How much exercise you need to keep your New Year's resolutions

If you're among the 40 percent of Americans who say they want to lose weight in 2016, Dr. Jon LaPook breaks down how to reach your goal

From: http://www.cbsnews.com/news/how-much-exercise-you-need-to-keep-your-new-years-resolutions/

Mosquito-borne Zika virus raises fears of birth defects

Rapidly spreading virus is detected in Puerto Rico; outbreak in Brazil has mothers "almost panicky"

From: http://www.cbsnews.com/news/mosquito-borne-zika-virus-found-in-puerto-rico/

Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver

Podoplanin/gp38⁺ stromal cells present in lymphoid organs play a central role in the formation and reorganization of the extracellular matrix and in the functional regulation of immune responses. Gp38⁺ cells are present during embryogenesis and in human livers of primary biliary cirrhosis. Since little is known about their function, we studied gp38⁺ cells during chronic liver inflammation in models of biliary and parenchymal liver fibrosis and steatohepatitis. Gp38⁺ cells were analyzed using flow cytometry and confocal microscopy, and the expression of their steady state and inflammation-associated genes was evaluated from healthy and inflamed livers. Gp38⁺ cells significantly expanded in all three models of liver injury and returned to baseline levels during regression of inflammation. Based on CD133 and gp38 expression in the CD45^–CD31^–Asgpr1^– liver cell fraction, numerous subsets could be identified that were negative for CD133 (gp38^hiCD133^–, gp38^lowCD133^–, and gp38^–CD133^–). Moreover, among the CD133⁺ cells, previously identified as progenitor population in injured liver, two subpopulations could be distinguished based on their gp38 expression (gp38^–CD133⁺ and CD133⁺gp38⁺). Importantly, the distribution of the identified subsets in inflammation illustrated injury-specific changes. Moreover, the gp38⁺CD133⁺ cells exhibited liver progenitor cell characteristics similar to the gp38^–CD133⁺ population, thus representing a novel subset within the classical progenitor cell niche. Additionally, these cells expressed distinct sets of inflammatory genes during liver injury. Our study illuminates a novel classification of the stromal/progenitor cell compartment in the liver and pinpoints a hitherto unrecognized injury-related alteration in progenitor subset composition in chronic liver inflammation and fibrosis.

From: Eckert, C., Kim, Y. O., Julich, H., Heier, E.-C., Klein, N., Krause, E., Tschernig, T., Kornek, M., Lammert, F., Schuppan, D., Lukacs-Kornek, V. http://ajpgi.physiology.org/cgi/content/abstract/310/1/G1?rss=1

PKC{alpha} regulates TMEM16A-mediated Cl- secretion in human biliary cells

TMEM16A is a newly identified Ca²⁺-activated Cl^– channel in biliary epithelial cells (BECs) that is important in biliary secretion. While extracellular ATP stimulates TMEM16A via binding P2 receptors and increasing intracellular Ca²⁺ concentration ([Ca²⁺]_i), the regulatory pathways have not been elucidated. Protein kinase C (PKC) contributes to ATP-mediated secretion in BECs, although its potential role in TMEM16A regulation is unknown. To determine whether PKCα regulates the TMEM16A-dependent membrane Cl^– transport in BECs, studies were performed in human biliary Mz-cha-1 cells. Addition of extracellular ATP induced a rapid translocation of PKCα from the cytosol to the plasma membrane and activation of whole cell Ca²⁺-activated Cl^– currents. Currents demonstrated outward rectification and reversal at 0 mV (properties consistent with TMEM16A) and were inhibited by either molecular (siRNA) or pharmacologic (PMA or Gö6976) inhibition of PKCα. Intracellular dialysis with recombinant PKCα activated Cl^– currents with biophysical properties identical to TMEM16A in control cells but not in cells after transfection with TMEM16A siRNA. In conclusion, our studies demonstrate that PKCα is coupled to ATP-stimulated TMEM16A activation in BECs. Targeting this ATP-Ca²⁺-PKCα signaling pathway may represent a therapeutic strategy to increase biliary secretion and promote bile formation.

From: Dutta, A. K., Khimji, A.-K., Liu, S., Karamysheva, Z., Fujita, A., Kresge, C., Rockey, D. C., Feranchak, A. P. http://ajpgi.physiology.org/cgi/content/abstract/310/1/G34?rss=1

Elevated IL-33 expression is associated with pediatric eosinophilic esophagitis, and exogenous IL-33 promotes eosinophilic esophagitis development in mice

