A Note Against the Use of “Belonging To” Properties in Multilevel Selection Theory

Acta Biotheoretica - In this short paper, I argue against what I call the “belonging to” interpretation of group selection in scenarios in which a group’s fitness is defined as...     

Spectral Phase Shift of Surface Plasmon Resonance in the Kretschmann Configuration: Theory and Experiment

The spectral phase shift of surface plasmon resonance (SPR) in the Kretschmann configuration is modeled for aqueous solutions of NaCl (analytes) and an SPR structure consisting of gold and chromium layers deposited on an SF10 glass slide. Using the material dispersion of the SPR structure and the analyte, the SPR phase shift, its spectral derivative, and the spectral dependence of the ratio of the reflectances of p- and s-polarized waves are determined for aqueous solutions of NaCl when the concentration of NaCl in water and the refractive index range from 0 to 10 weight percent (wt%) and from 1.3334 to 1.3515 RIU, respectively. In addition, theoretical modeling is accompanied by experiment and the position of a sharp maximum in the measured spectral derivative of the SPR phase shift changes in a range from 596 to 626 nm. From the measurements, a sensitivity to concentration of 3.83 nm/wt% and a detection limit of 7.3 × 10^?7 RIU at a wavelength of 612.36 nm are obtained, and very good agreement between theory and experiment is confirmed.     

Std1 and Mth1 Proteins Interact with the Glucose Sensors To Control Glucose-Regulated Gene Expression in Saccharomyces cerevisiae

The Std1 protein modulates the expression of glucose-regulated genes, but its exact molecular role in this process is unclear. A two-hybrid screen for Std1-interacting proteins identified the hydrophilic C-terminal domains of the glucose sensors, Snf3 and Rgt2. The homologue of Std1, Mth1, behaves differently from Std1 in this assay by interacting with Snf3 but not Rgt2. Genetic interactions between STD1, MTH1, SNF3, and RGT2 suggest that the glucose signaling is mediated, at least in part, through interactions of the products of these four genes. Mutations in MTH1 can suppress the raffinose growth defect of a snf3 mutant as well as the glucose fermentation defect present in cells lacking both glucose sensors (snf3 rgt2). Genetic suppression by mutations in MTH1 is likely to be due to the increased and unregulated expression of hexose transporter genes. In media lacking glucose or with low levels of glucose, the hexose transporter genes are subject to repression by a mechanism that requires the Std1 and Mth1 proteins. An additional mechanism for glucose sensing must exist since a strain lacking all four genes (snf3 rgt2 std1 mth1) is still able to regulate SUC2 gene expression in response to changes in glucose concentration. Finally, studies with green fluorescent protein fusions indicate that Std1 is localized to the cell periphery and the cell nucleus, supporting the idea that it may transduce signals from the plasma membrane to the nucleus.     

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.     

Hypoxia sensitivity of a voltage-gated potassium current in porcine intrapulmonary vein smooth muscle cells

Hypoxia contracts the pulmonary vein, but the underlying cellular effectors remain unclear. Utilizing contractile studies and whole cell patch-clamp electrophysiology, we report for the first time a hypoxia-sensitive K(+) current in porcine pulmonary vein smooth muscle cells (PVSMC). Hypoxia induced a transient contractile response that was 56 ± 7% of the control response (80 mM KCl). This contraction required extracellular Ca(2+) and was sensitive to Ca(2+) channel blockade. Blockade of K(+) channels by tetraethylammonium chloride (TEA) or 4-aminopyridine (4-AP) reversibly inhibited the hypoxia-mediated contraction. Single-isolated PVSMC (typically 159.1 ± 2.3 μm long) had mean resting membrane potentials (RMP) of -36 ± 4 mV with a mean membrane capacitance of 108 ± 3.5 pF. Whole cell patch-clamp recordings identified a rapidly activating, partially inactivating K(+) current (I(KH)) that was hypoxia, TEA, and 4-AP sensitive. I(KH) was insensitive to Penitrem A or glyburide in PVSMC and had a time to peak of 14.4 ± 3.3 ms and recovered in 67 ms following inactivation at +80 mV. Peak window current was -32 mV, suggesting that I(KH) may contribute to PVSMC RMP. The molecular identity of the potassium channel is not clear. However, RT-PCR, using porcine pulmonary artery and vein samples, identified Kv(1.5), Kv(2.1), and BK, with all three being more abundant in the PV. Both artery and vein expressed STREX, a highly conserved and hypoxia-sensitive BK channel variant. Taken together, our data support the hypothesis that hypoxic inhibition of I(KH) would contribute to hypoxic-induced contraction in PVSMC.     

