The neuroarchitecture of the circadian clock in the brain of Drosophila melanogaster

Neuroethologists try to assign behavioral functions to certain brain centers, if possible down to individual neurons and to the expression of specific genes. This approach has been successfully applied for the control of circadian rhythmic behavior in the fruit fly Drosophila melanogaster. Several so-called "clock genes" are expressed in specific neurons in the lateral and dorsal brain where they generate cell-autonomous molecular circadian oscillations. These clusters are connected with each other and contribute differentially to the control of behavioral rhythmicity. This report reviews the latest work on characterizing individual circadian pacemaker neurons in the fruit fly's brain that control activity and pupal eclosion, leading to the questions by which neuronal pathways they are synchronized to the external light-dark cycle, and how they impose periodicity on behavior.     

Uridine dynamic administration affects the circadian variation of bile acid metabolism in high-fat-diet-fed mice

High-fat diet (HFD) is demonstrated to disturb the bile acid metabolism. The rhythm of bile acid metabolism can also be affected by uridine, whose metabolism exhibits a daily rhythm. However, the mechanism of dynamic uridine administration affecting bile acid during HFD remains unclear. In this study, C57BL/6J mice were fed HFD (the control group; CON) or HFD with oral administration of uridine in the daytime (DUR) and nighttime (NUR) to investigate the mechanism of the effect of uridine on the bile acid. This study showed that the mRNA expression of uridine transporters and circadian clock genes in the jejunum was affected by zeitgeber time (ZT) (P < 0.001). Genes related to the metabolism of pyrimidines in the liver showed a high dependence on daily rhythm (P < 0.01), and DUR remarkably up-regulated the expression of ribonucleotide reductase regulatory subunit M2 (RRM2) (P < 0.05) compared to the CON group. Importantly, the mRNA expression of bile acids nuclear receptors, bile acid synthesis, and transporters in the liver showed significantly rhythmically changed (P < 0.05), and the expression of cholesterol 7-alpha-hydroxylase (CYP7A1), fibroblast growth factor receptor 4 (FGFR4), Na+/taurocholate co transporting polypeptide (NTCP), and bile salt export pump (BSEP) mRNAs of mice with uridine administration increased significantly (P < 0.05). The mRNA expression of the transporters of cholesterol and bile acids in the ileum was also affected by ZT (P < 0.01) and significantly dependent on uridine administration (P < 0.05). The expression of FXR and SHP was significantly affected by ZT and uridine, respectively. In conclusion, dynamic administration of uridine could regulate the rhythm of gene expression of pyrimidine and bile acid metabolism in the liver and ileum of HFD-fed mice, which contributed to the further study of circadian rhythmic physiological and pathological changes of bile acids.     

Circadian organization and the role of the pineal in birds

All organisms exhibit significant daily rhythms in a myriad of functions from molecular levels to the level of the whole organism. Significantly, most of these rhythms will persist under constant conditions, showing that they are driven by an internal circadian clock. In birds the circadian system is composed of several interacting sites, each of which may contain a circadian clock. These sites include the pineal organ, the suprachiasmatic nucleus (SCN) of the hypothalamus, and, in some species, the eyes. Light is the most powerful entraining stimulus for circadian rhythms and, in birds, light can affect the system via three different pathways: the eyes, the pineal, and extraretinal photoreceptors located in the deep brain. Circadian pacemakers in the pineal and in the eyes of some avian species communicate with the hypothalamic pacemakers via the rhythmic synthesis and release of the hormone melatonin. Often the hypothalamic pacemakers are unable to sustain persistent rhythmicity in constant conditions in the absence of periodic melatonin input from the pineal (or eyes). It has also been proposed that pineal pacemakers may be unable to sustain rhythmicity in constant conditions without periodic neural input from the SCN. Significant variation can occur among birds in the relative roles that the pineal, the SCN, and the eyes play within the circadian system; for example, in the house sparrow pacemakers in the pineal play the predominant role, in the pigeon circadian pacemakers in both the pineal and eyes play a significant role, and in Japanese quail ocular pacemakers play the predominant role.     

Symphony of rhythms in the Xenopus laevis retina

The photoreceptor layer in the retina of Xenopus laevis harbors a circadian clock. Many molecular components known to drive the molecular clock in other organisms have been identified in Xenopus, such as XClock, Xper2, and Xcrys, demonstrating phylogenetic conservation. This model system displays a wide array of rhythms, including melatonin release, ERG rhythms, and retinomotor movements, suggesting that the ocular clock is important for proper retinal function. A flow-through culture system allows measurements of retinal rhythms such as melatonin release in vitro over time from a single eyecup. This system is suited for pharmacological perturbations of the clock, and has led to important observations regarding the circadian control of melatonin release, the roles of light and dopamine as entraining agents, and the circadian mechanisms regulating retinomotor movements. The development of a transgenic technique in Xenopus allows precise and reliable molecular perturbations. Since it is possible to follow rhythms in eyecups obtained from adults or tadpoles, the combination of the flow-through culture system and the transgenic technique leads to the fast generation of transgenic tadpoles to monitor the effects of molecular perturbations on the clock.     

