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In tauopathy conditions, such as Alzheimer's disease (AD), highly soluble and natively unfolded tau polymerizes into an insoluble filament; however, the mechanistic details of this process remain unclear. In the brains of AD patients, only a minor segment of tau forms β-helix-stacked protofilaments, while its flanking regions form disordered fuzzy coats. Here, it is demonstrated that the tau AD nucleation core (tau-AC) sufficiently induced self-aggregation and recruited full-length tau to filaments. Unexpectedly, phospho-mimetic forms of tau-AC (at Ser324 or Ser356) show markedly reduced oligomerization and seeding propensities. Biophysical analysis reveal that the N-terminus of tau-AC facilitates the fibrillization kinetics as a nucleation motif, which becomes sterically shielded through phosphorylation-induced conformational changes in tau-AC. Tau-AC oligomers are efficiently internalized into cells via endocytosis and induced endogenous tau aggregation. In primary hippocampal neurons, tau-AC impaired axon initial segment plasticity upon chronic depolarization and is mislocalized to the somatodendritic compartments. Furthermore, it is observed significantly impaired memory retrieval in mice intrahippocampally injected with tau-AC fibrils, which corresponds to the neuropathological staining and neuronal loss in the brain. These findings identify tau-AC species as a key neuropathological driver in AD, suggesting novel strategies for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are effector molecules induced after microbial challenges. These form important components of innate host defense against the pathogens by exhibiting wide-spectrum antimicrobial activities. In this study, we identified three attacin-like genes from Tenebrio molitor RNASeq database using Tribolium castaneum attacin gene family as query. The T. molitor attacin gene family was annotated as TmAttacin-1a [comprising of 154 amino acids (aa)], TmAttacin-1b (150 aa) and TmAttacin-2 (164 aa), respectively. Temporal expression analysis shows that the TmAttacin-1a and -1b mRNAs are highly expressed in late larval stages, followed by a general decline in the pre-pupal stages. The mRNA level shows a decline during metamorphosis, and gets slightly overexpressed in pupal-adult transition stages. On the other hand, TmAttacin-2 is mainly overexpressed at 1-day old pupal stage. Spatial expression analysis indicates that TmAttacin-1a, -1b, and -2 mRNAs are primarily expressed in gut and fat body, but not in hemocytes and Malpighian tubules in T. molitor larvae. Interestingly, TmAttacin-1b showsmore than 20-fold expression in the ovary, whereas TmAttacin-1a and -2 show similar expression patterns in gut, fat body, hemocyte, ovary, and testis in T. molitor adults. Induction pattern analysis demonstrates that the intracellular Gram-positive bacteria, L. monocytogenes elicited the strongest response by inducing ∼1,000-fold expression of TmAttacin-1a mRNA. The highest level of TmAttacin-1b mRNA (∼350-fold) was induced by Gram-negative bacteria, E. coli. However, the TmAttacin-2 transcripts were not induced by microbial challenges. These results indicate that TmAttacin-1a and -1b may be required for antimicrobial defenses in T. molitor. [ABSTRACT FROM AUTHOR]

Cybister chinensis Motschulsky, 1854 (synonym Cybister japonicus Sharp, 1873) is a beetle found in ponds and irrigation canals near rice fields regulating the aquatic faunal community through predation. However, due to loss of natural habitats, use of pesticides, and invasion of alien species the beetle is threatened. With lack of understanding at the trophic ecology and genomics level, the conservation study is hindered to a larger extent. In the present study, Illumina HiSeq 4000 platform has been used to unravel the whole-larval transcriptome of the beetle. A total of 20,129 non-redundant unigenes were assembled from 67,260,666 clean read sequences. About 18,743 unigenes found a homologous match in any one of the databases like PANM, UniGene, Swiss-Prot, Clusters of Orthologous Groups (COG), Gene Ontology (GO), KEGG, and InterProScan. While the zinc finger domains topped the unigene hits, about 660 enzymes (2695 sequences) participating in metabolism, environmental information processing, genetic information processing and organismal system pathways were recorded. Furthermore, the HSP70 class, Toll-like receptors 4, insulin-receptor substrate, and AMP activated protein kinase showed conspicuous presence in the larval transcriptome. Out of a total of 12,491 unigene sequences examined, 1968 SSRswere detected. Majority of themwere dinucleotide repeats with six iterations followed by trinucleotide and tetranucleotide repeats with five and four iterations, respectively.This is the first report of cDNAresources fromC. japonicus till date. The datawould be crucial for the assessment of the beetle in the wild andmaking an inventory for utilisation in future genomics and ecological studies. [ABSTRACT FROM AUTHOR]

