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A series of novel 1-oxo-2,3,4-trisubstituted tetrahydroisoquinoline (THIQ) derivatives bearing other heterocyclic moieties in their structure were synthesized based on the reaction between homophthalic anhydride and imines. Initial studies were carried out to establish the anti-coronavirus activity of some of the newly obtained THIQ-derivatives against two strains of human coronavirus-229E and OC-43. Their antiviral activity was compared with that of their close analogues, piperidinones and thiomorpholinones, previously synthesized in our group, with aim to expand the range of the tested representative sample and to obtain valuable preliminary information about biological properties of a wider variety of compounds.

Aging is characterized by a progressive loss of brain volume at an estimated rate of 5% per decade after age 40. While these morphometric changes, especially those affecting gray matter and atrophy of the temporal lobe, are predictors of cognitive performance, the strong association with aging obscures the potential parallel, but more specific role, of individual subject physiology. Here, we studied a cohort of 554 human subjects who were monitored using structural MRI scans and blood immune protein concentrations. Using machine learning, we derived a cytokine clock (CyClo), which predicted age with good accuracy (Mean Absolute Error = 6 y) based on the expression of a subset of immune proteins. These proteins included, among others, Placenta Growth Factor (PLGF) and Vascular Endothelial Growth Factor (VEGF), both involved in angiogenesis, the chemoattractant vascular cell adhesion molecule 1 (VCAM-1), the canonical inflammatory proteins interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), the chemoattractant IP-10 (CXCL10), and eotaxin-1 (CCL11), previously involved in brain disorders. Age, sex, and the CyClo were independently associated with different functionally defined cortical networks in the brain. While age was mostly correlated with changes in the somatomotor system, sex was associated with variability in the frontoparietal, ventral attention, and visual networks. Significant canonical correlation was observed for the CyClo and the default mode, limbic, and dorsal attention networks, indicating that immune circulating proteins preferentially affect brain processes such as focused attention, emotion, memory, response to social stress, internal evaluation, and access to consciousness. Thus, we identified immune biomarkers of brain aging which could be potential therapeutic targets for the prevention of age-related cognitive decline.

The ongoing COVID-19 pandemic has caused over six million deaths and huge economic burdens worldwide. Antivirals against its causative agent, SARS-CoV-2, are in urgent demand. Previously, we reported that heterocylic compounds, i.e., chloroquine (CQ) and hydroxychloroquine (HCQ), are potent in inhibiting SARS-CoV-2 replication in vitro. In this study, we discussed the syntheses of two novel heterocylic compounds: tert-butyl rel-4-(((3R,4S)-3-(1H-indol-3-yl)-1-oxo-2-propyl-1,2,3,4-tetrahydroisoquinolin-4-yl)methyl)piperazine-1-carboxylate (trans-1) and rel-(3R,4S)-3-(1H-indol-3-yl)-4-(piperazin-1-ylmethyl)-2-propyl-3,4-dihydroisoquinolin-1(2H)-one (trans-2), which effectively suppressed authentic SARS-CoV-2 replication in Vero E6 cells. Compound trans-1 showed higher anti-SARS-CoV-2 activity than trans-2, with a half maximal effective concentration (EC50) of 3.15 μM and a selective index (SI) exceeding 63.49, which demonstrated comparable potency to CQ or HCQ. Additional anti-SARS-CoV-2 tests on Calu-3 human lung cells showed that trans-1 efficiently inhibited viral replication (EC50 = 2.78 μM; SI: > 71.94) and performed better than CQ (EC50 = 44.90 μM; SI = 2.94). The time of an addition assay showed that the action mechanism of trans-1 differed from that of CQ, as it mainly inhibited the post-entry viral replication in both Vero E6 and Calu-3 cells. In addition, the differences between the antiviral mechanisms of these novel compounds and CQ were discussed.

Alchemilla vulgaris L. (lady’s mantle) was used for centuries in Europe and Balkan countries for treatments of numerous conditions and diseases of the reproductive system, yet some of the biological activities of lady’s mantle have been poorly studied and neglected. The present study aimed to estimate the potential of A. vulgaris ethanolic extract from Southeast Serbia to prevent and suppress tumor development in vitro, validated by antioxidant, genoprotective, and cytotoxic properties. A total of 45 compounds were detected by UHPLC–HRMS analysis in A. vulgaris ethanolic extract. Measurement of antioxidant activity revealed the significant potential of the tested extract to scavenge free radicals. In addition, the analysis of micronuclei showed an in vitro protective effect on chromosome aberrations in peripheral human lymphocytes. A. vulgaris extract strongly suppressed the growth of human cell lines derived from different types of tumors (MCF-7, A375, A549, and HCT116). The observed antitumor effect is realized through the blockade of cell division, caspase-dependent apoptosis, and autophagic cell death. Our study has shown that Alchemilla vulgaris L. is a valuable source of bioactive compounds able to protect the subcellular structure from damage, thus preventing tumorigenesis as well as suppressing tumor cell growth. © 2022 by the authors.

