Chloroplast genome variation in upland and lowland switchgrass

Switchgrass (Panicum virgatum L.) exists at multiple ploidies and two phenotypically distinct ecotypes. To facilitate interploidal comparisons and to understand the extent of sequence variation within existing breeding pools, two complete switchgrass chloroplast genomes were sequenced from individuals representative of the upland and lowland ecotypes. The results demonstrated a very high degree of conservation in gene content and order with other sequenced plastid genomes. The lowland ecotype reference sequence (Kanlow Lin1) was 139,677 base pairs while the upland sequence (Summer Lin2) was 139,619 base pairs. Alignments between the lowland reference sequence and short-read sequence data from existing sequence datasets identified as either upland or lowland confirmed known polymorphisms and indicated the presence of other differences. Insertions and deletions principally occurred near stretches of homopolymer simple sequence repeats in intergenic regions while most Single Nucleotide Polymorphisms (SNPs) occurred in intergenic regions and introns within the single copy portions of the genome. The polymorphism rate between upland and lowland switchgrass ecotypes was found to be similar to rates reported between chloroplast genomes of indica and japonica subspecies of rice which were believed to have diverged 0.2-0.4 million years ago.     

Electrostatic potential of nucleotide-free protein is sufficient for discrimination between adenine and guanine-specific binding sites

Despite sharing many common features, adenine-binding and guanine-binding sites in proteins often show a clear preference for the cognate over the non-cognate ligand. We have analyzed electrostatic potential (ESP) patterns at adenine and guanine-binding sites of a large number of non-redundant proteins where each binding site was first annotated as adenine/guanine-specific or non-specific from a survey of primary literature. We show that more than 90% of ESP variance at the binding sites is accounted for by only two principal component ESP vectors, each aligned to molecular dipoles of adenine and guanine. Projected on these principal component vectors, the adenine/guanine-specific and non-specific binding sites, including adenine-containing dinucleotides, show non-overlapping distributions. Adenine or guanine specificities of the binding sites also show high correlation with the corresponding electrostatic replacement (cognate by non-cognate ligand) energies. High correlation coefficients (0.94 for 35 adenine-binding sites and 1.0 for 20 guanine-binding sites) were obtained when adenine/guanine specificities were predicted using the replacement energies. Our results demonstrate that ligand-free protein ESP is an excellent indicator for discrimination between adenine and guanine-specific binding sites and that ESP of ligand-free protein can be used as a tool to annotate known and putative purine-binding sites in proteins as adenine or guanine-specific.     

Osteosarcoma with cutaneous metastases. A case report

BACKGROUND: Osteosarcomas, despite their aggressive nature and propensity to metastasize, only rarely give rise to skin deposits. CASE: We report a case of a femoral osteosarcoma in which cutaneous scalp and neck metastases developed 3 years after treatment of the primary disease. Fine needle aspiration was pivotal in diagnosing the secondary disease. CONCLUSION: Only 8 instances of cutaneous metastases from an osteosarcoma have been previously reported. We recommend early investigation of such nodules with fine needle aspiration cytology and inclusion of multiagent chemotherapy as part of the treatment protocol in all patients with osteosarcoma.     

Phytoremediation of metals using lemongrass (Cymbopogon citratus (D.C.) Stapf.) grown under different levels of red mud in soil amended with biowastes

Due to hostile condition of red mud (RM), its utilization for vegetation is restricted. Therefore, RM with biowastes as soil amendment may offer suitable combination to support plant growth with reduced risk of metal toxicity. To evaluate the effects of RM on soil properties, plant growth performance, and metal accumulation in lemongrass, a study was conducted using different RM concentrations (0, 5, 10, and 15% w/w) in soil amended with biowastes [cow dung manure (CD) or sewage-sludge (SS)]. Application of RM in soil with biowastes improved organic matter and nutrient contents and caused reduction in phytoavailable metal contents. Total plant biomass was increased under all treatments, maximally at 5% RM in soil with SS (91.4%) and CD (51.7%) compared to that in control (no RM and biowastes). Lemongrass acted as a potential metal-tolerant plant as its metal tolerance index is >100%. Based on translocation and bioconcentration factors, lemongrass acted as a potential phytostabilizer of Fe, Mn, and Cu in roots and was found efficient in translocation of Al, Zn, Cd, Pb, Cr, As, and Ni from roots to shoot. The study suggests that 5% RM with biowastes preferably SS may be used to enhance phytoremediation potential of lemongrass.     

Human Epidermal Growth Factor Receptor 2 (HER2) Impedes MLK3 Kinase Activity to Support Breast Cancer Cell Survival

Human epidermal growth factor receptor 2 (HER2) is amplified in ∼15–20% of human breast cancer and is important for tumor etiology and therapeutic options of breast cancer. Up-regulation of HER2 oncogene initiates cascades of events cumulating to the stimulation of transforming PI3K/AKT signaling, which also plays a dominant role in supporting cell survival and efficacy of HER2-directed therapies. Although investigating the underlying mechanisms by which HER2 promotes cell survival, we noticed a profound reduction in the kinase activity of a pro-apoptotic mixed lineage kinase 3 (MLK3) in HER2-positive (HER2+) but not in HER2-negative (HER2−) breast cancer tissues, whereas both HER2+ and HER2− tumors expressed a comparable level of MLK3 protein. Furthermore, the kinase activity of MLK3 was inversely correlated with HER2+ tumor grades. Moreover, HER2-directed drugs such as trastuzumab and lapatinib as well as depletion of HER2 or HER3 stimulated MLK3 kinase activity in HER2+ breast cancer cell lines. In addition, the noted inhibitory effect of HER2 on MLK3 kinase activity was mediated via its phosphorylation on Ser⁶⁷⁴ by AKT and that pharmacological inhibitors of PI3K/AKT prevented trastuzumab- and lapatinib-induced stimulation of MLK3 activity. Consistent with the pro-apoptotic function of MLK3, stable knockdown of MLK3 in the HER2+ cell line blunted the pro-apoptotic effects of trastuzumab and lapatinib. These findings suggest that HER2 activation inhibits the pro-apoptotic function of MLK3, which plays a mechanistic role in mediating anti-tumor activities of HER2-directed therapies. In brief, MLK3 represents a newly recognized integral component of HER2 biology in HER2+ breast tumors.