Electrophysiological and anatomical characterization of PDF-positive clock neurons in the intact adult Drosophila brain

Daily biological rhythms in both prokaryotes and eukaryotes are controlled by circadian clocks. In Drosophila, there is a good basic understanding of both the molecular and anatomical components of the clock. In this study we directly measure, for the first time, electrophysiological properties and anatomy of individual filled large lateral PDF-positive clock neurons, a cell group believed to be involved in synchronization of the clock in constant conditions. We find that the large PDF-positive neurons are morphologically homogeneous and that their resting membrane potential is modulated both by the clock and by light inputs. Expression of a leak channel, dORK-C, which has been shown to disrupt circadian locomotor rhythms, hyperpolarizes these neurons, and blocks firing. These data imply that the firing properties of large PDF neurons are both regulated by and critical for clock function.     

One-pot synthesis of symmetric imidazolium ionic liquids N,N-disubstituted with long alkyl chains

The Debus–Radziszewski imidazole synthesis was adapted to directly yield long-chain imidazolium ionic liquids. Imidazolium acetate ionic liquids with side-chains up to sixteen carbon atoms were synthesised in excellent yields via an on-water, one-pot reaction. The imidazolium acetate ILs acted as surfactants when dissolved in various solvents. The imidazolium acetate ionic liquids were also derivatised via an acid metathesis to the chloride, nitrate, and hydrogen oxalate derivatives. The thermal behaviour of all the ionic liquids was determined via thermogravimetric and calorimetric analysis.

The modified Debus–Radziszewski reaction was used as a one-pot on-water reaction to allow a greener synthesis of long-chain 1,3-dialkylimidazolium acetate ionic liquids in high yield from long-chain linear amines.     

The effect of physician risk tolerance and the presence of an observation unit on decision making for ED patients with chest pain

Objectives

We sought to determine whether risk tolerance as measured by scales (malpractice fear scale [MFS], risk-taking scale [RTS], and stress from uncertainty scale [SUS]) is associated with decisions to admit or use computed tomography (CT) coronary angiogram and decisions to order cardiac markers in emergency department (ED) patients with chest pain. We also studied if the opening of an ED-based observation unit affected the relationship between risk scales and admission decisions.

Methods

Data from a prospective study of ED patients 30 years or older with chest pain were used. Risk scales were administered to ED attending physicians who initially evaluated them. Physicians were divided into quartiles for each separate risk scale. Fisher's exact test and logistic regression were used for statistical analysis.

Results

A total of 2872 patients were evaluated by 31 physicians. The most risk-averse quartile of RTS was associated with higher admission rates (78% vs 68%) and greater use of cardiac markers (83% vs 78%) vs the least risk-averse quartile. This was not true for MFS or SUS. Similar associations were observed in low-risk patients (Thrombolysis in Myocardial Infarction risk score of 0 or 1). The observation unit was not associated with a higher admission rate and did not modify the relationship between risk scales and admission rates.

Conclusion

The RTS was associated with the decision to admit or use computed tomography coronary angiogram, as well as the use of cardiac markers, whereas the MFS and SUS were not. The observation unit did not affect admission rates and nor did it affect how physician's risk tolerance affects admission decisions.     

Optical isomers of rocastine and close analogues: synthesis and H1 antihistaminic activity of its enantiomers and their structural relationship to the classical antihistamines.

The enantiomers of 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4- oxazapine-5(2H)-thione (rocastine) and two of its more potent analogues were prepared with an enantiomeric purity of greater than 99.9%. The antihistaminic activity of these compounds was assessed by their ability to block histamine-induced lethality in guinea pigs and to inhibit [3H]mepyramine binding to guinea pig cortex. In this series, compounds having the R configuration at the 2-position are at least 300 times more potent than the S isomers. Conformational analysis and molecular modeling suggest that rocastine can adopt a conformation in which the pyridine ring, ether oxygen, and protonated amine functions are positioned similarly to the corresponding elements of the probable binding conformers of some of the more classical antihistamines. This conformation, boatlike in the oxazepine ring with the side chain quasi-equatorial and folded back toward the ring, is the likely binding conformer at the histamine H1 receptor, and the available structure-activity relationship data is consistent with this interpretation.     

Human immunodeficiency virus receptor and coreceptor expression on human uterine epithelial cells: regulation of expression during the menstrual cycle and implications for human immunodeficiency virus infection

Human immunodeficiency virus-1 (HIV-1) is primarily a sexually transmitted disease. Identification of cell populations within the female reproductive tract that are initially infected, and the events involved in transmission of infection to other cells, remain to be established. In this report, we evaluated expression of HIV receptors and coreceptors on epithelial cells in the uterus and found they express several receptors critical for HIV infection including CD4, CXCR4, CCR5 and galactosylceramide (GalC). Moreover, expression of these receptors varied during the menstrual cycle. Expression of CD4 and CCR5 on uterine epithelial cells is high throughout the proliferative phase of the menstrual cycle when blood levels of oestradiol are high. In contrast, CXCR4 expression increased gradually throughout the proliferative phase. During the secretory phase of the cycle when both oestradiol and progesterone are elevated, CD4 and CCR5 expression decreased whereas CXCR4 expression remained elevated. Expression of GalC on endometrial glands is higher during the secretory phase than during the proliferative phase of the menstrual cycle. Because epithelial cells line the female reproductive tract and express HIV receptors and coreceptors, it is likely that they are one of the first cell types to become infected. The hormonal regulation of HIV receptor expression may affect a woman's susceptibility to HIV infection during her menstrual cycle. Moreover, selective coreceptor expression could account for the preferential transmission of R5-HIV-1 strains to women. In addition, these studies provide evidence that the uterus, and potentially the entire upper reproductive tract, are important sites for the initial events involved in HIV infection.     

体外循环对人体免疫功能的影响

为了研究体外循环(CPB)对人体免疫功能的影响,本文对CPB心脏手术成人10例(A组)、儿童9例(B组)围术期免疫功能进行了观察。两组间得出了相似的结果:除了白细胞数CPB后第1～7天内明显增多外,其余6项免疫指标在CPB第一小时后均表现免疫功能低下,术后1周才能恢复到术前水平,故此期监护要严格无菌操作,积极抗炎和支持疗法,对预防术后感染,促使患者早日康复甚为重要。     

Heterocyclen, 65. Mitt.: Darstellung und chemisches Verhalten einiger 2-Aryl-6-ethoxycarbonyl-5-methyl-thiazolo[3,2-b]-1,2,4-triazole

Heterocycles, LXV: Synthesis and Chemical Characterization of Some 2-Aryl-6-ethoxycarbonyl-5-methyl-thiazolo[3,2-b]-1,2,4-triazoles The syntheses of some 2-aryl-6-ethoxycarbonyl-5-methyl-thiazolo[3,2-b]-1,2,4-triazoles and their chemical and spectroscopic properties (IR, UV, MS) are described.