Investigation of phase separation within the generalized Lin-Taylor model for a binary liquid mixture of large hexagonal and small triangular particles

The generalized Lin-Taylor model defined on the hexagonal lattice is used to investigate the phase separation in an asymmetric binary liquid mixture consisting of large A (hexagons) and small B (triangles) particles. By considering interaction energies between A-A and A-B pairs of particles that occupy nearest-neighbour cells of the hexagonal lattice, we have derived an exact solution for the considered model system having established a mapping correspondence with the two-dimensional Ising model on its dual triangular lattice. Altogether, six different types of coexistence curves including those with reentrant miscibility regions (i.e. closed-loop coexistence curves) were found in dependence on the relative strength between both coupling constants.Comment: 8 pages, 4 figures, presented at 7th Liblice conference on the Statistical Mechanics of Liquids to be held in Lednice on June 11-16, 200

Genomic Footprints of Selective Sweeps from Metabolic Resistance to Pyrethroids in African Malaria Vectors Are Driven by Scale up of Insecticide-Based Vector Control

Insecticide resistance in mosquito populations threatens recent successes in malaria prevention. Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the `resistance curve' and to avert a public health catastrophe. Here, applying a combination of microsatellite analysis, whole genome sequencing and targeted sequencing of a resistance locus, we elucidated the continent-wide population structure of a major African malaria vector, Anopheles funestus. We identified a major selective sweep in a genomic region controlling cytochrome P450-based metabolic resistance conferring high resistance to pyrethroids. This selective sweep occurred since 2002, likely as a direct consequence of scaled up vector control as revealed by whole genome and fine-scale sequencing of pre- and post-intervention populations. Fine-scaled analysis of the pyrethroid resistance locus revealed that a resistanceassociated allele of the cytochrome P450 monooxygenase CYP6P9a has swept through southern Africa to near fixation, in contrast to high polymorphism levels before interventions, conferring high levels of pyrethroid resistance linked to control failure. Population structure analysis revealed a barrier to gene flow between southern Africa and other areas, which may prevent or slow the spread of the southern mechanism of pyrethroid resistance to other regions. By identifying a genetic signature of pyrethroid-based interventions, we have demonstrated the intense selective pressure that control interventions exert on mosquito populations. If this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

The Ecm11-Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast

During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation

Multi-photon ionisation spectroscopy for rotational state preparation of N+2

In this paper we investigate the 2 + 1′ resonance enhanced multi-photon ionisation (REMPI) of molecular nitrogen via the a1Πg(v = 6) intermediate state and analyse its feasibility to generate molecular nitrogen ions in a well defined ro-vibrational state. This is an important tool for high precision experiments based on trapped molecular ions, and is crucial for studying the time variation of the fundamental constant mp/me using N+2. The transition is not reported in the literature and detailed spectral analysis has been conducted to extract the molecular constants of the intermediate state. By carefully choosing the intermediate ro-vibrational state, the ionisation laser wavelength and controlling the excitation laser pulse energy, unwanted formation of rotationally excited molecular ions can be suppressed and ro-vibrational ground state ions can be generated with high purity

Supporting carers to manage pain medication in cancer patients at the end of life: A feasibility trial

Background: Carers of people with advanced cancer play a significant role in managing pain medication, yet they report insufficient information and support to do so confidently and competently. There is limited research evidence on the best ways for clinicians to help carers with medication management. Aims: To develop a pain medicines management intervention (Cancer Carers Medicines Management) for cancer patients’ carers near the end of life and evaluate feasibility and acceptability to nurses and carers. To test the feasibility of trial research procedures and to inform decisions concerning a full-scale randomised controlled trial. Design: Phase I-II clinical trial. A systematic, evidence-informed participatory method was used to develop CCMM: a nurse-delivered structured conversational process. A two-arm, cluster randomised controlled feasibility trial of Cancer Carers Medicines Management was conducted, with an embedded qualitative study to evaluate participants’ experiences of Cancer Carers Medicines Management and trial procedures. Setting: Community settings in two study sites. Participants: Phase I comprises 57 carers, patients and healthcare professionals and Phase II comprises 12 nurses and 15 carers. Results: A novel intervention was developed. Nurses were recruited and randomised. Carer recruitment to the trial was problematic with fewer than predicted eligible participants, and nurses judged a high proportion unsuitable to recruit into the study. Attrition rates following recruitment were typical for the study population. Cancer Carers Medicines Management was acceptable to carers and nurses who took part, and some benefits were identified. Conclusion: Cancer Carers Medicines Management is a robustly developed medicines management intervention which merits further research to test its effectiveness to improve carers’ management of pain medicines with patients at the end of life. The study highlighted aspects of trial design that need to be considered in future research

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis

Background: Hypoxia leads to the stabilisation of the hypoxia-inducible factor (HIF) transcription factor that drives the expression of target genes including microRNAs (miRNAs). MicroRNAs are known to regulate many genes involved in tumourigenesis. The aim of this study was to identify hypoxia-regulated miRNAs (HRMs) in bladder cancer and investigate their functional significance. Methods: Bladder cancer cell lines were exposed to normoxic and hypoxic conditions and interrogated for the expression of 384 miRNAs by qPCR. Functional studies were carried out using siRNA-mediated gene knockdown and chromatin immunoprecipitations. Apoptosis was quantified by annexin V staining and flow cytometry. Results: The HRM signature for NMI bladder cancer lines includes miR-210, miR-193b, miR-145, miR-125-3p, miR-708 and miR-517a. The most hypoxia-upregulated miRNA was miR-145. The miR-145 was a direct target of HIF-1a and two hypoxia response elements were identified within the promoter region of the gene. Finally, the hypoxic upregulation of miR-145 contributed to increased apoptosis in RT4 cells. Conclusions: We have demonstrated the hypoxic regulation of a number of miRNAs in bladder cancer. We have shown that miR- 145 is a novel, robust and direct HIF target gene that in turn leads to increased cell death in NMI bladder cancer cell lines

Comparison of the pathogenesis of the highly passaged MCMV Smith strain with that of the low passaged MCMV HaNa1 isolate in BALB/c mice upon oronasal inoculation

Murine cytomegalovirus (MCMV) Smith strain is widely used in mouse models to study HCMV infections. Due to high serial passages, MCMV Smith has acquired genetic and biological changes. Therefore, a low passaged strain would be more relevant to develop mouse models. Here, the pathogenesis of an infection with MCMV Smith was compared with that of an infection with a low passaged Belgian MCMV isolate HaNa1 in BALB/c adult mice following oronasal inoculation with either a low (10(4) TCID50/mouse) or high (10(6) TCID50/mouse) inoculation dose. Both strains were mainly replicating in nasal mucosa and submandibular glands for one to two months. In nasal mucosa, MCMV was detected earlier and longer (1-49 days post inoculation (dpi)) and reached higher titers with the high inoculation dose compared to the low inoculation dose (14-35 dpi). In submandibular glands, a similar finding was observed (high dose: 7-49 dpi; low dose: 14-42 dpi). In lungs, both strains showed a restricted replication. In spleen, liver and kidneys, only the Smith strain established a productive infection. The infected cells were identified as olfactory neurons and sustentacular cells in olfactory epithelium, macrophages and dendritic cells in NALT, acinar cells in submandibular glands, and macrophages and epithelial cells in lungs for both strains. Antibody analysis demonstrated for both strains that IgG(2a) was the main detectable antibody subclass. Overall, our results show that significant phenotypic differences exist between the two strains. MCMV HaNa1 has been shown to be interesting for use in mouse models in order to get better insights for HCMV infections in immunocompetent humans