Phylloseptin-1 (PSN-1) from Phyllomedusa sauvagei skin secretion: a novel broad-spectrum antimicrobial peptide with antibiofilm activity

Amphibian skin secretions have proven to be rich sources of antimicrobial peptides that are proposed to be fundamental components of the innate immune system. As amphibian skin is a multi-functional organ playing, among other things, a crucial role in respiration, it has been deemed that a core biological role for such peptides is control of microbial flora on this surface. To date, however, antimicrobial efficacy has been universally determined by means of establishing minimum inhibitory concentrations (MICs) using planktonic organisms rather than those within a biofilm such as would occur on this exposed surface. Here we describe the identification and structural characterisation of a novel 19 amino acid residue antimicrobial peptide of the phylloseptin family, named PSN-1, from the skin secretion of the waxy monkey frog, Phyllomedusa sauvagei. PSN-1 displayed broad-spectrum activity against a range of planktonic organisms with a high potency (MIC 5 µM) against Staphylococcus aureus. In a specific bioassay with the same organism grown as a biofilm, the minimal biofilm eradication concentration (MBEC) was found to be of the same high potency (5 µM). The present data would suggest that evaluation of actions and potency of amphibian skin secretion antimicrobial peptides might best be achieved by evaluating MBEC rather than MIC using planktonic organisms and that data arising from such studies may have more biological relevance in reflecting the purpose for which they have evolved through natural selection.

China’s New Approach to CSR in Congo: Is the leverage turning to China?

China has been the world’s fastest growing economy in the past 30 years with its enterprises rapidly emerging and becoming leading players globally. In particular, the progressive integration into the international system has been spurred by China’s entry into the global trading regime of the World Trade Organization (WTO) in 2001. The 'go global' policy has been facilitating the rapidly growing engagement on the African continent of Chinese multinational companies (MNCs). As a promising tri-polar global economic entity, its growth of relations with Africa has been both unprecedented and impressive. As the Sino-Africa economic and business partnership surges forward, the matter of corporate social responsibility (CSR) is increasingly becoming an imperative ingredient for any successful business. It is noteworthy that responsible corporate citizens should take account of the impact of their investment on both economic and social arenas. However, it still remains uncertain what role Chinese MNCs have been playing in the continent’s sustainable development.
A Sino-Congo deal seems a positive way forward, accelerating the Democratic Republic of Congo’s (hereinafter referred to as Congo) regional economy, depressed due to years of war. Meanwhile, the escalating investment into Congo has raised controversies for its no-attachment policy, with increasing pressure imposed on China’s MNCs to take CSR more seriously. Particular concerns are focused on the multinationals’ inadequate environmental and human rights protection. The recent massive infrastructure investment is arguably perceived as a different interpretation of CSR, which has aroused a hot debate about whether China is heading for status as a responsible stakeholder in the international community. It is conducive to clarifying the paradoxical issue by addressing whether China’s recent approaches have the potential to facilitate CSR initiatives or hinder them in the long run.

The Perils of Moviegoing in America, 1896-1950

The Perils of Moviegoing in America is a film history that examines the various physical and (perceived) moral dangers facing audiences during the first fifty years of film exhibition.

Chapter 1: “Conflagration”
As early as 1897, a major fire broke out at a film exhibition in San Francisco, with flames burning the projectionist and nearby audience members. From that point until the widespread adoption of safety stock in 1950, fires were a very common movie-going experience. Hundreds of audience members lost their lives in literally thousands of theatre fires, ranging from early nickelodeons to the movie palaces of the thirties and forties.

Chapter 2: “Thieves Among Us”
Bandits robbed movie theatres on hundreds of occasions from the early days of film exhibition through the end of the Great Depression. They held up ticket booths, and they dynamited theatre safes. They also shot theatre managers, ushers, and audience members, as a great many of the robberies occurred while movies were playing on the screens inside.

