Pathogenesis of Helicobacter pylori Infection

The clinical outcome of Helicobacter pylori infection is determined by a complex scenario of interactions between the bacterium and the host. The main bacterial factors associated with colonization and pathogenicity comprise outer membrane proteins including BabA, SabA, OipA, AlpA/B, as well as the virulence factors CagA in the cag pathogenicity island ( cag PAI) and the vacuolating cytotoxin VacA. The multitude of these proteins and allelic variation makes it extremely difficult to test the contribution of each individual factor. Much effort has been put into identifying the mechanism associated with H. pylori -associated carcinogenesis. Interaction between bacterial factors such as CagA and host signal transduction pathways seems to be critical for mediating the induction of membrane dynamics, actin-cytoskeletal rearrangements and the disruption of cell-to-cell junctions as well as proliferative, pro-inflammatory and antiapoptotic nuclear responses. An animal model using the Mongolian gerbil is a useful system to study the gastric pathology of H. pylori infection.     

Osmoregulation and expression of ion transport proteins and putative claudins in the gill of southern flounder (Paralichthys lethostigma)

The southern flounder is a euryhaline teleost that inhabits ocean, estuarine, and riverine environments. We investigated the osmoregulatory strategy of juvenile flounder by examining the time-course of homeostatic responses, hormone levels, and gill Na(+),K(+)-ATPase and Na(+),K(+),2Cl(-) cotransporter protein expression after salinity challenge. Transfer of freshwater (FW)-acclimated flounder to sea water (SW) induced an increase in plasma osmolality and cortisol and a decrease in muscle water content, plasma insulin-like growth factor I (IGF-I) and hepatic IGF-I mRNA, all returning to control levels after 4 days. Gill Na(+),K(+)-ATPase and Na(+),K(+),2Cl(-) cotransporter protein levels were elevated in response to SW after 4 days. Transfer of SW-acclimated flounder to FW reduced gill Na(+),K(+)-ATPase and Na(+),K(+),2Cl(-) cotransporter protein, increased plasma IGF-I, but did not alter hepatic IGF-I mRNA or plasma cortisol levels. Gill claudin-3 and claudin-4 immunoreactive proteins were elevated in FW versus SW acclimated flounder. The study demonstrates that successful acclimation of southern flounder to SW or FW occurs after an initial crisis period and that the salinity adaptation process is associated with changes in branchial expression of ion transport and putative tight junction claudin proteins known to regulate epithelial permeability in mammalian vertebrates.     

Predicting renal graft failure using multivariate longitudinal profiles

Patients who have undergone renal transplantation are monitored longitudinally at irregular time intervals over 10 years or more. This yields a set of biochemical and physiological markers containing valuable information to anticipate a failure of the graft. A general linear, generalized linear, or nonlinear mixed model is used to describe the longitudinal profile of each marker. To account for the correlation between markers, the univariate mixed models are combined into a multivariate mixed model (MMM) by specifying a joint distribution for the random effects. Due to the high number of markers, a pairwise modeling strategy, where all possible pairs of bivariate mixed models are fitted, is used to obtain parameter estimates for the MMM. These estimates are used in a Bayes rule to obtain, at each point in time, the prognosis for long-term success of the transplant. It is shown that allowing the markers to be correlated can improve this prognosis.     

Oxidatively damaged DNA and its repair after experimental exposure to wood smoke in healthy humans

