Astrocytes with previous chronic exposure to amyloid β‐peptide fragment 1–40 suppress excitatory synaptic transmission

Synaptic dysfunction and neuronal death are responsible for cognitive and behavioral deficits in Alzheimer's disease (AD). It is well known that such neurological abnormalities are preceded by long‐term exposure of amyloid β‐peptide (Aβ) and/or hyperphosphorylated tau prior. In addition to the neurological deficit, astrocytes as a major glial cell type in the brain, significantly participate in the neuropathogenic mechanisms underlying synaptic modulation. Although astrocytes play a significant key role in modulating synaptic transmission, little is known on whether astrocyte dysfunction caused by such long‐term Aβ exposure affects synapse formation and function. Here, we show that synapse formation and synaptic transmission are attenuated in hippocampal‐naïve neurons co‐cultured with astrocytes that have previously experienced chronic Aβ_1‐40 exposure. In this abnormal astrocytic condition, hippocampal neurons exhibit decrements of evoked excitatory post‐synaptic currents (EPSCs) and miniature EPSC frequency. Furthermore, size of readily releasable synaptic pools and number of excitatory synapses were also significantly decreased. Contrary to these negative effects, release probability at individual synapses was significantly increased in the same astrocytic condition. Taken together, our data indicate that lower synaptic transmission caused by astrocytes previously, and chronically, exposed to Aβ1–40 is attributable to a small number of synapses with higher release probability.

     

Unique arm-flapping behavior of the pharaoh cuttlefish, <Emphasis Type="Italic">Sepia pharaonis</Emphasis>: putative mimicry of a hermit crab

Cephalopods are able to control their arms sophisticatedly and use them for various behaviors, such as camouflage, startling predators and hunting prey. Here, we report a previously undescribed arm-flapping behavior of the pharaoh cuttlefish, Sepia pharaonis, observed in captivity. S. pharaonis raised the first pair of arms and wrinkled the parts near the distal end, where the skin color was darkened. Additionally, S. pharaonis spread the second and third pairs of arms and bent them as if they were jointed, and flapped the distal ends. S. pharaonis showed this behavior in two different situations: after being introduced into a large space, and during hunting. We discuss the putative functions of this behavior, including possible mimicry of a hermit crab, considering the situations in which the behavior was observed.     

Synthesis and biological activity of enantiomeric pairs of 5-[(E)-cycloalk-2-enylidenemethyl]thiolactomycin congeners

The title congeners were synthesized by employing our efficient synthetic route previously explored for preparing enantiomeric pairs of thiolactomycin and its 3-demethyl derivative. While all the synthesized congeners lacked in vitro antibacterial activity, some of the congeners bearing an (E)-cyclohept-2-enylidenemethyl or an (E)-cyclooct-2-enylidenemethyl group were found to exhibit more potent type I FAS inhibitory activity than (S)-3-demethylthiolactomycin having an unnatural configuration.     

Cryptococcus neoformans inhibits nitric oxide synthesis caused by CpG-oligodeoxynucleotide-stimulated macrophages in a fashion independent of capsular polysaccharides

Cryptococcus neoformans is eradicated by macrophages via production of NO. Unmethylated CpG-ODN protect mice from infection with this fungal pathogen by inducing IFN-gamma. The present study was designed to elucidate the effect of C. neoformans on the synthesis of NO by alveolar macrophages. For this purpose, MH-S, an alveolar macrophage cell line, was stimulated with CpG-ODN in the presence of IFN-gamma. A highly virulent strain of C. neoformans with thick capsule suppressed the production of NO. Capsular polysaccharides were not essential for this suppression, because there was no difference between acapsular mutant (Cap67) and its parent strain. Physical or close interaction of Cap67 with MH-S was necessary, as shown by the loss of such effect when direct contact was interfered by nitrocellulose membrane. Similar effects were observed by disrupted as well as intact Cap67. Whereas the inhibitory effect of intact Cap67 was completely abrogated by heat treatment, disrupted Cap67 did not receive such influence. Finally, disrupted Cap67 did not show any inhibitory effect on the TLR9-mediated activation of NF-kappaB in a luciferase reporter assay with HEK293T cells, although the TLR4-mediated activation was suppressed. These results revealed that C. neoformans suppressed the synthesis of NO by CpG-ODN and IFN-gamma-stimulated macrophages in a fashion independent of capsular polysaccharides, although the precise mechanism remains to be elucidated.     

Regulatory expression of Brachyury and Goosecoid in P19 embryonal carcinoma cells

Mouse P19 embryonal carcinoma cells can differentiate into various cell types depending on culture conditions. Here we show that the expression of the mesodermal genes Brachyury (Bra) and Goosecoid (Gsc) are under regulatory control in P19 cells. When P19 cells were cultured in a tissue culture dish in the presence of serum, Bra and Gsc were unexpectedly expressed. Expression of Bra and Gsc was greatly reduced with culture time, and expression levels at 144 h of culture were below 25% those at 48 h of culture. Members of the Tgf-beta family such as Activin and Nodal have been known to up-regulate expression of mesodermal genes. Treatment with SB431542, an Alk4/5/7 inhibitor, decreased Bra and Gsc in a dose-dependent manner, whereas it induced the expression of the neuroectodermal genes Mash-1 and Pax-6. Quantitative RT-PCR and dsRNAi transfection indicated Nodal as a possible ligand responsible for the regulation of Bra and Gsc. In addition, exogenous Nodal increased expression of Bra and Gsc in a dose-dependent manner. Serum concentration in culture medium positively related to expression of Nodal, Bra, Gsc, and Cripto, which encodes a membrane-tethered protein required for Nodal signaling. Addition of the culture supernatant of P19 cells at 144 h of culture to medium decreased expression of these genes. The present study reveals that stimulation and inhibition of the Nodal pathway increases mesodermal genes and neuroectodermal genes, respectively, indicating the importance of control of Nodal and Cripto expression for mesodermal formation and neurogenesis.     

Structural evidence that scytalidolisin (formerly scytalidopepsin A) is a serine-carboxyl peptidase of the sedolisin family

Scytalidopepsin A, a pepstatin-insensitive acid endopeptidase from the fungus Scytalidium lignicolum was found to be a member of the sedolisin family of serine-carboxyl peptidases through analyses of the amino acid sequences of peptides derived from the reduced, pyridylethylated enzyme by enzymatic digestion. Hence it should be renamed scytalidolisin (or Scytalidium sedolisin).     

Identification of differential gene expression for <Emphasis Type="Italic">Kr1</Emphasis> gene in bread wheat using annealing control primer system

Intergeneric hybridization is an important strategy to introgress alien genes into common wheat for its improvement. But presence of cross ability barrier mechanism regulated by Kr1 gene played a major destructive role for hybridization than other reported genes. In order to know the underlying molecular mechanism and to dissect out this barrier, a new annealing system, ACP (anneling control primer) system was used in chromosome 5B (containing Kr1 gene) specific Recombinant Inbred Line (RIL) population. Two differentially expressed fragments for Kr1 gene was identified, cloned and sequenced. Further the expression was confirmed by northern blotting analysis. Sequence analysis of the resulted clones revealed classes of putative genes, including stress responsive and signal transduction.