Synthesis and in vitro antitumor activity of asperphenamate derivatives as autophagy inducer

In an effort to improve the aqueous solubility and the antitumor activity of natural product asperphenamate, we have designed and synthesized three series of asperphenamate derivatives, including series I (simplifying molecular skeleton series), series II (introducing a hydroxyl group to A-phenyl ring series) and series III (disrupting molecular planarity series). All derivatives have displayed a significantly increased solubility compared with asperphenamate. Their growth inhibitory activities in vitro were screened by the standard MTT method in MCF-7, HeLa, and BEL-7402 cell lines. With the exception of the derivatives in series I, most of derivatives in series II and series III showed growth inhibitory activity. Among all derivatives, IM23b in series III showed the greatest potency in human breast cancer MCF-7 cells. The cellular potency of IM23b was approximately 1.5-fold more potent than that of cisplatin. The mechanism of cell death induced by IM23b in human breast cancer MCF-7 cells was further investigated. We concluded that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest.     

Induction of heart failure: haemodynamic comparison of three different canine models

We compared three methods: arteriovenous anastomosis, doxorubicin administration, and combination of anastomosis and doxorubicin, with the intention of designing a simple, stable model of chronic heart failure. Twelve dogs were divided into three groups of four. One group received carotid-jugular anastomosis (Ana series), another group received anastomosis and doxorubicin injection (A/D series), and the last group received only doxorubicin (Dox series). Animals were followed for eight weeks. Fifteen different haemodynamic parameters were tracked and compared to baseline values. After eight weeks, diastolic pressure in the right atrium increased from 3.8+/-2.0 mmHg at baseline to 5.3+/-5.9 mmHg in the Ana series, to 6.3+/-3.3 mmHg in the Dox series and to 8.0+/-2.0 mmHg in the A/D series (P<0.05 A/D vs. baseline). Systolic pulmonary wedge pressure increased from 11.6+/-2.0 mmHg at baseline to 15.5+/-3.4 mmHg in the Ana series, 14.0+/-3.7 mmHg in the Dox series and 17.3+/-4.2 mmHg in the A/D series (P = NS vs. baseline). Left ventricular ejection fraction decreased from 53.9+/-10% at baseline to 36.1+/-5.6% in the Ana series (P<0.05 vs. baseline), 31.5+/-5.4% in the Dox series (P<0.05 vs. baseline) and 25.8+/-5.8% in the A/D series (P<0.001 vs. baseline, P<0.05 vs. Ana series and Dox series). In conclusion, eight weeks are not enough to produce stable heart failure using arteriovenous anastomosis alone. Doxorubicin administration alone produces a left ventricular failure. However, a combination of both of these interventions provides a more stable model of right-and left-sided heart failure.     

Sex-diagnosis of isolated Os coxae by discriminant functions

After methodical preparatory work on the selection of the metric characters and their technical definition, 16 variables were measured on every right hip bone in our standard series (Weisbach series). The discriminant functions performed on our standard series proved to be very sharply discriminant. The methodical foundation gained from the Weisbach series was applied to a control series (Tyrol series), whose sex had not been determined. The application of the discriminant analyses enabled a complete and plausible sex diagnosis to be made.     

Duality between time series and networks

Studying the interaction between a system's components and the temporal evolution of the system are two common ways to uncover and characterize its internal workings. Recently, several maps from a time series to a network have been proposed with the intent of using network metrics to characterize time series. Although these maps demonstrate that different time series result in networks with distinct topological properties, it remains unclear how these topological properties relate to the original time series. Here, we propose a map from a time series to a network with an approximate inverse operation, making it possible to use network statistics to characterize time series and time series statistics to characterize networks. As a proof of concept, we generate an ensemble of time series ranging from periodic to random and confirm that application of the proposed map retains much of the information encoded in the original time series (or networks) after application of the map (or its inverse). Our results suggest that network analysis can be used to distinguish different dynamic regimes in time series and, perhaps more importantly, time series analysis can provide a powerful set of tools that augment the traditional network analysis toolkit to quantify networks in new and useful ways.     

