Patterns in Space: Coordinating Adhesion and Actomyosin Contractility at E-cadherin Junctions

Cadherin adhesion receptors are fundamental determinants of tissue organization in health and disease. Increasingly, we have come to appreciate that classical cadherins exert their biological actions through active cooperation with the contractile actin cytoskeleton. Rather than being passive resistors of detachment forces, cadherins can regulate the assembly and mechanics of the contractile apparatus itself. Moreover, coordinate spatial patterning of adhesion and contractility is emerging as a determinant of morphogenesis. Here we review recent developments in cadherins and actin cytoskeleton cooperativity, by focusing on E-cadherin adhesive patterning in the epithelia. Next, we discuss the underlying principles of cellular rearrangement during Drosophila germband extension and epithelial cell extrusion, as models of how planar and apical-lateral patterns of contractility organizes tissue architecture.Comment: 11 pages, 5 figures, PREVIEW OF PREPRINT ONL

Editorial overview: Membrane traffic and cell polarity

No abstract available

Engineering Dehydrated Amino Acid Residues in the Antimicrobial Peptide Nisin

The small antimicrobial peptide nisin, produced by Lactococcus lactis, contains the uncommon amino acid residues dehydroalanine and dehydrobutyrine and five thio ether bridges. Since these structures are posttranslationally formed from Ser, Thr, and Cys residues, it is feasible to study their role in nisin function and biosynthesis by protein engineering. Here we report the development of an expression system for mutated nisin Z (nisZ) genes, using nisin A producing L. lactis as a host. Replacement by site-directed mutagenesis of the Ser-5 codon in nisZ by a Thr codon, led to a mutant with a dehydrobutyrine instead of a dehydroalanine residue at position 5, as shown by NMR. Its antimicrobial activity was 2-10-fold lower relative to wild-type nisin Z, depending on the indicator strain used. In another mutagenesis study a double mutation was introduced in the nisZ gene by replacing the codons for Met-17 and Gly-18 by codons for Gln and Thr, respectively, as in the third lanthionine ring of the related antimicrobial peptide subtilin from Bacillus subtilis. This resulted in the simultaneous production of two mutant species, one containing a Thr residue and the other containing a dehydrobutyrine residue at position 18, both having different bacteriocidal properties.

Management and investigation of neonatal encephalopathy: 2017 update.

This review discusses an approach to determining the cause of neonatal encephalopathy, as well as current evidence on resuscitation and subsequent management of hypoxic-ischaemic encephalopathy (HIE). Encephalopathy in neonates can be due to varied aetiologies in addition to hypoxic-ischaemia. A combination of careful history, examination and the judicious use of investigations can help determine the cause. Over the last 7 years, infants with moderate to severe HIE have benefited from the introduction of routine therapeutic hypothermia; the number needed to treat for an additional beneficial outcome is 7 (95% CI 5 to 10). More recent research has focused on optimal resuscitation practices for babies with cardiorespiratory depression, such as delayed cord clamping after establishment of ventilation and resuscitation in air. Around a quarter of infants with asystole at 10 min after birth who are subsequently cooled have normal outcomes, suggesting that individualised decision making on stopping resuscitation is needed, based on access to intensive treatment unit and early cooling. The full benefit of cooling appears to have been exploited in our current treatment protocols of 72 hours at 33.5°C; deeper and longer cooling showed adverse outcome. The challenge over the next 5-10 years will be to assess which adjunct therapies are safe and optimise hypothermic brain protection in phase I and phase II trials. Optimal care may require tailoring treatments according to gender, genetic risk, injury severity and inflammatory status

Brexit and the Implications of Food Safety Cultural Compliance in the Food Manufacturing Sector

