Redrawing the map of Great Britain from a network of human interactions

Do regional boundaries defined by governments respect the more natural ways that people interact across space? This paper proposes a novel, fine-grained approach to regional delineation, based on analyzing networks of billions of individual human transactions. Given a geographical area and some measure of the strength of links between its inhabitants, we show how to partition the area into smaller, non-overlapping regions while minimizing the disruption to each person''s links. We tested our method on the largest non-Internet human network, inferred from a large telecommunications database in Great Britain. Our partitioning algorithm yields geographically cohesive regions that correspond remarkably well with administrative regions, while unveiling unexpected spatial structures that had previously only been hypothesized in the literature. We also quantify the effects of partitioning, showing for instance that the effects of a possible secession of Wales from Great Britain would be twice as disruptive for the human network than that of Scotland.     

Metabolic adaptations of Leishmania donovani in relation to differentiation,drug resistance,and drug pressure

Antimonial (sodium stibogluconate, SSG) resistance and differentiation have been shown to be closely linked in Leishmania donovani, with SSG‐resistant strains showing an increased capacity to generate infectious (metacyclic) forms. This is the first untargeted LC‐MS metabolomics study which integrated both phenomena in one experimental design and provided insights into metabolic differences between three clinical L. donovani strains with a similar genetic background but different SSG‐susceptibilities. We performed this analysis at different stages during promastigote growth and in the absence or presence of drug pressure. When comparing SSG‐resistant and SSG‐sensitive strains, a number of metabolic changes appeared to be constitutively present in all growth stages, pointing towards a clear link with SSG‐resistance, whereas most metabolic changes were only detected in the stationary stage. These changes reflect the close intertwinement between SSG‐resistance and an increased metacyclogenesis in resistant parasites. The metabolic changes suggest that SSG‐resistant parasites have (i) an increased capacity for protection against oxidative stress; (ii) a higher fluidity of the plasma membrane; and (iii) a metabolic survival kit to better endure infection. These changes were even more pronounced in a resistant strain kept under Sb^III drug pressure.     

Polymorphic nuclear gene sequences indicate a novel genome donor in the polyploid genus Thinopyrum

For decades, the wheatgrass genus Thinopyrum has been of interest to plant breeders as a source of genes that confer competitive traits. This genus has been a considerable challenge to plant systematists because of the impacts of polyploidization on the evolution of this group. This study was aimed to augment existing cytogenetic data with a sequence-based investigation of the genomes of these species. Sequences of the internal transcribed spacer 1 (ITS1), introns 9 through 11 of the granule-bound starch synthase (GBSSI) gene and intron III of the beta-amylase gene (Bmy1) were isolated from the genomes of polyploid Thinopyrum species by PCR, cloning and sequencing and the evolutionary distances between these species and putative diploid ancestors were estimated with Kimura's two-parameter method. Phylogenetic analysis of these sequences largely agrees with what has been established through cytogenetic means for the Th. caespitosum (Koch) Liu & Wang and Ps geniculata (Trin.) á. L?ve, and suggests a contribution of the St genome of Ps. spicata (Pursh) á. L?ve to the tetraploids Th. scirpeum (Presl) Dewey and Th. junceiforme (á. L?ve & D. L?ve) á. L?ve. A unique Bmy1 allele, divergent from other Triticeae but shared between Th. caespitosum, Th. intermedium (Host) Barkworth & Dewey, Th. junceum (L.) á. L?ve and Th. ponticum Barkworth & Dewey, implies a connection between these species. Distinct oligonucleotide polymorphisms and distance calculations based on the three loci implicate Crithopsis delileana (Schult.) Roshev. and Taeniatherum caput-medusae (L.) Nevski in the evolution of the hexaploid Th. intermedium and the decaploid Th. ponticum and also suggest a potential connection of these polyploids with Elytrigia repens (L.) Desv. ex Nevski. None of these species have been previously associated with the Thinopyrum genus. Allele-specific PCR was employed to detect the putative Crithopsis allele of ITS1 in a number of accessions. Real-time PCR indicates that two of six genomes of the hexaploid Th. intermedium have the Crithopsis-type ITS1 allele and that all ITS1 loci in the decaploid Th. ponticum are of this type. These results are supportive of the hypothesis that concerted evolution has homogenized the rDNA of Th. ponticum to the allele derived from the Crithopsis or Taeniatherum ancestor. Discovery of these novel alleles, with close homology to Ta. caput-medusae, may represent a fundamental change in the view of the evolution of Th. intermedium and Th. ponticum.     

Silica Nanoparticles as the Adjuvant for the Immunisation of Mice Using Hepatitis B Core Virus-Like Particles

Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10–20 nm) with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund''s adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs) formed by recombinant full-length Hepatitis B virus core (HBc) protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL) led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.     

Potato Virus Y-Like Particles as a New Carrier for the Presentation of Foreign Protein Stretches

Virus-like particle (VLP) technology represents a promising approach for the creation of efficient vaccines and materials for use in nanotechnological applications. For construction of a new carrier for foreign protein sequences, the coat protein (CP) gene from potato virus Y (PVY) was cloned and expressed in Escherichia coli cells. The PVY CP self-assembles into PVY-like particles, as demonstrated by electron microscopy analysis of purified VLP preparations. The PVY CP with an N-terminal insertion of a foreign epitope (preS1) or of a whole protein (rubredoxin) retains its ability to form filamentous particles, whereas adding a foreign sequence to the C-terminus of the PVY CP generates mostly unstructured protein aggregates. This new filamentous plant virus-derived VLP carrier accommodates a foreign protein sequence that is up to 71 amino acids in length on the VLP surface and can be produced in E. coli in preparative amounts. The PVY CP VLPs are stable in physiological conditions, but they are sensitive to EDTA, high salt, and extreme pH. The presence of the preS1 epitope decreases the stability of the chimeric PVY CP particles at elevated temperatures. Mice that are immunized with chimeric PVY CP particles carrying preS1 epitopes exhibit a strong anti-preS1 immune response, even in the absence of adjuvants.     

C-Terminal Mutants of Apolipoprotein L-I Efficiently Kill Both Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense

Apolipoprotein L-I (apoL1) is a human-specific serum protein that kills Trypanosoma brucei through ionic pore formation in endosomal membranes of the parasite. The T. brucei subspecies rhodesiense and gambiense resist this lytic activity and can infect humans, causing sleeping sickness. In the case of T. b. rhodesiense, resistance to lysis involves interaction of the Serum Resistance-Associated (SRA) protein with the C-terminal helix of apoL1. We undertook a mutational and deletional analysis of the C-terminal helix of apoL1 to investigate the linkage between interaction with SRA and lytic potential for different T. brucei subspecies. We confirm that the C-terminal helix is the SRA-interacting domain. Although in E. coli this domain was dispensable for ionic pore-forming activity, its interaction with SRA resulted in inhibition of this activity. Different mutations affecting the C-terminal helix reduced the interaction of apoL1 with SRA. However, mutants in the L370-L392 leucine zipper also lost in vitro trypanolytic activity. Truncating and/or mutating the C-terminal sequence of human apoL1 like that of apoL1-like sequences of Papio anubis resulted in both loss of interaction with SRA and acquired ability to efficiently kill human serum-resistant T. b. rhodesiense parasites, in vitro as well as in transgenic mice. These findings demonstrate that SRA interaction with the C-terminal helix of apoL1 inhibits its pore-forming activity and determines resistance of T. b. rhodesiense to human serum. In addition, they provide a possible explanation for the ability of Papio serum to kill T. b. rhodesiense, and offer a perspective to generate transgenic cattle resistant to both T. b. brucei and T. b. rhodesiense.     

Parallel expression profiling of barley–stem rust interactions

The dominant barley stem rust resistance gene Rpg1 confers resistance to many but not all pathotypes of the stem rust fungus Puccinia graminis f. sp. tritici (Pgt). Transformation of Rpg1 into susceptible cultivar Golden Promise rendered the transgenic plants resistant to Pgt pathotype MCC but not to Pgt pathotype QCC. Our objective was to identify genes that are induced/repressed during the early stages of pathogen infection to elucidate the molecular mechanisms and role of Rpg1 in defense. A messenger ribonucleic acid expression analysis using the 22K Barley1 GeneChip was conducted in all pair-wise combinations of two isolines (cv. Golden Promise and Rpg1 transgenic line G02-448F-3R) and two Pgt pathotypes (MCC and QCC) across six time points. Analysis showed that a total of 34 probe sets exhibited expression pattern differences between Golden Promise (susceptible) and G02-448F-3R (resistant) infected with Pgt-MCC. A total of 14 probe sets exhibited expression pattern differences between Pgt-MCC (avirulent) and Pgt-QCC (virulent) inoculated onto G02-448F-3R. These differentially expressed genes were activated during the early infection process, before the hypersensitive response or fungal growth inhibition occurred. Our analysis provides a list of candidate signaling components, which can be analyzed for function in Rpg1-mediated disease resistance.     

Parasiticidal 2-alkoxy- and 2-aryloxyiminoalkyl trifluoromethanesulfonanilides

A series of novel 2-alkoxy- and 2-aryloxyiminoalkyl trifluoromethanesulfonanilide derivatives have shown significant in vitro parasiticidal activity against the ectoparasites Ctenocephalides felis and Rhipicephalus sanguineus. A number of these compounds also displayed significant in vitro endoparasite activity against the nematode Haemonchus contortus.     

Quantitative relationship between synonymous codon usage bias and GC composition across unicellular genomes

Background  

Codon usage bias has been widely reported to correlate with GC composition. However, the quantitative relationship between codon usage bias and GC composition across species has not been reported.     

Insecticidal effect of three diatomaceous earth formulations against adults of Sitophilus oryzae (Coleoptera: Curculionidae) and Tribolium confusum (Coleoptera: Tenebrionidae) on oat, rye, and triticale

Bioassays were conducted in the laboratory to assess the effect of the diatomaceous earth (DE) formulations Insecto, SilicoSec, and PyriSec, on stored oat, rye, and triticale, against adults of the rice weevil, Sitophilus oryzae (L.), and the confused flour beetle, Tribolium confusum Jacquelin du Val. The DEs were tested at three dose rates, 0.75, 1, and 1.5 g of DE/kg of grain. Adults of the two aforementioned species were exposed to all combinations of grain-formulation-dose rate, at 26 degrees C and 60% RH. Mortality in DE-treated commodities was recorded after 24 h, 48 h, 7 d, and 14 d of exposure for S. oryzae and T. confusum and after 21 d for T. confusum. In S. oryzae, adult mortality was almost 100% after 7 d of exposure in all three grains examined. The mortality of T. confusum adults in DE-treated grains did not reach 100%, even after 21 d of exposure. Generally, the application of DE in rye caused higher adult mortality of T. confusum than in the other two products. All three dose rates tested provided the same mortality level of S. oryzae adults after 7 d of exposure. In contrast, 1.5 g of DE resulted in significant higher adult mortality of T. confusum, in comparison with the other dose rates, even after 21 d of exposure. All formulations were equally effective after 7 d of exposure against S. oryzae, but at 48 h of exposure, PyriSec caused significantly higher mortality than the other two formulations. For both species, progeny production in the treated grains was significantly reduced in comparison with the untreated grains, whereas significant differences were noted among commodities, formulations, and dose rates. No progeny were recorded in the treated rye for either species or in the treated triticale for S. oryzae.