The role of signal and motivational links of a conditioned reflex in the initiation of instrumental movements in dogs

Alimentary instrumental conditioned reflex (CR) was elaborated in dogs to light flashes (I series), electrostimulation (ES) of the hippocampus (II series) and the hypothalamus (III series). Nonreinforced ES of the hypothalamus, amygdala, hippocampus and septum reproduced pressings on the pedal to the least extent in the I series (17-40% of trials), increasing in the II-nd one up to 40-87% during stimulation of the lateral hypothalamus, medial amygdala and contralateral hippocampus. In the III-rd series the number of pressings increased statistically significantly in comparison with the I-st series for most structures. Probably, besides the artificial increase of motivation during ES of the limbic structures which took place in all series, in the II-nd and III-rd series significance for movement reproduction was acquired by CR generalization appearing due to close interconnection of the structures. In this phenomenon connections (evaluated by the EPs) from the tested structures to the initially signal one are important.     

An outline of a revised classification of Saxifraga L.

GORNALL, R. J., 1987. An outline of a revised classification of Saxifraga. A revised classification of Saxifraga is presented in which 15 sections, 19 subsections and 34 series are recognized. A total of 394 names are accounted for, including the following new taxa, combinations and names: series Hirculoideae (Engler & Irmscher) Gornall, stat. nov.; series Lychnitidae (Engler & Irmscher) Gornall, stat. nov.; series Nulanles (Engler & Irmscher) Gornall, stat. nov.; series Cinctae (H. Sm.) Gornall, stat. nov.; series Gemmiparae (Engler & Irmscher) Gornall, stat. nov.; series Spinulosae (C. B. Clarke) Gornall, stat. nov.; subsection Rosulares Gornall, nom. nov.; subsection Serpyllifoliae Gornall, subscct. nov.; subsection Hemisphaericae (Engler & Irmscher) Gornall, stat. nov.; section Merkianae (Engler & Irmscher) Gornall, stat. nov.; subsection Stellares (Engler & Irmscher) Gornall, stat. nov.; series Birostres Gornall, ser. nov.; series Melanocentrae (Engler & Irmscher) Gornall, stat. nov.; series Astasianlhes (Sternberg) Gornall, stat. nov.; subsection Micranthes (Haworth) Gornall, stat. nov.; series Aulaxis (Haworth) Gornall, stat. nov.; series Dermasea (Haworth) Gornall, stat. nov.; series Micranthes (Haworth) Gornall, stat. nov.; scries Aretioideae (Engler & Irmscher) Gornall, stat. nov.; series Juniperifoliae (Engler & Irmscher) Gornall, stat. nov.; series Lilacinae Gornall, ser. nov.; series Marginatae (Engler & Irmscher) Gornall, stat. nov.; series Squarrosae (Engler & Irmscher) Gornall, stat. nov.; series Rigidae (Engler & Irmscher) Gornall, stat. nov.; subsection Engleria (Siindermann) Gornall, stat. nov; series Subsessiliflorae Gornall, ser. nov.; series Oppositiofoliae (Hayek) Gornall, stat. nov.; series Tetrameridium (Engler) Gornall, stat. nov.; subsection Mutatae (Engler & Irmscher) Gornall, stat. nov.; subsection Florulentae (Engler & Irmscher) Gornall, stat. nov.; section Odontophyllae Gornall, sect, nov.; series Biternatae (Engler & Irmscher) Gornall, stat. nov.; subsection Triplinervium (Gaudin) Gornall, stat. nov.; series Arachnoideae (Engler & Irmscher) Gornall, stat. nov.; subsection Tridactylites (Haworth) Gornall, stat. nov.     