Lead-free tetragonal Ba(Cu1/3Nb2/3)O3 (BCN) was chosen to enhance the multiferroic characteristics of rhombohedral BiFeO3 (BFO). When the aerosol-deposited film with a composition of 0.9BFO-0.1BCN, chosen to be near that of the morphotropic phase boundary, was annealed at 600°C for 1 h, the film showed superior dielectric, ferroelectric, and magnetic properties to those of pure polycrystalline BFO films. TEM revealed that BCN addition and subsequent annealing process enlarged the lattice constant of the BFO film along the /111S direction. The greatly enhanced multiferroic properties were attributed to the distorted lattice structure induced by the BCN addition and the high residual stress effect. [ABSTRACT FROM AUTHOR]

Calreticulin (CRT) plays pivotal roles in Ca2+ homeostasis, molecular chaperoning, infection, inflammation and innate immunity. In an attempt to study the involvement of CRT in innate immunity, the full-length cDNA of calreticulin ( PxCRT) was cloned from the diamondback moth, Plutella xylostella. It consists of 1674 bp (excluding poly-A tail) with a longest open reading frame (ORF) of 1197 bp encoding 398 amino acids. In silico analysis of PxCRT ORF reveals that it has various repeat motifs and endoplasmic reticulum retention signal found in all the calreticulin proteins. As expected, high amino acid sequence identities were found from other CRTs identified from Bombyx mori (87%), Galleria mellonella (87%), Apis mellifera (74%), Anopheles gambiae (74%), Tribolium castaneum (73%), Culex quinquefasciatus (73%), Rhodnius prolixus (72%), Nasonia vitripennis (71%), Drosophila melanogaster (71%) and Haemaphysalis qinghaiensis (68%). During development, P. xylostella expressed PxCRT predominantly in the pupal stage. In addition, spatial expression pattern analysis indicates that PxCRT was highly expressed in the silk gland. PxCRT mRNA, furthermore, was strongly induced 3 to 6 h after laminarin treatment, suggesting that PxCRT appears to be involved in immune responses and also plays an important role in the silk gland. [ABSTRACT FROM AUTHOR]

Apolipophorin-III is known to play a role in transporting lipids in insects, and much attention has been paid to lepidopteran insects' apolipophorin. Thus, we were interested in examining the effects of blood-meal on the expression pattern of apolipophorin-III in mosquitoes. This led us to clone and partially characterize the full-length cDNA of apoLp-III ( AnsiApoLp-III) from Anopheles sinensis. Analysis of AnsiApoLp-III cDNA shows that the 728-bp sequence has a 582-bp protein-coding region with 94 bp of putative 5′ untranslated region and 152 bp of 3′ untranslated region. The deduced amino acid sequence begins with a methionine codon at position 95 and extends to position 674, encompassing a polypeptide of 193 amino acids. AnsiApoLp-III has the highest identity (63%) to Culex quinquefasciatus apoLp-III. Temporal expression pattern analysis shows that although AnsiApoLp-III was expressed at all developmental stages, it was highly detected at egg and adult stages in the female mosquitoes. In addition, we found out that AnsiApoLp-III was induced in An. sinensis adult females after uptaking a blood-meal. Spatial expression patterns of AnsiApoLp-III shows that AnsiApoLp-III mRNA was strongly induced at day 1 and gradually decreased from day 1 to day 4 in the ovaries. Most interestingly, AnsiApoLp-III mRNA in the Malpighian tubule was strongly induced at day 1, decreased during days 1–3, and then became elevated again at day 4. These data suggest that blood-meal influences AnsiApoLp-III mRNA induction in ovaries and Malpighian tubules. It remains to further elucidate the biological roles of AnsiApoLp-III in these organs. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is an emerging opportunistic pathogen responsible for healthcare-associated infections. The outer membrane protein A of A. baumannii (AbOmpA) is the most abundant surface protein that has been associated with the apoptosis of epithelial cells through mitochondrial targeting. The nuclear translocation of AbOmpA and the subsequent pathology on host cells were further investigated. AbOmpA directly binds to eukaryotic cells. AbOmpA translocates to the nucleus by a novel monopartite nuclear localization signal (NLS). The introduction of rAbOmpA into the cells or a transient expression of AbOmpA–EGFP causes the nuclear localization of these proteins, while the fusion proteins of AbOmpAΔNLS–EGFP and AbOmpA with substitutions in residues lysine to alanine in the NLS sequences represent an exclusively cytoplasmic distribution. The nuclear translocation of AbOmpA induces cell death in vitro. Furthermore, the microinjection of rAbOmpA into the nucleus of Xenopus laevis embryos fails to develop normal embryogenesis, thus leading to embryonic death. We propose a novel pathogenic mechanism of A. baumannii regarding the nuclear targeting of the bacterial structural protein AbOmpA. [ABSTRACT FROM AUTHOR]

Aplysia CCAAT enhancer-binding protein (ApC/EBP), a key molecular switch in 5-hydroxytryptamine (5-HT)-induced long-term facilitation of Aplysia, is quickly and transiently expressed in response to a 5-HT stimulus, but the mechanism underlying this dynamic expression profile remains obscure. Here, we report that the dynamic expression of ApC/EBP during long-term facilitation is regulated at the post-transcriptional level by AU-rich element (ARE)-binding proteins. We found that the 3′UTR of ApC/EBP mRNA contains putative sequences for ARE, which is a representative post-transcriptional cis-acting regulatory element that modulates the stability and/or the translatability of a distinct subset of labile mRNAs. We cloned the Aplysia homologue of embryonic lethal abnormal visual system homologue (ELAV/Hu) protein, one of the best-studied RNA-binding proteins that associate with ARE, and elucidated the involvement of Aplysia ELAV/Hu protein in ApC/EBP gene expressional regulation. Cloned Aplysia ELAV/Hu protein, Aplysia embryonic lethal abnormal visual system (ApELAV), bound to an AU-rich region within the 3′UTR of ApC/EBP mRNA. Additionally, ApELAV controlled the expression of ApC/EBP 3′UTR-containing reporter gene by functioning as a stability-enhancing factor. In particular, 5-HT-induced long-term facilitation was impaired when the AU-rich region within the 3′UTR of ApC/EBP was over-expressed, which suggests the significance of this region in 5-HT-induced ApC/EBP expression, and in the resultant formation of long-term facilitation. Our results imply that the Aplysia ARE-binding protein, ApELAV, can regulate ApC/EBP gene expression at the mRNA level, and accordingly, ARE-mediated post-transcriptional mechanism may serve a crucial function in regulating the expression of ApC/EBP in response to a 5-HT stimulus. [ABSTRACT FROM AUTHOR]

Chronic bacterial prostatitis (CBP) is the most common urological disease in adult men. Antibiotic therapy is the gold standard of treatment. However, long-term therapy resulted in many side-effects and bacterial resistance. Because of these reasons, we need new treatment modality that could replace traditional antibiotic therapy. Catechin, an extract of green tea, has antimicrobial effect against various bacteria and synergy effect to antibiotics. We evaluate the synergistic effects of catechin on the treatment of CBP in an animal model.An experimental CBP model was induced in 70 male Wistar rats by instillation of 0.2 mL bacterial suspension (E-coli Z17, O2:K1:H-) containing 1 × 108 CFU/mL into the prostatic urethra. Microbiologically and histologically proven CBP model was demonstrated in 58.6% (41 of 70) of the rats after 4 weeks of bacterial instillation. The 41 rats demonstrating CBP were randomly divided into four groups; the control, catechin, ciprofloxacin and catechin with ciprofloxacin groups. All drug treatments were conducted over a period of 2 weeks. After treatment, the results were analyzed with microbiological cultures and histological findings of the prostate and urine samples to compare each group.Microbiological cultures and histological findings of the prostate and urine samples demonstrated reduced bacterial growth and improved inflammatory responses in all three experimental groups compared with the control group. The catechin group showed coherent trends of decrease in bacterial growth and improvements in prostatic inflammation compared with the control group, but not to a statistically significant degree (P > 0.05). However, the ciprofloxacin and catechin with ciprofloxacin groups showed statistically significant decreases in bacterial growth and improvements in prostatic inflammation compared with the control group (P < 0.05). The catechin with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvements in prostatic inflammation compared with the ciprofloxacin group (P < 0.05).These results suggest that catechin may be an effective material in CBP treatment. Particularly, combination treatment of catechin and ciprofloxacin has synergistic effect. Therefore, we suggest that the combination of catechin and ciprofloxacin may be effective in treating CBP with a higher success rate. [ABSTRACT FROM AUTHOR]

BACKGROUND: and Purpose. Although the diagnosis of moyamoya disease may be confirmed by digital subtraction angiography, recent studies have shown the accuracy of mag netic resonance angiography. Characteristics of transcranial Doppler, a noninvasive and cost-effective method, and specific transcranial Doppler parameters reflecting distinct vascular status in moyamoya disease are explored. METHOD: and Patients. Consecutive patients (> 15 years of age) diagnosed with moyamoya disease by a typical clinical history and digital sub traction angiography or magnetic resonance angiography were included. The statuses of the anterior, middle, and posterior cerebral arteries were graded as stage 1, stage 2, and stage 3 by magnetic resonance angiography. Mean flow velocity and pulsatility index were compared between these groups, and the receiver operating characteristic analysis was used to define transcranial Doppler criteria for distinct vascular status. RESULTS: Forty-five patients were included (37 women; mean age, 34.9 ± 11.4 years). Mean flow velocity was higher and pulsatility index was lower in stage 2 (P < .01), while mean flow velocity was lower and pulsatility index was higher in stage 3 than in stage 1 (P < .01). Cutoff values reflecting stenosis or occlusion with substantial sensitivity and specificity were as follows: mean flow velocity > 85 cm/s or pulsatility index < 0.60 for stage 2, and mean flow velocity < 50 cm/s for stage 3 of middle cerebral artery; mean flow velocity > 80 cm/s or pulsatility index < 0.60 for stage 2 of anterior cerebral artery; and mean flow velocity > 60 cm/s or pulsatility index < 0.60 for stage 2 of posterior cerebral artery. CONCLUSION: Transcranial Doppler may help to refine magnetic resonance angiography findings and thus help clinicians differentiate severity or stages of moyamoya disease. [ABSTRACT FROM AUTHOR]

A nonpulsatile cerebral perfusion may be encountered in an artificial cardiopulmonary bypass used in cardiac surgery, which is exceptional in physiological conditions. The authors report on a 37-year-old woman with Takayasu's arteritis (TA) who had been suffering from progressive visual loss and recurrent seizures. Ocular findings of chronic ischemia and multiple, subcortical, high-signal lesions in magnetic resonance (MR) imaging were indicative of significant hemodynamic impairment. MR angiography showed the complete occlusion of the innominate artery, the left common carotid artery (CCA), and the subclavian artery from the orifice of the aortic arch. The patient's transcranial Doppler (TCD) waveform was flat throughout all segments of the intracranial arteries. Intravenous acetazolamide injection confirmed the severe impairment of vasoreactivity. After a bypass graft from the aorta to the left CCA, flow velocity and pulsatility were dramatically increased without postoperative complications. A nonpulsatile cerebral perfusion indicates severe hemodynamic impairment and is partially reversible by a surgical bypass graft. TCD seems to be useful to detect "high-risk" patients and to follow up in TA. [ABSTRACT FROM AUTHOR]