Physiological control of pituitary hormone secretory-burst mass,frequency, and waveform: a statistical formulation and analysis

The present study investigates the time-varying control of pituitary hormone secretion over the day and night (D/N). To this end, we implemented an analytical platform designed to reconstruct simultaneously 1) basal (nonpulsatile) secretion, 2) single or dual secretory-burst waveforms, 3) random effects on burst amplitude, 4) stochastic pulse-renewal properties, 5) biexponential elimination kinetics, and 6) experimental uncertainty. The statistical solution is conditioned on a priori pulse-onset times, which are estimated in the first stage. Primary data composed of thyrotropin (TSH) concentrations were monitored over 24 h in 27 healthy adults. According to statistical criteria, 21/27 profiles favored a dual compared with single secretory-burst waveform. An objectively defined waveform change point (D/N boundary) emerged at 2046 (+/-23 min), after which 1) the mass of TSH released per burst increases by 2.1-fold (P < 0.001), 2) TSH secretory-burst frequency rises by 1.2-fold (P < 0.001), 3) the latency to maximal TSH secretion within a burst decreases by 67% (P < 0.001), 4) variability in secretory-burst shape diminishes by 50% (P < 0.001), and 5) basal TSH secretion declines by 17% (P < 0.002). In contrast, the regularity of successive burst times and the slow-phase half-life are stable. In conclusion, nycthemeral mechanisms govern TSH secretory-burst mass, frequency, waveform, and variability but not evidently TSH elimination kinetics or the pulse-timing process. Further studies will be required to assess the generality of the foregoing distinctive control mechanisms in other hypothalamo-pituitary axes.     

Intranasal H5N1 Vaccines,Adjuvanted with Chitosan Derivatives,Protect Ferrets against Highly Pathogenic Influenza Intranasal and Intratracheal Challenge

We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model.Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings.In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals.This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and morbidity arising from infection with HPAI H5N1 virus.     

复方环丙酮胺治疗浅部真菌病的疗效观察

观察复方环丙酮胺喷剂治疗浅部真菌病的疗效。第Ⅰ批给予复方环丙酮胺喷剂,1次/d喷于患处,用药4周后观察疗效;第Ⅱ批随机入A、B组,A组给予复方环丙酮胺喷剂+曲安奈德喷剂,B组给予复方环丙酮胺喷剂,均1次/d喷于患处,用药2周、4周后观察疗效。第Ⅰ批治疗4周总有效率为80%;第Ⅱ批A、B组治疗2周总有效率分别为75%及82.35%,治疗4周总有效率分别为94.74%及100%。复方环丙酮胺喷剂和复方环丙酮胺喷剂+曲安奈德喷剂治疗浅部真菌病的疗效相似(P>0.05),且疗效显著、局部刺激小、瘙痒缓解明显、安全性较高。     

Variations in spatial and temporal distribution of Archaea in the North Sea in relation to environmental variables

The spatial and temporal distribution of pelagic Archaea was studied in the southern North Sea by rRNA hybridization, sequencing and quantification of 16S rRNA gene and membrane lipid analyses and related to physical, chemical and biological parameters to determine the factors influencing archaeal biogeography. A clear temporal variability was observed, with marine Crenarchaeota (Group I.1a) being relatively more abundant in winter and Euryarchaeota dominating the archaeal assemblage in spring and summer. Spatial differences in the lateral distribution of Crenarchaeota were also evident. In fact, their abundance was positively correlated with the copy number of the gene encoding the alpha subunit of crenarchaeotal ammonia monooxygenase (amoA) and with concentrations of ammonia, nitrate, nitrite and phosphorus. This suggests that most Crenarchaeota in the North Sea are nitrifiers and that their distribution is determined by nutrient concentrations. However, Crenarchaeota were not abundant when larger phytoplankton (>3 microm) dominated the algal population. It is hypothesized that together with nutrient concentration, phytoplankton biomass and community structure can predict crenarchaeotal abundance in the southern North Sea. Euryarchaeotal abundance was positively correlated with chlorophyll a concentrations, but not with phytoplankton community structure. Whether this is related to the potential of Euryarchaeota to perform aerobic anoxygenic phototrophy remains to be shown, but the conspicuous seasonal distribution pattern of Crenarchaeota and Euryarchaeota suggests that they occupy a different ecological niche.     

土壤增温与氮添加对杉木幼苗细根径级根长分布的影响

通过在福建省三明市陈大林业国有林场内开展土壤增温(增温5 ℃、不增温)和氮添加(不添加、4、8 g N·m^-2·a^-1)的交互试验(共6个处理),研究土壤增温、氮添加及二者交互作用对杉木细根径级根长分布的影响,用扩展模型可很好地拟合6个处理的径级根长分布(R²=0.97).结果表明: 增温使杉木细根总根长变小,但对细根直径影响不显著;氮添加使杉木细根总根长和直径均变小;增温和氮添加的交互作用对细根总根长有显著影响,但对细根直径无显著影响.6个处理细根径级根长分布均能用极值函数模型较好地拟合(R²>0.98).相关分析显示,直径<1 mm细根的比根长与极值模型拟合参数c值呈显著负相关,实际总根长与极值模型拟合参数b呈显著正相关.增温和氮添加及其交互作用可以影响杉木细根形态特征;极值模型拟合各处理径级根长分布所得参数在一定程度上可以反映细根形态特征对环境条件变化的响应.     