Development of PDF-immunoreactive cells,possible clock neurons,in the housefly Musca domestica

Even though the housefly Musca domestica shows clear circadian rhythms in its behavioural and physiological processes, a circadian pacemaker system controlling these rhythms has not yet been described morphologically in this species. In M. domestica, neurons immunoreactive to pigment-dispersing factor (PDF), a neurotransmitter/neuromodulator of circadian information arising from a circadian clock and transmitted to target cells, are similar in their number and distribution to the PDF neurons of Drosophila melanogaster. In D. melanogaster these neurons co-localize PER protein and have been identified as clock neurons in that species. Here we report PDF-immunoreactive cells in the housefly's brain during postembryonic development in the larval and pupal stages, as well as in the adult fly soon after eclosion. In the housefly's brain, there are three groups of PDF-immunoreactive neurons: two groups with small (sPDFMe) and large (lPDFMe) cell bodies in the proximal medulla of the optic lobe; and one group in the dorsal protocerebrum (PDFD). Three out of four sPDFMe can be detected during the first hour of larval development, but the fourth sPDFMe is observed in the larva only from 48 hours after hatching, along with five lPDFMe neurons, seen first as two subgroups, and three out of four PDFD neurons. During postembryonic development these neurons show changes in their structure and immunoreactivity. New PDF neurons are observed during pupal development but these neurons mostly do not survive into adulthood. In the adult fly's brain, the PDF neurons have also been examined in double-labelled preparations made with a second antibody directed against the product of one of several clock genes: period (per), timeless (tim), or cryptochrome (cry). Among them, only immunoreactivity to CRY-like protein has been detected in the brain of M. domestica and has shown a daily rhythm in its concentration, as examined immunocytochemically. CRY was co-localized with PDF in the sPDFMe of the housefly's brain fixed during the day. The possibility that the sPDFMe neurons are the housefly's clock neurons is discussed.     

Gene expression profile analysis reveals the effect of metformin treatment on HepG2 cells

Metformin is a first-line drug in the fight against type 2 diabetes. In recent years, studies have shown that metformin has some preventive and therapeutic effects on liver cancer, but the effects of metformin on the gene expression of liver cancer cells are not fully known. This study focused on the differences in the gene expression profiles in liver cancer cells treated with or without metformin. A total of 153 differentially expressed genes (DEGs) (FC > 2 and q-values < 0.001) were found, including 77 upregulated genes and 76 downregulated genes. These DEGs are involved in mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), cell adhesion molecules (CAMs), and leukocyte transendothelial migration signaling pathways. These findings reveal the effects of metformin treatment on gene expression profiles in liver cancer cells and provide new clues for unveiling the mechanism of the antitumor effects of metformin.     

采样噪声对北斗全球信号测距误差的影响分析

随着北斗卫星导航系统的全球化,基于软件定义无线电的北斗接收机在北斗导航定位中的应用越来越广泛。但是北斗接收机在实时动态差分等高精度测量应用场景下,其基带采样ADC受到采样时钟抖动影响,再叠加固有的量化噪声和热噪声,对北斗信号的扩频测距精度产生不可忽略的影响。本文首先针对北斗公开的B1I、B1C、B2I、B2a和B3I 5种全球信号,描述了ADC采样中时钟抖动、量化噪声和热噪声等采样噪声的数学模型,提出了影响测距的信噪比综合公式,再通过载噪比进而得出测距误差的一般表达式,并给出了高精度测量要求下不同参数选择的工程化定量分析方法,然后针对不同参数对北斗信号测距误差的影响进行了仿真分析,仿真结果表明,在0. 6 cm的测距误差目标下,要求时钟抖动不大于45 ps,接收机中心频率不大于80 MHz,带宽不小于25 MHz,量化位数不少于7位,载噪比不小于30 d B。最后,针对北斗B2I信号进行了实测实验,在时钟抖动为35 ps,接收机中心频率61. 38 MHz,带宽32 MHz,量化位数12位,载噪比67 d B时,解算的测距误差为0. 41 cm,验证了本文方法的有效性。     

Gene expression in the supraoptic nucleus.

The magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) express multiple kinds of genes, including not only the classical hormones arginine vasopressin (AVP) and oxytocin (OXT), but also other physiologically active substances including neuropeptides, their receptors, and nitric oxide (NO) synthase, the rate-limiting enzyme in the synthesis of NO under physiological condition. For example, osmotic stimuli such as dehydration and chronic salt loading cause a wide range of changes of the expression levels of the genes and marked induction of the expression of the genes in the SON. The expression of the NO synthase gene in the SON under physiological conditions is reviewed.     

Chloroplast ultrastructure in leaves of Urtica dioica L. analyzed after high-pressure freezing and freeze-substitution and compared with conventional fixation followed by room temperature dehydration

In this article, we report on the adaptation of high-pressure freezing and freeze-substitution (HPF-FS) for ultrastructural analysis of leaf tissue with special emphasis on chloroplasts. To replace the gas in the intercellular spaces, a mixture of water and methanol (MeOH) was employed. We compared three different supplements for FS--osmiumtetroxide, uranyl acetate, and safranin--with regard to the preservation of the ultrastructure of chloroplasts and other cellular compartments. The results show that (i) replacement of air within intercellular spaces by 8% (v/v) MeOH has no influence on the ultrastructure of the chloroplasts, (ii) undulation of membranes frequently observed after conventional preparation of specimens does not occur during chemical fixation but during room temperature dehydration, and (iii) uranyl acetate or osmium tetroxide employed during FS are not superior over safranin.     

基于鼓-缓冲器-绳子理论的半导体晶圆厂车间层控制

为了将鼓-缓冲器-绳子理论应用于带回流的半导体晶圆厂车间的作业控制,通过设置回流缓冲,对传统鼓-缓冲器-绳子理论进行了修正,提出了一套适合带回流生产线的生产作业方法。针对瓶颈资源上的负荷堆积情况,提出了基于EDD和CR法则的推平原则,将瓶颈负荷推平。负荷推平后,根据瓶颈设备的实际可用情况,对瓶颈设备上的生产安排进行合理化,得到各订单的投料时间及出货时问安排。算例结果证明了该方法的可行性和有效性。     

An effective warpage optimization method in injection molding based on the Kriging model

In this paper, an effective optimization method using the Kriging model is proposed to minimize the warpage in injection molding. The warpage deformations are nonlinear, implicit functions of the process conditions, which are typically evaluated by the solution of finite element (FE) equations, a complicated task which often involves huge computational effort. The Kriging model can build an approximate function relationship between warpage and the process conditions, replacing the expensive FE reanalysis of warpage in the optimization. In addition, a “space-filing” sampling strategy for the Kriging model, named rectangular grid, is modified. Moldflow Corporation’s Plastics Insight software is used to analyze the warpage deformations of the injection-molded parts. As an example, the warpage of a cellular phone cover is investigated, where the mold temperature, melt temperature, injection time, and packing pressure are regarded as the design variables. The result shows that the proposed optimization method can effectively decrease the warpage deformations of the cellular phone cover and that the injection time has the most important influence on warpage in the chosen range.     

冷藏车厢内温度波动特性分析

为了控制冷藏车厢内的温度波动,运用频域分析法对造成冷藏车厢内温度波动的4种温度扰动等因素进行了研究。研究结果表明:在保持车厢体积、当量换热面积、传热系数不变,减小系统交接频率,可对各温度扰动进行衰减;保持αF与ρсν的比值不变,可调整制冷机组运行频率及融霜频率处于系统衰减域,或使得制冷与融霜温度扰动的相角相同,达到对这两种扰动进行衰减的目的;减小车厢内外表面的对流换热系数、减少当量换热面积、减小车辆当量渗风孔面积越小、使车厢外表面颜色变浅、增大车速的变化频率等可达到降低车厢内温度波动的效果。     

Sperm ultrastructure and spermatogenesis in the lizard, <i>Tropidurus itambere</i>

Spermatogenesis, with emphasis on spermiogenesis, is described for the lizard, Tropidurus itambere, using light microscopy, phase contrast and epifluorescence, as well as scanning and transmission electron microscopy. Cellular differentiation involves events of chromatin condensation, nuclear elongation and the formation of structural complexes, such as the acrosomal and axonemal ones. Other new characteristics, exclusive for this species, include various aspects of the subacrosomal granule, the insertion of the proacrosomal vesicle and the development of these structures to participate in the acrosomal complex. Radial projections occur just above the nuclear shoulders, which have been recognized already from the beginning of cellular elongation. The development of the midpiece, the dense bodies, formation of the flagellum and elimination of residual cytoplasm result in the final characterization of the mature spermatozoon. Comparisons between Tropiduridae and other lizard families are made.