Anomalous dimensions and phase transitions in superconductors

The anomalous scaling in the Ginzburg-Landau model for the superconducting phase transition is studied. It is argued that the negative sign of the $\eta$ exponent is a consequence of a special singular behavior in momentum space. The negative sign of $\eta$ comes from the divergence of the critical correlation function at finite distances. This behavior implies the existence of a Lifshitz point in the phase diagram. The anomalous scaling of the vector potential is also discussed. It is shown that the anomalous dimension of the vector potential $\eta_A=4-d$ has important consequences for the critical dynamics in superconductors. The frequency-dependent conductivity is shown to obey the scaling $\sigma(\omega)\sim\xi^{z-2}$. The prediction $z\approx 3.7$ is obtained from existing Monte Carlo data.Comment: RevTex, 20 pages, no figures; small changes; version accepted in PR

Enhanced Transduction and Replication of RGD-Fiber Modified Adenovirus in Primary T Cells

Background: Adenoviruses are often used as vehicles to mediate gene delivery for therapeutic purposes, but their research scope in hematological cells remains limited due to a narrow choice of host cells that express the adenoviral receptor (CAR). T cells, which are attractive targets for gene therapy of numerous diseases, remain resistant to adenoviral infection because of the absence of CAR expression. Here, we demonstrate that this resistance can be overcome when murine or human T cells are transduced with an adenovirus incorporating the RGD-fiber modification (Ad-RGD). Methodology/Principal Finding: A luciferase-expressing replication-deficient Ad-RGD infected 3-fold higher number of activated primary T cells than an adenovirus lacking the RGD-fiber modification in vitro. Infection with replicationcompetent Ad-RGD virus also caused increased cell cycling, higher E1A copy number and enriched hexon antigen expression in both human and murine T cells. Transduction with oncolytic Ad-RGD also resulted in higher titers of progeny virus and enhanced the killing of T cells. In vivo, 35–45 % of splenic T cells were transduced by Ad-RGD. Conclusions: Collectively, our results prove that a fiber modified Ad-RGD successfully transduces and replicates in primary

Disturbance and diversity at two spatial scales

The spatial scale of disturbance is a factor potentially influencing the relationship between disturbance and diversity. There has been discussion on whether disturbances that affect local communities and create a mosaic of patches in different successional stages have the same effect on diversity as regional disturbances that affect the whole landscape. In a microcosm experiment with metacommunities of aquatic protists, we compared the effect of local and regional disturbances on the disturbance–diversity relationship. Local disturbances destroyed entire local communities of the metacommunity and required reimmigration from neighboring communities, while regional disturbances affected the whole metacommunity but left part of each local community intact. Both disturbance types led to a negative relationship between disturbance intensity and Shannon diversity. With strong local disturbance, this decrease in diversity was due to species loss, while strong regional disturbance had no effect on species richness but reduced the evenness of the community. Growth rate appeared to be the most important trait for survival after strong local disturbance and dominance after strong regional disturbance. The pattern of the disturbance–diversity relationship was similar for both local and regional diversity. Although local disturbances at least temporally increased beta diversity by creating a mosaic of differently disturbed patches, this high dissimilarity did not result in regional diversity being increased relative to local diversity. The disturbance–diversity relationship was negative for both scales of diversity. The flat competitive hierarchy and absence of a trade-off between competition and colonization ability are a likely explanation for this pattern

The Plasmodium Export Element Revisited

We performed a bioinformatical analysis of protein export elements (PEXEL) in the putative proteome of the malaria parasite Plasmodium falciparum. A protein family-specific conservation of physicochemical residue profiles was found for PEXEL-flanking sequence regions. We demonstrate that the family members can be clustered based on the flanking regions only and display characteristic hydrophobicity patterns. This raises the possibility that the flanking regions may contain additional information for a family-specific role of PEXEL. We further show that signal peptide cleavage results in a positional alignment of PEXEL from both proteins with, and without, a signal peptide

