Pirin delocalization in melanoma progression identified by high content immuno-detection based approaches

<p>Abstract</p> <p>Background</p> <p>Pirin (PIR) is a highly conserved nuclear protein originally isolated as an interactor of NFI/CTF1 transcription/replication factor. It is a member of the functionally diverse cupin superfamily and its activity has been linked to different biological and molecular processes, such as regulation of transcription, apoptosis, stress response and enzymatic processes. Although its precise role in these functions has not yet been defined, PIR expression is known to be deregulated in several human malignancies.</p> <p>Results</p> <p>We performed immunohistochemical analysis of PIR expression in primary samples from normal human tissues and tumors and identified a dislocation of PIR to the cytoplasm in a subset of melanomas, and a positive correlation between cytoplasmic PIR levels and melanoma progression. PIR localization was subsequently analyzed <it>in vitro </it>in melanoma cell lines through a high content immunofluorescence based approach (ImmunoCell-Array).</p> <p>Conclusions</p> <p>The high consistency between <it>in vivo </it>and <it>in vitro </it>results obtained by immunohistochemistry and ImmunoCell-Array provides a validation of the potential of ImmunoCell-Array technology for the rapid screening of putative biological markers, and suggests that cytoplasmic localization of PIR may represent a characteristic of melanoma progression.</p

Correction: Wound healing properties of hyaluronan derivatives bearing ferulate residues

Correction for 'Wound healing properties of hyaluronan derivatives bearing ferulate residues' by Giuseppe Valacchi et al., J. Mater. Chem. B, 2015, DOI: 10.1039/c5tb00661a

An Electroactive and Self-Assembling Bio-Ink, based on Protein-Stabilized Nanoclusters and Graphene, for the Manufacture of Fully Inkjet-Printed Paper-Based Analytical Devices

Hundreds of new electrochemical sensors are reported in literature every year. However, only a few of them makes it to the market. Manufacturability, or rather the lack of it, is the parameter that dictates if new sensing technologies will remain forever in the laboratory in which they are conceived. Inkjet printing is a low-cost and versatile technique that can facilitate the transfer of nanomaterial-based sensors to the market. Herein, an electroactive and self-assembling inkjet-printable ink based on protein-nanomaterial composites and exfoliated graphene is reported. The consensus tetratricopeptide proteins (CTPRs), used to formulate this ink, are engineered to template and coordinate electroactive metallic nanoclusters (NCs), and to self-assemble upon drying, forming stable films. The authors demonstrate that, by incorporating graphene in the ink formulation, it is possible to dramatically improve the electrocatalytic properties of the ink, obtaining an efficient hybrid material for hydrogen peroxide (H2O2) detection. Using this bio-ink, the authors manufactured disposable and environmentally sustainable electrochemical paper-based analytical devices (ePADs) to detect H2O2, outperforming commercial screen-printed platforms. Furthermore, it is demonstrated that oxidoreductase enzymes can be included in the formulation, to fully inkjet-print enzymatic amperometric biosensors ready to use

Grand Rounds: Could Occupational Exposure to n-Hexane and Other Solvents Precipitate Visual Failure in Leber Hereditary Optic Neuropathy?

CONTEXT: Leber hereditary optic neuropathy (LHON) is a maternally inherited loss of central vision related to pathogenic mutations in the mitochondrial genome, which are a necessary but not sufficient condition to develop the disease. Investigation of precipitating environmental/occupational (and additional genetic) factors could be relevant for prevention. CASE PRESENTATION: After a 6-month period of occupational exposure to n-hexane and other organic solvents, a 27-year-old man (a moderate smoker) developed an optic neuropathy. The patient had a full ophthalmologic and neurologic investigation, including standardized cycloergometer test for serum lactic acid levels and a skeletal muscle biopsy. His exposure history was also detailed, and he underwent genetic testing for LHON mitochondrial DNA mutations. The patient suffered a sequential optic neuropathy with the hallmarks of LHON and tested positive for the homoplasmic 11778G → A/ND4 mutation. Routine laboratory monitoring revealed increased concentrations of urinary 2.5 hexandione (n-hexane metabolite) and hippuric acid (toluene metabolite) in the period immediately preceding the visual loss. DISCUSSION: In a subject carrying an LHON mutation, the strict temporal sequence of prolonged appreciable occupational exposure followed by sudden onset of visual loss must raise a suspicion of causality (with a possible further interaction with tobacco smoke). RELEVANCE: In this article, we add to the candidate occupational/environmental triggers of LHON and highlight the need for appropriate case–control (and laboratory) studies to validate the causal effect of mixed toxic exposures

Detection of Geometric Phases in Superconducting Nanocircuits

When a quantum mechanical system undergoes an adiabatic cyclic evolution it acquires a geometrical phase factor in addition to the dynamical one. This effect has been demonstrated in a variety of microscopic systems. Advances in nanotechnologies should enable the laws of quantum dynamics to be tested at the macroscopic level, by providing controllable artificial two-level systems (for example, in quantum dots and superconducting devices). Here we propose an experimental method to detect geometric phases in a superconducting device. The setup is a Josephson junction nanocircuit consisting of a superconducting electron box. We discuss how interferometry based on geometrical phases may be realized, and show how the effect may applied to the design of gates for quantum computation.Comment: 12 page

