The role of tumor microenvironment in prostate cancer bone metastasis

Prostate cancer (PCa) epithelial cells require a number of factors to facilitate their establishment and growth at a distant site of metastasis. Their ability to adapt to their microenvironment, proliferate and recruit an underlying stroma is integral to the survival and growth of the metastasis. PCa predominantly metastasizes to the bone, and bone metastases are the main cause of morbidity. The bone marrow provides a permissive environment for the formation of a metastasis. In some cases, the cells may remain dormant for some time, eventually proliferating in response to an unknown "trigger." The marrow is rich in progenitor cells that differentiate into numerous cell types, producing new blood vessels, supporting fibroblasts, and an underlying extracellular matrix (ECM) that form the reactive stroma. By secreting a number of cytokines, growth factors and proteases they recruit auxiliary cells required to produce a functional stroma. These components are involved in a reciprocal interaction between the stroma and the PCa cells, allowing for the growth and survival of the tumor. Left unchecked, once a PCa tumor has established itself in the bone marrow it will eventually replace the marrow, interrupting bone homeostasis and typically promoting an osteoblastic response in the bone including osteoclastic events. The abundant deposition of new woven bone results in nerve compression, bone pain and an increase in fractures in patients with PCa bone metastases. This review will examine the tumor microenvironment, its role in facilitating tumor dissemination, growth and the resultant pathologies associated with PCa bone metastasis.     

Treatment of Helicobacter pylori infection 2012

Helicobacter pylori resistance rates to antibiotics vary in different countries and even in different regions of the same country. Choice of treatment is strongly dependent on antibiotic resistance rates. In some countries, triple therapy with a proton-pump inhibitor, amoxicillin, and clarithromycin is still the best option, but eradication results fall short of what would be desired (90-95%) in countries with clarithromycin resistance >20%, bismuth-containing quadruple therapy, or nonbismuth sequential or concomitant therapies may then be the preferred option. Newer antibiotic regimens are awaited. Vaccination would be the best option, especially for developing countries, but little progress has been made in designing a vaccine.     

Prevalence and identity of Cryptosporidium spp. in pig slurry

Cryptosporidium spp. were detected in 25 of 56 pig slurry samples from 33 Irish farms by PCR and DNA sequencing. The organisms detected included C. suis, Cryptosporidium pig genotype II, and C. muris. We concluded that Cryptosporidium oocysts can persist in treated slurry and potentially contaminate surface water through improper discharge or uncontrolled runoff.     

Biologically inspired control of physically simulated bipeds

Summary The basic rhythmicity underlying animal locomotion is created by dedicated neural structures called central pattern generators (CPGs). We describe the implementation of such structures in simulation and their successful use for the control of bipedal walking. Artificial evolution (in the form of genetic algorithms) is used as the optimisation procedure. Two CPG types are illustrated, the more advanced of which being based on recent theoretical findings on the nature of neural architectures required to drive animal locomotion. It is shown that CPGs in conjunction with simple reflex responses as well as an appropriate mechanical implementation of the biped are capable of producing stable walking patterns on planar surfaces. This finding corroborates circumstantial experimental evidence that limited bipedal locomotion is possible without the employment of higher level control centres.     

Epigenome dysregulation in cholangiocarcinoma

Epigenomics is a fast-evolving field of research that has lately attracted considerable interest, mainly due to the reversibility of epigenetic marks. Clinically, among solid tumors, the field is still limited. In cholangiocarcinoma (CCA) it is well known that the epigenetic landscape is deregulated both during carcinogenesis and disease progression as a consequence of aberrant mechanisms leading to genome instability. In this article, we will briefly review the molecular alterations that have been described in the transformation of normal cholangiocytes into malignant derivatives, focusing on the role of non-coding RNA (ncRNA) interactions, DNA methylation, post-translational modifications (PTMs) of histones and chromatin remodeling complexes.     

Natural and Modified (1→3)-β-D-Glucans in Health Promotion and Disease Alleviation

ABSTRACT

A number of polysaccharides with β -glycosidic linkage are widespread in nature in a variety of sources. All have a common structure and the (1→3)-β-D-glucan backbone is essential. They have attracted attention over the years because of their bioactive and medicinal properties. In many cases their functional role is a mystery, in others it is well established. Because of their insoluble chemical nature, particulate (1→3)-β-D-glucans are not suitable for many medical applications. Various methods of changing or modifying the β-D-glucan chemical structure and transforming it to a soluble form have been published. The β-D-glucan bioactive properties can be affected positively or negatively by such modifications. This review examines β-glucan sources in nature, health effects and structure-activity relationships. It presents the current state of β-D-glucan solubilization methods and discusses their effectiveness and application possibilities for the future.     

Identification of major histocompatibility complex genes in the guppy,Poecilia reticulata

The guppy, Poecilia reticulata, a teleostean fish of the order Cyprinodontiformes, has been used extensively in studies of host-parasite interactions, courtship behavior, and mating preference, as well as in ecological and evolutionary genetics. A related species was among the first poikilotherm vertebrates to be used in the study of histocompatibility genes. All these studies could benefit from the identification and characterization of the guppy major histocompatibility complex (Mhc) genes. Here, both class I and class II genes of the guppy are described. The number of expressed loci, as determined by representation of clones in a cDNA library, sequencing, and Southern blot analysis, may be low in both Mhc classes: combined evidence suggests that there may be one expressed class II locus only and one or two expressed class I loci. The variability of aquaristic guppy stocks is very low: only three and two genes have been detected at the class I and class II loci, respectively, in the stocks examined. This genetic paucity is most likely the consequence of breeding practices employed by aquarists and commercial establishments. Limited sampling of wild guppy populations revealed extensive Mhc polymorphism at loci of both classes in nature. Comparison of guppy Mhc sequences with those of other vertebrates has revealed the existence of a set of insertions/deletions which can be used as characters in cladistic analysis to infer phylogenetic relationships among vertebrate taxa and the Mhc genes themselves. These indels are particularly frequent in the regions coding for the loops of 1 and 2 domains of class I proteins.The nucleotide sequence data reported in this publication have been submitted to the EMBL nucleotide sequence database and have been assigned the accession numbers Z54076-Z54095