Mycobacterial immunotherapy for prostate cancer: where can we go from here?

The effects of mycobacteria in prostate cancer have not been fully elucidated. Results of early studies indicated that mycobacterial immunotherapy conferred a survival benefit in patients with advanced prostate cancer, and recent evidence supports the safety and efficacy of new mycobacterial agents in many malignancies; thus, modern, carefully designed, randomized controlled trials of mycobacterial immunotherapy for prostate cancer could be warranted

Anti-oxidative cellular protection effect of fasting-induced autophagy as a mechanism for hormesis

The aim of this investigation was to test the hypothesis that fasting-induced augmented lysosomal autophagic turnover of cellular proteins and organelles will reduce potentially harmful lipofuscin (age-pigment) formation in cells by more effectively removing oxidatively damaged proteins. An animal model (marine snail - common periwinkle, Littorina littorea) was used to experimentally test this hypothesis. Snails were deprived of algal food for 7 days to induce an augmented autophagic response in their hepatopancreatic digestive cells (hepatocyte analogues). This treatment resulted in a 25% reduction in the cellular content of lipofuscin in the digestive cells of the fasting animals in comparison with snails fed ad libitum on green alga (Ulva lactuca). Similar findings have previously been observed in the digestive cells of marine mussels subjected to copper-induced oxidative stress. Additional measurements showed that fasting significantly increased cellular health based on lysosomal membrane stability, and reduced lipid peroxidation and lysosomal/cellular triglyceride. These findings support the hypothesis that fasting-induced augmented autophagic turnover of cellular proteins has an anti-oxidative cytoprotective effect by more effectively removing damaged proteins, resulting in a reduction in the formation of potentially harmful proteinaceous aggregates such as lipofuscin. The inference from this study is that autophagy is important in mediating hormesis. An increase was demonstrated in physiological complexity with fasting, using graph theory in a directed cell physiology network (digraph) model to integrate the various biomarkers. This was commensurate with increased health status, and supportive of the hormesis hypothesis. The potential role of enhanced autophagic lysosomal removal of damaged proteins in the evolutionary acquisition of stress tolerance in intertidal molluscs is discussed and parallels are drawn with the growing evidence for the involvement of autophagy in hormesis and anti-ageing processes

Potent induction of antibody-secreting B-cells by human dermal-derived CD14+ dendritic cells triggered by dual toll-like receptor ligation

Targeting CD14(+) dermal-derived dendritic cells (DDCs) is a rational approach for vaccination strategies aimed at improving humoral immune responses, because of their natural ability to stimulate naïve B-cells. Here, we show that CD14(+) DDCs express mRNA for TLRs 1–9, but respond differentially to single or paired TLR ligands. Compared to single ligands, some combinations were particularly effective at activating CD14(+) DDCs, as shown by enhanced expression of B-cell stimulatory cytokines (IL-6, IL-10 and TNF-α) and more pronounced phenotypic maturation. These combinations were Resiquimod (R-848) plus Polyinosinic:polycytidylic acid (Poly(I:C)); R-848 plus LPS; Pam3CSK4 plus Poly(I:C); LPS plus Poly(I:C). We also found that selected TLR ligand pairs (R-848 plus either LPS or Poly(I:C)) were superior to individual agents at boosting the inherent capacity of CD14(+) DDCs to induce naïve B-cells to proliferate and differentiate into CD27(+) CD38(+) B-cells that secrete high levels of IgG and IgA. When treated with the same TLR ligand combinations, CD14(+) DDCs also promoted the differentiation of Th1 (IFN-γ-secreting) CD4(+) T-cells, but not of Th2 or Th17 CD4(+) T-cells. These observations may help to identify adjuvant strategies aimed at inducing protective immune responses to various pathogens, including but not limited to HIV-1

A live vaccine against Neospora caninum abortions in cattle

CommentaryMichael P. Reichel, Dadín P. Moore, Andrew Hemphill, Luis M. Ortega-Mora, J.P. Dubey, John T. Elli

Evidence for a fractional quantum Hall state with anisotropic longitudinal transport

