Primary biliary cirrhosis in classmates

Two former classmates aged 58 with a history of more than 20 years of elevated liver function tests presented to our clinic. As they were both tested positive for antimitochondrial antibodies and liver biopsy showed distinctive bile duct lesions, they were given the diagnosis of primary biliary cirrhosis. To confirm presence of AMAs and subtype of AMAs western blotting was performed showing two distinct bands at 62 kD (PDH-E2) and 48 kD (2ODH-E2) in patient 1 and only one band at 62 kD in patient 2. Searching for potential explanations for this unusual occurence of this rare disease in two close friends a comparison of restriction fragment lengths polymorphism was performed and excluded any familial relationship. Interestingly, histocompatibility leukocyte antigen typing revealed strong similarities as they both shared A2, B51, DR4, DR8 and DR53. These results may point to an unknown environmental factor what caused primary biliary cirrhosis in immunologically susceptible individuals

Dark Energy and Projective Symmetry

Nurowski [arXiv:1003.1503] has recently suggested a link between the observation of Dark Energy in cosmology and the projective equivalence of certain Friedman-Lemaitre-Robertson-Walker (FLRW) metrics. Specifically, he points out that two FLRW metrics with the same unparameterized geodesics have their energy densities differing by a constant. From this he queries whether the existence of dark energy is meaningful. We point out that physical observables in cosmology are not projectively invariant and we relate the projective symmetry uncovered by Nurowski to some previous work on projective equivalence in cosmology

pH-abhängige strukturelle und funktionelle Variationen des ß-Galactosid-bindenden Proteins Galectin-3

Die Zelle besitzt einen komplexen Apparat, um den gerichteten Transport von Proteinen und Lipiden in einem Epithel zu steuern. Zur Aufrechterhaltung der Sortierung wurden Kontrolleure entwickelt, die einem Cargoprotein den richtigen Weg zuweisen. Einer dieser Kontrolleure ist das Protein Galectin-3, welches zur Gruppe der ß-Galactosid-bindenden Proteine gehört und bevorzugt Lactose- bzw. N-Acetyllactosamin-enthaltende Glykoliganden bindet. Als ein wichtiges Sortiersignal wurden unterschiedliche Glykosylierungen identifiziert, die entscheidend für die apikale bzw. basolaterale Zuweisung sind. Es wird vermutet, dass nach Bindung eines Liganden Galectin-3 einen Komplex mit diesem eingeht und durch Assoziation mit gewissen Membranarealen eine Sortierung des Proteins einleitet, wobei ein direkter Beweis bisher noch nicht erbracht wurde. In dieser Arbeit konnten sowohl die Bindung zu komplexen Glykoliganden als auch die Assoziation zu gewissen Membranarealen gezeigt werden, wobei diese Untersuchungen zum ersten Mal in einer nahezu nativen Membran in Form von giant plasma membrane vesicles (GPMVs) durchgeführt wurden. Diese Modellmembran stammte aus dem apikalen Teil von MDCK II Zellen und wurde für die Verwendung mit unterschiedlichen methodischen Fragestellungen etabliert. Die Vesikel zeigten eine Zell-ähnliche Lipid- und Proteinkomposition, wodurch physiologische Prozesse im Vergleich zu anderen Modellen gezielter analysiert werden konnten. So wurde mit den komplex-glyksoylierten Liganden Asialofetuin und dem Neurotrophinrezeptor p75 die Wirkung von Galectin-3 spezifiziert, wobei die Sortierung von Proteinen in der Membran und die Bindungskapazitäten von Galectin-3 als Oligomer untersucht wurden. Galectin-3 kann als einziges Protein der Galectin-Familie hoch-molekulare Cluster mit seinen Liganden eingehen. Es konnte in in vitro Studien die Größe des Clusters mit einem freien Liganden und einen direkten Einfluss der Avidität auf die Interaktion zu komplexen Zuckern beschrieben werden. Die Oligomerisierung fand Liganden-induziert statt, wobei konzentrationsabhängig das Oligomer gezielt geformt oder wieder aufgelöst werden konnte. Da Galectin-3 endosomale Kompartimente durchquert, wurde weiterhin der Einfluss einer azideren Umgebung bei der Interaktion des Proteins zu diversen Liganden analysiert. Es zeigte sich, dass komplexe Liganden die Bindung zu Galectin-3 bei erniedrigtem pH verloren, wohingegen die Bindung zu einfachen Zuckern wie Lactose bestehen blieb. Ebenfalls wurde das Glykolipid Sulfatid als Bindungspartner identifiziert, das gezielt bei erniedrigtem pH an das Protein binden konnte. Diese Spezifitäten ergeben neue Einblicke in die Wirkung von Galectin-3, da sie den Wechsel zwischen Bindung von einem Cargoprotein an der Plasmamembran und Freisetzung in aziden endosomalen Kompartimenten beschreiben können. Zusammengefasst öffnen die Ergebnisse dieser Arbeit neue Einblicke in die Wirkungsweise von Galectin-3-abhängigen Sortierprozessen in epithelialen Zellen

New aspects of postmenopausal osteoporosis treatment with micronized estradiol and progesterone

