AS-48 bacteriocin: close to perfection

Bacteriocin AS-48 is an intriguing molecule because of its unique structural characteristics, genetic regulation, broad activity spectrum, and potential biotechnological applications. It was the first reported circular bacteriocin and has been undoubtedly the best characterized for the last 25 years. Thus, AS-48 is the prototype of circular bacteriocins (class IV), for which the structure and genetic regulation have been elucidated. This review discusses the state-of-the-art in genetic engineering with regard to this circular protein, with the use of site-directed mutagenesis and circular permutation. Mutagenesis studies have been used to unravel the role of (a) different residues in the biological activity, underlining the relevance of several residues involved in membrane interaction and the low correlation between stability and activity and (b) three amino acids involved in maturation, providing information on the specificity of the leader peptidase and the circularization process itself. To investigate the role of circularity in the stability and biological properties of the enterocin AS-48, two different ways of linearization have been attempted: in vitro by limited proteolysis experiments and in vivo by circular permutation in the structural gene as-48A. The results summarized here show the significance of circularization on the secondary structure, potency and, especially, the stability of AS-48 and point as well to a putative role of the leader peptide as a protecting moiety in the pre-proprotein. Taken all together, the data available on circular bacteriocins support the idea that AS-48 has been engineered by nature to make a remarkably active and stable protein with a broad spectrum of activity.     

A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by activation of the type I interferon (IFN) pathway. Here we convincingly replicate association of the IFN regulatory factor 5 (IRF5) rs2004640 T allele with SLE in four independent case-control cohorts (P = 4.4 x 10(-16)) and by family-based transmission disequilibrium test analysis (P = 0.0006). The rs2004640 T allele creates a 5' donor splice site in an alternate exon 1 of IRF5, allowing expression of several unique IRF5 isoforms. We also identify an independent cis-acting variant associated with elevated expression of IRF5 and linked to the exon 1B splice site. Haplotypes carrying the variant associated with elevated expression and lacking the exon 1B donor site do not confer risk of SLE. Thus, a common IRF5 haplotype driving elevated expression of multiple unique isoforms of IRF5 is an important genetic risk factor for SLE, establishing a causal role for type I IFN pathway genes in human autoimmunity.     

The effect of five proteins on stem cells used for osteoblast differentiation and proliferation: a current review of the literature

Bone-tissue engineering is a therapeutic target in the field of dental implant and orthopedic surgery. It is therefore essential to find a microenvironment that enhances the growth and differentiation of osteoblasts both from mesenchymal stem cells (MSCs) and those derived from dental pulp. The aim of this review is to determine the relationship among the proteins fibronectin (FN), osteopontin (OPN), tenascin (TN), bone sialoprotein (BSP), and bone morphogenetic protein (BMP2) and their ability to coat different types of biomaterials and surfaces to enhance osteoblast differentiation. Pre-treatment of biomaterials with FN during the initial phase of osteogenic differentiation on all types of surfaces, including slotted titanium and polymers, provides an ideal microenvironment that enhances adhesion, morphology, and proliferation of pluripotent and multipotent cells. Likewise, in the second stage of differentiation, surface coating with BMP2 decreases the diameter and the pore size of the scaffold, causing better adhesion and reduced proliferation of BMP-MSCs. Coating oligomerization surfaces with OPN and BSP promotes cell adhesion, but it is clear that the polymeric coating material BSP alone is insufficient to induce priming of MSCs and functional osteoblastic differentiation in vivo. Finally, TN is involved in mineralization and can accelerate new bone formation in a multicellular environment but has no effect on the initial stage of osteogenesis.     

Evaluating early warning and coincident indicators of business cycles using smooth trends

We present a composite coincident indicator designed to capture the state of the Spanish economy. Our approach, based on smooth trends, guarantees that the resulting indicators are reasonably smooth and issue stable signals, reducing the uncertainty. The coincident indicator has been checked by comparing it with the one recently proposed by the Spanish Economic Association index. Both indexes show similar behavior and ours captures very well the beginning and end of the official recessions and expansion periods. Our coincident indicator also tracks very well alternative mass media indicators typically used in the political science literature. We also update our composite leading indicator (Bujosa et al., Journal of Forecasting, 2013, 32(6), 481–499). It systematically predicts the peaks and troughs of the new Spanish Economic Association index and provides significant aid in forecasting annual gross domestic product growth rates. Using only real data available at the beginning of each forecast period, our indicator one-step-ahead forecast shows improvements over other individual alternatives and different forecast combinations.     

