WorldWideScience

Sample records for cellular restriction factors

  1. Cellular Restriction Factors of Feline Immunodeficiency Virus

    OpenAIRE

    Carsten Münk; Jörg Zielonka

    2011-01-01

    Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating...

  2. Human cellular restriction factors that target HIV-1 replication

    OpenAIRE

    Jeang Kuan-Teh; Luban Jeremy; Strebel Klaus

    2009-01-01

    Abstract Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G), bone marrow stromal cell antigen 2 (BST-2), cyclophilin A, tripartite motif protein 5 alpha (Trim5α), and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of th...

  3. Antiretroviral Restriction Factors in Mice

    OpenAIRE

    Nair, Smita; Rein, Alan

    2014-01-01

    One of the most exciting areas in contemporary retrovirus research is the discovery of “restriction factors”. These are cellular proteins that act after virus entry to inhibit infection by or replication of retroviruses (and other viruses and intracellular pathogens). We briefly discuss here three antiretroviral restriction factors in mice: Fv1, APOBEC3, and tetherin, touching on both biological and molecular aspects of these restriction systems.

  4. A new role for the cellular PABP repressor Paip2 as an innate restriction factor capable of limiting productive cytomegalovirus replication.

    Science.gov (United States)

    McKinney, Caleb; Yu, Dong; Mohr, Ian

    2013-08-15

    The capacity of polyadenylate-binding protein PABPC1 (PABP1) to stimulate translation is regulated by its repressor, Paip2. Paradoxically, while PABP accumulation promotes human cytomegalovirus (HCMV) protein synthesis, we show that this is accompanied by an analogous increase in the abundance of Paip2 and EDD1, an E3 ubiquitin ligase that destabilizes Paip2. Coordinate control of PABP1, Paip2, and EDD1 required the virus-encoded UL38 mTORC1 activator and resulted in augmented Paip2 synthesis, stability, and association with PABP1. Paip2 synthesis also increased following serum stimulation of uninfected normal fibroblasts, suggesting that this coregulation may play a role in how uninfected cells respond to stress. Significantly, Paip2 accumulation was dependent on PABP accrual, as preventing PABP1 accumulation suppressed viral replication and inhibited the corresponding Paip2 increase. Furthermore, depleting Paip2 restored the ability of infected cells to assemble the translation initiation factor eIF4F, promoting viral protein synthesis and replication without increasing PABP1. This establishes a new role for the cellular PABP1 inhibitor Paip2 as an innate defense that restricts viral protein synthesis and replication. Moreover, it illustrates how a stress-induced rise in PABP1 triggered by virus infection can counter and surpass a corresponding increase in Paip2 abundance and stability. PMID:23964095

  5. TRIM5 Acts as More Than a Retroviral Restriction Factor

    OpenAIRE

    Li Wu; Suresh De Silva

    2011-01-01

    The retrovirus restriction factor TRIM5α blocks post-entry infection of retroviruses in a species-specific manner. As a cellular E3 ubiquitin ligase, TRIM5α binds to the retroviral capsid lattice in the cytoplasm of an infected cell and accelerates the uncoating process of retroviral capsid, thus providing a potent restriction to HIV-1 and other retrovirus infections. The precise mechanism by which this restriction is imposed remains under scrutiny, and evidence is lacking to link the E3 ubiq...

  6. A whole genome screen for HIV restriction factors

    Directory of Open Access Journals (Sweden)

    Liu Li

    2011-11-01

    Full Text Available Abstract Background Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme, p21 and tetherin are well characterised. Results To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. Conclusions We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.

  7. Real Moments of the Restrictive Factor

    Indian Academy of Sciences (India)

    Andrew Ledoan; Alexandru Zaharescu

    2009-09-01

    Let be a real number such that 0 < < 1. We establish asymptotic formulas for the weighted real moments $\\sum_{n≤ x}R^(n)(1-n/x)$, where $R(n)=\\prod^k_{v=1}p^{ v-1}_v$ is the Atanassov strong restrictive factor function and $n=\\prod^k_{v=1}p^{ v}_v$ is the prime factorization of .