We tested whether the T helper (Th) type 2 (Th2) cell agonist and allergenic ligand IL-33 was associated with eosinophilic esophagitis (EoE) development in a pediatric cohort and whether IL-33 protein could induce disease symptoms in mice. Biopsies from EoE patients or controls were used to measure IL-33 mRNA and protein expression. Increased expression of IL-33 mRNA was found in the esophageal mucosa in EoE. IL-33 protein was detected in cells negative for CD45, mast cells, and epithelial cell markers near blood vessels. Circulating levels of IL-33 were not increased. The time course for IL-33 gene expression was quantified in an established Aspergillus fumigatus allergen mouse model of EoE. Because IL-33 induction was transient in this model and chronicity of IL-33 expression has been demonstrated in humans, naive mice were treated with recombinant IL-33 for 1 wk and esophageal pathology was evaluated. IL-33 application produced changes consistent with phenotypically early EoE, including transmural eosinophilia, mucosal hyperproliferation, and upregulation of eosinophilic genes and chemokines. Th2 cytokines, including IL-13, along with innate lymphoid cell group 2, Th1/17, and M2 macrophage marker genes, were increased after IL-33 application. IL-33-induced eosinophilia was ablated in IL-13 null mice. In addition, IL-33 induced a profound inhibition of the regulatory T cell gene signature. We conclude that IL-33 gene expression is associated with pediatric EoE development and that application of recombinant protein in mice phenocopies the early clinical phase of the human disease in an IL-13-dependent manner. IL-33 inhibition of esophageal regulatory T cell function may induce loss of antigenic tolerance, thereby providing a mechanistic rationale for EoE development.

From: Judd, L. M., Heine, R. G., Menheniott, T. R., Buzzelli, J., O'Brien-Simpson, N., Pavlic, D., O'Connor, L., Al Gazali, K., Hamilton, O., Scurr, M., Collison, A. M., Mattes, J., Allen, K. J., Giraud, A. S. http://ajpgi.physiology.org/cgi/content/abstract/310/1/G13?rss=1

Glucagon-like peptide-1 receptor is present in pancreatic acinar cells and regulates amylase secretion through cAMP

Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone that can act through its receptor (GLP-1R) on pancreatic β-cells and increase insulin secretion and production. GLP-1R agonists are used clinically to treat type 2 diabetes. GLP-1 may also regulate the exocrine pancreas at multiple levels, including inhibition through the central nervous system, stimulation indirectly through insulin, and stimulation directly on acinar cells. However, it has been unclear whether GLP-1R is present in pancreatic acini and what physiological functions these receptors regulate. In the current study we utilized GLP-1R knockout (KO) mice to study the role of GLP-1R in acinar cells. RNA expression of GLP-1R was detected in acutely isolated pancreatic acini. Acinar cell morphology and expression of digestive enzymes were not affected by loss of GLP-1R. GLP-1 induced amylase secretion in wild-type (WT) acini. In GLP-1R KO mice, this effect was abolished, whereas vasoactive intestinal peptide-induced amylase release in KO acini showed a pattern similar to that in WT acini. GLP-1 stimulated cAMP production and increased protein kinase A-mediated protein phosphorylation in WT acini, and these effects were absent in KO acini. These data show that GLP-1R is present in pancreatic acinar cells and that GLP-1 can regulate secretion through its receptor and cAMP signaling pathway.

From: Hou, Y., Ernst, S. A., Heidenreich, K., Williams, J. A. http://ajpgi.physiology.org/cgi/content/abstract/310/1/G26?rss=1

Cephalic phase secretion of insulin and other enteropancreatic hormones in humans

Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans is ambiguous. We studied vagally induced gut hormone responses with and without muscarinic blockade in 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means ± SE; body mass index: 24.0 ± 0.5 kg/m²; HbA_1c: 5.1 ± 0.1%/31.4 ± 0.5 mmol/mol). Cephalic activation was elicited by modified sham feeding (MSF, aka "chew and spit") with or without atropine (1 mg bolus 45 min before MSF + 80 ng·kg^–1·min^–1 for 2 h). To mimic incipient prandial glucose excursions, glucose levels were clamped at 6 mmol/l on all days. The meal stimulus for the MSF consisted of an appetizing breakfast. Participants (9/10) also had a 6 mmol/l glucose clamp without MSF. Pancreatic polypeptide (PP) levels rose from 6.3 ± 1.1 to 19.9 ± 6.8 pmol/l (means ± SE) in response to MSF and atropine lowered basal PP levels and abolished the MSF response. Neither insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), nor glucagon-like peptide-1 (GLP-1) levels changed in response to MSF or atropine. Glucagon and ghrelin levels were markedly attenuated by atropine prior to and during the clamp: at t = 105 min on the atropine (ATR) + clamp (CLA) + MSF compared with the saline (SAL) + CLA and SAL + CLA + MSF days; baseline-subtracted glucagon levels were –10.7 ± 1.1 vs. –4.0 ± 1.1 and –4.7 ± 1.9 pmol/l (means ± SE), P < 0.0001, respectively; corresponding baseline-subtracted ghrelin levels were 303 ± 36 vs. 39 ± 38 and 3.7 ± 21 pg/ml (means ± SE), P < 0.0001. Glucagon and ghrelin levels were unaffected by MSF. Despite adequate PP responses, a cephalic phase response was absent for insulin, glucagon, GLP-1, GIP, and ghrelin.

From: Veedfald, S., Plamboeck, A., Deacon, C. F., Hartmann, B., Knop, F. K., Vilsboll, T., Holst, J. J. http://ajpgi.physiology.org/cgi/content/abstract/310/1/G43?rss=1

Want to lose weight? Fewer Americans say yes

Survey finds more Americans are OK with what they weigh - but that doesn't mean they've gotten slimmer

From: http://www.cbsnews.com/news/want-to-lose-weight-fewer-americans-say-yes/

How to treat your New Year's hangover

Tips to help you detox after the big night out, and get off to a healthier start for 2016

From: http://www.cbsnews.com/news/how-to-treat-your-new-years-hangover/