxidative lipid metabolism, while PPARgamma is principally involved in the cellular assimilation of lipids via anabolic pathways. Our understanding of the functions of PPARgamma in humans has been increased by the clinical use of potent agonists and by the discovery of both rare and severely deleterious dominant-negative mutations leading to a stereotyped syndrome of partial lipodystrophy and severe insulin resistance, as well as more common sequence variants with a much smaller impact on receptor function. These may nevertheless have much greater significance for the public health burden of metabolic disease. This Review will focus on the role of PPARgamma in human physiology, with specific reference to clinical pharmacological studies, and analysis of PPARG gene variants in the abnormal lipid and carbohydrate metabolism of the metabolic syndrome.

Pain often exists in the absence of observable injury; therefore, the gold standard for pain assessment has long been self-report. Because the inability to verbally communicate can prevent effective pain management, research efforts have focused on the development of a tool that accurately assesses pain without depending on self-report. Those previous efforts have not proven successful at substituting self-report with a clinically valid, physiology-based measure of pain. Recent neuroimaging data suggest that functional magnetic resonance imaging (fMRI) and support vector machine (SVM) learning can be jointly used to accurately assess cognitive states. Therefore, we hypothesized that an SVM trained on fMRI data can assess pain in the absence of self-report. In fMRI experiments, 24 individuals were presented painful and nonpainful thermal stimuli. Using eight individuals, we trained a linear SVM to distinguish these stimuli using whole-brain patterns of activity. We assessed the performance of this trained SVM model by testing it on 16 individuals whose data were not used for training. The whole-brain SVM was 81% accurate at distinguishing painful from non-painful stimuli (p


Human Physiology Book By Chatterjee Free 143


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Ahara being one of the Upasthambha supports our Shareera for day to day activities and acts as Bala and Prakriti Dayaka, When it is consumed by following the rules and regulations. Wrong diet methods which are widely followed in this modern era result into Ajirna (Indigestion) which is the source of many diseases. Charakokta Ahara Vidhi Vidhana is not only a scientific method to maintain physical health but also to Maintain good mental health which results into proper digestion of the food which inturn promotes health and prevents many diseases. An attempt is made here to understand the physiology behind these rules and regulations and how they affect the process of digestion.

We also discuss what exactly is going on in the brain when we feel fearful and how something as simple as getting outside and looking at the horizon can completely change our physiology and powerfully inhibit anxiety.

Humans possess certain unique mental traits. Self-reflection, as well as ethic and aesthetic values, is among them, constituting an essential part of what we call the human condition. The human mental machinery led our species to have a self-awareness but, at the same time, a sense of justice, willing to punish unfair actions even if the consequences of such outrages harm our own interests. Also, we appreciate searching for novelties, listening to music, viewing beautiful pictures, or living in well-designed houses. But why is this so? What is the meaning of our tendency, among other particularities, to defend and share values, to evaluate the rectitude of our actions and the beauty of our surroundings? What brain mechanisms correlate with the human capacity to maintain inner speech, or to carry out judgments of value? To what extent are they different from other primates' equivalent behaviors?

In the Light of Evolution Volume VII aims to survey what has been learned about the human "mental machinery." This book is a collection of colloquium papers from the Arthur M. Sackler Colloquium "The Human Mental Machinery," which was sponsored by the National Academy of Sciences on January 11-12, 2013. The colloquium brought together leading scientists who have worked on brain and mental traits. Their 16 contributions focus the objective of better understanding human brain processes, their evolution, and their eventual shared mechanisms with other animals. The articles are grouped into three primary sections: current study of the mind-brain relationships; the primate evolutionary continuity; and the human difference: from ethics to aesthetics. This book offers fresh perspectives coming from interdisciplinary approaches that open new research fields and constitute the state of the art in some important aspects of the mind-brain relationships.

Interpretive Summary: Concerns have been raised that using beef cattle manure to amend croplands increases amount of antimicrobial resistant bacteria inthese soils. If the increases persist until crops are planted this could increase food-animal and human exposures to antimicrobialresistant bacteria through feed and produce. At three farms (one each in Nebraska, North Dakota, and South Dakota) croplandswere amended with either: beef cattle manure, inorganic fertilizer, or were not amended (control). Manure amendment did not change the levels of all 8 antimicrobial resistance bacteria measured. Manure amendment did not increase levels for 8 of the 10 antimicrobial resistance genes measured. For the other two antimicrobial resistance genes, AMR increases in manure amendment croplands only occurred at one location, were transient, and generally were within the abundance ranges observed for control croplands. Thus, we conclude that the common practice in U.S. Upper Midwest of region of land applying beef cattle manure likely has minimal impact on environmental antimicrobial resistance levels, feed safety, food safety, animal health, and human health.

