Loss of Courtship Suppression Memory in a Drosophila melanogaster Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is the most prevalent and lethal neurodegenerative disease. Memory loss and motor dysfunction are accompanied by pathological hallmarks like neurofibrillary tangles or amyloid plaques. In this study, courtship suppression assay was used to assess learning and memory of a transgenic Drosophila melanogaster (the fruit fly) line expressing human Amyloid beta 42 (Aβ42). At young age (4–6 days old), both parental control and AD flies displayed lower courtship indices during training after being rejected by previously mated females. However, in the subsequent testing phase, young AD flies showed compromised recall memory, unlike that of parental controls. Neither control nor AD flies at 16–18 days old showed significant learning or recall memory. AD flies also exhibited age-related motor defects and presented amyloid plaques in brain sections. Interestingly, older AD flies displayed persistent chasing throughout the one-hour training period, and they attempted copulation at higher frequency than the untrained AD controls. Thus, transgenic AD flies displayed early onset of memory deficit, and aggressive courtship behavior as they aged. This article was published Open Access through the CCU Libraries Open Access Publishing Fund. The article was first published in eBio: https://www.eaglehill.us/ebio-pdfs-regular/EBIO-009-Lin.pd

HII region G46.5-0.2: the interplay between ionizing radiation, molecular gas and star formation

HII regions are particularly interesting because they can generate dense layers of gas and dust, elongated columns or pillars of gas pointing towards the ionizing sources, and cometary globules of dense gas, where triggered star formation can occur. Understanding the interplay between the ionizing radiation and the dense surrounding gas is very important to explain the origin of these peculiar structures, and hence to characterize triggered star formation. G46.5-0.2 (G46), a poorly studied galactic HII region located at about 4 kpc, is an excellent target to perform this kind of studies. Using public molecular data extracted from the Galactic Ring Survey (13CO J=1-0) and from the James Clerk Maxwell Telescope data archive (12CO, 13CO, C18O J=3-2, HCO+ and HCN J=4-3), and infrared data from the GLIMPSE and MIPSGAL surveys, we perform a complete study of G46, its molecular environment and the young stellar objects placed around it. We found that G46, probably excited by an O7V star, is located close to the edge of the GRSMC G046.34-00.21 molecular cloud. It presents a horse-shoe morphology opening in direction of the cloud. We observed a filamentary structure in the molecular gas likely related to G46 and not considerable molecular emission towards its open border. We found that about 10' towards the southwest of G46 there are some pillar-like features, shining at 8 um and pointing towards the HII region open border. We propose that the pillar-like features were carved and sculpted by the ionizing flux from G46. We found several young stellar objects likely embedded in the molecular cloud grouped in two main concentrations: one, closer to the G46 open border consisting of Class II type sources, and other one mostly composed by Class I type YSOs located just ahead the pillars-like features, strongly suggesting an age gradient in the YSOs distribution.Comment: Accepted for publication in The Astronomical Journal (April 14, 2015). Some figures were degraded to reduce file siz

Interactions of the Infrared bubble N4 with the surroundings

The physical mechanisms that induce the transformation of a certain mass of gas in new stars are far from being well understood. Infrared bubbles associated with HII regions have been considered to be good samples of investigating triggered star formation. In this paper we report on the investigation of the dust properties of the infrared bubble N4 around the HII region G11.898+0.747, analyzing its interaction with its surroundings and star formation histories therein, with the aim of determining the possibility of star formation triggered by the expansion of the bubble. Using Herschel PACS and SPIRE images with a wide wavelength coverage, we reveal the dust properties over the entire bubble. Meanwhile, we are able to identify six dust clumps surrounding the bubble, with a mean size of 0.50 pc, temperature of about 22 K, mean column density of 1.7 $\times10^{22}$ cm$^{-2}$, mean volume density of about 4.4 $\times10^{4}$ cm$^{-3}$, and a mean mass of 320 $M_{\odot}$. In addition, from PAH emission seen at 8 $\mu$m, free-free emission detected at 20 cm and a probability density function in special regions, we could identify clear signatures of the influence of the HII region on the surroundings. There are hints of star formation, though further investigation is required to demonstrate that N4 is the triggering source.Comment: Accepted by ApJ (16 pages, 11 figures, 9 tables

