Calcium (Ca2+) is a key player in the regulation of many cell functions. Just like Ca2+, mitochondria are ubiquitous, versatile, and dynamic players in determining both cell survival and death decisions. Given their ubiquitous nature, the regulation of both is deeply intertwined, whereby Ca2+ regulates mitochondrial functions, while mitochondria shape Ca2+ dynamics. Deregulation of either Ca2+ or mitochondrial signaling leads to abnormal function, cell damage or even cell death, thereby contributing to muscle dysfunction or cardiac pathologies. Moreover, altered mitochondrial Ca2+ homeostasis has been linked to metabolic diseases like cancer, obesity, and pulmonary hypertension. In this review article, we summarize the mechanisms that coordinate mitochondrial and Ca2+ responses and how they affect human health. © 2017 American Physiological Society. Compr Physiol 7:623-634, 2017.

Helicobacter pylori (H. pylori) infection is the major risk factor associated with the development of gastric cancer. The transition from normal mucosa to non-atrophic gastritis, triggered primarily by H. pylori infection, initiates precancerous lesions which may then progress to atrophic gastritis and intestinal metaplasia. Further progression to dysplasia and gastric cancer is generally believed to be attributable to processes that no longer require the presence of H. pylori. The responses that develop upon H. pylori infection are directly mediated through the action of bacterial virulence factors, which drive the initial events associated with transformation of infected gastric cells. Besides genetic and to date poorly defined environmental factors, alterations in gastric cell stress-adaptive mechanisms due to H. pylori appear to be crucial during chronic infection and gastric disease progression. Firstly, H. pylori infection promotes gastric cell death and reduced epithelial cell turnover in the majority of infected cells, resulting in primary tissue lesions associated with an initial inflammatory response. However, in the remaining gastric cell population, adaptive responses are induced that increase cell survival and proliferation, resulting in the acquisition of potentially malignant characteristics that may lead to precancerous gastric lesions. Thus, deregulation of these intrinsic survival-related responses to H. pylori infection emerge as potential culprits in promoting disease progression. This review will highlight the most relevant cellular adaptive mechanisms triggered upon H. pylori infection, including endoplasmic reticulum stress and the unfolded protein response, autophagy, oxidative stress, and inflammation, together with a subsequent discussion on how these factors may participate in the progression of a precancerous lesion. Finally, this review will shed light on how these mechanisms may be exploited as pharmacological targets, in the perspective of opening up new therapeutic alternatives for non-invasive risk control in gastric cancer.

The placenta mediates maternal-fetal exchange and has historically been regarded as a passive conduit for nutrients. However, emerging evidence suggests that the placenta actively responds to nutritional and metabolic signals from the mother and the fetus. We propose that the placenta integrates a multitude of maternal and fetal nutritional cues with information from intrinsic nutrient-sensing signaling pathways to match fetal demand with maternal supply by regulating maternal physiolo-

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Obesity in pregnancy is associated with increased fetal growth and adiposity, which, in part, is determined by transplacental nutrient supply. Trophoblast uptake and intracellular trafficking of lipids are dependent on placental fatty acid transport proteins (FATP), translocase (FAT/CD36), and fatty acid binding proteins (FABP). We hypothesized that maternal obesity in mice leads to increased placental expression of FAT/CD36, FATPs, and FABPs, and lipid accumulation in the fetal liver. C57/BL6J female mice were fed either a control (C; n = 10) or an obesogenic (OB; n = 10) high-fat, high-sugar diet before mating and throughout pregnancy. At E18.5, placentas and fetal livers were collected. Trophoblast plasma membranes (TPM) were isolated from placental homogenates. Expression of FAT/CD36 and FATP (TPM) and FABP (homogenates) was determined by immunoblotting. Gene expression was assessed by RT-quantitative PCR. Sections of fetal livers were stained for Oil Red O, and lipid droplets were quantified. TPM protein expression of FAT/CD36, FATP 2, and FATP 4 was comparable between C and OB groups. Conversely, TPM FATP 6 expression was increased by 35% in OB compared with C placentas without changes in mRNA expression. FABPs 1, 3-5 and PPARγ were expressed in homogenates, and FABP 3 expression increased 27% in OB compared with C placentas; however, no changes were observed in mRNA expression. Lipid droplet accumulation was 10-fold higher in the livers of fetuses from OB compared with C group. We propose that increased lipid transport capacity in obese mice promotes transplacental fatty acid transport and contributes to excess lipid accumulation in the fetal liver.

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The plasma membrane distribution and related biological activity of nucleoside transporter proteins (NTs) were investigated in human syncytiotrophoblast from term placenta using a variety of approaches, including nucleoside uptake measurements into vesicles from selected plasma membrane domains, NT immunohistochemistry, and subcellular localization (basal, heavy, and light apical membranes as well as raft-enriched membranes from the apical domain). In contrast with other epithelia, in this epithelium, we have identified the high-affinity pyrimidine-preferring human concentrative nucleoside transporter (hCNT) 1 as the only hCNT-type protein expressed at both the basal and apical membranes. hCNT1 localization in lipid rafts is also dependent on its subcellular localization in the apical plasma membrane, suggesting a complex cellular and regional expression. Overall, this result favors the view that the placenta is a pyrimidine-preferring nucleoside sink from both maternal and fetal sides, and hCNT1 plays a major role in promoting pyrimidine salvage and placental growth. This finding may be of pharmacological relevance, because hCNT1 is known to interact with anticancer nucleoside-derived drugs and other molecules, such as nicotine and caffeine, for which a great variety of harmful effects on placental and fetal development, including intrauterine growth retardation, have been reported.

Data quality is a difficult notion to define precisely, and different communities have different views and understandings of the subject. This causes confusion, a lack of harmonization of data across communities and omission of vital quality information. For some existing data infrastructures, data quality standards cannot address the problem adequately and cannot fulfil all user needs or cover all concepts of data quality. In this study, we discuss some philosophical issues on data quality. We identify actual user needs on data quality, review existing standards and specifications on data quality, and propose an integrated model for data quality in the field of Earth observation (EO). We also propose a practical mechanism for applying the integrated quality information model to a large number of datasets through metadata inheritance. While our data quality management approach is in the domain of EO, we believe that the ideas and methodologies for data quality management can be applied to wider domains and disciplines to facilitate quality-enabled scientific research.