Heat shock proteins in three relatedDrosophila species belonging to theobscura group

The effect of heat shock on protein synthesis in three relatedDrosophila species belonging to theobscura group was analyzed on SDS-acrylamide gels. Four major heat shock proteins (hsps) were found in these species, in which synthesis reaches a maximum at 34°C. Although the higher molecular weight proteins are conserved, differences in size were found for the small hsps in these species. By means of in situ hybridization usingD. melanogaster probes for the small hsp genes, it was inferred that the small hsp genes of theobscura group species are clustered at the 27A locus in all three species.     

Effects of gastric secretagogues on tissue glycerol in the isolated amphibian gastric mucosa

Histamine and theophylline, two gastric secretagogues, significantly increased tissue glycerol content by 121 and 66%, respectively, in the isolated toad gastric mucosa. This is new evidence in favor of the hypothesis that gastric secretagogues may act via lipid mobilization.     

Basketball scoring in NBA games: An example of complexity

Abstract Scoring in a basketball game is a highly dynamic, non-linear process. NBA teams try to be more and more competitive each season. For instance, they incorporate into their rosters the best players in the world. This and other mechanisms concur to make the scoring process in NBA games exciting and rarely predictable. This paper is to study the behavior of timing and scoring in basketball games. The authors analyze all the games in five NBA regular seasons (2005–06, 2006–07, 2007–08, 2008–09, 2009–10), for a total of 6150 games. Scoring does not behave uniformly; therefore, the authors also analyze the distributions of the differences in points in the basketball games. To further analyze the behavior of the tail of the distribution, the authors also carry out a semilog-plot and a log-log plot to verify whether this trend approaches a Poisson distribution or a PL. This paper reveals different areas of behavior related to the score, with specific instances of time that could be considered tipping points of the game. The presence of these critical points suggests that there are phase transitions where the dynamic scoring of the games varies significantly.     

An Approach to the Notion of Reflective Teacher and Its Exemplification on Mathematics Education

Within research into the teaching profession, there are two main areas of interest, which have been thoroughly defined and consolidated: teacher’s knowledge and teacher’s professional development. This paper considers the latter area, and specifically sets out to define the concept of the reflective teacher and to show how we have applied this concept in our research. It aims at defining a more precise notion of teachers’ professional development linked to the concept of a reflective teacher, drawing on information from different interdisciplinary sources so as to frame the concept clearly. We discuss the conditions which determine the reflective teacher, and report on how these were put to use in a training course for practising teachers in which participants reflected on challenging episodes from their professional experience. We hope that clarifying this term will enable different educational agents (school teachers, teacher trainers or researchers) to have an informed view that can be interpreted and critiqued, and that it will also be of value to initial teacher training and to in-service courses.     

Widespread amphibian extinctions from epidemic disease driven by global warming

As the Earth warms, many species are likely to disappear, often because of changing disease dynamics. Here we show that a recent mass extinction associated with pathogen outbreaks is tied to global warming. Seventeen years ago, in the mountains of Costa Rica, the Monteverde harlequin frog (Atelopus sp.) vanished along with the golden toad (Bufo periglenes). An estimated 67% of the 110 or so species of Atelopus, which are endemic to the American tropics, have met the same fate, and a pathogenic chytrid fungus (Batrachochytrium dendrobatidis) is implicated. Analysing the timing of losses in relation to changes in sea surface and air temperatures, we conclude with 'very high confidence' (> 99%, following the Intergovernmental Panel on Climate Change, IPCC) that large-scale warming is a key factor in the disappearances. We propose that temperatures at many highland localities are shifting towards the growth optimum of Batrachochytrium, thus encouraging outbreaks. With climate change promoting infectious disease and eroding biodiversity, the urgency of reducing greenhouse-gas concentrations is now undeniable.