Programmable disorder in random DNA tilings

Scaling up the complexity and diversity of synthetic molecular structures will require strategies that exploit the inherent stochasticity of molecular systems in a controlled fashion. Here we demonstrate a framework for programming random DNA tilings and show how to control the properties of global patterns through simple, local rules. We constructed three general forms of planar network—random loops, mazes and trees—on the surface of self-assembled DNA origami arrays on the micrometre scale with nanometre resolution. Using simple molecular building blocks and robust experimental conditions, we demonstrate control of a wide range of properties of the random networks, including the branching rules, the growth directions, the proximity between adjacent networks and the size distribution. Much as combinatorial approaches for generating random one-dimensional chains of polymers have been used to revolutionize chemical synthesis and the selection of functional nucleic acids, our strategy extends these principles to random two-dimensional networks of molecules and creates new opportunities for fabricating more complex molecular devices that are organized by DNA nanostructures

Requirements for Receptor Engagement during Infection by Adenovirus Complexed with Blood Coagulation Factor X

Human adenoviruses from multiple species bind to coagulation factor X (FX), yet the importance of this interaction in adenovirus dissemination is unknown. Upon contact with blood, vectors based on adenovirus serotype 5 (Ad5) binds to FX via the hexon protein with nanomolar affinity, leading to selective uptake of the complex into the liver and spleen. The Ad5:FX complex putatively targets heparan sulfate proteoglycans (HSPGs). The aim of this study was to elucidate the specific requirements for Ad5:FX-mediated cellular uptake in this high-affinity pathway, specifically the HSPG receptor requirements as well as the role of penton base-mediated integrin engagement in subsequent internalisation. Removal of HS sidechains by enzymatic digestion or competition with highly-sulfated heparins/heparan sulfates significantly decreased FX-mediated Ad5 cell binding in vitro and ex vivo. Removal of N-linked and, in particular, O-linked sulfate groups significantly attenuated the inhibitory capabilities of heparin, while the chemical inhibition of endogenous HSPG sulfation dose-dependently reduced FX-mediated Ad5 cellular uptake. Unlike native heparin, modified heparins lacking O- or N-linked sulfate groups were unable to inhibit Ad5 accumulation in the liver 1h after intravascular administration of adenovirus. Similar results were observed in vitro using Ad5 vectors possessing mutations ablating CAR- and/or αv integrin binding, demonstrating that attachment of the Ad5:FX complex to the cell surface involves HSPG sulfation. Interestingly, Ad5 vectors ablated for αv integrin binding showed markedly delayed cell entry, highlighting the need for an efficient post-attachment internalisation signal for optimal Ad5 uptake and transport following surface binding mediated through FX. This study therefore integrates the established model of αv integrin-dependent adenoviral infection with the high-affinity FX-mediated pathway. This has important implications for mechanisms that define organ targeting following contact of human adenoviruses with blood

An expanded global inventory of allelic variation in the most extremely polymorphic region of Plasmodium falciparum merozoite surface protein 1 provided by short read sequence data.

