Effect of bio-engineering on size, shape, composition and rigidity of bacterial microcompartments

Bacterial microcompartments (BMCs) are proteinaceous organelles that are found in a broad range of bacteria and are composed of an outer shell that encases an enzyme cargo representing a specific metabolic process. The outer shell is made from a number of different proteins that form hexameric and pentameric tiles, which interact to allow the formation of a polyhedral edifice. We have previously shown that the Citrobacter freundii BMC associated with 1,2-propanediol utilization can be transferred into Escherichia coli to generate a recombinant BMC and that empty BMCs can be formed from just the shell proteins alone. Herein, a detailed structural and proteomic characterization of the wild type BMC is compared to the recombinant BMC and a number of empty BMC variants by 2D-gel electrophoresis, mass spectrometry, transmission electron microscopy (TEM) and atomic force microscopy (AFM). Specifically, it is shown that the wild type BMC and the recombinant BMC are similar in terms of composition, size, shape and mechanical properties, whereas the empty BMC variants are shown to be smaller, hollow and less malleable

Observation and electric current control of a local spin in a single-molecule magnet

In molecular spintronics, the spin state of a molecule may be switched on and off by changing the molecular structure. Here, we switch on and off the molecular spin of a double-decker bis(phthalocyaninato)terbium(III) complex (TbPc2) adsorbed on an Au(111) surface by applying an electric current via a scanning tunnelling microscope. The dI/dV curve of the tunnelling current recorded onto a TbPc2 molecule shows a Kondo peak, the origin of which is an unpaired spin of a π-orbital of a phthalocyaninato (Pc) ligand. By applying controlled current pulses, we could rotate the upper Pc ligand in TbPc2, leading to the disappearance and reappearance of the Kondo resonance. The rotation shifts the molecular frontier-orbital energies, quenching the π-electron spin. Reversible switching between two stable ligand orientations by applying a current pulse should make it possible to code information at the single-molecule level

Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis

Stathmin is an intracellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-cell carcinoma (OSCC)-derived cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-derived cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-derived cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase–polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P=0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC

Genetic and Structural Basis for Selection of a Ubiquitous T Cell Receptor Deployed in Epstein-Barr Virus Infection

Despite the ∼1018 αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A*0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR) loops, and was fastened to the peptide and HLA-A*0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(D)J recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems

Epigenetic abnormalities in myeloproliferative neoplasms: a target for novel therapeutic strategies

The myeloproliferative neoplasms (MPNs) are a group of clonal hematological malignancies characterized by a hypercellular bone marrow and a tendency to develop thrombotic complications and to evolve to myelofibrosis and acute leukemia. Unlike chronic myelogenous leukemia, where a single disease-initiating genetic event has been identified, a more complicated series of genetic mutations appear to be responsible for the BCR-ABL1-negative MPNs which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Recent studies have revealed a number of epigenetic alterations that also likely contribute to disease pathogenesis and determine clinical outcome. Increasing evidence indicates that alterations in DNA methylation, histone modification, and microRNA expression patterns can collectively influence gene expression and potentially contribute to MPN pathogenesis. Examples include mutations in genes encoding proteins that modify chromatin structure (EZH2, ASXL1, IDH1/2, JAK2V617F, and IKZF1) as well as epigenetic modification of genes critical for cell proliferation and survival (suppressors of cytokine signaling, polycythemia rubra vera-1, CXC chemokine receptor 4, and histone deacetylase (HDAC)). These epigenetic lesions serve as novel targets for experimental therapeutic interventions. Clinical trials are currently underway evaluating HDAC inhibitors and DNA methyltransferase inhibitors for the treatment of patients with MPNs

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Capsaicin decreases blood glucose, insulin and TRPV1 expression in sensory peripheral neurons in double transgenic diabetes mice

Introduction: Diabetic peripheral neuropathy is a common chronic complic ation of diabetes mellitus. Transient receptor potential (TRP) ion channels are involved in sensing physical and chemical stimuli. TRPV1 is a Ca2+ permeant non-selective cation channel expressed predominantly by unmyelinated C-fibers and thinlymyelinated A-d fibers and plays a major role in inflammatory thermal sensation. Capsaicin is the active component of chili peppers (which are plants belonging to the genus Capsicum) and is the main compound responsible for TRPV1 activation. Purpose: The goal of our study was to evaluate the effect of dietary capsaicin on the diabetic status of the double-transgenic mice. Material: We have used sensory neurons from dorsal root ganglia extracted from double transgenic TCR-HA+/-/Ins-HA+/- diabetic mice and Balb/c mice. Both strains of mice received a supplement in diet of 0.015% capsaicin for 10 weeks and were compared with unsupplemented controls. Method: Whole cell patch-clamp recording and immunofluorescence microscopy have been employed. PCR tests were employed to identify the presence of transgenes. Insulin and glucose were monitored using commercial strips.Results: Larger amplitude and a reduced desensitization of TRPV1 currents were induced by dietary capsaicin in TCR-HA+/-/Ins-HA+/- mice. These data closely resemble changes identified in streptozotocin-induced diabetes in rats upon superfusion of capsaicin in cell culture . Capsaicin treatment reduced the TRPV1 expression in the double-transgenic diabetic mice. Conclusions: In diabetes, the link between abnormal pain sensitivity and hyperglycemia resulting from insulin deficiency is not clear, but our study proves that capsaicin plays a major role in regulating TRPV1 function and expression in diabetes. In addition, dietary capsaicin is able to decrease the glucose and insulin levels, and in principal may reduce the oxidative status induced by hyperglycemia deficiency is not clear, but our study proves that capsaicin plays a major role in regulating TRPV1 function and expression in diabetes. In addition, dietary capsaicin is able to decrease the glucose and insulin levels, and in principal may reduce the oxidative status induced by hyperglycemia conditions. This study was financed by the research grant PNCDI2 41-074/2007