Histochemical localization of cholinesterases in the neural tissue of the pineal in the rhesus monkey.

The neural tissue of the monkey pineal contains both acetyl and butyryl cholinesterases. Acetylcholinesterase was localized in the cisternae of the nuclear membrane, rough endoplasmic reticulum, on the plasma membrane of the neurones, and on the axolemma of both non-myelinated and myelinated fibres. The enzyme was not found in the axosomatic or axo-dendritic synapses. It is therefore suggested that the pineal neurones have a cholinergic function rather than a cholinoceptive one.     

Transvascular delivery of small interfering RNA to the central nervous system

A major impediment in the treatment of neurological diseases is the presence of the blood-brain barrier, which precludes the entry of therapeutic molecules from blood to brain. Here we show that a short peptide derived from rabies virus glycoprotein (RVG) enables the transvascular delivery of small interfering RNA (siRNA) to the brain. This 29-amino-acid peptide specifically binds to the acetylcholine receptor expressed by neuronal cells. To enable siRNA binding, a chimaeric peptide was synthesized by adding nonamer arginine residues at the carboxy terminus of RVG. This RVG-9R peptide was able to bind and transduce siRNA to neuronal cells in vitro, resulting in efficient gene silencing. After intravenous injection into mice, RVG-9R delivered siRNA to the neuronal cells, resulting in specific gene silencing within the brain. Furthermore, intravenous treatment with RVG-9R-bound antiviral siRNA afforded robust protection against fatal viral encephalitis in mice. Repeated administration of RVG-9R-bound siRNA did not induce inflammatory cytokines or anti-peptide antibodies. Thus, RVG-9R provides a safe and noninvasive approach for the delivery of siRNA and potentially other therapeutic molecules across the blood-brain barrier.     

The rapid drift of the Indian tectonic plate

The breakup of the supercontinent Gondwanaland into Africa, Antarctica, Australia and India about 140 million years ago, and consequently the opening of the Indian Ocean, is thought to have been caused by heating of the lithosphere from below by a large plume whose relicts are now the Marion, Kerguelen and Réunion plumes. Plate reconstructions based on palaeomagnetic data suggest that the Indian plate attained a very high speed (18-20 cm yr(-1) during the late Cretaceous period) subsequent to its breakup from Gondwanaland, and then slowed to approximately 5 cm yr(-1) after the continental collision with Asia approximately 50 Myr ago. The Australian and African plates moved comparatively less distance and at much lower speeds of 2-4 cm yr(-1) (refs 3-5). Antarctica remained almost stationary. This mobility makes India unique among the fragments of Gondwanaland. Here we propose that when the fragments of Gondwanaland were separated by the plume, the penetration of their lithospheric roots into the asthenosphere were important in determining their speed. We estimated the thickness of the lithospheric plates of the different fragments of Gondwanaland around the Indian Ocean by using the shear-wave receiver function technique. We found that the fragment of Gondwanaland with clearly the thinnest lithosphere is India. The lithospheric roots in South Africa, Australia and Antarctica are between 180 and 300 km deep, whereas the Indian lithosphere extends only about 100 km deep. We infer that the plume that partitioned Gondwanaland may have also melted the lower half of the Indian lithosphere, thus permitting faster motion due to ridge push or slab pull.     

Optical parameters induced by phase transformation in RF magnetron sputtered TiO2nanostructured thin films

Pure TiO2 thin films were deposited onto quartz substrates using a ceramic TiO2 target at an elevated substrate temperature of 573 K by RF magnetron sputtering, and an analysis of structural, optical and photoluminescence characteristics of the films upon phase transformation is reported in this paper. Structural investigations using X-ray diffraction revealed that the as-deposited film was amorphous in nature. Thermal annealing for 2 h at 873 K in air resulted in the formation of anatase phase, and a phase transformation to rutile was observed at 1073 K.An increase in grain size and an improvement in crystallinity were also observed on annealing. Rod- like rutile crystallites were observed in the SEM images of the film annealed at 1273 K. As-deposited films and films annealed up to 1073 K were highly transparent in the visible region with a transparency 480%. Optical band gap of the films decreased upon thermal annealing which is attributed to phase transformation from amorphous to anatase and then to rutile. Optical parameters such as refractive index, optical conductivity and optical dielectric constant increased with increase in annealing temperature. Since rutile is the optically active phase, the superior refractive index of the film annealed at 1073 K along with its high transparency in visible region suggests the application of this film in antireflective coatings. Photoluminescence emission of maximum intensity was observed for the film annealed at 873 K, which exhibits anatase phase. Intense blue emission observed in this film makes it suitable for use in optoelectronic display devices.     