Analysis of cedar pollen time series: no evidence of low-dimensional chaotic behavior

Much of the current interest in pollen time series analysis is motivated by the possibility that pollen series arise from low-dimensional chaotic systems. If this is the case, short-range prediction using nonlinear modeling is justified and would produce high-quality forecasts that could be useful in providing pollen alerts to allergy sufferers. To date, contradictory reports about the characterization of the dynamics of pollen series can be found in the literature. Pollen series have been alternatively described as featuring and not featuring deterministic chaotic behavior. We showed that the choice of test for detection of deterministic chaos in pollen series is difficult because pollen series exhibit power spectra. This is a characteristic that is also produced by colored noise series, which mimic deterministic chaos in most tests. We proposed to apply the Ikeguchi–Aihara test to properly detect the presence of deterministic chaos in pollen series. We examined the dynamics of cedar (Cryptomeria japonica) hourly pollen series by means of the Ikeguchi–Aihara test and concluded that these pollen series cannot be described as low-dimensional deterministic chaos. Therefore, the application of low-dimensional chaotic deterministic models to the prediction of short-range pollen concentration will not result in high-accuracy pollen forecasts even though these models may provide useful forecasts for certain applications. We believe that our conclusion can be generalized to pollen series from other wind-pollinated plant species, as wind speed, the forcing parameter of the pollen emission and transport, is best described as a nondeterministic series that originates in the high dimensionality of the atmosphere.     

金叶银杏半同胞子代无性系的叶色和色素含量变化及呈色机制分析

对4月份至11月份金叶银杏‘万年金'( Ginkgo biloba ‘Wannianjin')32个半同胞子代无性系与亲本的叶色差异进行比较;比较了不同色系叶片的色素含量和比值及叶色参数(L*、a*和b*)的变化,分析了叶色参数与叶片色素含量的相关性;并观察了不同色系的叶绿体超微结构。结果表明：32个半同胞子代无性系可被分为金黄、浅黄、草绿和蓝绿4个色系。随时间推移,草绿和蓝绿色系叶片的总叶绿素( Chl)、叶绿素a( Chla)、叶绿素b( Chlb)和类胡萝卜素( Car)含量均呈“双峰型”变化趋势,Car/Chl和Car/Chla比值的变幅均较小;而金黄和浅黄色系叶片的上述色素含量呈“升高—降低—升高”变化趋势,Car/Chl和Car/Chla比值总体呈“迅速下降—相对稳定—缓慢升高”的变化趋势。各色系叶片的上述色素含量在夏季均不同程度下降,Car/Chlb比值变化差异较大,且金黄和浅黄色系的各色素含量均低于草绿和蓝绿色系。随时间推移,金黄和浅黄色系叶片的L*、a*和b*值以及草绿和蓝绿色系叶片的L*和b*值均先降低后升高,后2个色系的a*值则先升高后下降;并且,前2个色系的L*和b*值总体上显著高于后2个色系,而a*值则总体上低于后2个色系。金黄色系的Chla和Chl含量与L*和a*值显著负相关,而其Car/Chl和Car/Chla比值则与L*、a*和b*值显著或极显著正相关;浅黄色系的Chlb含量与a*值显著负相关,其Car/Chla比值与L*和b*值以及Car/Chlb比值与a*值均显著正相关;草绿色系的Chla含量与L*值显著负相关,其Car/Chla比值与L*和b*值以及Car/Chlb比值与a*值均显著正相关;这3个色系叶片的其余指标间以及蓝绿色系叶片的各指标间均无显著相关性。观察结果显示：金黄和浅黄色系的叶绿体基粒片层发育不健全,基粒片层可见但排列较疏松,且无明显垛叠,分布范围小而稀疏;蓝绿和草绿色系叶绿体的基粒类囊体垛叠层数均较多,基粒片层发达且排列紧致、整齐,分布范围大而稠密。综合分析结果表明：‘万年金'4个色系半同胞子代无性系叶片的呈色差异和叶色变化由多种因素控制,其中,Car/Chl和Car/Chla比值高且叶绿体基粒片层发育不健全是叶片呈黄色的主要原因。     

