Activation of membrane-bound proteins and receptor systems: A link between tissue kallikrein and the KLK-related peptidases

The 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and roles in a range of cellular processes, including proliferation, migration, invasion, differentiation, inflammation and angiogenesis that are required in both normal physiology as well as pathological conditions. These roles require cleavage of a range of substrates, including extracellular matrix proteins, growth factors, cytokines as well as other proteinases. In addition, it has been clear since the earliest days of KLK research that cleavage of cell surface substrates is also essential in a range of KLK-mediated cellular processes where these peptidases are essentially acting as agonists and antagonists. In this review we focus on these KLK-regulated cell surface receptor systems including bradykinin receptors, proteinase-activated receptors, as well as the plasminogen activator, ephrins and their receptors, and hepatocyte growth factor/Met receptor systems and other plasma membrane proteins. From this analysis it is clear that in many physiological and pathological settings KLKs have the potential to regulate multiple receptor systems simultaneously; an important issue when these peptidases and substrates are targeted in disease.

Taxonomic review of the chironomid genus Cricotopus v.d. Wulp (Diptera: Chironomidae) from Australia : keys to males, females, pupae and larvae, description of ten new species and comments on Paratrichocladius Santos Abreu

The Australian species of the Orthocladiinae genus Cricotopus Wulp (Diptera: Chironomidae) are revised for larval, pupal, adult male and female life stages. Eleven species, ten of which are new, are recognised and keyed, namely Cricotopus acornis Drayson & Cranston sp. nov., Cricotopus albitarsis Hergstrom sp. nov., Cricotopus annuliventris (Skuse), Cricotopus brevicornis Drayson & Cranston sp. nov., Cricotopus conicornis Drayson & Cranston sp. nov., Cricotopus hillmani Drayson & Cranston, sp. nov., Cricotopus howensis Cranston sp. nov., Cricotopus parbicinctus Hergstrom sp. nov., Cricotopus tasmania Drayson & Cranston sp. nov., Cricotopus varicornis Drayson & Cranston sp. nov. and Cricotopus wangi Cranston & Krosch sp. nov. Using data from this study, we consider the wider utility of morphological and molecular diagnostic tools in untangling species diversity in the Chironomidae. Morphological support for distinguishing Cricotopus from Paratrichocladius Santo-Abreu in larval and pupal stages appears lacking for Australian taxa and brief notes are provided concerning this matter.

A computer generated model of adenosine receptors rationalising binding and selectivity of receptor ligands

Computer graphic analyses on a broad spectrum of adenosine receptor ligands has shown that both the A1 and A2 adenosine receptors have three binding sites. The spatial relationship of these three binding sites has been defined. Adenosine orientation at A1 and A2 is different.

A semi-alternating direction method for a 2-D fractional FitzHugh–Nagumo monodomain model on an approximate irregular domain

A FitzHugh-Nagumo monodomain model has been used to describe the propagation of the electrical potential in heterogeneous cardiac tissue. In this paper, we consider a two-dimensional fractional FitzHugh-Nagumo monodomain model on an irregular domain. The model consists of a coupled Riesz space fractional nonlinear reaction-diffusion model and an ordinary differential equation, describing the ionic fluxes as a function of the membrane potential. Secondly, we use a decoupling technique and focus on solving the Riesz space fractional nonlinear reaction-diffusion model. A novel spatially second-order accurate semi-implicit alternating direction method (SIADM) for this model on an approximate irregular domain is proposed. Thirdly, stability and convergence of the SIADM are proved. Finally, some numerical examples are given to support our theoretical analysis and these numerical techniques are employed to simulate a two-dimensional fractional Fitzhugh-Nagumo model on both an approximate circular and an approximate irregular domain.

Sub-genomic RNA of defective interfering (D.I.) dengue viral particles is replicated in the same manner as full length genomes

The predicted secondary structure of sub-genomic RNA in dengue virus defective interfering (D.I.) particles from patients, or generated in vitro, resembled that of the 3′ and 5′ regions of wild type dengue virus (DENV) genomes. While these structures in the sub-genomic RNA were found to be essential for its replication, their nucleotide sequences were not, so long as any new sequences maintained wild type RNA secondary structure. These observations suggested that these sub-genomic fragments of RNA from dengue viruses were replicated in the same manner as the full length genomes of their wild type, “helper”, viruses and that they probably represent the smallest fragments of DENV RNA that can be replicated during a natural infection. While D.I. particles containing sub-genomic RNA are completely parasitic, the relationship between wild type and D.I. DENV may be symbiotic, with the D.I. particles enhancing the transmission of infectious DENV.

Crystal structure of the magnesium salt of the herbicide 2,4-D: pentaaqua[(2,4-dichlorophenoxy)acetato-kO]magnesium (2,4-dichlorophenoxy)acetate hemihydrate

In the structure of the title magnesium complex with the phenoxy herbicide (2,4-dichlorophenoxy)acetic acid (2,4-D), [Mg(H2O)5(C8H5Cl2O3)]+ C8H5Cl2O3)- . 0.5H2O, the discrete cationic MgO6 complex units comprise a carboxyl O-donor from a monodentate 2,4-D cationic ligand and five water molecules in a slightly distorted octahedral coordination. The 2,4-D anions are linked to the complex units through duplex water O-H...O(carboxyl) hydrogen bonds through the coordinated water molecules. In the crystal inter-unit O-H...O hydrogen-bonding interactions involving coordinated water molecules as well as the hemi-hydrate solvate molecule with carboxyl O-atom acceptors, give a two-dimensional layered structure lying parallel (001), in which pi-pi ligand-cation interactions [minimum ring centroid separation, 3.6405(17)A] and a short O-H...Cl interaction [3.345(2)A] are also found.

GABAA and NMDA receptors contribute to synaptic integration in lateral amygdala neurons

In classical fear conditioning a neutral conditioned stimulus (CS), is paired with an aversive unconditioned stimulus (US). The CS thereby acquires the capacity to elicit a fear response. This type of associative learning is thought to require co-activation of principal neurons in the lateral nucleus of the amygdala (LA) by two sets of synaptic inputs...

GABAa receptors contribute to synaptic integration in lateral amygdala neurons

In classical fear conditioning a neutral conditioned stimulus (CS) such as a tone, is paired with an aversive unconditioned stimulus (US) such as a shock. The CS thereby acquires the capacity to elicit a fear response. This type of associative learning is thought to require co-activation of principle neurons in the lateral nucleus of the amygdala (LA) by two sets of synaptic inputs, a weak CS and a strong US...