Particulate matter from wood smoke may cause health effects through generation of oxidative stress with resulting damage to DNA. We investigated oxidatively damaged DNA and related repair capacity in peripheral blood mononuclear cells (PBMC) and measured the urinary excretion of repair products after controlled short-term exposure of human volunteers to wood smoke. Thirteen healthy adults were exposed first to clean air and then to wood smoke in a chamber during 4h sessions, 1 week apart. Blood samples were taken 3h after exposure and on the following morning, and urine was collected after exposure, from bedtime until the next morning. We measured the levels of DNA strand breaks (SB), oxidized purines as formamidopyrimidine-DNA-glycosylase (FPG) sites and activity of oxoguanine glycosylase 1 (hOGG1) in PBMC by the comet assay, whereas mRNA levels of hOGG1, nucleoside diphosphate linked moiety X-type motif 1 (hNUDT1) and heme oxygenase 1 (hHO1) were determined by real-time RT-PCR. The excretion of 8-oxo-7,8-dihydro-oxoguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in urine was measured by high performance liquid chromatography purification followed by gas chromatography with mass spectrometry. The morning following exposure to wood smoke the PBMC levels of SB were significantly decreased and the mRNA levels of hOGG1 significantly increased. FPG sites, hOGG1 activity, expression of hNUDT1 and hHO1, urinary excretion of 8-oxodG and 8-oxoGua did not change significantly. Our findings support that exposure to wood smoke causes systemic effects, although we could not demonstrate genotoxic effects, possibly explained by enhanced repair and timing of sampling.     

The allene oxide cyclase family of Arabidopsis thaliana: localization and cyclization

Jasmonates are derived from oxygenated fatty acids (oxylipins) via the octadecanoid pathway and are characterized by a pentacyclic ring structure. They have regulatory functions as signaling molecules in plant development and adaptation to environmental stress. Recently, we solved the structure of allene oxide cyclase 2 (AOC2) of Arabidopsis thaliana, which is, together with the other three AOCs, a key enzyme in the biosynthesis of jasmonates, in that it releases the first cyclic and biologically active metabolite -- 12-oxo-phytodienoic acid (OPDA). On the basis of models for the bound substrate, 12,13(S)-epoxy-9(Z),11,15(Z)-octadecatrienoic acid, and the product, OPDA, we proposed that a conserved Glu promotes the reaction by anchimeric assistance. According to this hypothesis, the transition state with a pentadienyl carbocation and an oxyanion is stabilized by a strongly bound water molecule and favorable pi-pi interactions with aromatic residues in the cavity. Stereoselectivity results from steric restrictions to the necessary substrate isomerizations imposed by the protein environment. Here, site-directed mutagenesis was used to explore and verify the proposed reaction mechanism. In a comparative analysis of the AOC family from A. thaliana involving enzymatic characterization, in vitro import, and transient expression of AOC-enhanced green fluorescent protein fusion proteins for analysis of subcellular targeting, we demonstrate that all four AOC isoenzymes may contribute to jasmonate biosynthesis, as they are all located in chloroplasts and, in concert with the allene oxide synthase, they are all able to convert 13(S)-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid into enantiomerically pure cis(+)-OPDA.     

Radiocarbon dating of the human eye lens crystallines reveal proteins without carbon turnover throughout life

Background

Lens crystallines are special proteins in the eye lens. Because the epithelial basement membrane (lens capsule) completely encloses the lens, desquamation of aging cells is impossible, and due to the complete absence of blood vessels or transport of metabolites in this area, there is no subsequent remodelling of these fibers, nor removal of degraded lens fibers. Human tissue ultimately derives its ¹⁴C content from the atmospheric carbon dioxide. The ¹⁴C content of the lens proteins thus reflects the atmospheric content of ¹⁴C when the lens crystallines were formed. Precise radiocarbon dating is made possible by comparing the ¹⁴C content of the lens crystallines to the so-called bomb pulse, i.e. a plot of the atmospheric ¹⁴C content since the Second World War, when there was a significant increase due to nuclear-bomb testing. Since the change in concentration is significant even on a yearly basis this allows very accurate dating.

Methodology/Principal Findings

Our results allow us to conclude that the crystalline formation in the lens nucleus almost entirely takes place around the time of birth, with a very small, and decreasing, continuous formation throughout life. The close relationship may be further expressed as a mathematical model, which takes into account the timing of the crystalline formation.

