Inter‐Fullerene Electronic Coupling Controls the Efficiency of Photoinduced Charge Generation in Organic Bulk Heterojunctions

Photoinduced charge generation (PCG) dynamics are notoriously difficult to correlate with specific molecular properties in device relevant polymer:fullerene organic photovoltaic blend films due to the highly complex nature of the solid state blend morphology. Here, this study uses six judiciously selected trifluoromethylfullerenes blended with the prototypical polymer poly(3‐hexylthiophene) and measure the PCG dynamics in 50 fs–500 ns time scales with time‐resolved microwave conductivity and femtosecond transient absorption spectroscopy. The isomeric purity and thorough chemical characterization of the fullerenes used in this study allow for a detailed correlation between molecular properties, driving force, local intermolecular electronic coupling and, ultimately, the efficiency of PCG yield. The findings show that the molecular design of the fullerene not only determines inter‐fullerene electronic coupling, but also influences the decay dynamics of free holes in the donor phase even when the polymer microstructure remains unchanged.     

Conformation-specific anti-Mad2 monoclonal antibodies for the dissection of checkpoint signaling

The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation during mitosis by delaying the activation of the anaphase-promoting complex/cyclosome (APC/C) in response to unattached kinetochores. The Mad2 protein is essential for a functional checkpoint because it binds directly to Cdc20, the mitotic co-activator of the APC/C, thereby inhibiting progression into anaphase. Mad2 exists in at least 2 different conformations, open-Mad2 (O-Mad2) and closed-Mad2 (C-Mad2), with the latter representing the active form that is able to bind Cdc20. Our ability to dissect Mad2 biology in vivo is limited by the absence of monoclonal antibodies (mAbs) useful for recognizing the different conformations of Mad2. Here, we describe and extensively characterize mAbs specific for either O-Mad2 or C-Mad2, as well as a pan-Mad2 antibody, and use these to investigate the different Mad2 complexes present in mitotic cells. Our antibodies validate current Mad2 models but also suggest that O-Mad2 can associate with checkpoint complexes, most likely through dimerization with C-Mad2. Furthermore, we investigate the makeup of checkpoint complexes bound to the APC/C, which indicate the presence of both Cdc20-BubR1-Bub3 and Mad2-Cdc20-BubR1-Bub3 complexes, with Cdc20 being ubiquitinated in both. Thus, our defined mAbs provide insight into checkpoint signaling and provide useful tools for future research on Mad2 function and regulation.     

Patellofemoral cartilage stresses are most sensitive to variations in vastus medialis muscle forces

The purpose of this study was to evaluate the effects of variations in quadriceps muscle forces on patellofemoral stress. We created subject-specific finite element models for 21 individuals with chronic patellofemoral pain and 16 pain-free control subjects. We extracted three-dimensional geometries from high resolution magnetic resonance images and registered the geometries to magnetic resonance images from an upright weight bearing squat with the knees flexed at 60°. We estimated quadriceps muscle forces corresponding to 60° knee flexion during a stair climb task from motion analysis and electromyography-driven musculoskeletal modelling. We applied the quadriceps muscle forces to our finite element models and evaluated patellofemoral cartilage stress. We quantified cartilage stress using an energy-based effective stress, a scalar quantity representing the local stress intensity in the tissue. We used probabilistic methods to evaluate the effects of variations in quadriceps muscle forces from five trials of the stair climb task for each subject. Patellofemoral effective stress was most sensitive to variations in forces in the two branches of the vastus medialis muscle. Femur cartilage effective stress was most sensitive to variations in vastus medialis forces in 29/37 (78%) subjects, and patella cartilage effective stress was most sensitive to variations in vastus medialis forces in 21/37 (57%) subjects. Femur cartilage effective stress was more sensitive to variations in vastus medialis longus forces in subjects classified as maltrackers compared to normal tracking subjects (p?=?0.006). This study provides new evidence of the importance of the vastus medialis muscle in the treatment of patellofemoral pain.     

Promoting proteomics knowledge in Europe: report on the activities of the EuPA Education Committee 2006-2007

The early transition of knowledge from highly specialised and sophisticated proteomics research to a diverse community in need of know-how is a challenge that requires backing from advanced research centres and groups, and a coordinating body for the dissemination of this knowledge. The European Proteomics Association (EuPA) Education Committee signified this as a priority area when the EuPA was formed, and began its program to coordinate proteomics training and knowledge dissemination in 2006. This report serves as an update of our past activities and an announcement of upcoming events. Over the last year the EuPA Education Committee has coordinated or supported different educational activities including basic and advanced courses, a summer school, workshops and tutorials. A new programme of basic courses dubbed "Teaching the Teachers" has been initiated. These courses reach a larger, Europe wide, audience in a short timeframe, thus improving the opportunities for trainees of elementary proteomics techniques. Another important event has been the merger of the EuPA and HUPO (Human Proteome Organisation) Education Committees into a single one in order to combine ideas and ef for ts that will favour global education in proteomics.     

Concentration-dependent differential induction of necrosis or apoptosis by HIV-1 lytic peptide 1

The mechanism by which human immunodeficiency virus type 1 induces depletion of CD4+ T-lymphocytes remains controversial, but may involve cytotoxic viral proteins. Synthetic peptides (lentivirus lytic peptide type 1) corresponding to the carboxyl terminus of the human immunodeficiency virus type 1 transmembrane glycoprotein induce cytopathology at concentrations of 100 nM and above. At these concentrations lentivirus lytic peptide type 1 disrupts mitochondrial integrity of CD4+ T-lymphoblastoid cells and induces other changes characteristic of necrosis. In contrast, at concentrations of 20 nM, lentivirus lytic peptide type 1 potently induces apoptosis. Thus, the mechanism by which human immunodeficiency virus type 1 mediates cell death, necrosis or apoptosis, may depend, in part, on the tissue concentration of transmembrane glycoprotein.     

Strong positional preference in the interaction of LNA oligonucleotides with DNA polymerase and proofreading exonuclease activities: implications for genotyping assays

The effect of locked nucleic acid (LNA) modification position upon representative DNA polymerase and exonuclease activities has been examined for potential use in primer extension genotyping applications. For the 3′→5′ exonuclease activities of four proofreading DNA polymerases (Vent, Pfu, Klenow fragment and T7 DNA polymerase) as well as exonuclease III, an LNA at the terminal (L-1) position of a primer is found to provide partial protection against the exonucleases of the two family B polymerases only. In contrast, an LNA residue at the penultimate (L-2) position generates essentially complete nuclease resistance. The polymerase active sites of these enzymes also display a distinct preference. An L-1 LNA modification has modest effects upon poly merization, but an L-2 LNA group slows dTTP incorporation somewhat while virtually abolishing extension with ddTTP or acyTTP terminators, even with A488L Vent DNA polymerase engineered for terminator incorporation. These observations on active site preference have been utilized to demonstrate two novel assays: exonuclease-mediated single base extension (E-SBE) and proofreading allele-specific extension (PRASE). We show that a model PRASE genotyping reaction with L-2 LNA primers offers greater specificity than existing non-proofreading assays, whether or not the non-proofreading reaction employs LNA-modified primers.