If only it were true: the problem with the four conditionals

The traditional division of conditionals into four main types (zero, first, second, and third) has long been called into question. Unfortunately, the awareness that this description does not reflect conditional patterns in actual usage has not generally been reflected in EFL coursebooks. This article re-examines the arguments for a description of conditional patterns which reflects actual usage and uses corpus data to demonstrate the kind of patterns in frequent use. It then suggests two teaching approaches that may help teachers to tackle a variety of conditional patterns in the classroom

<i>Schistosoma mansoni</i> cercariae experience influx of macromolecules during skin penetration

We have observed that when cercariae penetrate the skin of mice, there is influx into their tissues of Lucifer Yellow and certain labelled molecules of up to 20 kDa molecular weight. This observation was made using a variety of fluorescent membrane-impermeant compounds injected into the skin before the application of cercariae. This unexpected phenomenon was investigated further by transforming cercariae in vitro in the presence of the membrane-impermeant compounds and examining the distribution by microscopy. In schistosomula derived from this procedure, the nephridiopore and surface membrane were labelled while the pre- and post-acetabular glands were not labelled. The region associated with the oesophagus within the pharyngeal muscle clearly contained the fluorescent molecules, as did the region adjacent to the excretory tubules and the germinal mass. We used cercariae stained with carmine to aid identification of regions labelled with Lucifer Yellow. Although the mechanism of this influx is unclear, the observation is significant. From it, we can suggest an hypothesis that, during skin penetration, exposure of internal tissues of the parasite to external macromolecules represents a novel host-parasite interfac

Extensive telomere repeat arrays in mouse are hypervariable

In this study we have analysed mouse telomeres by Pulsed Field Gel Electrophoresis (PFGE). A number of specific restriction fragments hybridising to a (TTA-GGG)4 probe in the size range 50-150kb can be detected. These fragments are devoid of sites for most restriction enzymes suggesting that they comprise simple repeats; we argue that most of these are likely to be (TTAGGG)n. Each discrete fragment corresponds to the telomere of an individual chromosome and segregates as a Mendelian character. However, new size variants are being generated in the germ line at very high rates such that inbred mice are heterozygous at all telomeres analysable. In addition we show that specific small (approximately 4-12kb) fragments can be cleaved within some terminal arrays by the restriction enzyme MnII which recognises 5'(N7)GAGG3'. Like the complete telomere-repeat arrays (TRA's) these fragments form new variants at high rates and possibly by the same process. We speculate on the mechanisms that may be involved

Prolyl 4-hydroxlase activity is essential for development and cuticle formation in the human infective parasitic nematode Brugia malayi

Collagen prolyl 4-hydroxylases (C-P4H) are required for formation of extracellular matrices in higher eukaryotes. These enzymes convert proline residues within the repeat regions of collagen polypeptides to 4-hydroxyproline, a modification essential for the stability of the triple helix. C-P4Hs are most often oligomeric complexes, with enzymatic activity contributed by the α subunits, and the β subunits formed by protein disulfide isomerase (PDI). Here we characterise this enzyme class in the important human parasitic nematode Brugia malayi. All potential C-P4H subunits were identified by detailed bioinformatic analysis of sequence databases, function was investigated both by RNAi in the parasite and heterologous expression in Caenorhabditis elegans, while biochemical activity and complex formation were examined via co-expression in insect cells. Simultaneous RNAi of two B. malayi C-P4H α subunit-like genes resulted in a striking, highly penetrant body morphology phenotype in parasite larvae. This was replicated by single RNAi of a B. malayi C-P4H β subunit-like PDI. Surprisingly however, the B. malayi proteins were not capable of rescuing a C. elegans α subunit mutant, whereas the human enzymes could. In contrast, the B. malayi PDI did functionally complement the lethal phenotype of a C. elegans β subunit mutant. Comparison of recombinant and parasite derived material indicates that enzymatic activity may be dependent on a non-reducible, inter-subunit cross-link, present only in the parasite. We therefore demonstrate that C-P4H activity is essential for development of B. malayi and uncover a novel parasite-specific feature of these collagen biosynthetic enzymes that may be exploited in future parasite control

Rapid Monitoring of Bacteria and Fungi aboard the International Space Station (ISS)

Microorganisms within spacecraft have traditionally been monitored with culture-based techniques. These techniques involve growth of environmental samples (cabin water, air or surfaces) on agar-type media for several days, followed by visualization of resulting colonies or return of samples to Earth for ground-based analysis. Data obtained over the past 4 decades have enhanced our understanding of the microbial ecology within space stations. However, the approach has been limited by the following factors: i) Many microorganisms (estimated > 95%) in the environment cannot grow on conventional growth media; ii) Significant time lags (3-5 days for incubation and up to several months to return samples to ground); iii) Condensation in contact slides hinders colony counting by crew; and iv) Growth of potentially harmful microorganisms, which must then be disposed of safely. This report describes the operation of a new culture-independent technique onboard the ISS for rapid analysis (within minutes) of endotoxin and beta-1, 3-glucan, found in the cell walls of gramnegative bacteria and fungi, respectively. The technique involves analysis of environmental samples with the Limulus Amebocyte Lysate (LAL) assay in a handheld device, known as the Lab-On-a-Chip Application Development Portable Test System (LOCAD-PTS). LOCADPTS was launched to the ISS in December 2006, and here we present data obtained from Mach 2007 until the present day. These data include a comparative study between LOCADPTS analysis and existing culture-based methods; and an exploratory survey of surface endotoxin and beta-1, 3-glucan throughout the ISS. While a general correlation between LOCAD-PTS and traditional culture-based methods should not be expected, we will suggest new requirements for microbial monitoring based upon culture-independent parameters measured by LOCAD-PTS

