Electrostatic and non-electrostatic contributions of proteoglycans to the compressive equilibrium modulus of bovine articular cartilage

This study presents direct experimental evidence for assessing the electrostatic and non-electrostatic contributions of proteoglycans to the compressive equilibrium modulus of bovine articular cartilage. Immature and mature bovine cartilage samples were tested in unconfined compression and their depth-dependent equilibrium compressive modulus was determined using strain measurements with digital image correlation analysis. The electrostatic contribution was assessed by testing samples in isotonic and hypertonic saline; the combined contribution was assessed by testing untreated and proteoglycan-depleted samples.Though it is well recognized that proteoglycans contribute significantly to the compressive stiffness of cartilage, results demonstrate that the combined electrostatic and non-electrostatic contributions may add up to more than 98% of the modulus, a magnitude not previously appreciated. Of this contribution, about two thirds arises from electrostatic effects. The compressive modulus of the proteoglycan-depleted cartilage matrix may be as low as 3 kPa, representing less than 2% of the normal tissue modulus; experimental evidence also confirms that the collagen matrix in digested cartilage may buckle under compressive strains, resulting in crimping patterns. Thus, it is reasonable to model the collagen as a fibrillar matrix that can sustain only tension. This study also demonstrates that residual stresses in cartilage do not arise exclusively from proteoglycans, since cartilage remains curled relative to its in situ geometry even after proteoglycan depletion. These increased insights on the structure–function relationships of cartilage can lead to improved constitutive models and a better understanding of the response of cartilage to physiological loading conditions.     

Characterization of PfiT/PfiA toxin–antitoxin system of Pseudomonas aeruginosa that affects cell elongation and prophage induction

Toxin–antitoxin (TA) systems are small genetic modules usually consisting of two elements—a toxin and an antitoxin. The abundance of TA systems among various bacterial strains may indicate an important evolutionary role. Pseudomonas aeruginosa, which can be found in a variety of niches in nature, is an opportunistic pathogen for various hosts. While P. aeruginosa strains are very versatile and diverse, only a few TA systems were characterized in this species. Here, we describe a newly characterized TA system in P. aeruginosa that is encoded within the filamentous Pf4 prophage. This system, named PfiT/PfiA, is a homologue of the ParE/YefM TA system. It is a type II TA system, in which the antitoxin is a protein that binds the toxic protein and eliminates the toxic effect. PfiT/PfiA carries several typical type II characteristics. Specifically, it constitutes two small genes expressed in a single operon, PfiT inhibits growth and PfiA eliminates this effect, PfiA binds PfiT, and PfiT expression results in elongated cells. Finally, we assigned a novel function to this TA system, where an imbalance between PfiT and PfiA, favouring the toxin, resulted in cell elongation and an increase in virion production.     

Modeling force application configurations and morphologies required for cancer cell invasion

Biomechanics and Modeling in Mechanobiology - We show that cell-applied, normal mechanical stresses are required for cells to penetrate into soft substrates, matching experimental observations in...     

Simulation and study of the geometric parameters in the inguinal area and the genesis of inguinal hernias

We are interested in studying the genesis of a very common pathology: the human inguinal hernia. How the human inguinal hernia appears is not definitively clear, but it is accepted that it is caused by a combination of mechanical and biochemical alterations, and that muscular simulation plays an important role in this. This study proposes a model to explain how some physical parameters affect the ability to simulate the region dynamically and how these parameters are involved in generating inguinal hernias. We are particularly interested in understanding the mechanical alterations in the inguinal region because little is known about them or how they behave dynamically. Our model corroborates the most important theories regarding the generation of inguinal hernias and is an initial approach to numerically evaluating this affection.     

Synthesis of 1,5-Anhydrohexitol Nucleosides as Mimics of AZT,D4T and DDC

Abstract

1,5-Anhydrohexitol congeners of AZT, D4T and DDC were synthesized. These compounds did not show anti-HIV activity.

     

Potential effects of climate change on biological control systems: case studies from New Zealand

Biological control systems are integral to New Zealand’s success as a nation reliant on exporting quality agricultural, forestry and horticultural products. The likely impacts of climate change projections to 2090 on one weed and four invertebrate management systems in differing production sectors were investigated, and it was concluded that most natural enemies will track the changing distributions of their hosts. The key climate change challenges identified were: disparities in natural enemy capability to change distribution, lack of frosts leading to emergence of new pests and additional pest generations, non-target impacts from range and temperature changes, increased disruptions caused by extreme weather events, disruption of host-natural enemy synchrony, and insufficient genetic diversity to allow evolutionary adaptation. Five classical biological control systems based on the introduced species Longitarsus jacobaeae, Cotesia kazak, Aphelinus mali, Microctonus aethiopoides and Microctonus hyperodae are discussed in more detail.     

Wheat Zapper: a flexible online tool for colinearity studies in grass genomes

In the course of evolution, the genomes of grasses have maintained an observable degree of gene order conservation. The information available for already sequenced genomes can be used to predict the gene order of nonsequenced species by means of comparative colinearity studies. The “Wheat Zapper” application presented here performs on-demand colinearity analysis between wheat, rice, Sorghum, and Brachypodium in a simple, time efficient, and flexible manner. This application was specifically designed to provide plant scientists with a set of tools, comprising not only synteny inference, but also automated primer design, intron/exon boundaries prediction, visual representation using the graphic tool Circos 0.53, and the possibility of downloading FASTA sequences for downstream applications. Quality of the “Wheat Zapper” prediction was confirmed against the genome of maize, with good correlation (r?>?0.83) observed between the gene order predicted on the basis of synteny and their actual position on the genome. Further, the accuracy of “Wheat Zapper” was calculated at 0.65 considering the “Genome Zipper” application as the “gold” standard. The differences between these two tools are amply discussed, making the point that “Wheat Zapper” is an accurate and reliable on-demand tool that is sure to benefit the cereal scientific community. The Wheat Zapper is available at http://wge.ndsu.nodak.edu/wheatzapper/.     

Dectin-1 Is Essential for Reverse Transcytosis of Glycosylated SIgA-Antigen Complexes by Intestinal M Cells

Intestinal microfold (M) cells possess a high transcytosis capacity and are able to transport a broad range of materials including particulate antigens, soluble macromolecules, and pathogens from the intestinal lumen to inductive sites of the mucosal immune system. M cells are also the primary pathway for delivery of secretory IgA (SIgA) to the gut-associated lymphoid tissue. However, although the consequences of SIgA uptake by M cells are now well known and described, the mechanisms whereby SIgA is selectively bound and taken up remain poorly understood. Here we first demonstrate that both the Cα1 region and glycosylation, more particularly sialic acid residues, are involved in M cell–mediated reverse transcytosis. Second, we found that SIgA is taken up by M cells via the Dectin-1 receptor, with the possible involvement of Siglec-5 acting as a co-receptor. Third, we establish that transcytosed SIgA is taken up by mucosal CX3CR1⁺ dendritic cells (DCs) via the DC-SIGN receptor. Fourth, we show that mucosal and systemic antibody responses against the HIV p24-SIgA complexes administered orally is strictly dependent on the expression of Dectin-1. Having deciphered the mechanisms leading to specific targeting of SIgA-based Ag complexes paves the way to the use of such a vehicle for mucosal vaccination against various infectious diseases.