  8. The design of artificial retroviral restriction factors

    International Nuclear Information System (INIS)

    In addition to the ability to bind the retroviral capsid protein, the retroviral restriction factors Fv1, Trim5α and Trim5-CypA share the common property of containing sequences that promote self-association. Otherwise Fv1 and Trim5α appear unrelated. Mutational analyses showed that restriction was invariably lost when changes designed to disrupt the sequences responsible for multimerization were introduced. A novel restriction protein could be obtained by substituting sequences from the self-associating domain of Fv1 for the Trim5 sequences in Trim5-CypA. Similarly, a fusion protein containing cyclophilin A joined to arfaptin2, a protein known to form extended dimers, was also shown to restrict HIV-1. Hence, multimerization of a capsid-binding domain could be the common minimum design feature for capsid-dependent retroviral restriction factors. However, not all domains that promote multimerization can substitute for the N-terminal domains of Fv1 and Trim5α. Moreover, only CypA can provide a capsid-binding site with different N-terminal domains. It is suggested that the spatial relationship between the multiple target binding sites may be important for restriction

  9. TRIM5 Acts as More Than a Retroviral Restriction Factor

    Directory of Open Access Journals (Sweden)

    Li Wu

    2011-07-01

    Full Text Available The retrovirus restriction factor TRIM5α blocks post-entry infection of retroviruses in a species-specific manner. As a cellular E3 ubiquitin ligase, TRIM5α binds to the retroviral capsid lattice in the cytoplasm of an infected cell and accelerates the uncoating process of retroviral capsid, thus providing a potent restriction to HIV-1 and other retrovirus infections. The precise mechanism by which this restriction is imposed remains under scrutiny, and evidence is lacking to link the E3 ubiquitin ligase activity of TRIM5α to its ability to restrict retrovirus infection. In a recent study, Pertel and colleagues have uncovered the link between the two, providing compelling evidence to suggest that following the interaction with the retroviral capsid, TRIM5 triggers an antiviral innate immune response by functioning as a pattern recognition receptor [1]. This unique function of TRIM5 is dependent on its association with the E2 ubiquitin-conjugating enzyme complex UBC13-UEV1A and subsequent activation of the TAK1 kinase complex and downstream genes involved in innate immune responses. These findings have defined a novel function for TRIM5 as a pattern recognition receptor in innate immune recognition and provided valuable mechanistic insight into its role as a retroviral restriction factor. Here we discuss the significance of these new findings in understanding TRIM5-mediated HIV restriction.

  10. TRIM5 acts as more than a retroviral restriction factor.

    Science.gov (United States)

    de Silva, Suresh; Wu, Li

    2011-07-01

    The retrovirus restriction factor TRIM5α blocks post-entry infection of retroviruses in a species-specific manner. As a cellular E3 ubiquitin ligase, TRIM5α binds to the retroviral capsid lattice in the cytoplasm of an infected cell and accelerates the uncoating process of retroviral capsid, thus providing a potent restriction to HIV-1 and other retrovirus infections. The precise mechanism by which this restriction is imposed remains under scrutiny, and evidence is lacking to link the E3 ubiquitin ligase activity of TRIM5α to its ability to restrict retrovirus infection. In a recent study, Pertel and colleagues have uncovered the link between the two, providing compelling evidence to suggest that following the interaction with the retroviral capsid, TRIM5 triggers an antiviral innate immune response by functioning as a pattern recognition receptor. This unique function of TRIM5 is dependent on its association with the E2 ubiquitin-conjugating enzyme complex UBC13-UEV1A and subsequent activation of the TAK1 kinase complex and downstream genes involved in innate immune responses. These findings have defined a novel function for TRIM5 as a pattern recognition receptor in innate immune recognition and provided valuable mechanistic insight into its role as a retroviral restriction factor. Here we discuss the significance of these new findings in understanding TRIM5-mediated HIV restriction. PMID:21866272

  11. Cellular factors required for papillomavirus DNA replication.

    OpenAIRE

    Melendy, T; Sedman, J; Stenlund, A

    1995-01-01

    In vitro replication of papillomavirus DNA has been carried out with a combination of purified proteins and partially purified extracts made from human cells. DNA synthesis requires the viral E1 protein and the papillomavirus origin of replication. The E2 protein stimulates DNA synthesis in a binding site-independent manner. Papillomavirus DNA replication is also dependent on the cellular factors replication protein A, replication factor C, and proliferating-cell nuclear antigen as well as a ...

  12. Cellular factors implicated in filovirus entry.

    Science.gov (United States)

    Bhattacharyya, Suchita; Hope, Thomas J

    2013-01-01

    Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replication cycle and different studies have reported the involvement of a myriad of cellular factors including plasma membrane components, cytoskeletal proteins, endosomal components, and cytosolic factors in this process. Signaling molecules such as the TAM family of receptor tyrosine kinases comprising of Tyro3, Axl, and Mer have also been implicated as putative entry factors. Additionally, filoviruses are suggested to bind to a common receptor and recent studies have proposed T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) as potential receptor candidates. This paper summarizes the existing literature on filoviral entry with a special focus on cellular factors involved in this process and also highlights some fundamental questions. Future research aimed at answering these questions could be very useful in designing novel antiviral therapeutics. PMID:23365575

  13. Cellular Factors Implicated in Filovirus Entry

    Directory of Open Access Journals (Sweden)

