Course of back pain across 5 years: a retrospective cohort study in the general population of Switzerland.

Study Design: A retrospective cohort study in the general population of Switzerland.

Objective: To investigate the course of back pain (BP) across 5 years and the impact of BP history on its incidence and recurrence.

Summary Of Background Data: Longitudinal studies on BP performed in the general population have reported varying prevalence and incidence rates.

Th cells act via two synergistic pathways to promote antiviral CD8+ T cell responses.

The mechanisms of how Th cells promote CD8(+) T cell responses during viral infections are largely unknown. In this study, we unraveled the mechanisms of T cell help for CD8(+) T cell responses during vaccinia virus infection. Our results demonstrate that Th cells promote vaccinia virus-specific CD8(+) T cell responses via two interconnected synergistic pathways: First, CD40L expressed by activated CD4(+) T cells instructs dendritic cells to produce bioactive IL-12p70, which is directly sensed by Ag-specific CD8(+) T cells, resulting in increased IL-2Rα expression.

No need to discriminate? Reproductive diploid males in a parasitoid with complementary sex determination.

Diploid males in hymenopterans are generally either inviable or sterile, thus imposing a severe genetic load on populations. In species with the widespread single locus complementary sex determination (sl-CSD), sex depends on the genotype at one single locus with multiple alleles. Haploid (hemizygous) individuals are always males.

Rupture pathway of phosphatidylcholine liposomes on silicon dioxide.

We have investigated the pathway by which unilamellar POPC liposomes upon adsorption undergo rupture and form a supported lipid bilayer (SLB) on a SiO(2) surface. Biotinylated lipids were selectively incorporated in the outer monolayer of POPC liposomes to create liposomes with asymmetric lipid compositions in the outer and inner leaflets. The specific binding of neutravidin and anti-biotin to SLBs formed by liposome fusion, prior to and after equilibrated flip-flop between the upper and lower monolayers in the SLB, were then investigated.

Formation of supported bacterial lipid membrane mimics.

In recent years, a large effort has been spent on advancing the understanding of how surface-supported membranes are formed through vesicle fusion. The aim is to find simple model systems for investigating biophysical and biochemical interactions between constituents of cell membranes and, for example, drugs and toxins altering membrane function. Designing and controlling the self-assembly of model membranes onto sensor substrates thus constitutes an important field of research, enabling applications in, e.

How force might activate talin's vinculin binding sites: SMD reveals a structural mechanism.

Upon cell adhesion, talin physically couples the cytoskeleton via integrins to the extracellular matrix, and subsequent vinculin recruitment is enhanced by locally applied tensile force. Since the vinculin binding (VB) sites are buried in the talin rod under equilibrium conditions, the structural mechanism of how vinculin binding to talin is force-activated remains unknown. Taken together with experimental data, a biphasic vinculin binding model, as derived from steered molecular dynamics, provides high resolution structural insights how tensile mechanical force applied to the talin rod fragment (residues 486-889 constituting helices H1-H12) might activate the VB sites.

Pharmacologic transgene control systems for gene therapy.

Pharmacologic transgene-expression dosing is considered essential for future gene therapy scenarios. Genetic interventions require precise transcription or translation fine-tuning of therapeutic transgenes to enable their titration into the therapeutic window, to adapt them to daily changing dosing regimes of the patient, to integrate them seamlessly into the patient's transcriptome orchestra, and to terminate their expression after successful therapy. In recent years, decisive progress has been achieved in designing high-precision trigger-inducible mammalian transgene control modalities responsive to clinically licensed and inert heterologous molecules or to endogenous physiologic signals.

The cell penetrating peptides pVEC and W2-pVEC induce transformation of gel phase domains in phospholipid bilayers without affecting their integrity.

The cell penetrating peptide (CPP) pVEC has been shown to translocate efficiently the plasma membrane of different mammalian cell lines by a receptor-independent mechanism without exhibiting cellular toxicity. This ability renders CPPs of broad interest in cell biology, biotechnology, and drug delivery. To gain insight into the interaction of CPPs with biomembranes, we studied the interaction of pVEC and W2-pVEC, an Ile --> Trp modification of the former, with phase-separated supported phospholipid bilayers (SPB) by atomic force microscopy (AFM).

Development and evaluation of a standard method for the quantitative determination of elements in float glass samples by LA-ICP-MS.

Forensic analysis of glass samples was performed in different laboratories within the NITE-CRIME (Natural Isotopes and Trace Elements in Criminalistics and Environmental Forensics) European Network, using a variety of Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) systems. The main objective of the interlaboratory tests was to cross-validate the different combinations of laser ablation systems with different ICP-MS instruments. A first study using widely available samples, such as the NIST SRM 610 and NIST SRM 612 reference glasses, led to deviations in the determined concentrations for trace elements amongst the laboratories up to 60%.

Membrane surface-associated helices promote lipid interactions and cellular uptake of human calcitonin-derived cell penetrating peptides.

hCT(9-32) is a human calcitonin (hCT)-derived cell-penetrating peptide that has been shown to translocate the plasma membrane of mammalian cells. It has been suggested as a cellular carrier for drugs, green fluorescent protein, and plasmid DNA. Because of its temperature-dependent cellular translocation resulting in punctuated cytoplasmatic distribution, its uptake is likely to follow an endocytic pathway.

Insulin-like growth factor I-releasing alginate-tricalciumphosphate composites for bone regeneration.

