Limnonectins: A new class of antimicrobial peptides from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis)

Amphibian skin secretions are rich sources of biologically-active peptides with antimicrobial peptides predominating in many species. Several studies involving molecular cloning of biosynthetic precursor-encoding cDNAs from skin or skin secretions have revealed that these exhibit highly-conserved domain architectures with an unusually high degree of conserved nucleotide and resultant amino acid sequences within the signal peptides. This high degree of nucleotide sequence conservation has permitted the design of primers complementary to such sites facilitating “shotgun” cloning of skin or skin secretion-derived cDNA libraries from hitherto unstudied species. Here we have used such an approach using a skin secretion-derived cDNA library from an unstudied species of Chinese frog – the Fujian large-headed frog, Limnonectes fujianensis – and have discovered two 16-mer peptides of novel primary structures, named limnonectin-1Fa (SFPFFPPGICKRLKRC) and limnonectin-1Fb (SFHVFPPWMCKSLKKC), that represent the prototypes of a new class of amphibian skin antimicrobial peptide. Unusually these limnonectins display activity only against a Gram-negative bacterium (MICs of 35 and 70 µM) and are devoid of haemolytic activity at concentrations up to 160 µM. Thus the “shotgun” cloning approach described can exploit the unusually high degree of nucleotide conservation in signal peptide-encoding domains of amphibian defensive skin secretion peptide precursor-encoding cDNAs to rapidly expedite the discovery of novel and functional defensive peptides in a manner that circumvents specimen sacrifice without compromising robustness of data

Biaryl polyamides as a new class of DNA quadruplex-binding ligands

We report a novel class of biaryl polyamides highly selective for G-quadruplex DNA, and with significant cytotoxicity in several cancer cell lines; they form planar U-shaped structures that match the surface area dimensions of a terminal G-quartet in quadruplex structures rather than the grooves of duplex DNA.

Tetra-end-linked oligonucleotides forming DNA G-quadruplexes: a new class of aptamers showing anti-HIV activity.

The biophysical and biological properties of unprecedented anti-HIV aptamers are presented. The most active aptamer (1L) shows a significant affinity to the HIV protein gp120.

Computational Investigation of Inlet Distortion at High Angles of Attack

Lip separation is one of the primary sources of inlet distortion, which can result in a loss in fan stability. High angles of incidence are one of several critical causes of lip separation. There have been many studies into inlet performance at high incidence, including the resulting distortion levels when lip separation occurs. However, the vast majority of these investigations have been carried out experimentally, with little in the way of computational results for inlet performance at high incidence. The flow topology within an inlet when lip separation has occurred is also not well understood. This work aims to demonstrate a suitable model for the prediction of inlet flows at high incidence using ANSYS CFX, looking at both the performance of the inlet and the separated flow topology within the inlet. The attenuating effect of the fan is also investigated, with particular emphasis on the flow redistribution ahead of the fan. The results show that the model used is suitable for predicting inlet performance in adverse operating conditions, showing good agreement with experimental results. In addition, the attenuation of the distortion by the fan is also captured by the numerical model.

Analysis and Design of Class-E3F and Transmission-Line Class-E3F2 Power Amplifiers

In this paper, analysis and synthesis approach for two new variants within the Class-EF power amplifier (PA) family is elaborated. These amplifiers are classified here as Class-E3 F2 and transmission-line (TL) Class-E3 F 2. The proposed circuits offer means to alleviate some of the major issues faced by existing topologies such as substantial power losses due to the parasitic resistance of the large inductor in the Class-EF load network and deviation from ideal Class-EF operation due to the effect of device output inductance at high frequencies. Both lumped-element and transmission-line load networks for the Class-E 3 F PA are described. The load networks of the Class-E3 F and TL Class-E 3 F2amplifier topologies developed in this paper simultaneously satisfy the Class-EF optimum impedance requirements at fundamental frequency, second, and third harmonics as well as simultaneously providing matching to the circuit optimum load resistance for any prescribed system load resistance. Optimum circuit component values are analytically derived and validated by harmonic balance simulations. Trade-offs between circuit figures of merit and component values with some practical limitations being considered are discussed. © 2010 IEEE.