Chapter 3: “Bombs Away”
Bombings at movie theatres became common in small towns and large cities on literally hundreds of occasions from 1914 to the start of World War II. Some were incendiary bombs, and some were stench bombs; both could be fatal, whether due to explosions or to the trampling of panicked moviegoers

Chapter 4: “It’s Catching”
Widespread movie-going in the early 20th century provoked an outcry from numerous doctors and optometrists who believed that viewing films could do irreparable harm to the vision of audience members. Medical publications (including the Journal of the American Medical Association) published major studies on this perceived problem, which then filtered into popular-audience magazines and newspapers.

Chapter 5: “The Devil’s Apothecary Shops”
Sitting in the dark with complete strangers proved worrisome for many early filmgoers, who had good reason to be concerned. Darkness meant that prostitutes could easily work in the balconies of some movie theatres, as could “mashers” who molested female patrons (and sometimes children) after the lights were dimmed. That was all in addition to the various murderers who used the cover of darkness to commit their crimes at movie theatres.

Chapter 6: “Blue Sundays”
Blue laws were those regulations that prohibited businesses from operating on Sundays. Most communities across the US had such legislation on their books, which by the nickelodeon era were at odds with the thousands of filmgoers who went to the movies every Sunday. Theatre managers were often arrested, making newspaper headlines over and over again. Police sometimes even arrested entire film audiences as accomplices in the Blue Law violations.

Chapter 7: “Something for Nothing”
In an effort to bolster ticket sales, many movie theatres in the 1910s began to hold lotteries in which lucky audience members won cash prizes; by the time of the Great Depression, lotteries like “Bank Night” became a common aspect of the theatre-going enterprise. However, reception studies have generally overlooked the intense (and sometimes coordinated) efforts by police, politicians, and preachers to end this practice, which they viewed as illegal and immoral gambling.

"The pride of noise": drums and their repercussions in early modern England

This article draws on a wide range of literary and archival sources in order to explore the cultural resonances of drumming in England during the 16th and 17th centuries. It concentrates not on instrument design and playing techniques but on the varied meanings that contemporaries attached to the ubiquitous sound of the drum. The discussion begins and ends with the unmistakable military associations of drumming. In between, consideration is also given to a range of interconnected but sometimes contradictory resonances that appear to have endowed drums with considerable cultural significance. Drums spoke, for example, of authority and they worked hard to impose order in urban streets. They also played their part in the contemporary culture of punishment, and many miscreants were subjected to the humiliation of public percussion. Beyond this, drums were particularly potent in their ability to express masculinity, and female drummers were rare and remarkable. The primal potency of the instrument also rendered it valuable to the insubordinate, and rioters—like soldiers— were regularly called together 'by the drum'. Lastly, the sound of the drum was sometimes intensely festive and could also be used to publicize special events such as dramatic performances and the display of curiosities. The repercussions of drumming were thus varied, and confusion sometimes resulted when the different possibilities became entangled.

Differential Hox Expression in Murine Embryonic Stem Cell Models of Normal and Malignant Hematopoiesis.

The Hox family are master transcriptional regulators of developmental processes, including hematopoiesis. The Hox regulators, caudal homeobox factors (Cdx1-4), and Meis1, along with several individual Hox proteins, are implicated in stem cell expansion during embryonic development, with gene dosage playing a significant role in the overall function of the integrated Hox network. To investigate the role of this network in normal and aberrant, early hematopoiesis, we employed an in vitro embryonic stem cell differentiation system, which recapitulates mouse developmental hematopoiesis. Expression profiles of Hox, Pbx1, and Meis1 genes were quantified at distinct stages during the hematopoietic differentiation process and compared with the effects of expressing the leukemic oncogene Tel/PDGFRß. During normal differentiation the Hoxa cluster, Pbx1 and Meis1 predominated, with a marked reduction in the majority of Hox genes (27/39) and Meis1 occurring during hematopoietic commitment. Only the posterior Hoxa cluster genes (a9, a10, a11, and a13) maintained or increased expression at the hematopoietic colony stage. Cdx4, Meis1, and a subset of Hox genes, including a7 and a9, were differentially expressed after short-term oncogenic (Tel/PDGFRß) induction. Whereas Hoxa4-10, b1, b2, b4, and b9 were upregulated during oncogenic driven myelomonocytic differentiation. Heterodimers between Hoxa7/Hoxa9, Meis1, and Pbx have previously been implicated in regulating target genes involved in hematopoietic stem cell (HSC) expansion and leukemic progression. These results provide direct evidence that transcriptional flux through the Hox network occurs at very early stages during hematopoietic differentiation and validates embryonic stem cell models for gaining insights into the genetic regulation of normal and malignant hematopoiesis.