Algal biomass as a global source of transport fuels: Overview and development perspectives

As a result of the global fuel crisis of the early 1970 s,coupled with concerns for the environment,the use of biofuel has been on the increase in many regions throughout the world.At present,a total of approximately 30 billion(30×109) liters of biofuel are utilized worldwide annually,although most countries rely hugely on the first generation biofuel.The limitations of the first and second generation biofuel gave rise to current interest in algae as a promising alternative to these conventional biofuel sources.Algal biomass could provide a lion’s share of the global transport fuel requirements in future.The present review highlights some important developments in,and potentials of algaculture as a major biomass resource of the future.However,the major constraint to commercial-scale algae farming for energy production is the cost factor,which must be addressed adequately before its potentials can be harnessed.     

Bioportide: an emergent concept of bioactive cell-penetrating peptides

Cell-penetrating peptides (CPPs) have proven utility for the highly efficient intracellular delivery of bioactive cargoes that include peptides, proteins, and oligonucleotides. The many strategies developed to utilize CPPs solely as pharmacokinetic modifiers necessarily requires them to be relatively inert. Moreover, it is feasible to combine one or multiple CPPs with bioactive cargoes either by direct chemical conjugation or, more rarely, as non-covalent complexes. In terms of the message-address hypothesis, this combination of cargo (message) linked to a CPP (address) as a tandem construct conforms to the sychnological organization. More recently, we have introduced the term bioportide to describe monomeric CPPs that are intrinsically bioactive. Herein, we describe the design and biochemical properties of two rhegnylogically organized monometic CPPs that collectively modulate a variety of biological and pathophysiological phenomena. Thus, camptide, a cell-penetrant sequence located within the first intracellular loop of a human calcitonin receptor, regulates cAMP-dependent processes to modulate insulin secretion and viral infectivity. Nosangiotide, a bioportide derived from endothelial nitric oxide synthase, potently inhibits many aspects of the endothelial cell morphology and movement and displays potent anti-angiogenic activity in vivo. We conclude that, due to their capacity to translocate and target intracellular signaling events, bioportides represent an innovative generic class of bioactive agents.     

Role of the ubiquitin-like protein Hub1 in splice-site usage and alternative splicing

Alternative splicing of pre-messenger RNAs diversifies gene products in eukaryotes and is guided by factors that enable spliceosomes to recognize particular splice sites. Here we report that alternative splicing of Saccharomyces cerevisiae SRC1 pre-mRNA is promoted by the conserved ubiquitin-like protein Hub1. Structural and biochemical data show that Hub1 binds non-covalently to a conserved element termed HIND, which is present in the spliceosomal protein Snu66 in yeast and mammals, and Prp38 in plants. Hub1 binding mildly alters spliceosomal protein interactions and barely affects general splicing in S. cerevisiae. However, spliceosomes that lack Hub1, or are defective in Hub1-HIND interaction, cannot use certain non-canonical 5' splice sites and are defective in alternative SRC1 splicing. Hub1 confers alternative splicing not only when bound to HIND, but also when experimentally fused to Snu66, Prp38, or even the core splicing factor Prp8. Our study indicates a novel mechanism for splice site utilization that is guided by non-covalent modification of the spliceosome by an unconventional ubiquitin-like modifier.     

Cross-presentation of IgG-containing immune complexes

IgG is a molecule that functionally combines facets of both innate and adaptive immunity and therefore bridges both arms of the immune system. On the one hand, IgG is created by adaptive immune cells, but can be generated by B cells independently of T cell help. On the other hand, once secreted, IgG can rapidly deliver antigens into intracellular processing pathways, which enable efficient priming of T cell responses towards epitopes from the cognate antigen initially bound by the IgG. While this process has long been known to participate in CD4⁺ T cell activation, IgG-mediated delivery of exogenous antigens into a major histocompatibility complex (MHC) class I processing pathway has received less attention. The coordinated engagement of IgG with IgG receptors expressed on the cell-surface (FcγR) and within the endolysosomal system (FcRn) is a highly potent means to deliver antigen into processing pathways that promote cross-presentation of MHC class I and presentation of MHC class II-restricted epitopes within the same dendritic cell. This review focuses on the mechanisms by which IgG-containing immune complexes mediate such cross-presentation and the implications that this understanding has for manipulation of immune-mediated diseases that depend upon or are due to the activities of CD8⁺ T cells.