Objectives: The aim of the study was to assess the effectiveness of postmenopausal osteoporosis treatment with natural sex hormones.Material and methods: The single-blind study included 210 women, randomly allocated to three different groups, with various methods of treatment: Group I (70 controls) received transcutaneous placebo for the course of one year, Group II (70 females, aged 52.2 ± 3.1 years) used oral hormone supplementary therapy (HST), and Group III (70 females, aged 51.9 ± 3.5 years) received transcutaneous modified hormone replacement therapy (MHRT), supplemented with intravaginal lutein, dietary minerals, and 1000 IU of vitamin D3/day.Results: No increase in bone mineral density was observed in the control group. However, mineral density of the vertebral bodies was significantly higher after 3 and 5 years in the HST group (p < 0.05), and after 1 year in the MHRT group (p < 0.01). This increase was even more significant (p < 0.001) after 3 and 5 years in the MHRT group.Conclusions: Transcutaneous hormone therapy with micronized estradiol and progesterone is the treatment of choice in postmenopausal osteoporosis, as evidenced by bone mineral density and biochemical markers

Effects of extreme weather events on child mood and behavior

Extreme weather events (EWEs) are increasing in frequency and severity as the planet continues to become warmer. Resulting disasters have the potential to wreak havoc on the economy, infrastructure, family unit, and human health. Global estimates project that children will be disproportionately impacted by the changing climate – shouldering 88% of the related burdens. Exposure to EWEs in childhood is traumatic, with ramifications for mental health specifically. Symptoms of posttraumatic stress, depression, and anxiety have all been associated with childhood EWE exposure and have the potential to persist under certain circumstances. Conversely, many childhood survivors of EWE also demonstrate resilience and experience only transient symptoms. While the majority of studies are focused on the effects resulting from one specific type of disaster (hurricanes), we have synthesized the literature across the various types of EWEs. We describe psychological symptoms and behavior, the potential for long-term effects, and potential protective factors and risk factors

Infotropism as the underlying principle of perceptual organization

Whether perceptual organization favors the simplest or most likely interpretation of a distal stimulus has long been debated. An unbridgeable gulf has seemed to separate these, the Gestalt and Helmholtzian viewpoints. But in recent decades, the proposal that likelihood and simplicity are two sides of the same coin has been gaining ground, to the extent that their equivalence is now widely assumed. What then arises is a desire to know whether the two principles can be reduced to one. Applying Occam's Razor in this way is particularly desirable given that, as things stand, an account referencing one principle alone cannot be completely satisfactory. The present paper argues that unification of the two principles is possible, and that it can be achieved in terms of an incremental notion of `information seeking' (infotropism). Perceptual processing that is infotropic can be shown to target both simplicity and likelihood. The ability to see perceptual organization as governed by either objective can then be explained in terms of it being an infotropic process. Infotropism can be identified as the principle which underlies, and thus generalizes the principles of likelihood and simplicity

Long-Range Chromosomal Mapping of the Carcinoembryonic Antigen (CEA) Gene Family Cluster

A long-range physical map of the carcinoembryonic antigen (CEA) gene family cluster, which is located on the long arm of chromosome 19, has been constructed. This was achieved by hybridization analysis of large DNA fragments separated by pulse-field gel electrophoresis and of DNA from human/rodent somatic cell hybrids, as well as the assembly of ordered sets of cosmids for this gene region into contigs. The different approaches yielded very similar results and indicate that the entire gene family is contained within a region located at position 19q13.1–q13.2 between the CYP2A and the D19S15/D19S8 markers. The physical linkage of nine genes belonging to the CEA subgroup and their location with respect to the pregnancy-specific glycoprotein (PSG) subgroup genes have been determined, and the latter are located closer to the telomere. From large groups of ordered cosmid clones, the identity of all known CEA subgroup genes has been confirmed either by hybridization using gene-specific probes or by DNA sequencing. These studies have identified a new member of the CEA subgroup (CGM8), which probably represents a pseudogene due to the existence of two stop codons, one in the leader and one in the N-terminal domain exons. The gene order and orientation, which were determined by hybridization with probes from the 5′ and 3′ regions of the genes, are as follows: cen/3′-CGM7-5′/3′-CGM2-5′/5′-CEA-3′/5′-NCA-3′/5′- CGM1-3′/3′-BGP-5′/3′-CGM9-5′/3′-CGM6-5′/5′-CGM8-3′/PSGcluster/qter

Influence of Selenium on Oxidative Stress in Athletes. Review Article.

The aim of the study was to analyze the influence of selenium (Se) on the course of oxidative stress in trained athletes, on the basis of own former published studies and the reference of literature. In a number of references it was shown that the application of Se led to the diminishing of oxidative stress during the physical exercises in athletes. The application of Se to athletes − led to the increase of peroxidase glutathione the main selen − dependent enzyme. The fact of increased concentration of malondialdehyde (MDA) in blood serum, the main metabolite of lipid peroxidation can indirectly evidence about the intensity of physical endurance. This increase is significantly smaller in individuals taking exogenous antioxidative diet supplement containing Se. Moreover there is the evidence that oxidative muscles damage during physical effort could be diminished by compounds with antioxidative properties. Taking into consideration, the obtained results by many of authors empower to the conclusion that application of Se diminishes the degree of peroxidation of lipids in trained athletes