Out-of-field cell survival following exposure to intensity-modulated radiation fields

PURPOSE:
To determine the in-field and out-of-field cell survival of cells irradiated with either primary field or scattered radiation in the presence and absence of intercellular communication.
METHODS AND MATERIALS:
Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and primary fibroblast (AGO1552) cells following exposure to different field configurations delivered using a 6-MV photon beam produced with a Varian linear accelerator.
RESULTS:
Nonuniform dose distributions were delivered using a multileaf collimator (MLC) in which half of the cell population was shielded. Clonogenic survival in the shielded region was significantly lower than that predicted from the linear quadratic model. In both cell lines, the out-of-field responses appeared to saturate at 40%-50% survival at a scattered dose of 0.70 Gy in DU-145 cells and 0.24 Gy in AGO1522 cells. There was an approximately eightfold difference in the initial slopes of the out-of-field response compared with the a-component of the uniform field response. In contrast, cells in the exposed part of the field showed increased survival. These observations were abrogated by direct physical inhibition of cellular communication and by the addition of the inducible nitric oxide synthase inhibitor aminoguanidine known to inhibit intercellular bystander effects. Additional studies showed the proportion of cells irradiated and dose delivered to the shielded and exposed regions of the field to impact on response.
CONCLUSIONS:
These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields with cellular communication between differentially irradiated cell populations playing an important role. Validation of these observations in additional cell models may facilitate the refinement of existing radiobiological models and the observations considered important determinants of cell survival.

A Frequency Domain Algorithm for Wave Separation

We propose a frequency domain adaptive algorithm for
wave separation in wind instruments. Forward and backward travelling waves are obtained from the signals acquired by two microphones placed along the tube, while the
separation ?lter is adapted from the information given by a
third microphone. Working in the frequency domain has a
series of advantages, among which are the ease of design of
the propagation ?lter and its differentiation with respect to
its parameters.
Although the adaptive algorithm was developed as a ?rst
step for the estimation of playing parameters in wind instruments it can also be used, without any modi?cations, for
other applications such as in-air direction of arrival (DOA)
estimation. Preliminary results on these applications will
also be presented.

Maternal situations: Sectarianism and civility in a divided city

This paper explores the tensions between civility and sectarianism in contemporary Belfast. Drawing on interviews with mothers engaged in raising young children in the largely working class and divided inner city, the paper offers a pragmatic account of the dynamics of social reproduction and change. This is pursued through an analysis of the interplay between expectations of civility and sectarianism in four specific situations: walking, shopping, playing and schooling. The tensions and dilemmas of maternal action as the divided inner city is navigated indicate the constitutive role situations play in shaping maternal action. The situation of motherhood itself, both at the centre of ethno-national reproduction and at the interface of public and private life, is not insignificant in routinely drawing mothers into the everyday dynamics of post-conflict continuity and change.

Direct Quantification of Inorganic Polyphosphate in Microbial Cells Using 4 '-6-Diamidino-2-Phenylindole (DAPI)

Inorganic polyphosphate (polyP) is increasingly being recognized as an important phosphorus sink within the environment, playing a central role in phosphorus exchange and phosphogenesis. Yet despite the significant advances made in polyP research there is a lack of rapid and efficient analytical approaches for the quantification of polyP accumulation in microbial cultures and environmental samples. A major drawback is the need to extract polyP from cells prior to analysis. Due to extraction inefficiencies this can lead to an underestimation of both intracellular polyP levels and its environmental pool size: we observed 23-58% loss of polyP using standard solutions and current protocols. Here we report a direct fluorescence based DAPI assay system which removes the requirement for prior polyP extraction before quantification. This increased the efficiency of polyP detection by 28-55% in microbial cultures suggesting quantitative measurement of the intracellular polyP pool. It provides a direct polyP assay which combines quantification capability with technical simplicity. This is an important step forward in our ability to explore the role of polyP in cellular biology and biogeochemical nutrient cycling.