Inhibition of brain nitric oxide synthesis enhances and prolongs the hypertensive effect of centrally administered interleukin-1beta in rats

The present study was designed to find out whether brain nitric oxide (NO) influences hemodynamic response to intracerebroventricular (ICV) infusion of interleukin-1 beta (IL-1beta). Mean arterial blood pressure (MAP) and heart rate (HR) were recorded in seven series of experiments performed on conscious Sprague-Dawley rats receiving during 60 min ICV infusion of: 0.9% NaCl (5 microl/h; series 1), IL-1beta (100 ng/h; series 2), NO synthase inhibitor (L-NAME, 1mg/h; series 3), IL-1beta together with L-NAME (series 4), IL-1beta together with inactive isomer of NO synthase inhibitor (D-NAME, 1mg/h; series 5), NO donor (SNAP, 40 microg/h; series 6) and IL-1beta together with SNAP (series 7). ICV infusion of saline did not influence MAP while administration of IL-1beta as well as IL-1beta together with D-NAME elicited a significant, though transient, increase in MAP. In series 4, combined infusion of IL-1beta and L-NAME exerted an increase in MAP, which persisted until the end of the experiment and was significantly higher than in series 2 and 5. In series 7, infusion of SNAP together with IL-1beta abolished the pressor effect of IL-1beta. HR was not significantly altered in any of the experimental series. These results demonstrate that inhibition of NO synthesis in the brain enhances and prolongs the pressor response to IL-1beta, whereas concomitant administration of NO donor abolishes the hemodynamic effect of IL-1beta. Therefore, we conclude that NO generated in the brain is involved in buffering the pressor response to IL-1beta.     

中国温带阔叶红松林不同演替系列土壤有机碳矿化特征

土壤有机碳矿化与陆地生态系统碳循环和全球气候变化关系密切,为准确评估中国温带小兴安岭阔叶红松林不同演替系列土壤有机碳矿化特征及变化规律。以年代序列法代替群落次生演替过程,采用室内恒温培养(碱液吸收法)测定阔叶红松林不同演替系列(中生演替系列、湿生演替系列、旱生演替系列)6种群落类型土壤有机碳矿化量和矿化速率。3个演替系列土壤有机碳含量均表现出一致的剖面变化特征,随着土层深度的加深有机碳矿化量逐渐降少。且不同演替系列土层间有机碳矿化量不同,中生演替系列原始阔叶红松林土壤有机碳累计矿化量最大,其次为旱生演替系列,湿生演替系列最小。3个演替系列土壤有机碳矿化速率随时间变化呈现基本一致的趋势,即培养前期快速下降、后期逐渐趋于平稳。3个演替系列6种群落类型土壤有机碳矿化差异显著,表现为原始阔叶红松林白桦次生林云冷杉红松林红松枫桦次生林蒙古栎红松林蒙古栎、黑桦次生林。阔叶红松林不同演替系列土壤有机矿化采用非线性指数拟合效果较好。阔叶红松林不同演替系列土壤有机碳矿化与土壤全氮、凋落物量显著正相关,与土壤含水率、容重、土壤酸碱度显著负相关。不同演替系列群落的演替历史、土壤质地和养分状况等生态因子是导致阔叶红松林不同演替系列土壤有机碳矿化差异的原因。     

Life stress on the Roman limes in continental Croatia

The purpose of the paper is to analyze and compare the demographic profiles and disease frequencies between a skeletal series from Zmajevac, a settlement on the Danubian limes, and a composite «non-limes» skeletal series consisting of human osteological remains from three large urban settlements to the west of the limes; roman Mursa (modern Osijek), Cibalae (Vinkovci) and Certissia (Štrbinci). To determine if life stresses were different in settlements on the limes the age and sex distribution in Zmajevac was compared to the composite «non-limes» series. All skeletons were also analyzed for the presence of dental pathology, dental enamel hypoplasia, cribra orbitalia, trauma, and physical stress.