Globalization has permeated all aspects of social life (economic, political, cultural) and affected the daily life of people. Postindustrial society and postmodern culture have made a significant impact on the transformation of identities, which have truly become liquid - multidimensional, discontinuous, decentralized, fragmented, unstable and inconstant. Parallel with this, new tendencies in culture have almost completely narrowed the boundary between high and popular creativity, thus challenging the status of the established, until then recognized values. These changes have also become evident in the contemporary Serbian society, which is obsessed by preserving the tradition and long-developed identities. By chance, that society has had one foot in the postmodern information world, with the other stuck in the quagmire of old habits and misconceptions inherited from the period of premodern social awareness. By analysing crucial value aspects (traditionalism, conformism, authoritarianism and nationalism), the author of this paper attempts to provide an explanation (which is the basic precondition for the resolution) of the ambivalent and, seemingly, inescapable situation in which the culture of Serbian society finds itself.

The paper points to the disappearance of the division of art into 'high' and 'popular', with a particular emphasis on popular music, which under given circumstances adopts certain aesthetic standards of classical music forms. The authors also analyse the reverse process: the popularisation of classical music, in the composing-arranging and the performing sense. Particular attention is paid to the role, status and reach of popular culture/art in contemporary postmodern ventures. In this context, the Beatles represent a paradigmatic example, due to the fact that they used a plethora of postmodern creative procedures. The authors conduct an analysis of two characteristic Beatles' albums (Sgt. Pepper's Lonely Hearts Club Band and The Beatles, known as 'The White Album') that incorporate the key principles of postmodern aesthetics.

INTRODUCTION: Occupational stress is connected with own profession. Commonly follows usually or unexpectedly pressures or responsibilities. AIM: Presenting ways in which working conditions can affect quality of life, and reflection on means of channeling occupational stress. METHOD: The results of a survey concerning occupational stress, conducted in April 2013. were analyzed. 200 physicians from 15 Emergency Medicine Services were meant to participate, but only ~50% of them (103 physicians from 12 centers) answered our questionnaire. Statistical analysis was performed with program spss 11 for windows. RESULTS: 54 (53%) of the total number of participants were females and 49 (47%) were males. The age structure showed the highest percentage of those between 31 and 40 years of age. The respondents declared themselves mainly as non-smokers - 87 (84%) and moderate alcohol consumers - 43 (42%). 9 (8,7%) of them admitted they need to take tranquilizers. Reviewing the health condition of the participants, we found that 31 of them (30%) had one or more chronic diseases. Low wages and public exposure had a great impact on physicians' attitude about their profession. Physicians without any stress related symptoms were present in the highest number - 31 (30%), while a minor group reported frequent fatigue and weariness - 23 (22%). For 39 people (38%), the best way for channeling occupational stress was an active use of free time, for 24 of them (23%) it was conversation with colleagues, and for 21 (20%) the solution was simply keeping to themselves. 64 (62%) respondents said that they take their professional problems home after work, and 25 (24%) said they forget about them when the shift ends. CONCLUSION: Working conditions do not have a significant impact on employees in Emergency Medicine Services. Occupational stress related symptoms are present in young doctors as well as in those older than 56 years. The most common ways for stress channeling are free activities and conversations with colleagues.

There is an extensive modification of the functional organization of the brain in the congenital blind human, although there is little understanding of the structural underpinnings of these changes. The visual system of macaque has been extensively characterized both anatomically and functionally. We have taken advantage of this to examine the influence of congenital blindness in a macaque model of developmental anophthalmia. Developmental anophthalmia in macaque effectively removes the normal influence of the thalamus on cortical development leading to an induced “hybrid cortex (HC)” combining features of primary visual and extrastriate cortex. Here we show that retrograde tracers injected in early visual areas, including HC, reveal a drastic reduction of cortical projections of the reduced lateral geniculate nucleus. In addition, there is an important expansion of projections from the pulvinar complex to the HC, compared to the controls. These findings show that the functional consequences of congenital blindness need to be considered in terms of both modifications of the interareal cortical network and the ascending visual pathways.

There is extensive modification of the functional organization of the brain in the congenital blind human, although there is little understanding of the structural underpinnings of these changes. The visual system of macaque has been extensively characterized both anatomically and functionally. We have taken advantage of this to examine the influence of the congenital blindness in macaque resulting from the removal of the retina during in utero development. Developmental anophthalmia in macaque effectively removes the normal influence of the thalamus on cortical development leading to an induced hybrid cortex (HC) combining features of primary visual and extrastriate cortex. Here we show that retrograde tracers injected in early visual areas including hybrid cortex reveals a drastic reduction of cortical projections of the reduced lateral geniculate nucleus. In addition, there is an important expansion of projections from the pulvinar complex to the hybrid cortex, compared to the controls. These findings show that the functional consequences of congenital blindness need to be considered in terms of both modifications of the inter-areal cortical network and the ascending visual pathways.

Environmental challenges and natural disasters demand new tools to support the performance of public institutions in emergency situations. This paper contributes to one of the fundamental objectives – inter–organizational collaboration, namely to the objective to share experience from the implementation of methods and tools and latest research results in support of management in the new security environment. In addition, it focuses on the cognitive and human aspects of collaboration. The goal of the paper is to investigate the impact of different factors and tools for understanding, explaining, and measuring collaborative capacity of public sector institutions’ control organism in emergency situations. The paper will present intermediate results from the research on “Inter–organizational collaborative capacity of public sector institutions’ control entities in emergency situations”. Based on a theoretical model, a draft instrument was developed (i.e., a questionnaire) for data collection that can be used to 1) investigate the impact of different factors, 2) localize inefficiencies in public sector institutions’ control organs, and 3) determine measures to achieve better organizational effectiveness of public sector institutions’ control entities in emergency situations.