Multiphoton Quantum Optics and Quantum State Engineering

We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously vast subject. Here we choose to concentrate our attention on parametric processes in nonlinear media, with special emphasis on the engineering of nonclassical states of photons and atoms. We present a detailed analysis of the methods and techniques for the production of genuinely quantum multiphoton processes in nonlinear media, and the corresponding models of multiphoton effective interactions. We review existing proposals for the classification, engineering, and manipulation of nonclassical states, including Fock states, macroscopic superposition states, and multiphoton generalized coherent states. We introduce and discuss the structure of canonical multiphoton quantum optics and the associated one- and two-mode canonical multiphoton squeezed states. This framework provides a consistent multiphoton generalization of two-photon quantum optics and a consistent Hamiltonian description of multiphoton processes associated to higher-order nonlinearities. Finally, we discuss very recent advances that by combining linear and nonlinear optical devices allow to realize multiphoton entangled states of the electromnagnetic field, that are relevant for applications to efficient quantum computation, quantum teleportation, and related problems in quantum communication and information.Comment: 198 pages, 36 eps figure

Incidence rates of in-hospital carpal tunnel syndrome in the general population and possible associations with marital status

<p>Abstract</p> <p>Background</p> <p>Carpal tunnel syndrome (CTS) is a socially relevant condition associated with biomechanical risk factors. We evaluated age-sex-specific incidence rates of in-hospital cases of CTS in central/northern Italy and explored relations with marital status.</p> <p>Methods</p> <p>Seven regions were considered (overall population, 14.9 million) over 3–6-year periods between 1997 and 2002 (when out-of-hospital CTS surgery was extremely rare). Incidence rates of in-hospital cases of CTS were estimated based on 1) codified demographic, diagnostic and intervention data in obligatory discharge records from all Italian public/private hospitals, archived (according to residence) on regional databases; 2) demographic general population data for each region. We compared (using the χ_scoretest) age-sex-specific rates between married, unmarried, divorced and widowed subsets of the general population. We calculated standardized incidence ratios (SIRs) for married/unmarried men and women.</p> <p>Results</p> <p>Age-standardized incidence rates (per 100,000 person-years) of in-hospital cases of CTS were 166 in women and 44 in men (106 overall). Married subjects of both sexes showed higher age-specific rates with respect to unmarried men/women. SIRs were calculated comparing married vs unmarried rates of both sexes: 1.59 (95% confidence interval [95% CI], 1.57–1.60) in women, and 1.42 (95% CI, 1.40–1.45) in men. As compared with married women/men, widows/widowers both showed 2–3-fold higher incidence peaks during the fourth decade of life (beyond 50 years of age, widowed subjects showed similar trends to unmarried counterparts).</p> <p>Conclusion</p> <p>This large population-based study illustrates distinct age-related trends in men and women, and also raises the question whether marital status could be associated with CTS in the general population.</p

Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis

Protection against deadly pathogens requires the production of high-affinity antibodies by B cells, which are generated in germinal centers (GCs). Alteration of the GC developmental program is common in many B cell malignancies. Identification of regulators of the GC response is crucial to develop targeted therapies for GC B cell dysfunctions, including lymphomas. The histone H3 lysine 27 methyltransferase enhancer of zeste homolog 2 (EZH2) is highly expressed in GC B cells and is often constitutively activated in GC-derived non-Hodgkin lymphomas (NHLs). The function of EZH2 in GC B cells remains largely unknown. Herein, we show that Ezh2 inactivation in mouse GC B cells caused profound impairment of GC responses, memory B cell formation, and humoral immunity. EZH2 protected GC B cells against activation-induced cytidine deaminase (AID) mutagenesis, facilitated cell cycle progression, and silenced plasma cell determinant and tumor suppressor B-lymphocyte–induced maturation protein 1 (BLIMP1). EZH2 inhibition in NHL cells induced BLIMP1, which impaired tumor growth. In conclusion, EZH2 sustains AID function and prevents terminal differentiation of GC B cells, which allows antibody diversification and affinity maturation. Dysregulation of the GC reaction by constitutively active EZH2 facilitates lymphomagenesis and identifies EZH2 as a possible therapeutic target in NHL and other GC-derived B cell diseases.Published versio

Risk factors for operated carpal tunnel syndrome: a multicenter population-based case-control study

Background. Carpal tunnel syndrome (CTS) is a socially and economically relevant disease caused by compression or entrapment of the median nerve within the carpal tunnel. This population-based case-control study aims to investigate occupational/non-occupational risk factors for surgically treated CTS. Methods. Cases (n = 220) aged 18-65 years were randomly drawn from 13 administrative databases of citizens who were surgically treated with carpal tunnel release during 2001. Controls (n = 356) were randomly sampled from National Health Service registry records and were frequency matched by age-gender-specific CTS hospitalization rates. Results. At multivariate analysis, risk factors were blue-collar/housewife status, BMI ≥ 30 kg/m2, sibling history of CTS and coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles: women ≥165 cm; men ≥175 cm) was associated with lower risk. Blue-collar work was a moderate/strong risk factor in both sexes. Raised risks were apparent for combinations of biomechanical risk factors that included frequent repetitivity and sustained force. Conclusion. This study strongly underlines the relevance of biomechanical exposures in both non-industrial and industrial work as risk factors for surgically treated CTS