Clinical Burkholderia pseudomallei isolates from north Queensland carry diverse bimABm genes that are associated with central nervous system disease and are phylogenomically distinct from other Australian strains

BackgroundBurkholderia pseudomallei is an environmental gram-negative bacterium that causes the disease melioidosis and is endemic in many countries of the Asia-Pacific region. In Australia, the mortality rate remains high at approximately 10%, despite curative antibiotic treatment being available. The bacterium is almost exclusively found in the endemic region, which spans the tropical Northern Territory and North Queensland, with clusters occasionally present in more temperate climates. Despite being endemic to North Queensland, these infections remain understudied compared to those of the Northern Territory.Methodology/Principal findingsThis study aimed to assess the prevalence of central nervous system (CNS) disease associated variant bimA_Bm, identify circulating antimicrobial resistance mutations and genetically distinct strains from Queensland, via comparative genomics. From 76 clinical isolates, we identified the bimA_Bm variant in 20 (26.3%) isolates and in 9 (45%) of the isolates with documented CNS infection (n = 18). Explorative analysis suggests a significant association between isolates carrying the bimA_Bm variant and CNS disease (OR 2.8, 95% CI 1.3–6.0, P = 0.009) compared with isolates carrying the wildtype bimA_Bp. Furthermore, 50% of isolates were identified as novel multi-locus sequence types, while the bimA_Bm variant was more commonly identified in isolates with novel sequence types, compared to those with previously described. Additionally, mutations associated with acquired antimicrobial resistance were only identified in 14.5% of all genomes.Conclusions/SignificanceThe findings of this research have provided clinically relevant genomic data of B. pseudomallei in Queensland and suggest that the bimA_Bm variant may enable risk stratification for the development CNS complications and be a potential therapeutic target.     

流式细胞术研究细胞凋亡的方法与技术

细胞发生凋亡时,会伴随着一系列形态学、生物化学及分子生物学性质的变化,包括细胞皱缩,核染色质凝聚,细胞膜通透性改变,Caspases激活,线粒体跨膜电位降低,膜磷酯酰丝氨酸外化,胞质Ca2+浓度升高,DNA片段化及含量变化等特点.应用流式细胞术进行细胞凋亡的研究,对于探讨胚胎发育、衰老以及研究肿瘤的发生、发展和转化等病理生理过程和病毒感染及免疫等具有十分重要的意义.本文就细胞凋亡的特征、基于细胞膜功能的流式细胞术检测方法和基于细胞器功能的流式细胞术检测方法等关键性问题进行了阐述.     

Combined Review: Experiencing the New Genetics: Family and Kinship on the Medical Frontier and Born and Bred: Idioms and New Reproductive Technologies in England

Experiencing the New Genetics: Family and Kinship on the Medical Frontier. Kaja Finkler. Philadelphia: University of Pennsylvania Press, 2000. 296 pp.
Born and Bred: Idioms and New Reproductive Technologies in England. Jeanette Edwards. New York: Oxford University Press, 2000. 264 pp.     

Maturation of spontaneous and agonist-induced uterine contractions in the peripartum mouse uterus.

This study tested the hypothesis that the uterus achieves maximum contractile capabilities before the onset of labor. Basal and agonist-stimulated contractions were assessed in uterine strips on Day 15 or 18 of pregnancy, the day of parturition, or 1 day postpartum (n = 4-13 per group). Spontaneous contractions were evident in all groups (n = 4-13 per gestational group); contraction frequency was greater in peripartum groups than in virgin controls ( approximately 4.6 versus 2.8/200 sec). Peak amplitude was nearly 9-fold higher on Days 15 and 18 and over 30-fold higher in the postpartum and 1 day postpartum groups than in nonpregnant mice. Maximum frequency and peak amplitude were achieved in response to 10(-6) to 10(-8) M oxytocin or arginine vasopressin (OT(max) or AVP(max)). Frequency of contractions in response to OT(max) peaked on Day 18 and then declined. Contraction amplitude increased 5-fold on Day 15, declined on the day of birth (equivalent to nonpregnant level), then rebounded to peak on postpartum Day 1. AVP(max) similarly increased frequency and amplitude of contractions, except that maximum contraction amplitude occurred postpartum. Thus, an endogenous oscillator, residing in the uterus, sustains high basal and agonist-induced contraction frequency during pregnancy. Although acceleration of this pacemaker occurred before term, the data suggest that peripartum increases in contraction amplitude characterize the transition to the powerful synchronous contractions of parturition.