Insights into the cooperative nature of ATP hydrolysis in actin filaments

Actin filaments continually assemble and disassemble within a cell. Assembled filaments "age" as a bound nucleotide ATP within each actin subunit quickly hydrolyzes, followed by a slower release of the phosphate Pi, leaving behind a bound ADP. This subtle change in nucleotide state of actin subunits affects filament rigidity as well as its interactions with binding partners. We present here a systematic multi-scale ultra-coarse-graining (UCG) approach that provides a computationally efficient way to simulate a long actin filament undergoing ATP hydrolysis and phosphate release reactions, while systematically taking into account available atomistic details.

https://ift.tt/2orTvZu

Mechanics of virus-like particles labeled with green fluorescent protein

Nanoindentation with an atomic force microscope was used to investigate the mechanical properties of virus-like-particles (VLPs) derived from the avian pathogen infectious bursal disease virus (IBDV), in which the major capsid protein was modified by fusion with enhanced green fluorescent protein (EGFP). These IBDV-based VLPs assemble as ∼70-nm-diameter T=13 icosahedral capsids with large cargo space. The effect of the insertion of heterologous proteins in the capsid was characterized in the elastic regime, revealing that EGFP-labeled chimeric VLPs are more rigid than unmodified VLPs.

https://ift.tt/2PlRcCH

Ca2+ and Myosin Cycle States Work as Allosteric Effectors of Troponin Activation

In cardiac muscle, troponin (Tn) and tropomyosin (Tm) inhibit actin and myosin interactions through the steric blocking of myosin binding to F-actin. Ca2+ binding to TnC modulates this inhibition. Thin filaments become activated upon Ca2+ binding, which enables strong binding of myosin with concomitant release of ATP hydrolysis products and level arm swinging responsible for force generation. Despite this level of description, the current cross-bridge cycle model does not fully define the structural events that take place within Tn during combinatorial myosin and Ca2+ interventions.

https://ift.tt/2Pr05Lg

Preparation of Asymmetric Liposomes using a Phosphatidylserine Decarboxylase

Lipid asymmetries between the outer and inner leaflet of the lipid bilayer exist in nearly all biological membranes. Although living cells spend great effort to adjust and maintain these asymmetries, little is known about the biophysical phenomena within asymmetric membranes and their role in cellular function. One reason for this lack of insight into such a fundamental membrane property is the fact that the majority of model-membrane studies have been performed on symmetric membranes.Our aim is to overcome this problem by employing a targeted, enzymatic reaction to prepare asymmetric liposomes with phosphatidylserine (PS) primarily in the inner leaflet.

https://ift.tt/2N9221w

Discovery of pre-therapy 2-deoxy-2- 18 F-fluoro-D-glucose positron emission tomography-based radiomics classifiers of survival outcome in non-small-cell lung cancer patients

Abstract

Purpose

The aim of this multi-center study was to discover and validate radiomics classifiers as image-derived biomarkers for risk stratification of non-small-cell lung cancer (NSCLC).

Patients and methods

Pre-therapy PET scans from a total of 358 Stage I–III NSCLC patients scheduled for radiotherapy/chemo-radiotherapy acquired between October 2008 and December 2013 were included in this seven-institution study. A semi-automatic threshold method was used to segment the primary tumors. Radiomics predictive classifiers were derived from a training set of 133 scans using TexLAB v2. Least absolute shrinkage and selection operator (LASSO) regression analysis was used for data dimension reduction and radiomics feature vector (FV) discovery. Multivariable analysis was performed to establish the relationship between FV, stage and overall survival (OS). Performance of the optimal FV was tested in an independent validation set of 204 patients, and a further independent set of 21 (TESTI) patients.

Results

Of 358 patients, 249 died within the follow-up period [median 22 (range 0–85) months]. From each primary tumor, 665 three-dimensional radiomics features from each of seven gray levels were extracted. The most predictive feature vector discovered (FVX) was independent of known prognostic factors, such as stage and tumor volume, and of interest to multi-center studies, invariant to the type of PET/CT manufacturer. Using the median cut-off, FVX predicted a 14-month survival difference in the validation cohort (N = 204, p = 0.00465; HR = 1.61, 95% CI 1.16–2.24). In the TESTI cohort, a smaller cohort that presented with unusually poor survival of stage I cancers, FVX correctly indicated a lack of survival difference (N = 21, p = 0.501). In contrast to the radiomics classifier, clinically routine PET variables including SUV_max, SUV_mean and SUV_peak lacked any prognostic information.

Conclusion

PET-based radiomics classifiers derived from routine pre-treatment imaging possess intrinsic prognostic information for risk stratification of NSCLC patients to radiotherapy/chemo-radiotherapy.

https://ift.tt/2NIYuzO

Treatment of angiomatoid fibrous histiocytoma after unplanned excision: a case report

Angiomatoid fibrous histiocytoma (AFH) is a relatively uncommon soft tissue tumor of intermediate biologic potential. It occurs in subcutaneous regions of the extremities or the trunk, usually presenting in ch...

https://ift.tt/2PSU5fc

Analysis of amino acid motif of penicillin-binding proteins 1a, 2b, and 2x in invasive Streptococcus pneumoniae nonsusceptible to penicillin isolated from pediatric patients in Casablanca, Morocco

This study aimed to investigate the nature of the amino acid motifs found in PBPs of Streptococcus pneumoniae isolates in invasive diseases from pediatric patients at Casablanca, Morocco. Five penicillin-suscepti...

https://ift.tt/2PpPf8q