Single-channel analysis of a ClC-2-like chloride conductance in cultured rat cortical astrocytes

AbstractThe single-channel behavior of the hyperpolarization-activated, ClC-2-like inwardly rectifying Cl− current (IClh), induced by long-term dibutyryl-cyclic-AMP-treated cultured cortical rat astrocytes, was analyzed with the patch-clamp technique. In outside-out patches in symmetrical 144 mM Cl− solutions, openings of hyperpolarization-activated small-conductance Cl− channels revealed burst activity of two equidistant conductance levels of 3 and 6 pS. The unitary openings displayed slow activation kinetics. The probabilities of the closed and conducting states were consistent with a double-barrelled structure of the channel protein. These results suggest that the astrocytic ClC-2-like Cl− current IClh is mediated by a small-conductance Cl− channel, which has the same structural motif as the Cl− channel prototype ClC-0

Shaping and Dilating the Fitness Landscape for Parameter Estimation in Stochastic Biochemical Models

The parameter estimation (PE) of biochemical reactions is one of the most challenging tasks in systems biology given the pivotal role of these kinetic constants in driving the behavior of biochemical systems. PE is a non-convex, multi-modal, and non-separable optimization problem with an unknown fitness landscape; moreover, the quantities of the biochemical species appearing in the system can be low, making biological noise a non-negligible phenomenon and mandating the use of stochastic simulation. Finally, the values of the kinetic parameters typically follow a log-uniform distribution; thus, the optimal solutions are situated in the lowest orders of magnitude of the search space. In this work, we further elaborate on a novel approach to address the PE problem based on a combination of adaptive swarm intelligence and dilation functions (DFs). DFs require prior knowledge of the characteristics of the fitness landscape; therefore, we leverage an alternative solution to evolve optimal DFs. On top of this approach, we introduce surrogate Fourier modeling to simplify the PE, by producing a smoother version of the fitness landscape that excludes the high frequency components of the fitness function. Our results show that the PE exploiting evolved DFs has a performance comparable with that of the PE run with a custom DF. Moreover, surrogate Fourier modeling allows for improving the convergence speed. Finally, we discuss some open problems related to the scalability of our methodology

A lattice study of the strangeness content of the nucleon

We determine the quark contributions to the nucleon spin Delta s, Delta u and Delta d as well as their contributions to the nucleon mass, the sigma-terms. This is done by computing both, the quark line connected and disconnected contributions to the respective matrix elements, using the non-perturbatively improved Sheikholeslami-Wohlert Wilson Fermionic action. We simulate n_F=2 mass degenerate sea quarks with a pion mass of about 285 MeV and a lattice spacing a = 0.073 fm. The renormalization of the matrix elements involves mixing between contributions from different quark flavours. The pion-nucleon sigma-term is extrapolated to physical quark masses exploiting the sea quark mass dependence of the nucleon mass. We obtain the renormalized value sigma_{piN}=38(12) MeV at the physical point and the strangeness fraction f_{Ts}=sigma_s/m_N=0.012(14)(+10-3) at our larger than physical sea quark mass. For the strangeness contribution to the nucleon spin we obtain in the MSbar scheme at the renormalization scale of 2.71 GeV Delta s = -0.020(10)(2).Comment: 7 pages, 3 figures, Invited Talk at the 33rd Erice School on Nuclear Physics, Erice, 16-24 September 2011, Ital

Occurrence of antibiotics in mussels and clams from various FAO areas

Filter feeders, like mussels and clams, are suitable bioindicators of environmental pollution. These shellfish, when destined for human consumption, undergo a depuration step that aims to nullify their pathogenic microorganism load and decrease chemical contamination. Nevertheless, the lack of contamination by drugs may not be guaranteed. Antimicrobials are a class of drugs of particular concern due to the increasing phenomenon of antibiotic resistance. Their use in breeding and aquaculture is a major cause of this. We developed a multiclass method for the HPLC\ue2\u80\u93MS/MS analysis of 29 antimicrobials, validated according to the Commission Decision 2002/657/UE guidelines, and applied it to 50 mussel and 50 clam samples derived from various Food and Agricultural Organisation marine zones. The results obtained, indicate a negligible presence of antibiotics. Just one clam sample showed the presence of oxytetracycline at a concentration slightly higher than the European Union Maximum residue limit set for fish

Altered Prostasin (CAP1/Prss8) Expression Favors Inflammation and Tissue Remodeling in DSS-induced Colitis.

Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are diseases with impaired epithelial barrier function. We aimed to investigate whether mutated prostasin and thus, reduced colonic epithelial sodium channel activity predisposes to develop an experimentally dextran sodium sulfate (DSS)-induced colitis. Wildtype, heterozygous (fr/+), and homozygous (fr/fr) prostasin-mutant rats were treated 7 days with DSS followed by 7 days of recovery and analyzed with respect to histology, clinicopathological parameters, inflammatory marker mRNA transcript expression, and sodium transporter protein expression. In this study, a more detailed analysis on rat fr/fr colons revealed reduced numbers of crypt and goblet cells, and local angiodysplasia, as compared with heterozygous (fr/+) and wildtype littermates. Following 2% DSS treatment for 7 days followed by 7 days recovery, fr/fr animals lost body weight, and reached maximal diarrhea score and highest disease activity after only 3 days, and strongly increased cytokine levels. The histology score significantly increased in all groups, but fr/fr colons further displayed pronounced histological alterations with near absence of goblet cells, rearrangement of the lamina propria, and presence of neutrophils, eosinophils, and macrophages. Additionally, fr/fr colons showed ulcerations and edemas that were absent in fr/+ and wildtype littermates. Following recovery, fr/fr rats reached, although significantly delayed, near-normal diarrhea score and disease activity, but exhibited severe architectural remodeling, despite unchanged sodium transporter protein expression. In summary, our results demonstrate a protective role of colonic prostasin expression against experimental colitis, and thus represent a susceptibility gene in the development of inflammatory bowel disease

Avoiding spurious feedback loops in the reconstruction of gene regulatory networks with dynamic bayesian networks

Feedback loops and recurrent structures are essential to the regulation and stable control of complex biological systems. The application of dynamic as opposed to static Bayesian networks is promising in that, in principle, these feedback loops can be learned. However, we show that the widely applied BGe score is susceptible to learning spurious feedback loops, which are a consequence of non-linear regulation and autocorrelation in the data. We propose a non-linear generalisation of the BGe model, based on a mixture model, and demonstrate that this approach successfully represses spurious feedback loops

Shelf life of Stracciatella cheese under modified-atmosphere packaging

The aim of this work is to evaluate the shelf life of Stracciatella cheese packaged in a protective atmosphere, using 4 different CO(2):N(2):O(2) gas mixtures [50:50:0 (M1), 95:5:0 (M2), 75:25:0 (M3), and 30:65:5 (M4) vol/vol] and stored at 8 degrees C. Cheese in traditional tubs and under vacuum were used as the controls. Results showed that the modified-atmosphere packaging, in particular M1 and M2, delayed microbial growth of spoilage bacteria, without affecting the dairy microflora, and prolonged the sensorial acceptability limit

Coriolis Effect on Dynamic Stall in a Vertical Axis Wind Turbine at Moderate Reynolds Number

The immersed boundary method is used to simulate the flow around a two-dimensional rotating NACA 0018 airfoil at sub-scale Reynolds number in order to investigate the separated flow occurring on a vertical-axis wind turbine. The influence of dynamic stall on the forces is characterized as a function of tip-speed ratio. The influence of the Coriolis effect is also investigated by comparing the rotating airfoil to one undergoing a equivalent planar motion, which is composed of surging and pitching motions that produce an equivalent speed and angle-of-attack variation over the cycle. When the angle of attack of a rotating airfoil starts to decrease in the upwind half cycle, the Coriolis force leads to a wake-capturing phenomenon of a vortex pair at low tip-speed ratio. This effects occurs at a slightly different phase in each cycle and leads to a significant decrease in the average lift during the downstroke phase. Moreover, the wake-capturing is only observed when the combination of surging, pitching, and Coriolis force are present. Finally, an actuator model is placed at an appropriate location on the suction side of the airfoil surface to control the wake-capturing phenomenon. Based on preliminary simulations, a momentum coefficient above 0.02 was able to increase the average lift by more than 70% over the upwind-half cycle