Conclusions/Significance

Such a life-long permanence of human tissue has hitherto only been described for dental enamel. In confront to dental enamel it must be held in mind that the eye lens is a soft structure, subjected to almost continuous deformation, due to lens accommodation, yet its most important constituent, the lens crystalline, is never subject to turnover or remodelling once formed. The determination of the ¹⁴C content of various tissues may be used to assess turnover rates and degree of substitution (for example for brain cell DNA). Potential targets may be nervous tissues in terms of senile or pre-senile degradation, as well as other highly specialised structures of the eyes. The precision with which the year of birth may be calculated points to forensic uses of this technique.     

Lessons Learnt from Spatially Resolved Electro‐ and Photoluminescence Imaging: Interfacial Delamination in CH3NH3PbI3 Planar Perovskite Solar Cells upon Illumination

The influence of illumination on the long‐term performance of planar structured perovskite solar cells (PSCs) is investigated using fast and spatially resolved luminescence imaging. The authors analyze the effect of illuminated current density–voltage (J–V) and light‐soaking measurements on pristine PSCs by providing visual evidence for the spatial inhomogeneous evolution of device performance. Regions that are exposed to light initially produce stronger electroluminescence signals than surrounding unilluminated regions, mainly due to a lower contact resistance and, possibly, higher charge collection efficiency. Over a period of several days, however, these initially illuminated regions appear to degrade more quickly despite the device being stored in a dark, moisture‐ and oxygen‐free environment. Using transmission electron microscopy, this accelerated degradation is attributed to delamination between the perovskite and the titanium dioxide (TiO₂) layer. An ion migration mechanism is proposed for this delamination process, which is in accordance with previous current–voltage hysteresis observations. These results provide evidence for the intrinsic instability of CH₃NH₃PbI₃‐based devices under illumination and have major implications for the design of PSCs from the standpoint of long‐term performance and stability.     

Seasonal migration strategies of Common Ringed Plovers Charadrius hiaticula

How individual birds schedule their movements and use different sites during the non‐breeding season are fundamental issues in avian migration ecology, and studies have often revealed strong seasonal variation in such strategies. Using geolocators we tracked Common Ringed Plovers Charadrius hiaticula from northern Norway to West Africa and back to assess whether there were differences in migratory speed, duration and stopover use between autumn and spring migration and whether birds used multiple sites during the non‐breeding season. Although the pace of migration was similar between autumn and spring, the length of flight bouts and duration of the preceding stopovers were positively correlated only in autumn. Four of five birds showed a marked southward movement in mid‐winter.     

Individuality of distress and discomfort calls in neonates with bass voices: Wild‐living goitred gazelles (Gazella subgutturosa) and saiga antelopes (Saiga tatarica)

Neonate ruminants produce distress calls when captured by a predator and discomfort milk begging calls when hungry. In many neonate ruminants, the distress and discomfort calls are high‐frequency vocalizations, in which the fundamental frequency is the key variable for recognition of their emotional arousal by caregivers. In contrast, in this study, we examine the low‐frequency open‐mouth distress and discomfort calls in the neonates of two species of wild‐living ungulates, which clearly highlight vocal tract resonances (formants). In the goitred gazelle (Gazella subgutturosa), the distress calls were higher in fundamental frequency (f0) and in the first and third formants than the discomfort calls. The accuracy of classifying individuals by variables of distress calls with discriminant function analysis (67%) was significantly lower than that of discomfort calls (85%). In the saiga (Saiga tatarica), only the third formant was higher in the distress calls than in the discomfort calls. The accuracy of classifying individuals by variables of distress calls (89%) did not differ significantly from that of discomfort calls (94%). Thus, the use of acoustic cues to vocal identity and to the degree of arousal differs between the two species. Calls were significantly more individualistic in the saiga, probably because this species lives in large herds and neonates use a ‘following’ antipredatory strategy, in which vocal individuality is crucial for mother–offspring communication. In contrast, goitred gazelles live in smaller groups and neonates use a ‘hiding’ antipredatory strategy. Accordingly, mothers can rely on additional environmental cues for spotting their young and this may decrease the necessity for individualization of the calls of neonates.