Technical Abstract: Concerns exist that beef cattle manure amendment may increase antimicrobial resistance (AMR) in cropland soils and persist over time, potentially increasing food-animal and human exposure via feed and produce. Manure and soil contain many types of antibiotic-resistant bacteria. However, zoonotic pathogens and fecal indicators are most directly linked to human disease and environmental surveillance efforts. We measured the levels of eight antimicrobial resistant zoonotic pathogens and fecal indicators at experimental farms at three locations: Nebraska (silt loam), North Dakota (silty clay), and South Dakota (silty clay loam). Each location had four treatments: beef cattle manure, beef cattle manure with corn stover bedding, inorganic fertilizer, and unamended control. Tetracycline-resistant (TETr), nalidixic- acid resistant, and third-generation cephalosporin-resistant (3GCr) Salmonella enterica were not detected in any cropland samples. Treatments did not significantly affect cropland levels of TETr Escherichia coli, trimethoprim-sulfamethoxazole-resistant E. coli, 3GCr E. coli, TETr Enterococcus spp., or erythromycin-resistant Enterococcus. Additionally, levels of 10 antimicrobial resistance genes (ARGs) were assessed in all soil samples. Except for erm(B) and tet(M) at Nebraska, ARG increases after manure application dissipated before planting occurred. Treatment did not affect the following ARGs: aac(6)-Ie-aph(2)-Ia, aadA1, blaCMY-2, blaCTX-M, mecA, tet(A), and tet(B). The replicated experimental design, quantification data, and paired genotypic and phenotypic information collected for this study can be used to inform risk assessment models. The common US Upper Midwest practice of land applying beef cattle manure in fall does not result in significantly higher levels of the AMR tested in spring cropland soils.

Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor predisposition syndrome Neurofibromatosis-1 (NF1), with different propensities to develop nervous system cancers. We show that central and peripheral nervous system neurons from mice with tumor-causing Nf1 gene mutations exhibit hyperexcitability and increased secretion of activity-dependent tumor-promoting paracrine factors. We discovered a neurofibroma mitogen (COL1A2) produced by peripheral neurons in an activity-regulated manner, which increases NF1-deficient Schwann cell proliferation, establishing that neurofibromas are regulated by neuronal activity. In contrast, mice with the Arg1809Cys Nf1 mutation, found in NF1 patients lacking neurofibromas or optic gliomas, do not exhibit neuronal hyperexcitability or develop these NF1-associated tumors. The hyperexcitability of tumor-prone Nf1-mutant neurons results from reduced NF1-regulated hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function, such that neuronal excitability, activity-regulated paracrine factor production, and tumor progression are attenuated by HCN channel activation. Collectively, these findings reveal that NF1 mutations act at the level of neurons to modify tumor predisposition by increasing neuronal excitability and activity-regulated paracrine factor production.

N2 - Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor predisposition syndrome Neurofibromatosis-1 (NF1), with different propensities to develop nervous system cancers. We show that central and peripheral nervous system neurons from mice with tumor-causing Nf1 gene mutations exhibit hyperexcitability and increased secretion of activity-dependent tumor-promoting paracrine factors. We discovered a neurofibroma mitogen (COL1A2) produced by peripheral neurons in an activity-regulated manner, which increases NF1-deficient Schwann cell proliferation, establishing that neurofibromas are regulated by neuronal activity. In contrast, mice with the Arg1809Cys Nf1 mutation, found in NF1 patients lacking neurofibromas or optic gliomas, do not exhibit neuronal hyperexcitability or develop these NF1-associated tumors. The hyperexcitability of tumor-prone Nf1-mutant neurons results from reduced NF1-regulated hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function, such that neuronal excitability, activity-regulated paracrine factor production, and tumor progression are attenuated by HCN channel activation. Collectively, these findings reveal that NF1 mutations act at the level of neurons to modify tumor predisposition by increasing neuronal excitability and activity-regulated paracrine factor production. be457b7860

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