The impact of utilizing different optical coherence tomography devices for clinical purposes and in multiple sclerosis trials

Optical coherence tomography (OCT) derived retinal measures, particularly peri-papillary retinal nerve fiber layer (RNFL) thickness, have been proposed as outcome measures in remyelinating and neuroprotective trials in multiple sclerosis (MS). With increasing utilization of multiple centers to improve power, elucidation of the impact of different OCT technologies is crucial to the design and interpretation of such studies. In this study, we assessed relation and agreement between RNFL thickness and total macular volume (in MS and healthy controls) derived from three commonly used OCT devices: Stratus time-domain OCT, and Cirrus HD-OCT and Spectralis, two spectral-domain (SD) OCT devices. OCT was performed on both Cirrus HD-OCT and Stratus in 229 participants and on both Cirrus HD-OCT and Spectralis in a separate cohort of 102 participants. Pearson correlation and Bland-Altman analyses were used to assess correlation and agreement between devices. All OCT retinal measures correlated highly between devices. The mean RNFL thickness was 7.4 μm lower on Cirrus HD-OCT than Stratus, indicating overall poor agreement for this measurement between these machines. Further, the limits of agreement (LOA) between Cirrus HD-OCT and Stratus were wide (-4.1 to 18.9 μm), indicating poor agreement at an individual subject level. The mean RNFL thickness was 1.94 μm (LOA: -5.74 to 9.62 μm) higher on Spectralis compared to Cirrus HD-OCT, indicating excellent agreement for this measurement across this cohort. Although these data indicate that these three devices agree poorly at an individual subject level (evidenced by wide LOA in both study cohorts) precluding their co-utilization in everyday practice, the small difference for mean measurements between Cirrus HD-OCT and Spectralis indicate pooled results from these two SD-devices could be used as outcome measures in clinical trials, provided patients are scanned on the same machine throughout the trial, similar to the utilization of multiple different MRI platforms in MS clinical trials.     

Survival of cold-adapted species in isolated mountains: the population genetics of the Sudeten ringlet,Erebia sudetica sudetica,in the Jeseník Mts., Czech Republic

Relic populations of cold-adapted species, trapped in isolated mountain pockets within the temperate zone, are predicted to suffer considerably due to ongoing climate warming. The butterfly Erebia sudetica sudetica is an example restricted to the Eastern Sudety Mts. Here, the butterfly forms permanent populations on subalpine tall-herb grasslands, but also occupies woodland clearings and hay meadows at lower altitudes. We assume differences among the genetic diversities of the populations due to differences in the temporal continuity of these habitats. Therefore, 17 allozyme loci were analysed for 276 individuals from 13 different localities (six tall-herb stands, two meadows, five forest clearings) in the Jeseník Mts. with a maximum distance of 20 km among them. We obtained a significantly higher genetic diversity for the subalpine populations than for the forest clearing populations. The genetic differentiation among the forest clearing populations was higher than among the subalpine ones. They also showed a significant isolation-by-distance system. These findings support the idea that the lower-elevation populations might have been founded by more than one dispersal event from the subalpine sites, but also secondary colonisations and gene flow in the forest belt. Due to founder effects and possibly further subsequent bottlenecks, these forest clearing populations did not harbour the entire genetic diversity of the taxon. Therefore, conservation actions should focus on the subalpine tall-herb formation.