LOCAD-PTS: Operation of a New System for Microbial Monitoring Aboard the International Space Station (ISS)

Microorganisms within the space stations Salyut, Mir and the International Space Station (ISS), have traditionally been monitored with culture-based techniques. These techniques involve growing environmental samples (cabin water, air or surfaces) on agar-type media for several days, followed by visualization of resulting colonies; and return of samples to Earth for ground-based analysis. This approach has provided a wealth of useful data and enhanced our understanding of the microbial ecology within space stations. However, the approach is also limited by the following: i) More than 95% microorganisms in the environment cannot grow on conventional growth media; ii) Significant time lags occur between onboard sampling and colony visualization (3-5 days) and ground-based analysis (as long as several months); iii) Colonies are often difficult to visualize due to condensation within contact slide media plates; and iv) Techniques involve growth of potentially harmful microorganisms, which must then be disposed of safely. This report describes the operation of a new culture-independent technique onboard the ISS for rapid analysis (within minutes) of endotoxin and -1, 3-glucan, found in the cell walls of gram-negative bacteria and fungi, respectively. This technique involves analysis of environmental samples with the Limulus Amebocyte Lysate (LAL) assay in a handheld device. This handheld device and sampling system is known as the Lab-On-a-Chip Application Development Portable Test System (LOCAD-PTS). A poster will be presented that describes a comparative study between LOCAD-PTS analysis and existing culture-based methods onboard the ISS; together with an exploratory survey of surface endotoxin throughout the ISS. It is concluded that while a general correlation between LOCAD-PTS and traditional culture-based methods should not necessarily be expected, a combinatorial approach can be adopted where both sets of data are used together to generate a more complete story of the microbial ecology on the ISS

Cadherin-Mediated Differential Cell Adhesion Controls Slow Muscle Cell Migration in the Developing Zebrafish Myotome

AbstractSlow-twitch muscle fibers of the zebrafish myotome undergo a unique set of morphogenetic cell movements. During embryogenesis, slow-twitch muscle derives from the adaxial cells, a layer of paraxial mesoderm that differentiates medially within the myotome, immediately adjacent to the notochord. Subsequently, slow-twitch muscle cells migrate through the entire myotome, coming to lie at its most lateral surface. Here we examine the cellular and molecular basis for slow-twitch muscle cell migration. We show that slow-twitch muscle cell morphogenesis is marked by behaviors typical of cells influenced by differential cell adhesion. Dynamic and reciprocal waves of N-cadherin and M-cadherin expression within the myotome, which correlate precisely with cell migration, generate differential adhesive environments that drive slow-twitch muscle cell migration through the myotome. Removing or altering the expression of either protein within the myotome perturbs migration. These results provide a definitive example of homophilic cell adhesion shaping cellular behavior during vertebrate development

Cluster Dynamical Mean-field calculations for TiOCl

Based on a combination of cluster dynamical mean field theory (DMFT) and density functional calculations, we calculated the angle-integrated spectral density in the layered $s=1/2$ quantum magnet TiOCl. The agreement with recent photoemission and oxygen K-edge X-ray absorption spectroscopy experiments is found to be good. Th e improvement achieved with this calculation with respect to previous single-site DMFT calculations is an indication of the correlated nature and low-dimensionality of TiOCl.Comment: 9 pages, 3 figures, improved version as publishe

Annexin 2A sustains glioblastoma cell dissemination and proliferation.

Glioblastoma (GBM) is the most devastating tumor of the brain, characterized by an almost inevitable tendency to recur after intensive treatments and a fatal prognosis. Indeed, despite recent technical improvements in GBM surgery, the complete eradication of cancer cell disseminated outside the tumor mass still remains a crucial issue for glioma patients management. In this context, Annexin 2A (ANXA2) is a phospholipid-binding protein expressed in a variety of cell types, whose expression has been recently associated with cell dissemination and metastasis in many cancer types, thus making ANXA2 an attractive putative regulator of cell invasion also in GBM.Here we show that ANXA2 is over-expressed in GBM and positively correlates with tumor aggressiveness and patient survival. In particular, we associate the expression of ANXA2 to a mesenchymal and metastatic phenotype of GBM tumors. Moreover, we functionally characterized the effects exerted by ANXA2 inhibition in primary GBM cultures, demonstrating its ability to sustain cell migration, matrix invasion, cytoskeletal remodeling and proliferation. Finally, we were able to generate an ANXA2-dependent gene signature with a significant prognostic potential in different cohorts of solid tumor patients, including GBM.In conclusion, we demonstrate that ANXA2 acts at multiple levels in determining the disseminating and aggressive behaviour of GBM cells, thus proving its potential as a possible target and strong prognostic factor in the future management of GBM patients