Leaky membrane fusion: an ambivalent effect induced by antimicrobial polycations.

Both antimicrobial peptides and their synthetic mimics are potential alternatives to classical antibiotics. They can induce several membrane perturbations including permeabilization. Especially in model studies, aggregation of vesicles by such polycations is often reported.

Pilot study of an online training program to increase genetic literacy and communication skills in oncology healthcare professionals discussing BRCA1/2 genetic testing with breast and ovarian cancer patients.

The increasing use of genetic testing for BRCA1/2 and other pathogenic variants in the management of women with breast and ovarian cancer necessitates increased genetic literacy in oncology healthcare professionals. This pilot study aimed to evaluate an online training program to increase genetic literacy and communication skills in Australian oncology healthcare professionals tasked with discussing and coordinating mainstream genetic testing with breast and ovarian cancer patients. A training website with embedded videos was developed.

Digitonin does not flip across cholesterol-poor membranes.

Digitonin is commonly used to permeabilize cell membranes and solubilize membrane components. It interacts specifically with cholesterol in the membrane which leads to the formation of pores. Thus far, the mechanism by which digitonin interacts with the membrane has only been described qualitatively.

"Staying Out" Rather than "Cracking In": Asymmetric Membrane Insertion of 12:0 Lysophosphocholine.

Interactions between detergents and model membranes are well described by the three-stage model: saturation and solubilization boundaries divide bilayer-only, bilayer-micelle coexistence, and micelle-only ranges. An underlying assumption of the model is the equilibration of detergent between the two membrane leaflets. However, many detergents partition asymmetrically at room temperature due to slow flip-flop, such as sodium dodecyl sulfate (SDS) and lysolipids.

Design and Characterization of a Multifunctional pH-Triggered Peptide C8 for Selective Anticancer Activity.

Most drug delivery systems have been developed for efficient delivery to tumor sites via targeting and on-demand strategies, but the carriers rarely execute synergistic therapeutic actions. In this work, C8, a cationic, pH-triggered anticancer peptide, is developed by incorporating histidine-mediated pH-sensitivity, amphipathic helix, and amino acid pairing self-assembly design. We designed C8 to function as a pH-responsive nanostructure whose cytotoxicity can be switched on and off by its self-assembly: Noncytotoxic β-sheet fibers at high pH with neutral histidines, and positively charged monomers with membrane lytic activity at low pH.

Utilizing zeta potential measurements to study the effective charge, membrane partitioning, and membrane permeation of the lipopeptide surfactin.

The effective charge of membrane-active molecules such as the fungicidal lipopeptide surfactin (SF) is a crucial property governing solubility, membrane partitioning, and membrane permeability. We present zeta potential measurements of liposomes to measure the effective charge as well as membrane partitioning of SF by utilizing what we call an equi-activity analysis of several series of samples with different lipid concentrations. We observe an effective charge of -1.

Effect of hydrophobic interactions on volume and thermal expansivity as derived from micelle formation.

Volumetric parameters have long been used to elucidate the phenomena governing the stability of protein structures, ligand binding, or transitions in macromolecular or colloidal systems. In spite of much success, many problems remain controversial. For example, hydrophobic groups have been discussed to condense adjacent water to a volume lower than that of bulk water, causing a negative contribution to the volume change of unfolding.

High dose methotrexate and extended hours high-flux hemodialysis for the treatment of primary central nervous system lymphoma in a patient with end stage renal disease.

This report discusses the case of a 52 year old female with post-transplant lymphoproliferative disorder, confined to the central nervous system, which was managed with high dose methotrexate (HDMTX) in the context of end stage renal disease. The patient received two doses of HDMTX followed by extended hours high-flux hemodialysis, plasma methotrexate concentration monitoring and leucovorin rescue. The hemodialysis technique used was effective in clearing plasma methotrexate and allowed delivery of HDMTX to achieve complete remission with limited and reversible direct methotrexate-related toxicity.

Valproic acid combined with cytosine arabinoside in elderly patients with acute myeloid leukemia has in vitro but limited clinical activity.

Elderly patients with acute myeloid leukemia (AML) have a poor prognosis. The authors examined the in vitro and clinical activity of the histone deacetylase inhibitor valproic acid (VA) combined with cytosine arabinoside (AraC) in elderly patients with AML unsuited to intensive therapy. For the in vitro studies, primary AML cells from 11 patients were treated with AraC and VA and analyzed for apoptosis, cytostatic effects, differentiation and acetyl histone H3 induction.

Estimating species trees using approximate Bayesian computation.

Development of methods for estimating species trees from multilocus data is a current challenge in evolutionary biology. We propose a method for estimating the species tree topology and branch lengths using approximate Bayesian computation (ABC). The method takes as data a sample of observed rooted gene tree topologies, and then iterates through the following sequence of steps: First, a randomly selected species tree is used to compute the distribution of rooted gene tree topologies.