Data collected from the skeletal series show that, with the exception of some indicators of physical stress, no significant differences in quality of life is evident. Both series are characterized by an underrepresentation of subadults from the youngest age category and by similar average adult male and female ages at death. In Zmajevac the average ages at death for adult males and females were 40.0 and 39.0 years respectively, in the composite «non-limes» series 37.4 years for both males and females. The frequencies of dental disease, subadult stress indicators, and trauma are similar in both series. The only consistent difference between the two series is noted in the frequencies of skeletal markers of physical stress, in particular the frequencies of vertebral osteoarthritis and Schmorl's defects. Total male and total female vertebral osteoarthritis frequencies in the two series are significantly different, as is the difference in total male frequencies of Schmorl's defects. Young adult males in the Zmajevac series seem to have been experiencing particularly heavy physical strain on the vertebral column. They exhibit significantly higher frequencies of both vertebral osteoarthritis and Schmorl's defects than young adult males from the composite non-limes series.     

Alterative and repair processes in lymph nodes under the direct and mediated effects of radiation]

Under study were the popliteal lymph nodes of rats at different times after total irradiation of animals (the 1st series), total irradiation with screening the left node (the 2nd series) and local screening of other parts of the body (the 3rd series). X-ray irradiation in all experiments was performed under standard conditions in dosage of 800 r. The amount of mitoses (MC 0/00) in light centers and cortical substance was counted in addition to histological alterations. In shielded lymph nodes (2nd series) mediate effects of irradiation were observed characterized by a decrease of the MK amount and massive death of lymphocytes in later terms than after direct effects (1st series). In irradiated nodes (3rd series) the reparative process was more rapid than in the first series due to migration of lymphocytes from non-irradiated parts of the body. The mediate effect of radiation results also in increased amount of plasma cells in lymphatic nodes of animals subjected to total irradiation (1st and 2nd series). It is suggested by the absence of such increase of amount of plasma cells in locally irradiated lymphatic nodes when screening other parts of the body (3rd series). availability of individual distinctions in the character of the lymphoid tissue response to effects of ionizing radiation puts a question of division of experimental animals at least into 2 subgroups which have different indices of proliferative processes.     

Sulfonamide derivatives of bridgehead substituted bicyclo[4.2.1]nonanes as gamma-secretase inhibitors

Bridgehead substituted derivatives of bicyclo[4.2.1]nonanes were synthesized and shown to be potent inhibitors of gamma-secretase. Two related series were synthesized to explore the SARs. More potent compounds were found in the non-benzofused series compared with the benzofused series. One compound from each series showed good exposure in the hepatic portal vein (HPV) following oral dosing to rats.     

Structure-affinity relationships of the affinity of 2-pyrazolyl adenosine analogues for the adenosine A2A receptor

The structure-affinity relationships of two novel 2-substituted adenosine series containing a substituted pyrazole attached at the N-1 or C-4 position for the adenosine (ADO) A2A receptor are described. Compounds in the 2-(N-1-pyrazolyl) adenosine series IV provided the highest affinity for the ADO A2A receptor as compared to the 2-(C-4-pyrazolyl) series V. The main structural differences between the two series point to the N-1 nitrogen of series IV imparting more favorable binding interactions with the receptor than those of series V.     

Le revêtement cutané des raies (Chondrichthyes,Elasmobranchii, Batoidea). II. Morphologie et arrangement des tubercules cutanés

The dermal covering of most batoid fish is constituted by dermal denticles and by different series of tubercles or thorns. The repartition and the morphological variations of these structures can provide complementary information about the taxonomy of skates and rays. The variations in these dermal structures within Pristiforms, Rajiforms and Myliobatiforms have been studied, taking into consideration the number of tubercles, their location and their arrangement in different series. Following Hubbs and Ishiyama [30], two new terms and 15 new series are indicated. The characteristics of the arrangement and of the morphology of these structures can separate the Rajiforms, having spiny tubercles or thorns, from the Myliobatiformes, bearing lanceolate or heart-shaped tubercles. The main taxinomic characters found are: guitar fish characterized by two scapular series, one well-developed rostral series and tubercles with an anterolateral ornamentation (relief). Within this group, Rhinidae and Rhynchobatidae are set apart by the morphology of their tubercles (devoid of any anterolateral ornamentation), by the absence of a middorsal caudal series and by the presence of an outer supraspiracular series. Platyrhina and Platyrhinoidis are distinguishable by the absence of anterolateral relief and by the presence of anterolateral, lateral and parallel series. Rajoids are characterized by thorns, only one scapular series and sometimes a nucho-scapular triangle, malar and alar thorns in adults, and well-developed parallel and lateral series. Myliobatiforms are devoid of rostral, orbito-spiracular, malar, alar, anterolateral, parallel and lateral series but a caudal sting is present in most species. Sawfish are almost entirely devoid of tubercules, except for rostral ‘teeth’. The morphology and arrangement of the rostral teeth can differenciate the two genera within this family.     

Effect of rifampicin on development of tolerance to analgesic actions.

Two series of experiments were performed. In the first series the reaction times of mice were determined using the hotplate technique. In the second series of experiments the reactions of rats were determined using the electric footshock technique. In both series of experiments morphine was observed to alter the responses, and chronic morphine administration resulted in tolerance to these actions of morphine. In both series of experiments, tolerance, defined by these same criteria, was inhibited by the concurrent administration of rifampicin.     

Human assessment of time intervals depending on the manner of their representation

On 42 subject three experimental series were carried out: in the first (12 persons) and second (24 persons) series the presented interval was limited by two short clicks, in the third series (6 persons)--by electrocutaneous stimuli. Duration of the stimuli was 1 ms. There were three regimes of work in the first and third series: the intervals successively increased from 100 to 500 ms with a step of 100 ms (1), decreased from 5000 to 100 ms (2) or varied in a random order (3). In the second series only the regime 3 was applied. In all series the method of temporal intervals reproduction was used. The means of the reproduction varied: in the second and third series the interval was reproduced by button pressing according to the presented duration: in the first series the end of the interval was marked by a short button push, and the beginning was the moment of the second stimulus presentation. With the first means a considerable overreproduction was observed of the presented duration at all intervals and all regimes. At the second and third series a phasic character of the reproduction duration was noted: up to 1000 ms the interval mostly was overestimated, over 2000 ms--it was significantly underestimated. It is suggested that as the estimation of the temporal interval implies some motor reaction, the afferent flow of signals from the active muscles can change the value of the reproduced duration. In the first series, the subjects probably do not take into account the time necessary for the realized signal perception.     

Unbiased pattern detection in microarray data series

MOTIVATION: Following the advent of microarray technology in recent years, the challenge for biologists is to identify genes of interest from the thousands of genetic expression levels measured in each microarray experiment. In many cases the aim is to identify pattern in the data series generated by successive microarray measurements. RESULTS: Here we introduce a new method of detecting pattern in microarray data series which is independent of the nature of this pattern. Our approach provides a measure of the algorithmic compressibility of each data series. A series which is significantly compressible is much more likely to result from simple underlying mechanisms than series which are incompressible. Accordingly, the gene associated with a compressible series is more likely to be biologically significant. We test our method on microarray time series of yeast cell cycle and show that it blindly selects genes exhibiting the expected cyclic behaviour as well as detecting other forms of pattern. Our results successfully predict two independent non-microarray experimental studies.     

Ovulation and implantation in montane voles (Microtus montanus) as a function of varying amounts of copulatory stimulation

Estrous female voles (Microtus montanus) received (a) no copulation, (b) one ejaculatory series, (c) two ejaculatory series, or (d) more than two series. Copulation was shown to be essential for ovulation, and increasing amounts of copulatory stimulation were demonstrated to increase the probability of ovulation. Only 25% of females receiving one ejaculatory series ovulated, whereas 100% of those receiving more than two series ovulated. Thus, multiple ejaculations play an important role in successful reproduction in this species.