In theory food safety is a critical measurement, not just for economic and legal reasons but also for the moral integrity of the organisation. However, in reality, the number of accidents or incidents particularly in the food manufacturing sector is a serious cause for concern. The problem is further compounded with the onset of Brexit. Given the UK government’s floundering negotiation talks and the pending conservative leadership challenge, it has resulted in a climate of uncertainty, a devaluation of currency and economic instability. Food manufacturers along with other commercial businesses are reluctant to further invest until the economic future is more transparent. In consequence, food manufacturers are seeking efficiency savings, whilst aiming not to compromise food safety compliance. Whilst there are areas of best practice, sadly there are an increasing number of examples in which failure to comply to food safety is resulting in lost of business, serious injury and in certain cases fatalities. This paper addresses Food Safety Cultural Compliance within UK Food Manufacturers and identifies core issues that hinder the establishment of a proactive food safety culture. The research study adopts a mixed methods approach in which five UK food manufacturers were consulted via 15 semi-structured interviews with management and three focused groups. The data collected clearly indicates a commitment to food safety compliance. However, the majority of organisations struggled to maintain consistent levels of food safety compliance despite implementing costly training and development initiatives. Their strategic and operational drive to both enhance and maintain a positive food safety culture was also undermined with the uncertainty of economic pressures and the quagmire of Brexit. The paper concludes with a series of commercially viable recommendations within the context of the Brexit divorce and provides a clear contribution to the community of practice

Contact inhibition of locomotion and mechanical cross-talk between cell-cell and cell-substrate adhesion determines the pattern of junctional tension in epithelial cell aggregates

We generated a computational approach to analyze the biomechanics of epithelial cell aggregates, either island or stripes or entire monolayers, that combines both vertex and contact-inhibition-of-locomotion models to include both cell-cell and cell-substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of basal protrusions, traction forces and apical aspect ratios that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell-cell junctions and apical stress is not homogeneous across the island. Instead, these parameters are higher at the island center and scales up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Without formally being a 3-dimensional model, our approach has the minimal elements necessary to reproduce the distribution of cellular forces and mechanical crosstalk as well as distribution of principal stress in cells within epithelial cell aggregates. By making experimental testable predictions, our approach would benefit the mechanical analysis of epithelial tissues, especially when local changes in cell-cell and/or cell-substrate adhesion drive collective cell behavior.Comment: 39 pages, 8 Figures. Supplementary Information is include

Investigating the Presence of Regional Economic Growth Convergence in the Philippines using Kalman Filter

This paper investigates the presence of stochastic and dynamic convergence of the 14 regional economies in the Philippines in terms of per capita Gross Regional Domestic Product (GRDP) using regional panel data from 1988 to 2007. Stochastic convergence, which indicates convergence of regions in the long-run, is tested using Levin, Lin & Chu (LLC) and Im, Pesaran & Shin (IPS) panel unit root tests. The presence of convergence, on one hand, indicates that the economically laggard regions are gaining on the economically better-performing regions with respect to per capita GRDP. On the other hand, the lack of convergence indicates a need to reevaluate existing regional and national economic policies on development. Dynamic convergence reveals several convergence characteristics of individual regions over time. Dynamic convergence is determined by the time-varying parameter (TVP) model derived using the Kalman Filter. The paper proceeds to examine the individual convergence behavior of each region based on the value of the estimate of the parameter of the TVP. The results show that out of the 14 regions studied, seven regions are found to converge towards the average of the national per capita GDP growth rate over 1988 to 2007 while six regions lag behind the average of the national per capita GDP growth rate over the same period. No region converges towards the economic growth rate of National Capital Region, the lead region used in the study.Panel Unit Root Test, Time-varying Parameter (TVP) Model, Kalman Filter, Stochastic Convergence, Dynamic Convergence

Reconciling taxonomy and phylogenetic inference: formalism and algorithms for describing discord and inferring taxonomic roots

Although taxonomy is often used informally to evaluate the results of phylogenetic inference and find the root of phylogenetic trees, algorithmic methods to do so are lacking. In this paper we formalize these procedures and develop algorithms to solve the relevant problems. In particular, we introduce a new algorithm that solves a "subcoloring" problem for expressing the difference between the taxonomy and phylogeny at a given rank. This algorithm improves upon the current best algorithm in terms of asymptotic complexity for the parameter regime of interest; we also describe a branch-and-bound algorithm that saves orders of magnitude in computation on real data sets. We also develop a formalism and an algorithm for rooting phylogenetic trees according to a taxonomy. All of these algorithms are implemented in freely-available software.Comment: Version submitted to Algorithms for Molecular Biology. A number of fixes from previous versio