抗抑郁新药的研究与开发

随着社会经济高速发展,人们面临的社会竞争和心理压力加大,导致抑郁症逐渐成为现代社会的常见及高发疾病,所以临床上对 抗抑郁新药的需求日益增长。概述近年来欧美上市的抗抑郁新药和目前临床III期在研的部分抗抑郁小分子药物的合成工艺及临床研究进 展。     

Differences in variation of human immunodeficiency virus type 1 sequences from Henan and Shanghai regions of China

Illegally paid blood donation was a risk factor for HIV acquisition exclusively in Henan and Hubei Provinces of China, and not in Shanghai. Nucleotide sequences in the gag and env genes of HIV-1 were compared between isolates from Henan and Shanghai regions of China to test whether an expected higher degree of a common source of infections from this unique blood donation transmission risk would be evident as decreased variation among Henan isolates in an exploratory cross-sectional analysis. Among 38 isolates studied, 23 of 23 (100%) from Henan and 8 of 15 (54%) from Shanghai were subtype B. In addition, fewer sequence differences were found in gp41 of subtype B isolates from Henan than from Shanghai isolates. Further studies with additional controls are therefore warranted to confirm the role of the degree of a common source of infections in differences in HIV variation across populations. Fundation items: The Vanderbilt-Meharry Center for AIDS Research (P30 AI 54999); R.T.D (R01 AI 29193); Start Fund of Ministry of Education of China (for Hong-zhou LU, 2004BA719A10).     

Cohabitation of a <Emphasis Type="Italic">Brucella melitensis</Emphasis> infected Alpine ibex (<Emphasis Type="Italic">Capra ibex</Emphasis>) with domestic small ruminants in an enclosure in Gran Paradiso National Park,in Western Italian Alps

After the first report of Brucella melitensis infection from a 7-year-old alpine ibex (Capra ibex) buck living in Gran Paradiso National Park (GPNP), further studies demonstrated the presence of the infection in ibex and chamois. Considering that livestock herds keep on sharing pastures with more than 3,500 ibex and 9,000 chamois in the park, our aim was to demonstrate under controlled conditions the possibility of Brucella infection passing from wild ruminants to livestock. A 7-year-old male alpine ibex with clinical signs of brucellosis and serologically positive was released in a 5,000 m² enclosure together with five goats and two sheep rams. Due to poor condition, ibex was suppressed at day 40, domestic ruminants stayed into the enclosure potentially contaminated by ibex for further 38 days. During this period, we had monitored our animals taking blood from domestic ruminants every 15 days and tested the serum to Rose Bengal agglutination test and Complement Fixation test. Domestic animals tested negative at serology at all sampling time and at isolation, while B. melitensis biovar 3 was isolated from ibex tissues. Our data show that transmission of infection from ibex to livestock is not easy. After 40 days of strict cohabitation and 38 days of permanence in an area where an infected ibex lives, no one of the domestic animals contracted infection. In spite of the limitation of our field trial, we have demonstrated that long direct and indirect contact between alpine ibex and domestic animals will not easily lead to an infection of the latter. Further investigations are needed to confirm our results and evaluate the effective risk of B. melitensis transmission from alpine ibex to livestock.     

Bactericidal activity of some plant essential oils against Ralstonia solanacearum infection

Potato plants and their tubers in Egypt are affected by one of the most renowned soil-borne pathogen, Ralstonia solanacearum, that caused brown rot in potato tubers and wilt in plants. There is no efficient therapeutic bactericide so; control of bacterial wilt is very rough.The study investigated three different concentrations of seven essential plant oils under in vitro and in vivo conditions as a result of their effects on Ralstonia solanacearum growth and their possibility use as potato seed pieces dressing for controlling bacterial wilt disease incidence. In vitro, anise oil at the three tested different concentrations (0.04, 0.07, and 0.14% vol/vol) was the most effective one inhibiting the growth of T4 and W9 isolates of Ralstonia solanacearum then pursued by thyme, lemongrass, and clove oils. On the other hand, rocket oil at the tested concentration was the least effective one followed by fennel oil. However, wheat germ oil was not completely effective. In vivo, experiment revealed that anise oil at the three concentrations significantly reduced disease incidence and severity in sponta and hermes potato cultivars and their effect was associated with increase of peroxidase, polyphenoloxidase, phenols and the foliar fresh weight of treated plants as well as the weight of tubers/plant followed by thyme and lemongrass oils compared to the infected untreated control.Morphological differences in bacterial cell structure have been observed using a transmission electron microscope (TEM). Anise oil at higher concentration caused of cell wall rupture and degraded cellular components.     