CD18-dependent activation of the neutrophil NADPH oxidase during phagocytosis of Escherichia coli or Staphylococcus aureus is regulated by class III but not class I or II PI3Ks

Phagocytosis and activation of the NADPH oxidase are important mechanisms by which neutrophils and macrophages engulf and kill microbial pathogens. We investigated the role of PI3K signaling pathways in the regulation of the oxidase during phagocytosis of Staphylococcus aureus and Escherichia coli by mouse and human neutrophils, a mouse macrophage-like cell line and a human myeloid-like cell line. Phagocytosis of these bacteria was promoted by serum, independent of serum-derived antibodies, and effectively abolished in mouse neutrophils lacking the beta(2)-integrin common chain, CD18. A combination of PI3K isoform-selective inhibitors, mouse knock-outs, and RNA-interference indicated CD18-dependent activation of the oxidase was independent of class I and II PI3Ks, but substantially dependent on the single class III isoform (Vps34). Class III PI3K was responsible for the synthesis of PtdIns( 3) P on phagosomes containing either bacteria. The use of mouse neutrophils carrying an appropriate knock-in mutation indicated that PtdIns(3) P binding to the PX domain of their p40(phox) oxidase subunit is important for oxidase activation in response to both S aureus and E coli. This interaction does not, however, account for all the PI3K sensitivity of these responses, particularly the oxidase response to E coli, suggesting that additional mechanisms for PtdIns( 3) P-regulation of the oxidase must exist. ( Blood. 2008; 112: 5202-5211)

Langerin(+) Dermal Dendritic Cells Are Critical for CD8(+) T Cell Activation and IgH gamma-1 Class Switching in Response to Gene Gun Vaccines

The C-type lectin langerin/CD207 was originally discovered as a specific marker for epidermal Langerhans cells (LC). Recently, additional and distinct subsets of langerin(+) dendritic cells (DC) have been identified in lymph nodes and peripheral tissues of mice. Although the role of LC for immune activation or modulation is now being discussed controversially, other langerin(+) DC appear crucial for protective immunity in a growing set of infection and vaccination models. In knock-in mice that express the human diphtheria toxin receptor under control of the langerin promoter, injection of diphtheria toxin ablates LC for several weeks whereas other langerin(+) DC subsets are replenished within just a few days. Thus, by careful timing of diphtheria toxin injections selective states of deficiency in either LC only or all langerin(+) cells can be established. Taking advantage of this system, we found that, unlike selective LC deficiency, ablation of all langerin(+) DC abrogated the activation of IFN-gamma producing and cytolytic CD8(+) T cells after gene gun vaccination. Moreover, we identified migratory langerin(+) dermal DC as the subset that directly activated CD8(+) T cells in lymph nodes. Langerin(+) DC were also critical for IgG1 but not IgG2a Ab induction, suggesting differential polarization of CD4(+) T helper cells by langerin(+) or langerin-negative DC, respectively. In contrast, protein vaccines administered with various adjuvants induced IgG1 independently of langerin(+) DC. Taken together, these findings reflect a highly specialized division of labor between different DC subsets both with respect to Ag encounter as well as downstream processes of immune activation. The Journal of Immunology, 2011, 186: 1377-1383.

An Introduction to the Special issue - Housing in Hard Times: Marginality, Inequality and Class, with Kim McKee

‘Housing in Hard Times’ was the theme of the Housing Studies Association annual conference in April 2011. The papers featured in this special issue are drawn from that conference. They examine the uneven impact of economic change on housing policy and related areas, with reference to conceptual ideas pertaining to urban marginality, inequality and class. Whilst the empirical focus of the papers is the UK, their intellectual contribution represents an attempt to ‘bring class back in’ to the housing studies literature and encourage more critical, theoretically informed scholarship.

Transmission-Line Class-E Power Amplifier With Extended Maximum Operating Frequency

A novel Class-E power amplifier (PA) topology with transmission-line load network is presented in this brief. When compared with the classic Class-E topology, the new circuit can increase the maximum operating frequency up to 50% higher without trading the other Class-E figures of merit. Neither quarterwave line/massive radio-frequency choke for collector/drain biasing nor additional fundamental-frequency output matching circuit are needed in the proposed PA, thus resulting in a compact design. Closed-form formulations are derived and verified by simulations with practical design limitations carefully taken into consideration and good agreement achieved.