Volumetric characterization of sodium-induced G-quadruplex formation.

Oligodeoxyribonucleotides (ODN) with repeats of the human telomeric sequence can adopt different tetrahelical conformations that exhibit similar energetic parameters. We studied the volumetric properties of the folded and unfolded states of an ODN with four repeats of the human telomeric sequence, d[A(GGGTTA)(3)GGG], by combining pressure-perturbation calorimetry (PPC), vibrating tube densimetry, ultrasonic velocimetry, and UV melting under high pressure. We carried out our volumetric measurements in aqueous buffers at pH 7 containing 20, 50, and 100 mM NaCl.

Utilize conjugated melanotropins for the earlier diagnosis and treatment of melanoma.

Peptides serve as effective drugs and contrast agents in the clinic today. However the inherent drawbacks of peptide structures can limit their efficacy as drugs. To overcome this we have been developing new methods to create 'tailor-made' peptides and peptide mimetics with improved pharmacological and physical properties.

Volume and expansivity changes of micelle formation measured by pressure perturbation calorimetry.

We present the application of pressure perturbation calorimetry (PPC) as a new method for the volumetric characterization of the micelle formation of surfactants. The evaluation is realized by a global fit of PPC curves at different surfactant concentration ranging, if possible, from below to far above the CMC. It is based on the knowledge of the temperature dependence of the CMC, which can for example be characterized by isothermal titration calorimetry.

Improving a designed photocontrolled DNA-binding protein.

Photocontrolled transcription factors could be powerful tools for probing the roles of transcriptional processes in a variety of settings. Previously, we designed a photocontrolled DNA-binding protein based on a fusion between the bZIP region of GCN4 and photoactive yellow protein from Halorhodospira halophila [Morgan, S. A.

DR with a DSLR: Digital Radiography with a Digital Single-Lens Reflex camera.

An inexpensive, portable digital radiography (DR) detector system for use in remote regions has been built and evaluated. The system utilizes a large-format digital single-lens reflex (DSLR) camera to capture the image from a standard fluorescent screen. The large sensor area allows relatively small demagnification factors and hence minimizes the light loss.

Fatigue, menopausal symptoms, and cognitive function in women after adjuvant chemotherapy for breast cancer: 1- and 2-year follow-up of a prospective controlled study.

Purpose: We previously evaluated fatigue, menopausal symptoms, and cognitive dysfunction in patients receiving adjuvant therapy for breast cancer and matched healthy women. Here we report assessment of these women 1 and 2 years later.

Patients And Methods: Patients without relapse and controls were evaluated by the Functional Assessment of Cancer Treatment-General Quality of Life questionnaire, with subscales for fatigue and endocrine symptoms, and by the High Sensitivity Cognitive Screen.

Polymethylated DOTA ligands. 2. Synthesis of rigidified lanthanide chelates and studies on the effect of alkyl substitution on conformational mobility and relaxivity.

M4DOTA, [(2S,5S,8S,11S)-4,7,10-tris-carboxymethyl-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid (2e), and M4DOTMA, (R)-2-[(2S,5S,8S,11S)-4,7,10-tris-((R)-1-carboxyethyl)-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecan-1-yl]propionic acid (3e), are derivatives of ligand DOTA (1e) that form sterically crowded lanthanide chelates. M4DOTMA forms highly symmetric and totally rigid single Y(3+) and Yb(3+) species in which the ring substituents occupy corner positions in a square antiprismatic arrangement as shown by molecular mechanics calculations and by a quantitative interpretation of the relative magnitudes of the paramagnetic (1)H NMR shifts of dipolar origin. The NMR spectrum of YbM4DOTMA(-) displays two intense methyl peaks outside the 0-10 ppm range whose shift difference is strongly temperature dependent.

Polymethylated DOTA ligands. 1. Synthesis of rigidified ligands and studies on the effects of alkyl substitution on acid-base properties and conformational mobility.

This work describes the synthesis and the conformational properties of new polymethylated macrocyclic ligands of potential interest for magnetic resonance imaging. M4cyclen, (2S,5S,8S,11S)-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecane, was obtained by cyclotetramerization of (2S)-1-benzyl-2-methylaziridine followed by catalytic hydrogenation. The ligands M4DOTA, [(2S,5S,8S,11S)-4,7,10-tris-carboxymethyl-2,5,8,11-tetramethyl- 1,4,7,10-tetraazacyclododecan-1-yl]acetic acid, and M4DOTMA, (R)-2-[(2S,5S,8S,11S)-4,7,10-tris-((R)-1-carboxyethyl)-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecan-1-yl]propionic acid, were prepared by carboxyalkylation of M4cyclen in the presence of Na(2)CO(3).