Potassium {4-[(3S,6S,9S)-3,6-dibenzyl-9-isopropyl-4,7,10-trioxo-11–oxa-2,5,8-triazadodecyl]phenyl}trifluoroborate

[[abstract]]The reported compound 4 was synthesized and fully characterized by 1H NMR, 13C NMR, 11B NMR, 19F NMR, and high resolution mass spectrometry.[[booktype]]電子版[[countrycodes]]CH

Severe pulmonary complications after initial treatment with rituximab for the Asian-variant of intravascular lymphoma

Rituximab improves response to treatment and outcome for patients with CD20+ B-cell lymphoma. Herein, however, we report the occurrence of severe pulmonary complications shortly after rituximab infusion in three patients with the newly diagnosed Asian variant of intravascular lymphoma. It is suggested that patients with this sub-type of lymphoma are monitored carefully for possible drug reactions during the use of rituximab

Different Influences on Tacrolimus Pharmacokinetics by Coadministrations of Zhi Ke and Zhi Shi in Rats

Tacrolimus, an immunosuppressant with narrow therapeutic window, has been used widely in transplant patients. Grapefruit juice and pomelo have been reported to increase the blood levels of tacrolimus. Zhi Ke and Zhi Shi, the ripe peels and unripe fruits of Citrus aurantium which is chemotaxonomically related to grapefruit and pomelo, are in wide use in clinical Chinese medicine. To investigate the possible interaction of these two Citrus herbs with tacrolimus, male Sprague-Dawley rats were orally given tacrolimus (1.5 mg/kg) with and without Zhi Ke and Zhi Shi decoctions in a cross-over design. Blood samples were withdrawn via cardiopuncture at specific time and quantitated by a microparticle enzyme immunoassay. In addition, to explore the mechanism of interaction, LS 180 cell line was used for the transport study of rhodamine 123, a typical substrate of P-glycoprotein (P-gp). The results showed that Zhi Shi significantly decreased the Cmax and AUC0−t of tacrolimus by 72.4% and 72.0%, respectively, whereas Zhi Ke did not affect tacrolimus pharmacokinetics. LS 180 cell line study indicated that Zhi Shi increased the efflux activity of P-gp, enabling us to explain the decreased oral bioavailability of tacrolimus caused by Zhi Shi. Hence, we suggest that Zhi Shi be contraindicated for transplant patients treated with tacrolimus to reduce the risk of allograft rejection

Mixed Infections of Helicobacter pylori

Background. Persistent Helicobacter pylori infection may induce several upper gastrointestinal diseases. Two major virulence factors of H. pylori, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), are thought to be associated with the severity of disease progression. The distribution of vacA and cag-pathogenicity island (cag-PAI) alleles varies in H. pylori isolated from patients in different geographic regions. Aim. To assess the association between mixed infection of H. pylori clinical isolates from Taiwanese patients and the severity of gastrointestinal diseases. Methods. A total of 70 patients were enrolled in this study. Six distinct and well-separated colonies were isolated from each patient and 420 colonies were analyzed to determine the genotypes of virulence genes. Results. The prevalence of mixed infections of all H. pylori-infected patients was 28.6% (20/70). The rate of mixed infections in patients with duodenal ulcer (47.6%) was much higher than that with other gastrointestinal diseases (P<0.05). Conclusions. H. pylori mixed infections show high genetic diversity that may enhance bacterial adaptation to the hostile environment of the stomach and contribute to disease development

A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein

Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past 2 decades, which highlights the pressing need for antiviral therapeutics. In a high-throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV-infected cultures with 2 MBDAA reduced the virion production by greater than 2 logs, the compound was not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug-resistant viruses revealed that replacement of the proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine, or alanine conferred YFV with resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, replacement of P219 with glycine conferred BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 amino acid is localized at the endoplasmic reticulum lumen side of the fifth putative transmembrane domain of NS4B, and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed an important role and the structural basis for the NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs, and attenuated virus infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever