Angular transformation – another effect of different sample sizes

Angular transformation has been widely used to analyze proportions or percentages in ecology. A new type of artifact can arise by applying angular transformation to proportions or percentages. Proportions with the same mean or expected value, but with different sample sizes (denominator of proportions), have different means or expected values after this transformation. Overdispersion causes a larger deviation of the expected value after the transformation. Angular transformation should be avoided unless the sample size (denominator of proportions) is the same for all the proportions analyzed.     

Lipid shape is a key factor for membrane interactions of amphipathic helical peptides

The membrane alignment of the amphiphilic α-helical model peptide MSI-103 (sequence [KIAGKIA](3)-NH(2)) was examined by solid state (2)H-NMR in different lipid systems by systematically varying the acyl chain length and degree of saturation, the lipid head group type, and the peptide-to-lipid molar ratio. In liquid crystalline phosphatidylcholine (PC) lipids with saturated chains, the amphiphilic helix changes its orientation from a surface-bound "S-state" to a tilted "T-state" with increasing peptide concentration. In PC lipids with unsaturated chains, on the other hand, the S-state is found throughout all concentrations. Using phosphatidylethanolamine lipids with a small head group or by addition of lyso-lipids with only one acyl chain, the spontaneous curvature of the bilayer was purposefully changed. In the first case with a negative curvature only the S-state was found, whereas in systems with a positive curvature the peptide preferred the obliquely immersed T-state at high concentration. The orientation of MSI-103 thus correlates very well with the shape of the lipid molecules constituting the membrane. Lipid charge, on the other hand, was found to affect only the initial electrostatic attraction to the membrane surface but not the alignment preferences. In bilayers that are "sealed" with 20% cholesterol, MSI-103 cannot bind in a well-oriented manner and forms immobilized aggregates instead. We conclude that the curvature properties of a membrane are a key factor in the interactions of amphiphilic helical peptides in general, whose re-alignment and immersion preferences may thus be inferred in a straightforward manner from the lipid-shape concept.     

Long-term Safety and Efficacy of Human-Induced Pluripotent Stem Cell (iPS) Grafts in a Preclinical Model of Retinitis Pigmentosa

The U.S. Food and Drug Administration recently approved phase I/II clinical trials for embryonic stem (ES) cell–based retinal pigmented epithelium (RPE) transplantation, but this allograft transplantation requires lifelong immunosuppressive therapy. Autografts from patient-specific induced pluripotent stem (iPS) cells offer an alternative solution to this problem. However, more data are required to establish the safety and efficacy of iPS transplantation in animal models before moving iPS therapy into clinical trials. This study examines the efficacy of iPS transplantation in restoring functional vision in Rpe65^rd12/Rpe65^rd12 mice, a clinically relevant model of retinitis pigmentosa (RP). Human iPS cells were differentiated into morphologically and functionally RPE-like tissue. Quantitative real-time polymerase chain reaction (RT-PCR) and immunoblots confirmed RPE fate. The iPS-derived RPE cells were injected into the subretinal space of Rpe65^rd12/Rpe65^rd12 mice at 2 d postnatally. After transplantation, the long-term surviving iPS-derived RPE graft colocalized with the host native RPE cells and assimilated into the host retina without disruption. None of the mice receiving transplants developed tumors over their lifetimes. Furthermore, electroretinogram, a standard method for measuring efficacy in human trials, demonstrated improved visual function in recipients over the lifetime of this RP mouse model. Our study provides the first direct evidence of functional recovery in a clinically relevant model of retinal degeneration using iPS transplantation and supports the feasibility of autologous iPS cell transplantation for retinal and macular degenerations featuring significant RPE loss.     

Parkinson Subtypes Progress Differently in Clinical Course and Imaging Pattern

Objective

To elucidate whether Parkinson’s disease (PD) subtypes show a differential pattern of FP-CIT-SPECT binding during the disease course.

Methods

We examined 27 patients (10 female, 17 male, mean age 61.68±11.24 years, 14 tremordominant, 13 akinetic-rigid) with [¹²³I]FP-CIT-SPECT and clinical ratings including UPDRS III after at baseline and after a mean period of 2.47 years. Patients had been classified at baseline as tremordominant or akinetic-rigid according to a “tremor score” and “non-tremor score”. These subgroups were compared for differences in disease progression. Means of clinical ratings and the quantitative analyses of FP-CIT-SPECT for ipsi- and contralateral putamen and caudate nucleus were calculated and compared between baseline and follow-up.

Results

There were no statistical differences concerning age, disease duration, L-Dopa equivalent dose, disease severity (UPDRS III) or dopaminergic uptake in FP-CIT-SPECT at baseline between both subgroups. At follow-up, akinetic-rigid patients showed a distinct and statistically significant reduction of the dopaminergic uptake associated with significant progression of the clinical symptoms (UPDRS III). In contrast, in tremor patients the aggravation of clinical symptoms and dopaminergic deficit was less pronounced without statistical significance among assessments.

Conclusions

This study shows for the first time a considerable progression of clinical symptoms and in-vivo dopaminergic deficit of akinetic-rigid compared to tremordominant PD patients over time. Our data may help to improve strategic planning of further therapeutic trials and to provide a clearer prognosis for patients regarding the perspective of their disease.     

Pre-, Per- and Postoperative Factors Affecting Performance of Postlinguistically Deaf Adults Using Cochlear Implants: A New Conceptual Model over Time

Objective

To test the influence of multiple factors on cochlear implant (CI) speech performance in quiet and in noise for postlinguistically deaf adults, and to design a model of predicted auditory performance with a CI as a function of the significant factors.

Study Design

Retrospective multi-centre study.

Methods

Data from 2251 patients implanted since 2003 in 15 international centres were collected. Speech scores in quiet and in noise were converted into percentile ranks to remove differences between centres. The influence of 15 pre-, per- and postoperative factors, such as the duration of moderate hearing loss (mHL), the surgical approach (cochleostomy or round window approach), the angle of insertion, the percentage of active electrodes, and the brand of device were tested. The usual factors, duration of profound HL (pHL), age, etiology, duration of CI experience, that are already known to have an influence, were included in the statistical analyses.

Results

The significant factors were: the pure tone average threshold of the better ear, the brand of device, the percentage of active electrodes, the use of hearing aids (HAs) during the period of pHL, and the duration of mHL.

Conclusions

A new model was designed showing a decrease of performance that started during the period of mHL, and became faster during the period of pHL. The use of bilateral HAs slowed down the related central reorganization that is the likely cause of the decreased performance.     

Aggregatibacter actinomycetemcomitans GroEL Protein Promotes Conversion of Human CD4+ T Cells into IFNγ IL10 Producing Tbet+ Th1 Cells

One of the heat shock family protein (Hsp) expressing bacteria is the gram negative, periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa). A. actinomycetemcomitans’ Hsp is a 64-kDa GroEL-protein, which has been shown to influence the host cells. In this study we used recombinant A. actinomycetemcomitans GroEL (rAaGroEL) protein as a model antigen to study GroEL-mediated T cell immune response. Human peripheral mononuclear cells (PBMCs), when stimulated with recombinant rAaGroEL, expressed early activation marker CD69 and IL-2R (CD25). CD25 and CD69 expressions were higher in CD4+ T cells compared to CD8+ T cells. rAaGroEL-responding CD4+ T cells expressed IL-10, IFNγ and TNFα cytokines. Interestingly, there were also IL-10 and IFNγ double cytokine producing CD4+ T cells. Additionally, IFNγ expressing CD4+ T cells were also T-bet positive. Altogether the results suggest that rAaGroEL protein affects CD4+ T cells to differentiate into IFNγ IL10-secreting T-bet+ Th1 cells.     

A novel approach to yard planning under vessel arrival uncertainty

Many container terminals in the world adopt the consolidated yard planning strategy, where containers to be loaded into the same vessel are stacked in groups. This has been a good strategy because when a vessel is loading, yard cranes will be stationed at these locations, and the trucks shuttle between the quay cranes and the yard cranes almost in a conveyor belt fashion. These locations are optimally chosen such that no two groups of containers are stacked in close vicinity if they are to be loaded simultaneously. However, when there is a change in vessel arrival schedule, it may cause congestion of trucks at yard locations where groups of containers in near vicinity are loading simultaneously. While the Robust Optimisation community may suggest having a robust plan—a plan that is immune to uncertainty, in this paper, we will like to find a solution that allows us to change easily when uncertainty reveals—a plan that is nimble. While the optimum solution for the nimble plan could be intractable, we explore various heuristics that enable us to find good solutions.     

Arsenate V induced glutathione efflux from human erythrocytes

ObjectiveThe objective of the present study was to investigate if arsenate V exposure results in glutathione efflux from human erythrocytes.ProcedureThe changes in intracellular and extracellular nonprotein sulfhydryl and glutathione levels were determined in arsenate (V) exposed erythrocytes. Presence of any cellular membrane damage was assessed by lactate dehydrogenase activity measurement in the supernatant.ResultsWhen erythrocytes were exposed to 10 mM of arsenate (V) for 4 h, the intracellular NPSH level decreased to 0.28 ± 0025 μmol/ml erythrocyte. In contrast, extracellular nonprotein thiol level was increased to 0.180 ± 0.010 μmol/ml erythrocyte in 4 h. Extracellular glutathione levels reached to 0.028 ± 0.001, 0.052 ± 0.002, and 0.054 ± 0.004 μmol/ml erythrocyte with 1, 5, and 10 mM of arsenate (V), respectively. Utilization of MK571 a multi drug resistance-associated protein 1 inhibitor decreased the rate of glutathione efflux from erythrocytes suggesting a role for this membrane transporter in the process.ConclusionThe results of the present study indicate that erythrocytes efflux glutathione when exposed to arsenate (V).