Epidemiology of Adolescent Rugby Injuries: A Systematic Review

OBJECTIVE: Despite recent increases in the volume of research in professional rugby union, there is little consensus on the epidemiology of injury in adolescent players. We undertook a systematic review to determine the incidence, severity, and nature of injury in adolescent rugby union players.

DATA SOURCES: In April 2009, we performed a computerized literature search on PubMed, Embase, and Cochrane Controlled Trials Register (via Ovid). Population-specific and patient-specific search terms were combined in the form of MEDLINE subject headings and key words (wound$ and injur$, rugby, adolescent$). These were supplemented with related-citation searches on PubMed and bibliographic tracking of primary and review articles.

STUDY SELECTION: Prospective epidemiologic studies in adolescent rugby union players.

DATA SYNTHESIS: A total of 15 studies were included, and the data were analyzed descriptively. Two independent reviewers extracted key study characteristics regarding the incidence, severity, and nature of injuries and the methodologic design.

CONCLUSIONS: Wide variations existed in the injury definitions and data collection procedures. The incidence of injury necessitating medical attention varied with the definition, from 27.5 to 129.8 injuries per 1000 match hours. The incidence of time-loss injury (>7 days) ranged from 0.96 to 1.6 per 1000 playing hours and from 11.4/1000 match hours (>1 day) to 12-22/1000 match hours (missed games). The highest incidence of concussion was 3.3/1000 playing hours. No catastrophic injuries were reported. The head and neck, upper limb, and lower limb were all common sites of injury, and trends were noted toward greater time loss due to upper limb fractures or dislocations and knee ligament injuries. Increasing age, the early part of the playing season, and the tackle situation were most closely associated with injury. Future injury-surveillance studies in rugby union must follow consensus guidelines to facilitate interstudy comparisons and provide further clarification as to where injury-prevention strategies should be focused.

Vapour layer formation by electrical discharges through electrically conducting liquids-modelling and experiment

Experimental and finite element modelling methods are used to study the formation of vapour layers in electrical discharges through saline solutions. The experiments utilize shadowgraphic and photometric methods to observe the time dependence of thin vapour layers and plasma formation around electrodes driven by moderate voltage (<500 V) pulses, applied to an electrode immersed in a conducting saline solution. Finite element multiphysics software, coupling thermal and electrical effects, is employed to model the vapour layer formation. All relevant electrical and thermal properties of the saline are incorporated into the model, but hydrodynamic and surface tension effects are ignored. Experimental shadowgraph and modelling images are compared, as are current histories, and the agreement is very good. The comparison of experiment and modelling gives insight into both vapour layer production and subsequent plasma production. We show that, for example, superheating of the saline above its normal vaporization temperature may be playing a significant role in vapour formation. We also show that electric fields of approaching 10(7) V m(-1) can be achieved in the vapour layer.

Estimation of Clarinet Reed Parameters by Inverse Modelling

Analysis of the acoustical functioning of musical instruments invariably involves the estimation of model parameters. The broad aim of this paper is to develop methods for estimation of clarinet reed parameters that are representative of actual playing conditions. This presents various challenges because of the di?culties of measuring the directly relevant variables without interfering with the control of the instrument. An inverse modelling approach is therefore proposed, in which the equations governing the sound generation mechanism of the clarinet
are employed in an optimisation procedure to determine the reed parameters from the mouthpiece pressure and volume ?ow signals. The underlying physical model captures most of the reed dynamics and is simple enough to be used in an inversion process. The optimisation procedure is ?rst tested by applying it to numerically synthesised signals, and then applied to mouthpiece signals acquired during notes blown by a human player. The proposed inverse modelling approach raises the possibility of revealing information about the way in which the embouchure-related reed parameters are controlled by the player, and also facilitates physics-based re-synthesis of clarinet sounds.

Functional characterization and membrane topology of Escherichia coli WecA, a sugar-phosphate transferase initiating the biosynthesis of enterobacterial common antigen and O-antigen lipopolysaccharide

WecA is an integral membrane protein that initiates the biosynthesis of enterobacterial common antigen and O-antigen lipopolysaccharide (LPS) by catalyzing the transfer of N-acetylglucosamine (GlcNAc)-1-phosphate onto undecaprenyl phosphate (Und-P) to form Und-P-P-GlcNAc. WecA belongs to a large family of eukaryotic and prokaryotic prenyl sugar transferases. Conserved aspartic acids in putative cytoplasmic loops 2 (Asp90 and Asp91) and 3 (Asp156 and Asp159) were targeted for replacement mutagenesis with either glutamic acid or asparagine. We examined the ability of each mutant protein to complement O-antigen LPS synthesis in a wecA-deficient strain and also determined the steady-state kinetic parameters of the mutant proteins in an in vitro transfer assay. Apparent K(m) and V(max) values for UDP-GlcNAc, Mg(2+), and Mn(2+) suggest that Asp156 is required for catalysis, while Asp91 appears to interact preferentially with Mg(2+), possibly playing a role in orienting the substrates. Topological analysis using the substituted cysteine accessibility method demonstrated the cytosolic location of Asp90, Asp91, and Asp156 and provided a more refined overall topological map of WecA. Also, we show that cells expressing a WecA derivative C terminally fused with the green fluorescent protein exhibited a punctate distribution of fluorescence on the bacterial surface, suggesting that WecA localizes to discrete regions in the bacterial plasma membrane.

Cities as Organisms

Since the UN report by the Brundtland Committee, sustainability in the built environment has mainly been seen from a technical focus on single buildings or products. With the energy efficiency approaching 100%, fossil resources depleting and a considerable part of the world still in need of better prosperity, the playing field of a technical focus has become very limited. It will most probably not lead to the sustainable development needed to avoid irreversible effects on climate, energy provision and, not least, society.
Cities are complex structures of independently functioning elements, all of which are nevertheless connected to different forms of infrastructure, which provide the necessary sources or solve the release of waste material. With the current ambitions regarding carbon- or energy-neutrality, retreating again to the scale of a building is likely to fail. Within an urban context a single building cannot become fully resource-independent, and need not, from our viewpoint. Cities should be considered as an organism that has the ability to intelligently exchange sources and waste flows. Especially in terms of energy, it can be made clear that the present situation in most cities are undesired: there is simultaneous demand for heat and cold, and in summer a lot of excess energy is lost, which needs to be produced again in winter. The solution for this is a system that intelligently exchanges and stores essential sources, e.g. energy, and that optimally utilises waste flows.
This new approach will be discussed and exemplified. The Rotterdam Energy Approach and Planning (REAP) will be illustrated as a means for urban planning, whereas Swarm Planning will be introduced as another nature-based principle for swift changes towards sustainability

Medicalization, markets and consumers.

This paper examines the impact of changes in the medical marketplace on medicalization in U.S. society. Using four cases (Viagra, Paxil, human growth hormone and in vitro fertilization), we focus on two aspects of the changing medical marketplace: the role of direct-to-consumer advertising of prescription drugs and the emergence of private medical markets. We demonstrate how consumers and pharmaceutical corporations contribute to medicalization, with physicians, insurance coverage, and changes in regulatory practices playing facilitating roles. In some cases, insurers attempt to counteract medicalization by restricting access. We distinguish mediated and private medical markets, each characterized by differing relationships with corporations, insurers, consumers, and physicians. In the changing medical environment, with medical markets as intervening factors, corporations and insurers are becoming more significant determinants in the medicalization process.