Therapeutic targets for bone metastases in breast cancer

Breast cancer is prone to metastasize to bone. Once metastatic cells are in the bone marrow, they do not, on their own, destroy bone. Instead, they alter the functions of bone-resorbing (osteoclasts) and bone-forming cells (osteoblasts), resulting in skeletal complications that cause pathological fractures and pain. In this review, we describe promising molecular bone-targeted therapies that have arisen from recent advances in our understanding of the pathogenesis of breast cancer bone metastases. These therapies target osteoclasts (receptor activator of nuclear factor kB ligand, integrin αvβ3, c-Src, cathepsin K), osteoblasts (dickkopf-1, activin A, endothelin A) and the bone marrow microenvironment (transforming growth factor β, bone morphogenetic proteins, chemokine CXCL-12 and its receptor CXCR4). The clinical exploitation of these bone-targeted agents will provide oncologists with novel therapeutic strategies for the treatment of skeletal lesions in breast cancer

Widespread Endogenization of Genome Sequences of Non-Retroviral RNA Viruses into Plant Genomes

Non-retroviral RNA virus sequences (NRVSs) have been found in the chromosomes of vertebrates and fungi, but not plants. Here we report similarly endogenized NRVSs derived from plus-, negative-, and double-stranded RNA viruses in plant chromosomes. These sequences were found by searching public genomic sequence databases, and, importantly, most NRVSs were subsequently detected by direct molecular analyses of plant DNAs. The most widespread NRVSs were related to the coat protein (CP) genes of the family Partitiviridae which have bisegmented dsRNA genomes, and included plant- and fungus-infecting members. The CP of a novel fungal virus (Rosellinia necatrix partitivirus 2, RnPV2) had the greatest sequence similarity to Arabidopsis thaliana ILR2, which is thought to regulate the activities of the phytohormone auxin, indole-3-acetic acid (IAA). Furthermore, partitivirus CP-like sequences much more closely related to plant partitiviruses than to RnPV2 were identified in a wide range of plant species. In addition, the nucleocapsid protein genes of cytorhabdoviruses and varicosaviruses were found in species of over 9 plant families, including Brassicaceae and Solanaceae. A replicase-like sequence of a betaflexivirus was identified in the cucumber genome. The pattern of occurrence of NRVSs and the phylogenetic analyses of NRVSs and related viruses indicate that multiple independent integrations into many plant lineages may have occurred. For example, one of the NRVSs was retained in Ar. thaliana but not in Ar. lyrata or other related Camelina species, whereas another NRVS displayed the reverse pattern. Our study has shown that single- and double-stranded RNA viral sequences are widespread in plant genomes, and shows the potential of genome integrated NRVSs to contribute to resolve unclear phylogenetic relationships of plant species

The proximate composition of three marine pelagic fish: blue whiting (Micromesistius poutassou), boarfish (Capros aper) and Atlantic herring (Clupea harengus)

peer reviewedThis study presents data from an in-depth proximate compositional analysis of three marine fish species: blue whiting (Micromesistius poutassou), boarfish (Capros aper) and Atlantic herring (Clupea harengus). These fish contained significant amounts of protein (16–17%), lipids (4–11%) and minerals (2–6% ash). The proteins, particularly from boarfish, had close to optimum amino acid profiles for human and fish nutrition. They compared favourably with other fish species in terms of total lipids and relative concentration of the omega-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid (11.8–13.3% and 5.9–8.1% in triacylglycerols [TG] and 24.6–35.4% and 5.8–12.0% in phospholipids [PL]). Atlantic herring had the highest lipid content among the three fish and was found to contain high levels of PL poly-unsaturated fatty acids, including omega-3 fatty acids. Minerals detected in the fish included calcium (272–1,520 mg/100 g), phosphorus (363–789 mg/100 g), iron (1.07–2.83 mg/100 g), magnesium (40.70–62.10 mg/100 g), potassium (112.00–267.00 mg/100 g), selenium (0.04–0.06 mg/100 g), sodium (218.00–282.00 mg/100 g) and zinc (1.29–5.57 mg/100 g). Boarfish had the highest ash fraction and also the highest levels of all the minerals, except potassium. Atlantic herring had considerably lower mineral content compared with the other two species and, levels detected were also lower than those reported in previously published studies. Heavy metals contents were quantified, and levels were significantly below the maximum allowable limits for all elements except arsenic, which ranged from 1.34 to 2.44 mg/kg in the three fish species. Data outlined here will be useful for guiding product development. Future studies would benefit from considering catch season, sex and developmental stage of the fish

Inclusion complexes of α-cyclodextrins with poly(d,l-lactic acid) : structural, characterization, and glass transition dynamics

Poly (d,l-lactic acid) (PDLLA) was combined with α-CD to form inclusion complexes (ICs) with distinct PDLLA fractions. The structural changes resulting from this coalescence process were analyzed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), and X-ray diffraction (XRD). The presence of both components in the ICs was confirmed byFTIR. The encapsulated PDLLA fraction was quantified by 1H NMR. XRD data evidenced that it was possible to transform the amorphous PDLLA into a well-organized channel-type crystalline structure. DSC showed that the glass transition temperature of the PDLLA fraction in the ICs was higher than in the pure polymer, indicating that the ultra-confinement effect imposed by the ICs organization clearly limits PDLLA molecular dynamics. The confinement effect on the glass transition dynamics was investigated by unconventional dynamic mechanical analysis experiments, which confirmed that ICs segmental mobility is highly restricted when compared with the one of pure PDLLA. Bulk PDLLA presents a typical VFTH behavior while the ICs dynamics shows an Arrhenius trend.Portuguese Foundation for Science and Technology (FCT) for financial support through the PTDC/FIS/115048/2009 project and to the NMR Portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support to the Research Centre, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)]