At high magnetic fields, where the Fermi level lies in the N=0 lowest Landau level (LL), a clean two-dimensional electron system (2DES) exhibits numerous incompressible liquid phases which display the fractional quantized Hall effect (FQHE) (Das Sarma and Pinczuk, 1997). These liquid phases do not break rotational symmetry, exhibiting resistivities which are isotropic in the plane. In contrast, at lower fields, when the Fermi level lies in the $N\ge2$ third and several higher LLs, the 2DES displays a distinctly different class of collective states. In particular, near half filling of these high LLs the 2DES exhibits a strongly anisotropic longitudinal resistance at low temperatures (Lilly et al., 1999; Du et al., 1999). These "stripe" phases, which do not exhibit the quantized Hall effect, resemble nematic liquid crystals, possessing broken rotational symmetry and orientational order (Koulakov et al., 1996; Fogler et al., 1996; Moessner and Chalker, 1996; Fradkin and Kivelson, 1999; Fradkin et al, 2010). Here we report a surprising new observation: An electronic configuration in the N=1 second LL whose resistivity tensor simultaneously displays a robust fractionally quantized Hall plateau and a strongly anisotropic longitudinal resistance resembling that of the stripe phases.Comment: Nature Physics, (2011

Quality care and safety know no borders

The public, governmental agencies, and payers expect medical professional organisations to develop practice guidelines and technical standards. The American College of Radiology proactively addresses these topics as well as other quality and safety interests including appropriateness criteria and accreditation. The College is also actively involved in development of a national radiology data base to collect data regarding quality and safety metrics in multiple areas. In addition, the College has developed RADPEER™, a simple, cost-effective process that allows peer review to be performed during the routine interpretation of current images. This paper discusses the efforts of the ACR in all of these areas

The Effect on Retinal Structure and Function of 15 Specific ABCA4 Mutations: A Detailed Examination of 82 Hemizygous Patients

Purpose: To determine the effect of 15 individual ABCA4 mutations on disease severity. Methods: Eighty-two patients harboring 15 distinct ABCA4 mutations in trans with null (hemizygous), 10 homozygous, and 20 nullizygous patients were recruited. Age of onset was determined from medical histories. Electroretinography (ERG) responses were classified into three groups (normal; cone dysfunction; cone and rod dysfunction). The dark-adapted bright-flash (DA 10.0) a-wave amplitudes and the light-adapted flicker ERG (LA 3.0 30 Hz) amplitudes were plotted against age and compared with the nullizygous patients. Fundus autofluorescence imaging (FAF) was assessed when available. Results: Patients hemizygous for p.G1961E and p.R2030Q had normal ERGs. Patients harboring p.R24H, p.R212C, p.G863A/delG, p.R1108C, p.P1380L, p.L2027F, and c.5714+5G>A had abnormal ERGs (ERG group 2 or 3) at older ages, in most cases with significantly higher amplitudes than nullizygous patients. Mutations p.L541P+A1038V, p.E1022K, p.C1490Y, p.E1087K, p.T1526M, and p.C2150Y were associated with abnormal ERGs (group 2 or 3) and amplitudes comparable to those of nullizygous patients. The majority of patients, including those harboring p.G1961E, had foveal atrophy; while both patients harboring p.R2030Q had foveal sparing. Most patients harboring intermediate and null-like mutations displayed FAF abnormalities extending beyond the vascular arcades. Conclusions: In the hemizygous state, 2/15 ABCA4 alleles retain preserved peripheral retinal function; 7/15 are associated with either preserved or only mildly abnormal retinal function, worse in older patients; 6/15 behave like null mutations. These data help characterize the degree of dysfunction conferred by specific mutant ABCA4 proteins in the human retina

Pointlike probes of superstring-theoretic superfluids

In analogy with an experimental setup used in liquid helium, we use a pointlike probe to study superfluids which have a gravity dual. In the gravity description, the probe is represented by a hanging string. We demonstrate that there is a critical velocity below which the probe particle feels neither drag nor stochastic forces. Above this critical velocity, there is power-law scaling for the drag force, and the stochastic forces are characterized by a finite, velocity-dependent temperature. This temperature participates in two simple and general relations between the drag force and stochastic forces. The formula we derive for the critical velocity indicates that the low-energy excitations are massless, and they demonstrate the power of stringy methods in describing strongly coupled superfluids.Comment: 17 pages, 2 figures, added a figure, a reference, and moved material to an appendi