We present the detailed science case, and brief descriptions of the telescope design, site, and first light instrument plans for a new ultra-wide field submillimeter observatory, CCAT-prime, that we are constructing at a 5600 m elevation site on Cerro Chajnantor in northern Chile. Our science goals are to study star and galaxy formation from the epoch of reionization to the present, investigate the growth of structure in the Universe, improve the precision of B-mode CMB measurements, and investigate the interstellar medium and star formation in the Galaxy and nearby galaxies through spectroscopic, polarimetric, and broadband surveys at wavelengths from 200 um to 2 mm. These goals are realized with our two first light instruments, a large field-of-view (FoV) bolometer-based imager called Prime-Cam (that has both camera and an imaging spectrometer modules), and a multi-beam submillimeter heterodyne spectrometer, CHAI. CCAT-prime will have very high surface accuracy and very low system emissivity, so that combined with its wide FoV at the unsurpassed CCAT site our telescope/instrumentation combination is ideally suited to pursue this science. The CCAT-prime telescope is being designed and built by Vertex Antennentechnik GmbH. We expect to achieve first light in the spring of 2021., Presented at SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy IX, June 14th, 2018

The processes which are responsible for breakdown initiation in nitrogen-filled tube at 6.6×102 Pa (6.6 mbar) and inter electrode gap 0.1 mm have been investigated. These processes have been monitored based on experimental data of electrical breakdown time delay td as a function of relaxation time τ. It was shown that, for τ 150 s breakdown is initiated by cosmic rays. Also, it was shown that the increase in applied voltage and glow current, as well as presence of external radiation, lead to the decrease of td value.

This is the final peer-reviewed manuscript accepted for publication in Organic Preparations and Procedures International. Citation of the published version is: Organic Preparations and Procedures International48:425–467, 2016.

The purpose of this experimental study was to determine the effects of vertical and horizontal models of plyometric training explosive strength development in cadet volleyball cadets. Forty -four participants were randomly assigned to one of two experimental groups: vertical plyometric (Е1; n=20; BH=185.5 ± 7.02 cm; BM=71.1 ± 7.44 kg), horizontal plyometric (Е2; n=24; BH=183.8 ± 7.79 cm; BM=68.7 ± 8.69 kg). The training programs lasted 6 weeks and it consisted of two training sessions per week. All subjects were tested for each of the following jumps: squat jump (SJ), countermovement jump (CMJ), drop jump (DJ) and continous jumps (CJ). After a 6-week plyometric training some of the tested parameters of SJ increased in the vertical plyometrics group (Hmax 13.7%; Fmax 3.4%; Vmax 6.2%; IMPcon 4.1%; Pmax_con 10.2%), as well as in the horizontal plyometrics group (Hmax12.2%; Fmax 5.1%; Fmax/TT 6.0%; Vmax 5.9%; IMPcon 3.7%; Pmax_con 9.5%). Some of the tested parameters of CMJ increased in the vertical plyometrics group (Hmax 9.8%; Vmax 1.5%; IMPcon 7.2%; IMPuk 2.0%; Pmax_con 2,8%), as well as in the horizontal plyometric group (Hmax 10.1%; Vmax 3.4%; IMPcon 8.5%; IMPuk 5.0%; Pmax_con 3.9%), while lower values compared to the initial measurement were recorded in Fmax/TМ (5.2%) in the vertical plyometric group. In DJ some of the tested parameters increased in the vertical plyometric group (Hmax 15.7%; Tcon 14.9%; Vmax 9.9%; IMPcon 14.4%; Pmax_con 10.4%), as well as in the horizontal plyometrics group (Hmax 23.4%; Vmax 10.6%; Pmax_con 11.9%), while lower values compared to the initial measurement were recorded in parameter Pmax_exc (13.3%) in horizontal plyometric group. The CJ parameters showed in the vertical plyometrics group increased (Hmax 8.2%; IMPuk 6.8%; Pmax_uk 4.8%), as well as in the horizontal plyometrics group (Hmax 14.5%; Texc 6.0%; IMPexc 12.2%; IMPuk 7.5%; Pmax_exc 13.8; Pmax_uk 6.2%). The results of this thesis showed that there were no significant differences in the effects of different models of plyometric program in tested parameters, except for CMJ, in favor of horizontal plyometric group. The results suggest that both training programs were effective in the development of various parameters of jumping ability. In practice exercises from these plyometric training program should be combined due to a greater effect on certain parameters of jumps.

The laminar location of the cell bodies and terminals of interareal connections determines the hierarchical structural organization of the cortex and has been intensively studied. However, we still have only a rudimentary understanding of the connectional principles of feedforward (FF) and feedback (FB) pathways. Quantitative analysis of retrograde tracers was used to extend the notion that the laminar distribution of neurons interconnecting visual areas provides an index of hierarchical distance (percentage of supragranular labeled neurons [SLN]). We show that: 1) SLN values constrain models of cortical hierarchy, revealing previously unsuspected areal relations; 2) SLN reflects the operation of a combinatorial distance rule acting differentially on sets of connections between areas; 3) Supragranular layers contain highly segregated bottom-up and top-down streams, both of which exhibit point-to-point connectivity. This contrasts with the infragranular layers, which contain diffuse bottom-up and top-down streams; 4) Cell filling of the parent neurons of FF and FB pathways provides further evidence of compartmentalization; 5) FF pathways have higher weights, cross fewer hierarchical levels, and are less numerous than FB pathways. Taken together, the present results suggest that cortical hierarchies are built from supra- and infragranular counterstreams. This compartmentalized dual counterstream organization allows point-to-point connectivity in both bottom-up and top-down directions.

SummaryRecent advances in neuroscience have engendered interest in large-scale brain networks. Using a consistent database of cortico-cortical connectivity, generated from hemisphere-wide, retrograde tracing experiments in the macaque, we analyzed interareal weights and distances to reveal an important organizational principle of brain connectivity. Using appropriate graph theoretical measures, we show that although very dense (66%), the interareal network has strong structural specificity. Connection weights exhibit a heavy-tailed lognormal distribution spanning five orders of magnitude and conform to a distance rule reflecting exponential decay with interareal separation. A single-parameter random graph model based on this rule predicts numerous features of the cortical network: (1) the existence of a network core and the distribution of cliques, (2) global and local binary properties, (3) global and local weight-based communication efficiencies modeled as network conductance, and (4) overall wire-length minimization. These findings underscore the importance of distance and weight-based heterogeneity in cortical architecture and processing.

Our understanding of cortical electrophysiology and anatomy at the single-cell level has led to the present day insight in to the function of connections linking cortical areas. This made it possible to elaborate the cortical hierarchy in the early 1990s and was a prerequisite for the development of present day generative models of perception. These computational hierarchical models make strong predictions concerning the roles of feedforward (FF) and feedback (FB) pathways, including their segregation and topographical precision in both directions. This shows that instead of a single stream in the upper and lower compartments of the cortex there is in fact a bi-directional counter-stream in each compartment of the cortex. A significant advance in this field will require more detailed anatomy hand in hand with a network analysis of the directed and weighted cortical matrix.

The processes responsible for initiation of electrical breakdown in xenon-filled tube with two spherical iron electrodes at 2.7-mbar pressure have been analyzed. The analysis is based on the experimental data of electrical breakdown time delay as a function of afterglow period. It is shown that positive ions remaining from previous discharge, as well as positive ions created in mutual collisions of metastable atoms in afterglow, have a dominant role in secondary emission of electrons from the cathode which lead to initiation of breakdown in early afterglow. In late afterglow, dominant role in initiation of breakdown is taken by N(4S) atoms formed during the discharge by dissociation of ground state nitrogen molecules that are present as impurities in xenon. When the concentration of N(4S) atoms decreases sufficiently, the initiation of breakdown is caused by cosmic radiation. Small doses of gamma-ray irradiation also contribute to the initiation of breakdown, but only for large values of the afterglow period.

This paper presents the experimental data of breakdown voltage and electrical breakdown time delay for air-filled tube at p = 0.7 mbar pressure. The breakdown voltage was measured for product p·d (d is inter-electrode gap) from 0.005 to 0.2 mbar cm, i.e. when breakdown was a consequence of gas and vacuum mechanisms combined. It was shown that the static breakdown voltage, which was determined from experimental data of the dynamic breakdown voltage, retains approximately constant value. The shape of the memory curve, which displays the mean value of electrical breakdown time delay t ¯ d vs. relaxation time τ, is very similar to that previously obtained in the case of breakdown induced by Townsend's mechanism alone. UV and gamma radiation lead to the decrease of t ¯ d values for values τ > 30 ms and this decrease is larger in the presence of UV radiation. UV and gamma radiation shorten the relaxation time needed for memory curve to reach saturation. On the basis of exponential and Gaussian distributions of experimental data, the contribution of the statistical time delay and the formative time to total electrical breakdown time delay for different values of relaxation time is considered.

The paper analyzes the works of Umberto Eco and John Fiske, which are dedicated to the consideration of the audience of popular culture/arts. It is a comparative analysis performed from a sociological-aesthetic standpoint. The author of this paper claims that the oeuvres of these two theoreticians differ in both their scopes and their theoretical aspirations. However, they are close in at least one thing, and that is the relation toward the audience of popular culture. Eco's 'open' or 'empty' form of literary and artistic works allows for the activity of the audience in the communication process, while Fiske finds that the activity of the recipients of popular culture is not merely allowed but also compelling. On the one hand, Umberto Eco examines art in the wider sense, touching upon the phenomenon of the popular as well (pop-art, beat literature, film, television), while John Fiske, on the other, dedicated his entire body of work to popular culture - understanding the popular, reading the popular, the audience of the popular. They treat it as free, active and creative, and believe that it, more or less, participates in the act of creation and final shaping of a work. The audience, therefore, not only receives the aesthetic messages but also creates them. For Fiske, the study of popular culture is the study of the circulation of a text meaning, and each act of cultural consumption an act of meaning production as well. However, while Eco does not observe 'openness' as indeterminacy and creation in the chaos of uncontrolled freedom, Fiske gives the audience total freedom in the selection of meanings and pleasures. He excludes any value (aesthetic and moral) criteria, and deems the activity of the audience subversive in relation to the mainstream culture. Finally, the author provides a critical review of Eco's and Fiske's notions of the audience of popular culture. The critique implies emphasizing both the negative and the positive aspects of the analyzed theoretical concepts. The paper also contains the opinions of other theoreticians of popular culture who criticize Fiske's anti-aestheticism and 'cultural populism'.

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation

Cerebellar glioblastoma (cGBM) is a rare, inadequately characterized disease, without detailed information on its molecular basis. This is the first report analyzing both TP53 and RAS alterations in cGBM. TP53 mutations were detected in more than half of the samples from our cohort, mainly in hotspot codons. There were no activating mutations in hotspot codons 12/13 and 61 of KRAS and HRAS genes in cGBM samples but we detected alterations in other parts of exons2 and 3 of these genes, including premature induction of STOP codon. This mutation was present in 3 out of 5 patients. High incidence of RAS mutations, as well as significantly longer survival of cGBM patients compared to those with supratentorial GBM suggest that cGBM may have different mechanisms of occurrence. Our results suggest that inactivation of TP53 and MS may play an important role in the progression of cerebellar GBM. (C) 2014 Elsevier Inc. All rights reserved. Ministry of Education, Science, and Technical Development, Republic of Serbia {[}III41031]

We investigated the influence of interareal distance on connectivity patterns in a database obtained from the injection of retrograde tracers in 29 areas distributed over six regions (occipital, temporal, parietal, frontal, prefrontal, and limbic). One-third of the 1,615 pathways projecting to the 29 target areas were reported only recently and deemed new-found projections (NFPs). NFPs are predominantly long-range, low-weight connections. A minimum dominating set analysis (a graph theoretic measure) shows that NFPs play a major role in globalizing input to small groups of areas. Randomization tests show that ( i ) NFPs make important contributions to the specificity of the connectivity profile of individual cortical areas, and ( ii ) NFPs share key properties with known connections at the same distance. We developed a similarity index, which shows that intraregion similarity is high, whereas the interregion similarity declines with distance. For area pairs, there is a steep decline with distance in the similarity and probability of being connected. Nevertheless, the present findings reveal an unexpected binary specificity despite the high density (66%) of the cortical graph. This specificity is made possible because connections are largely concentrated over short distances. These findings emphasize the importance of long-distance connections in the connectivity profile of an area. We demonstrate that long-distance connections are particularly prevalent for prefrontal areas, where they may play a prominent role in large-scale communication and information integration.

Glioblastoma is the most frequent and malignant human brain tumor. High level of genomic instability detected in glioma cells implies that numerous genetic alterations accumulate during glioma pathogenesis. We investigated alterations in AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11 genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1, CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations revealed that 8 genes might play important role in pathogenesis of glial tumors, while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger mutations, consequence of high level of genomic instability. Identified genes have a significant role in signal transduction or cell adhesion, which are important processes for cancer development and progression. According to our results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4, ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic astrocytoma, suggesting their role in progression of secondary glioblastoma, while alterations of PDE4D seem to have important role in development of both glioblastoma subtypes. Some of the identified genes showed significant association with p53, p16, and EGFR, but there was no significant correlation between loss of PTEN and any of identified genes. In conclusion our study revealed genetic alterations that were not previously associated with glioma pathogenesis and could be potentially used as molecular markers of different glioblastoma subtypes. Ministry of Education, Science and Technological Development, Republic of Serbia [III41031]

Ribosomal 18S RNA is widely used as a housekeeping gene in expression studies, including end-point PCR, Northern analysis, and real-time experiments. However, there are two disadvantages and two points of error introduction in using 18S rRNA as a reference gene. First, 18S has no poly(A) tail, so it is commonly reverse transcribed with specific primers or random hexamers, independently from poly(dT)-primed transcripts. Secondly, due to its abundance, the 18S cDNA must be extensively diluted to be comparable to the tested genes. In this study, 18S rRNA from five taxonomically diverse plant species, including Physcomitrella patens, Adiantum capillus-veneris, Centaurium erythraea, Arabidopsis thaliana, and Zea mays, was successfully reverse transcribed (RT) using poly(dT)(18). As all other homopolymers, including poly(dA)(18), poly(dC)(18), and poly(dG)(18), could serve as RT primers, it was concluded that homopolymers anneal by mispriming at the sites of complementary homopolymeric runs or segments rich in complementary base. Poly(dC)(18) was the most efficient as RT primer, and the only one which interfered with subsequent PCR, giving species-specific pattern of products. Poly(dT)-primed RT reactions were less efficient in comparison to specific primer or random hexamer-primed reactions. Homopolymeric priming of 18S in RT reactions is general in terms of RNA origin and the method of RNA isolation and is possibly applicable to other tailless housekeeping genes. Ministry of Education and Science of the Republic of Serbia [OI 173024]

International audience; Small-world networks provide an appealing description of cortical architecture owing to their capacity for integration and segregation combined with an economy of connectivity. Previous reports of low-density interareal graphs and apparent small-world properties are challenged by data that reveal high-density cortical graphs in which economy of connections is achieved by weight heterogeneity and distance-weight correlations. These properties define a model that predicts many binary and weighted features of the cortical network including a core-periphery, a typical feature of self-organizing information processing systems. Feedback and feedforward pathways between areas exhibit a dual counterstream organization, and their integration into local circuits constrains cortical computation. Here, we propose a bow-tie representation of interareal architecture derived from the hierarchical laminar weights of pathways between the high-efficiency dense core and periphery.

The author of this paper deals with the problem of cultural difference through the analysis of the relationship “us” – “others”. He searches for the answer to the question why the culture of other peoples or individuals are often considered inferior in many societies. This type of treatment leads to the extreme where the position of the “other” is reduced to the level of “primitive” (less valuable, lowly, and brutal). In such a context, the author analyzes theoretical concepts of the Enlightenment rationalism of the 18th century and the anthropological evolutionism of the 19th century, believing that the roots of the negative assessment of the “other” can be found in them. Namely, the majority of these theories conduct a hierarchization of culture according to the time and value principles, from which peoples and cultures can be classified as “primitive” and “civilized”. European modernism provided the vision of history as one of linear growth, which led to modern cultures being a priori declared more valuable and culturally more sublime. However, modern cultures are also classified among themselves according to value principles. The differentiation of cultures is performed using various stereotypes, and the idea of progress as rational improvement in the sphere of material culture, science, and technology legitimizes the transformation of the different (other) into primitive. From this prejudice, according to the author, emerges the Eurocentric thought on the exclusiveness of the European culture, which latently justifies colonialism and other negative phenomena coming from the European civilization. Primitivism is being presented as an objective state, while it is, in fact, the case of a socialconstruction which has the aim of proclaiming the “other” as “primitive”.

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Most chemotherapeutics harm normal cells causing severe side effects and induce the development of resistance in cancer cells. Antimicrobial peptides (AMPs), recognized as anticancer agents, may overcome these limitations. The most studied mechanism underlying multidrug resistance (MDR) is the over-expression of cell membrane transporter P-glycoprotein (P-gp), which extrudes a variety of hydrophobic drugs. Additionally, P-gp contributes to cell membrane composition and increases the net negative charge on cell surface. We postulated that NK-lysin derived cationic peptide NK-2 might discriminate and preferentially eliminate P-gp over-expressing cancer cells. To test this hypothesis, we employed MDR non-small cell lung carcinoma (NCI-H460/R) and colorectal carcinoma (DLD1-TxR) cell lines with high P-gp expression. MDR cancer cells that survived NK-2 treatment had decreased P-gp expression and were more susceptible to doxorubicin. We found that NK-2 more readily eliminated P-gp high-expressing cells. Acting in 'carpet-like' manner NK-2 co-localized with P-gp on the MDR cancer cell membrane. The inhibition of P-gp reduced the NK-2 effect in MDR cancer cells and, vice versa, NK-2 decreased P-gp transport activity. In conclusion, NK-2 could modulate MDR in unique way, eliminating the P-gp high-expressing cells from heterogeneous cancers and making them more vulnerable to classical drug treatment. (C) 2012 Elsevier Inc. All rights reserved. Ministry of Education, Science and Technological Development of Republic of Serbia [III41031]; German Science Foundation (DFG) [AN301/5-1]

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The purpose of this study was to detect the level of genomic instability and p53 alterations in anaplastic astrocytoma and primary glioblastoma patients, and to evaluate their impact on glioma pathogenesis and patients outcome. AP-PCR DNA profiling revealed two types of genetic differences between tumor and normal tissue: qualitative changes which represent accumulation of changes in DNA sequence and are the manifestation of microsatellite and point mutation instability (MIN-PIN) and quantitative changes which represent amplifications or deletions of existing chromosomal material and are the manifestation of chromosomal instability (CIN). Both types of alterations were present in all analyzed samples contributing almost equally to the total level of genomic instability, and showing no differences between histological subtypes. p53 alterations were detected in 40% of samples, predominantly in anaplastic astrocytoma. The higher level of genomic instability was observed in elderly patients (>50 years) and patents with primary glioblastoma. Level of genomic instability had no impact on patients' survival, while presence of p53 alterations seemed to be a favorable prognostic factor in this case. Our results indicate that extensive genomic instability is one of the main features of malignant gliomas. (C) 2012 Elsevier Inc. All rights reserved. Ministry of Education and Science, Republic of Serbia [III41031]

This paper presents realization of a digital embedded system for measuring electrical breakdown time delay. The proposed system consists of three major parts: dc voltage supply, analog subsystem, and a digital subsystem. Any dc power source with the range from 100 to 1000 V can be used in this application. The analog subsystem should provide fast and accurate voltage switching on the testing device as well as transform the signals that represent the voltage pulse on the device and the device breakdown into the form suitable for detection by a digital subsystem. The insulated gate bipolar transistor IRG4PH40KD driven by TC429 MOSFET driver is used for high voltage switching on the device. The aim of a digital subsystem is to detect the signals from the analog subsystem and to measure the elapsed time between their occurrences. Moreover, the digital subsystem controls various parameters that influence time delay and provides fast data storage for a large number of measured data. For this propose, we used the PIC18F4550 microcontroller with a full-speed compatible universal serial bus (USB) engine. Operation of this system is verified on different commercial and custom made gas devices with different structure and breakdown mechanisms. The electrical breakdown time delay measurements have been carried out as a function of several parameters, which dominantly influence electrical breakdown time delay. The obtained results have been verified using statistical methods, and they show good agreement with the theory. The proposed system shows good repeatability, sensitivity, and stability for measuring the electrical breakdown time delay.

We have studied the molecular hydrogen energetics of the edge-on spiral galaxy NGC\,891, using a 34-position map in the lowest three pure rotational H$_2$ lines observed with the Spitzer Infrared Spectrograph. The S(0), S(1), and S(2) lines are bright with an extinction corrected total luminosity of $\sim2.8 \times 10^{7}$ L$_{\odot}$, or 0.09\% of the total-infrared luminosity of NGC\,891. The H$_2$ line ratios are nearly constant along the plane of the galaxy -- we do not observe the previously reported strong drop-off in the S(1)/S(0) line intensity ratio in the outer regions of the galaxy, so we find no evidence for the very massive cold CO-free molecular clouds invoked to explain the past observations. The H$_2$ level excitation temperatures increase monotonically indicating more than one component to the emitting gas. More than 99\% of the mass is in the lowest excitation (T$_{ex}$ $\sim$125 K) ``warm'' component. In the inner galaxy, the warm H$_2$ emitting gas is $\sim$15\% of the CO(1-0)-traced cool molecular gas, while in the outer regions the fraction is twice as high. This large mass of warm gas is heated by a combination of the far-UV photons from stars in photo-dissociation regions (PDRs) and the dissipation of turbulent kinetic energy. Including the observed far-infrared [OI] and [CII] fine-structure line emission and far-infrared continuum emission in a self-consistent manner to constrain the PDR models, we find essentially all of the S(0) and most (70\%) of the S(1) line arises from low excitation PDRs, while most (80\%) of the S(2) and the remainder of the S(1) line emission arises from low velocity microturbulent dissipation., Comment: Accepted for publication in The Astrophysical Journal. Figure 10 available at http://www.physics.uoc.gr/~vassilis/papers/ngc891.pdf

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We report the detection of 13CO(J=6-5) emission from the nucleus of the starburst galaxy NGC 253 with the redshift (z) and Early Universe Spectrometer (ZEUS), a new submillimeter grating spectrometer. This is the first extragalactic detection of the 13CO(J=6-5) transition, which traces warm, dense molecular gas. We employ a multi-line LVG analysis and find ~ 35% - 60% of the molecular ISM is both warm (T ~ 110 K) and dense (n(H2) ~ 10^4 cm^-3). We analyze the potential heat sources, and conclude that UV and X-ray photons are unlikely to be energetically important. Instead, the molecular gas is most likely heated by an elevated density of cosmic rays or by the decay of supersonic turbulence through shocks. If the cosmic rays and turbulence are created by stellar feedback within the starburst, then our analysis suggests the starburst may be self-limiting., Comment: 4 pages, 2 figures, accepted by ApJ Letters

Accurate normalization is the prerequisite for obtaining reliable results in the quantification of gene expression. Using TaqMan Real Time RT-PCR, we carried out an extensive evaluation of five most commonly used endogenous controls, gapdh, beta-actin, 18S rRNA, hprt and cypB, for their presumed stability of expression, in rat cortex and hippocampus, during aging, under dietary restriction and dexamethasone treatment. Valid reference genes (HKGs) were identified using GeNorm and NormFinder software packages and by direct comparison of Ct values. Analysis revealed gapdh and P-actin as the most stable HKGs for all treatments analyzed, combined or separately, in the cortex, while in the hippocampus gapdh/ hprt and beta-actin/hprt are the combination of choice for the single or combined effects of dietary restriction/dexamethasone, respectively. All treatments significantly influenced expression of 18S rRNA and cypB in both structures. In addition, we used gapdh and normalization factor, calculated by GeNorm, to compare the expression of a-syn in the cortex. Our results demonstrate the importance of the right choice of HKG and suggest the appropriate endogenous control to be used for TaqMan RT-PCR analysis of mRNA expression in rat cortex and hippocampus for selected experimental paradigms. null

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Dietary restriction (DR) is one of the promising environmental interventions known to attenuate aging and decrease risk of age-related neurodegenerative disorders. The aim of this study was to assess the effects of DR on expression of a-synuclein, a presynaptic protein involved in pathogenesis of Parkinson's and some other neurodegenerative diseases, in the cortex and hippocampus of adult, middle-aged, late middle-aged, and aged rats. Using Real Time RT-PCR, the authors report that aging regulates the expression of alpha-synuclein in a tissue-specific manner and that long-term DR reverts the late age-related changes of alpha-synuclein expression. (c) 2007 Wiley-Liss, Inc. null

Purpose In addition to Estrogen Receptor alpha (ER alpha) and Progesterone Receptor (PR), the Second Estrogen Receptor (ER beta) appears to play an important role not only in estrogen signaling, but also in the pathogenesis of cancer in estrogen dependent tissues. The existence of various isoforms and splice variants of both ERs additionally complicates elucidation of their physiological role and involvement in the process of carcinogenesis. Methods In this study, the expression of ER beta 1 mRNA (wild type of beta receptor) and splice variant ER beta Delta 5 mRNA (which codes for truncated protein) was measured by the quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and correlated with ER alpha and PR protein levels and with clinical and histopathological parameters. Results We found the inverse correlation of ER beta Delta 5 mRNA expression with the levels of PR and ER alpha proteins in the group of postmenopausal patients; we also report the lower expression of ER beta 1 and ER beta Delta 5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller ones (

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We present an 11 arcsec resolution map of the central two parsecs of the Galaxy in the CO J =7->6 rotational transition. The CO emission shows rotation about Sgr A*, but also evidence for non-circular turbulent motion and a clumpy morphology. We combine our dataset with available CO measurements to model the physical conditions in the disk. We find that the molecular gas in the region is both warm and dense, with T~200-300 K, n_H2~50,000-70,000 cm^-3. The mass of warm molecular gas we measure in the central two parsecs is at least 2000 M_solar, about 20 times the UV-excited atomic gas mass, ruling out an UV heating scenario for the molecular material. We compare the available spectral tracers with theoretical models and conclude that molecular gas is heated with magneto-hydrodynamic shocks with v~10-20 kms and B~0.3-0.5 mG. Using the conditions derived with the CO analysis, we include the other important coolants--neutral oxygen and molecular hydrogen--to estimate the total cooling budget of the molecular material. We derive a mass to luminosity ratio of 2-3 M_solar/ L_solar, which is consistent with the total power dissipated via turbulent decay in 0.1 pc cells with v_rms~15 kms. These size and velocity scales are comparable to the observed clumping scale and the velocity dispersion. At this rate, the material near Sgr A* its dissipating its orbital energy on an orbital timescale, and cannot last for more than a few orbits. Our conclusions support a scenario in which the features near Sgr A* such as the CND and northern arm are generated by infalling clouds with low specific angular momentum., 31 pages, including 5 figures, accepted for publication in ApJ

We report observations of the CO J=7->6 transition toward the starburst nucleus of NGC 253. This is the highest-excitation CO measurement in this source to date, and allows an estimate of the molecular gas excitation conditions. Comparison of the CO line intensities with a large velocity gradient, escape probability model indicates that the bulk of the 2-5 x 10^7 solar masses of molecular gas in the central 180 pc is highly excited. A model with T ~ 120 K, n_H_2 ~ 4.5 x 10^4 cm^-3 is consistent with the observed CO intensities as well as the rotational H2 lines observed with ISO. The inferred mass of warm, dense molecular gas is 10--30 times the atomic gas mass as traced through its [CII] and [OI] line emission. This large mass ratio is inconsistent with photodissociation region models where the gas is heated by far-UV starlight. It is also not likely that the gas is heated by shocks in outflows or cloud-cloud collisions. We conclude that the best mechanism for heating the gas is cosmic rays, which provide a natural means of uniformly heating the full volume of molecular clouds. With the tremendous supernova rate in the nucleus of NGC 253, the CR heating rate is at least ~800 times greater than in the Galaxy, more than sufficient to match the cooling observed in the CO lines., 12+ pages, 4 figures, to appear in The Astrophysical Journal (now includes tables)

Kinetics of positive ions and electrically neutral active particles formed during breakdown and successive discharge in neon-filled tube at 6.6 millibars pressure had been analyzed. This analysis was performed on the basis of mean value of electrical breakdown time delay t¯d dependence on afterglow period τ (memory curve). It was shown that positive ions are present in the 1μs 3 s, breakdown is initiated by cosmic rays and natural radioactivity. The increase of discharge current leads to ...

We present observations of NGC 4038/39 in the [CII] 158 micron fine structure line taken with the MPE/UCB Far-infrared Imaging Fabry-Perot Interferometer (FIFI) on the KAO with 55" resolution. The total [CII] luminosity of the Antennae is 3.7x10^8 L(sun), which is about 1% of the FIR luminosity. The main part of the [CII] emission probably arises from photodissociation regions (PDRs). Up to 1/3 of the observed [CII] emission may originate from the CNM for higher temperatures and densities. From PDR models we derive densities and FUV intensities for the nuclei and the interaction zone. The minimum masses in the [CII] emitting regions in the interaction zone and the nuclei are a few x 10^(7) M(sun). We find that the [CII] to CO intensity ratio at the interaction zone is a factor of 2.6 lower than usually observed in starburst galaxies, but still a factor of about 1.3 to 1.4 higher than at the nuclei of NGC 4038/39, indicating no global starburst is taking place in the Antennae. [CII] emission arising partly from confined starburst regions and partly from surrounding quiescent clouds could explain the observed [CII] radiation at the interaction zone and the nuclei. There are small confined regions with high star formation activity in the interaction zone and with a lower star formation activity in the nuclei. This supports the high density and high FUV intensity for the PDRs in the interaction zone and the nuclei., Latex File 22 pages with 7 figures. Accepted by ApJ

The processes which are a consequence of neutral active particles presence in post-discharge nitrogen-filled tube at 13.3 mbar pressure have been analyzed. The analysis has been performed based on the experimental data of electrical breakdown time delay as a function of afterglow period τ. The most significant parameters such as applied voltage, discharge current, time, and exposure to radiation have been varied. It has been shown that the increase in applied voltage and discharge time, as well as exposure to UV radiation, leads to the decrease of the mean value of electrical breakdown time delay t¯d. This decrease occurs for τ>70 ms, when N(S4) atoms play a dominant role in breakdown initiation. The increase in discharge current leads to the decrease of t¯d values for τ≤70 ms, when positive ions dominantly induce breakdown. The most important reactions which lead to formation of positive ions and neutral active particles are also presented in the paper.

Memory effect in nitrogen based on experimental data of electrical breakdown time delay as a function of afterglow period in the presence of additional electrons has been investigated. The additional electrons were supplied as a result of extraction from the auxiliary electrode pair or nitrogen irradiation with the radioactive source of low activity. The results show that these electrons have an important role in the recombination of positive ions formed in mutual metastable molecules' collisions and collisions between metastable and highly vibrationally excited molecules in the early afterglow. As a consequence of the ion–electron recombination N(4S) atoms are formed which, as well as N(4S) atoms formed in previous discharge, have a significant influence on the memory effect in late afterglow. The presence of N(4S) atoms in the late afterglow is tracked by monitoring the secondary emission which they induce via catalytic recombination on the cathode of a nitrogen-filled tube. Also, it has been shown that the contribution of secondary electrons which originate from N(4S) atoms and Compton electrons when the radioactive source is and isn't present can be distinguished.