2020年邳州市草地贪夜蛾初迁虫源的迁入路径及气象背景

2020年江苏省邳州市于3月31日发现草地贪夜蛾Spodoptera frugiperda成虫,远早于该地区2019年草地贪夜蛾的始见期6月份。为明确该地区草地贪夜蛾种群性质,利用昆虫轨迹分析方法,模拟分析了2020年江苏省邳州市早期发现的草地贪夜蛾的迁飞路径及天气背景场。结果表明：邳州市2019年12月-2020年2月温度低,草地贪夜蛾无法在此地越冬存活,2020年3月31日所诱捕的草地贪夜蛾为外地迁入,其虫源来自广西和广东西部的周年繁殖区;虽然邳州市3月份常年盛行北风和西北风,西南风发生概率低导致草地贪夜蛾迁入邳州市概率较小,但2020年3月底850 hPa的强西南气流为草地贪夜蛾从我国华南地区迁入邳州市提供了条件。本研究结果阐明了在极端条件下草地贪夜蛾从华南地区迁入江苏省的可能性,丰富了江苏省草地贪夜蛾春季早期迁入的理论依据。     

Temperature and pCO2 jointly affect the emergence and survival of cercariae from a snail host: implications for future parasitic infections in the Humboldt Current system

Ocean warming and acidification are general consequences of rising atmospheric CO₂ concentrations. In addition to future predictions, highly productive systems such as the Humboldt Current System are characterized by important variations in both temperature and pCO₂ level, but how these physical–chemical ocean changes might influence the transmission and survival of parasites has not been assessed. This study experimentally evaluated the effects of temperature (14, 18 and 25 °C) and the combined effects of temperature (∼15 and 20 °C) and pCO₂ level (∼500 and 1400 microatmospheres (µatm) on the emergence and survival of two species of marine trematodes—Echinostomatidae gen. sp. and Philophthalmidae gen. sp.—both of which infect the intertidal snail Echinolittorina peruviana. Snails were collected from intertidal rocky pools in a year-round upwelling area of the northern Humboldt Current System (23°S). Two experiments assessed parasite emergence and survival by simulating emersion-immersion tidal cycles. To assess parasite survival, 2 h old cercariae (on average) were taken from a pool of infected snails incubated at 20–25 °C, and their mortality was recorded every 6 h until all the cercariae were dead. For both species, a trade-off between high emergence and low survival of cercariae was observed in the high temperature treatment. Species-specific responses to the combination of temperature and pCO₂ levels were also observed: the emergence of Echinostomatidae cercariae was highest at 20 °C regardless of the pCO₂ levels. By contrast, the emergence of Philophthalmidae cercariae was highest at elevated pCO₂ (15 and 20 °C), suggesting that CO₂ may react synergistically with temperature, increasing transmission success of this parasite in coastal ecosystems of the Humboldt Current System where water temperature and pH are expected to decrease. In conclusion, our results suggest that integrating temperature-pCO₂ interactions in parasite studies is essential for understanding the consequence of climate change in future marine ecosystem health.     

Pseudomonas aeruginosa β-carbonic anhydrase,psCA1, is required for calcium deposition and contributes to virulence