BACKGROUND: Within Plasmodium falciparum merozoite surface protein 1 (MSP1), the N-terminal block 2 region is a highly polymorphic target of naturally acquired antibody responses. The antigenic diversity is determined by complex repeat sequences as well as non-repeat sequences, grouping into three major allelic types that appear to be maintained within populations by natural selection. Within these major types, many distinct allelic sequences have been described in different studies, but the extent and significance of the diversity remains unresolved. METHODS: To survey the diversity more extensively, block 2 allelic sequences in the msp1 gene were characterized in 2400 P. falciparum infection isolates with whole genome short read sequence data available from the Pf3K project, and compared with the data from previous studies. RESULTS: Mapping the short read sequence data in the 2400 isolates to a reference library of msp1 block 2 allelic sequences yielded 3815 allele scores at the level of major allelic family types, with 46% of isolates containing two or more of these major types. Overall frequencies were similar to those previously reported in other samples with different methods, the K1-like allelic type being most common in Africa, MAD20-like most common in Southeast Asia, and RO33-like being the third most abundant type in each continent. The rare MR type, formed by recombination between MAD20-like and RO33-like alleles, was only seen in Africa and very rarely in the Indian subcontinent but not in Southeast Asia. A combination of mapped short read assembly approaches enabled 1522 complete msp1 block 2 sequences to be determined, among which there were 363 different allele sequences, of which 246 have not been described previously. In these data, the K1-like msp1 block 2 alleles are most diverse and encode 225 distinct amino acid sequences, compared with 123 different MAD20-like, 9 RO33-like and 6 MR type sequences. Within each of the major types, the different allelic sequences show highly skewed geographical distributions, with most of the more common sequences being detected in either Africa or Asia, but not in both. CONCLUSIONS: Allelic sequences of this extremely polymorphic locus have been derived from whole genome short read sequence data by mapping to a reference library followed by assembly of mapped reads. The catalogue of sequence variation has been greatly expanded, so that there are now more than 500 different msp1 block 2 allelic sequences described. This provides an extensive reference for molecular epidemiological genotyping and sequencing studies, and potentially for design of a multi-allelic vaccine

Model and experiences of initiating collaboration with traditional healers in validation of ethnomedicines for HIV/AIDS in Namibia

Many people with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) in Namibia have access to antiretroviral drugs but some still use traditional medicines to treat opportunistic infections and offset side-effects from antiretroviral medication. Namibia has a rich biodiversity of indigenous plants that could contain novel anti-HIV agents. However, such medicinal plants have not been identified and properly documented. Various ethnomedicines used to treat HIV/AIDS opportunistic infections have not been scientifically validated for safety and efficacy. These limitations are mostly attributable to the lack of collaboration between biomedical scientists and traditional healers. This paper presents a five-step contextual model for initiating collaboration with Namibian traditional healers in order that candidate plants that may contain novel anti-HIV agents are identified, and traditional medicines used to treat HIV/AIDS opportunistic infections are subjected to scientific validation. The model includes key structures and processes used to initiate collaboration with traditional healers in Namibia; namely, the National Biosciences Forum, a steering committee with the University of Namibia (UNAM) as the focal point, a study tour to Zambia and South Africa where other collaborative frameworks were examined, commemorations of the African Traditional Medicine Day (ATMD), and consultations with stakeholders in north-eastern Namibia. Experiences from these structures and processes are discussed. All traditional healers in north-eastern Namibia were willing to collaborate with UNAM in order that their traditional medicines could be subjected to scientific validation. The current study provides a framework for future collaboration with traditional healers and the selection of candidate anti-HIV medicinal plants and ethnomedicines for scientific testing in Namibia

RNAcontext: A New Method for Learning the Sequence and Structure Binding Preferences of RNA-Binding Proteins

Metazoan genomes encode hundreds of RNA-binding proteins (RBPs). These proteins regulate post-transcriptional gene expression and have critical roles in numerous cellular processes including mRNA splicing, export, stability and translation. Despite their ubiquity and importance, the binding preferences for most RBPs are not well characterized. In vitro and in vivo studies, using affinity selection-based approaches, have successfully identified RNA sequence associated with specific RBPs; however, it is difficult to infer RBP sequence and structural preferences without specifically designed motif finding methods. In this study, we introduce a new motif-finding method, RNAcontext, designed to elucidate RBP-specific sequence and structural preferences with greater accuracy than existing approaches. We evaluated RNAcontext on recently published in vitro and in vivo RNA affinity selected data and demonstrate that RNAcontext identifies known binding preferences for several control proteins including HuR, PTB, and Vts1p and predicts new RNA structure preferences for SF2/ASF, RBM4, FUSIP1 and SLM2. The predicted preferences for SF2/ASF are consistent with its recently reported in vivo binding sites. RNAcontext is an accurate and efficient motif finding method ideally suited for using large-scale RNA-binding affinity datasets to determine the relative binding preferences of RBPs for a wide range of RNA sequences and structures