Leydig cell andΔ 5-3β-hydroxysteroid dehydrogenase activity in the testis of toad (Bufo melanostictus) following cold exposuredehydrogenase activity in the testis of toad (Bufo melanostictus) following cold exposure

Summary Leydig cell nuclear area and ⁵-3-hydroxysteroid dehydrogenase activity were increased in the testis ofBufo melanostictus 2 days after a single short-term cold exposure. Both parameters returned to normal values 4 days later.     

Effect of molasses binder on the physical and mechanical properties

Molasses was used as an alternative binder to the bentonite binder. The change in moisture absorption by pellets prepared with different iron ores and different molasses contents were investigated. Iron ore properties exerted the major effect on pellet behavior and final pellet quality. The absorbed moisture content of pellets prepared without binder, bentonite-added pellets, and molasses-added pellets were in the range of 7.72%–9.95%, 9.62%–10.84%, and 6.14%-6.69%, respectively. The wet pellet compressive strength of molasses-added pellets(43–230 N/pellet) was superior to that of bentonite-added pellets(9.47–11.92 N/pellet). The compressive strength of dried molasses-modified pellets increased to 222–394 N/pellet, which is currently the highest value achieved for dried pellets.     

Mechanisms of cellular invasion by intracellular parasites

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world’s population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite–host cell interactions, forming the basis of the parasite’s cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.     

Coulomb blockade and the Kondo effect in single-atom transistors

Using molecules as electronic components is a powerful new direction in the science and technology of nanometre-scale systems. Experiments to date have examined a multitude of molecules conducting in parallel, or, in some cases, transport through single molecules. The latter includes molecules probed in a two-terminal geometry using mechanically controlled break junctions or scanning probes as well as three-terminal single-molecule transistors made from carbon nanotubes, C(60) molecules, and conjugated molecules diluted in a less-conducting molecular layer. The ultimate limit would be a device where electrons hop on to, and off from, a single atom between two contacts. Here we describe transistors incorporating a transition-metal complex designed so that electron transport occurs through well-defined charge states of a single atom. We examine two related molecules containing a Co ion bonded to polypyridyl ligands, attached to insulating tethers of different lengths. Changing the length of the insulating tether alters the coupling of the ion to the electrodes, enabling the fabrication of devices that exhibit either single-electron phenomena, such as Coulomb blockade, or the Kondo effect.     

Apolipoprotein E controls cerebrovascular integrity via cyclophilin A

Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and individuals with APOE4-associated disorders. In mice, lack of Apoe leads to blood-brain barrier (BBB) breakdown, whereas APOE4 increases BBB susceptibility to injury. How APOE genotype affects brain microcirculation remains elusive. Using different APOE transgenic mice, including mice with ablation and/or inhibition of cyclophilin A (CypA), here we show that expression of APOE4 and lack of murine Apoe, but not APOE2 and APOE3, leads to BBB breakdown by activating a proinflammatory CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes. This, in turn, leads to neuronal uptake of multiple blood-derived neurotoxic proteins, and microvascular and cerebral blood flow reductions. We show that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes. Astrocyte-secreted APOE3, but not APOE4, suppressed the CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes through a lipoprotein receptor. Our data suggest that CypA is a key target for treating APOE4-mediated neurovascular injury and the resulting neuronal dysfunction and degeneration.     

Accurate whole human genome sequencing using reversible terminator chemistry

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.     

Effectiveness of phosphocitrate and N-sulpho-2-amino tricarballylate,a new analogue of phosphocitrate,in blocking hydroxyapatite induced crystal growth and calcium accumulation by matrix vesicles

Summary Phosphocitrate and its analogue N-sulpho-2-amino tricarballylate were compared with ethane-1-hydroxy-1, 1-diphosphonate for inhibition of calcium phosphate crystallization in hydroxyapatite induced crystal growth and⁴⁵Ca uptake by matrix vesicles. Phosphocitrate (1 M) was the most potent inhibitor followed by ethane-1-hydroxy-1, 1-diphosphonate and N-sulpho-2-amino tricarballylate, the latter requiring a high concentration (100 M) to be equally effective as an inhibitor.Acknowledgments. We wish to thank Mr J. Jordan and Miss L.C. Ward for the excellent technical assistance and Mr R.J. Tennant for the transmission electron microscopy. We also thank the Golden Poultry Farming Industries Ltd., Hobart, Tasmania for their generous supply of broiler strain chickens.     

The Molecule Pages database

The Alliance for Cellular Signaling (AfCS)-Nature Molecule Pages will be a comprehensive database of key facts about more than 3,000 proteins involved in cell signalling. Each entry will be created by invited experts and be peer-reviewed. Alongside the large-scale experiments being conducted by the AfCS scientists, the wealth of information contained in this database offers the potential of accelerating the pace of discovery in signal transduction research.     

TiB2和Al3Ti对近共晶Al?12.6Si合金组织、力学性能和断裂行为的影响

A near eutectic Al?12.6Si alloy was developed with 0.0wt%, 2.0wt%, 4.0wt%, and 6.0wt% Al?5Ti?1B master alloy. The microstructural morphology, hardness, tensile strength, elongation, and fracture behaviour of the alloys were studied. The unmodified Al?12.6Si alloy has an irregular needle and plate-like eutectic silicon (E_Si) and coarse polygonal primary silicon (P_Si) particles in the matrix-like α-Al phase. The P_Si, E_Si, and α-Al morphology and volume fraction were changed due to the addition of the Al?5Ti?1B master alloy. The hardness, UTS, and elongation improved due to the microstructural modification. Nano-sized in-situ Al₃Ti particles and ex-situ TiB₂ particles caused the microstructural modification. The fracture images of the developed alloys exhibit a ductile and brittle mode of fracture at the same time. The Al?5Ti?1B modified alloys have a more ductile mode of fracture and more dimples compared to the unmodified alloy.