Calcification of soft tissue leads to serious diseases and has been associated with bacterial chronic infections. However, the origin and the molecular mechanisms of calcification remain unclear. Here we hypothesized that a human pathogen Pseudomonas aeruginosa deposits extracellular calcium, a process requiring carbonic anhydrases (CAs). Transmission electron microscopy confirmed the formation of 0.1-0.2 μm deposits by P. aeruginosa PAO1 growing at 5 mM CaCl₂, and X-ray elemental analysis confirmed they contain calcium. Quantitative analysis of deposited calcium showed that PAO1 deposits 0.35 and 0.75 mM calcium/mg protein when grown at 5 mM and 10 mM CaCl₂, correspondingly. Fluorescent microscopy indicated that deposition initiates at the cell surface. We have previously characterized three PAO1 β-class CAs: psCA1, psCA2, and psCA3 that hydrate CO₂ to HCO₃⁻, among which psCA1 showed the highest catalytic activity (Lotlikar et. al. 2013). According to immunoblot and RT-qPCR, growth at elevated calcium levels increases the expression of psCA1. Analyses of the deletion mutants lacking one, two or all three psCA genes, determined that psCA1 plays a major role in calcium deposition and contributes to the pathogen’s virulence. In-silico modeling of the PAO1 β-class CAs identified four amino acids that differ in psCA1 compared to psCA2, and psCA3 (T59, A61A, A101, and A108), and these differences may play a role in catalytic rate and thus calcium deposition. A series of inhibitors were tested against the recombinant psCA1, among which aminobenzene sulfonamide (ABS) and acetazolamide (AAZ), which inhibited psCA1 catalytic activity with K_Is of 19 nM and 37 nM, correspondingly. The addition of ABS and AAZ to growing PAO1 reduced calcium deposition by 41 and 78, respectively. Hence, for the first time, we showed that the β-CA psCA1 in P. aeruginosa contributes to virulence likely by enabling calcium salt deposition, which can be partially controlled by inhibiting its catalytic activity.     

东亚-澳大利西亚候鸟迁飞区中杓鹬 的迁徙追踪

追踪候鸟的迁徙活动是全面认识其生活史年周期的重要途径。中杓鹬(Numeniusphaeopus)在全球广泛分布,但在东亚-澳大利西亚候鸟迁飞区的迁徙活动一直缺乏追踪研究。2018年2月,在澳大利亚西北部的布鲁姆为捕捉到的中杓鹬成鸟佩戴平台发射终端或全球定位系统-全球移动通讯系统追踪器,以确定其迁徙日程、迁徙路线以及迁徙停歇地和繁殖地的地理位置。我们从成功追踪的7只个体获取了6 378条精度高于1 km的位点数据。分析结果表明,在春季,中杓鹬的迁徙时长为(36±4)d,其间在1～3个迁徙停歇地的停留日期为(23±2)d,从越冬地到繁殖地的迁徙距离为(9 795±346)km(n=7)。追踪的中杓鹬在俄罗斯东部和中部区域繁殖,不同个体的繁殖地纬度相近而经度范围较广。在秋季,中杓鹬的迁徙时长为(90±27)d,相比春季迁徙时长更长;其间,在2～4个迁徙停歇地停留(79±29)d,从繁殖地到越冬地的迁徙距离为(10 101±520)km(n=5)。无论在春季还是秋季迁徙,迁徙停歇地广泛分布于东亚、东南亚沿海及内陆区域。大部分个体春季和秋季的迁徙路线相近,成功追踪的个体均在秋季返回了上一年的越冬地,这表明中杓鹬对越冬地具有很高的忠诚度。     

Long-distance,low-frequency elephant communication

The production, transmission, and reception of and the behavioral response to long-distance, low-frequency sound by elephants is reviewed. The structure of low-frequency calls generated by elephants is separated into the source and the filter roles played by the lungs, larynx and vocal track, the composition of the expired air and the ambient air temperature. Implications regarding the size, age, sex, sexual and physical status follow from the call structure and detection. Reception of the signal is discussed in terms of the characteristics of the elephants ear with particular attention to the determination of the threshold of hearing and the ability to locate the source of low-frequency sounds. Factors which influence the transmission of near infrasound are related to atmospheric structure. The critical role played by the thermal stratification and vertical gradient and magnitude of the wind in determining both the range and the detection of a signal are discussed for open and closed elephant habitats. Infrasound plays a pervasive role in reproduction, resource utilization, avoidance of predation and other social interactions. Current and future technology can be expected to contribute to the detection and interpretation of elephant communication. This will aid in the understanding of behavior and in efforts to sustain the species.An erratum to this article can be found at