Purpose: Development and characterization of an in situ-forming, osteoconductive, and growth factor-releasing bone implant.

Methods: Injectable in situ-forming scaffolds were prepared from a 2% (m/v) alginate solution, tricalciumphosphate (TCP) granules, and poly(lactide-co-glycolide) microspheres (MS), loaded with the osteoinductive growth factor insulin-like growth factor I (IGF-I). Scaffolds were prepared by mixing the components followed by hydrogel formation through calcium carbonate-induced physical cross-linking of the alginate at slightly acidic pH.

Bilayer interaction and localization of cell penetrating peptides with model membranes: a comparative study of a human calcitonin (hCT)-derived peptide with pVEC and pAntp(43-58).

Cell-penetrating peptides (CPPs) are able to translocate problematic therapeutic cargoes across cellular membranes. The exact mechanisms of translocation are still under investigation. However, evidence for endocytic uptake is increasing.

New field method: gas push-pull test for the in-situ quantification of microbial activities in the vadose zone.

Quantitative information on microbial processes in the field is important. Here we propose a new field method, the "gas push-pull test" (GPPT) for the in-situ quantification of microbial activities in the vadose zone. To evaluate the new method, we studied microbial methane oxidation above an anaerobic, petroleum-contaminated aquifer.

Transport of surface-modified nanoparticles through cell monolayers.

We synthesized three peptides, a D-polyarginyl peptide (r8(FITC)), a Tat peptide (Tat(FITC)), and a control peptide (Cp(FITC)) and attached each to amino-CLIO, a nanoparticle 30 nm in diameter. We then examined the effective permeability, Peff, of all six materials through CaCo-2 monolayers. The transport of peptide-nanoparticles was characterized by a lag phase (0-8 h) and a steady-state phase (9-27 h).

Effect of oil-in-water emulsions on 5-aminolevulinic acid uptake and metabolism to PpIX in cultured MCF-7 cells.

Purpose: To identify the optimal vehicle for fast and efficient cellular production of the photosensitizer, protoporphyrin IX (PpIX), upon administration of 5-aminolevulinic acid (ALA).

Methods: ALA in various oil/water o/w emulsions was applied to the human mammary epithelial cell line (MCF-7) cultured in microplates. Upon incubation for 14 h, the accumulated amount of PpIX was determined by fluorescence spectroscopy.

Decoding the entry of two novel cell-penetrating peptides in HeLa cells: lipid raft-mediated endocytosis and endosomal escape.

Cellular entry of peptide, protein, and nucleic acid biopharmaceuticals is severely impeded by the cell membrane. Linkage or assembly of such agents and cell-penetrating peptides (CPP) with the ability to cross cellular membranes has opened a new horizon in biomedical research. Nevertheless, the uptake mechanisms of most CPP have been controversially discussed and are poorly understood.

Transfection of a mouse dendritic cell line by plasmid DNA-loaded PLGA microparticles in vitro.

Targeting of DC for DNA vaccination may be achieved by DNA-loaded poly(lactide-co-glycolide) (PLGA) biodegradable microparticles, since DC efficiently capture these microparticles in vitro and in vivo. DNA was encapsulated in PLGA microparticles by spray-drying. Various additives were tested and process parameters adjusted in order to prevent degradation of the DNA during encapsulation.

Localized delivery of growth factors for bone repair.

Delivery of growth factors for tissue (e.g. bone, cartilage) or cell repair (e.

Cellular uptake but low permeation of human calcitonin-derived cell penetrating peptides and Tat(47-57) through well-differentiated epithelial models.

Purpose: To investigate whether cell penetrating peptides (CPP) derived from human calcitonin (hCT) possess, in addition to cellular uptake, the capacity to deliver their cargo through epithelial barriers.

Methods: Cellular uptake of hCT(9-32) and permeation of six hCT-derived peptides, namely, hCT(9-32), hCT(12-32), hCT(15-32), hCT(18-32), hCT(21-32), and a random sequence of hCT(9-32) were evaluated in fully organized confluent Madin-Darby canine kidney (MDCK), Calu-3, and TR146 cell culture models. For comparison, Tat(47-57) and penetratin(43-58) were investigated.

Metabolic cleavage of cell-penetrating peptides in contact with epithelial models: human calcitonin (hCT)-derived peptides, Tat(47-57) and penetratin(43-58).

We assessed the metabolic degradation kinetics and cleavage patterns of some selected CPP (cell-penetrating peptides) after incubation with confluent epithelial models. Synthesis of N-terminal CF [5(6)-carboxyfluorescein]-labelled CPP, namely hCT (human calcitonin)-derived sequences, Tat(47-57) and penetratin(43-58), was through Fmoc (fluoren-9-ylmethoxycarbonyl) chemistry. Metabolic degradation kinetics of the tested CPP in contact with three cell-cultured epithelial models, MDCK (Madin-Darby canine kidney), Calu-3 and TR146, was evaluated by reversed-phase HPLC.

Cellular internalization of human calcitonin derived peptides in MDCK monolayers: a comparative study with Tat(47-57) and penetratin(43-58).

Purpose: The objective of this study was to evaluate key motif requirements of human calcitonin (hCT)-derived peptides for the permeation through the plasma membrane of MDCK monolayers, as epithelial model.

Methods: Truncated and sequence-modified fluorescent-labeled hCT-derived peptides were synthesized through Fmoc chemistry. Peptide uptake by confluent MDCK was observed by confocal laser scanning microscopy.