    Suchita Bhattacharyya

    2013-01-01

    Full Text Available Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replication cycle and different studies have reported the involvement of a myriad of cellular factors including plasma membrane components, cytoskeletal proteins, endosomal components, and cytosolic factors in this process. Signaling molecules such as the TAM family of receptor tyrosine kinases comprising of Tyro3, Axl, and Mer have also been implicated as putative entry factors. Additionally, filoviruses are suggested to bind to a common receptor and recent studies have proposed T-cell immunoglobulin and mucin domain 1 (TIM-1 and Niemann-Pick C1 (NPC1 as potential receptor candidates. This paper summarizes the existing literature on filoviral entry with a special focus on cellular factors involved in this process and also highlights some fundamental questions. Future research aimed at answering these questions could be very useful in designing novel antiviral therapeutics.

  14. 76 FR 82179 - Drivers of CMVs: Restricting the Use of Cellular Phones

    Science.gov (United States)

    2011-12-30

    ..., 2011 (76 FR 75470), which restricted the use of ] hand-held mobile telephones by drivers of commercial... . SUPPLEMENTARY INFORMATION: For FMCSA and PHMSA's Final Rule published on December 2, 2011 (76 FR 75470), the... Cellular Phones AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Final...

  15. Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys

    OpenAIRE

    McKiernan, Susan H; Colman, Ricki J; Aiken, Erik; Evans, Trent D.; Beasley, T.Mark; Aiken, Judd M.; Weindruch, Richard; Anderson, Rozalyn M.

    2011-01-01

    We have previously shown that a 30% reduced calorie intake diet delayed the onset of muscle mass loss in adult monkeys between ~16 and ~22 years of age and prevented multiple cellular phenotypes of aging. In the present study we show the impact of long term (~17 years) calorie restriction (CR) on muscle aging in very old monkeys (27–33yrs) compared to age-matched Control monkeys fed ad libitum, and describe these data in the context of the whole longitudinal study. Muscle mass was preserved i...

  16. Paternal Metabolic and Cardiovascular Risk Factors for Fetal Growth Restriction

    OpenAIRE

    Hillman, Sara; Peebles, Donald M.; Williams, David J.

    2013-01-01

    OBJECTIVE Fathers of low–birth weight offspring are more likely to have type 2 diabetes and cardiovascular disease in later life. We investigated whether paternal insulin resistance and cardiovascular risk factors were evident at the time that fetal growth–restricted offspring were born. RESEARCH DESIGN AND METHODS We carried out a case-control study of men who fathered pregnancies affected by fetal growth restriction, in the absence of recognized fetal disease (n = 42), compared with men who...

  17. Maintenance of cellular ATP level by caloric restriction correlates chronological survival of budding yeast

    International Nuclear Information System (INIS)

    Highlights: •CR decreases total ROS and mitochondrial superoxide during the chronological aging. •CR does not affect the levels of oxidative damage on protein and DNA. •CR contributes extension of chronological lifespan by maintenance of ATP level -- Abstract: The free radical theory of aging emphasizes cumulative oxidative damage in the genome and intracellular proteins due to reactive oxygen species (ROS), which is a major cause for aging. Caloric restriction (CR) has been known as a representative treatment that prevents aging; however, its mechanism of action remains elusive. Here, we show that CR extends the chronological lifespan (CLS) of budding yeast by maintaining cellular energy levels. CR reduced the generation of total ROS and mitochondrial superoxide; however, CR did not reduce the oxidative damage in proteins and DNA. Subsequently, calorie-restricted yeast had higher mitochondrial membrane potential (MMP), and it sustained consistent ATP levels during the process of chronological aging. Our results suggest that CR extends the survival of the chronologically aged cells by improving the efficiency of energy metabolism for the maintenance of the ATP level rather than reducing the global oxidative damage of proteins and DNA

  18. Maintenance of cellular ATP level by caloric restriction correlates chronological survival of budding yeast

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Joon-Seok; Lee, Cheol-Koo, E-mail: cklee2005@korea.ac.kr

    2013-09-13

    Highlights: •CR decreases total ROS and mitochondrial superoxide during the chronological aging. •CR does not affect the levels of oxidative damage on protein and DNA. •CR contributes extension of chronological lifespan by maintenance of ATP level -- Abstract: The free radical theory of aging emphasizes cumulative oxidative damage in the genome and intracellular proteins due to reactive oxygen species (ROS), which is a major cause for aging. Caloric restriction (CR) has been known as a representative treatment that prevents aging; however, its mechanism of action remains elusive. Here, we show that CR extends the chronological lifespan (CLS) of budding yeast by maintaining cellular energy levels. CR reduced the generation of total ROS and mitochondrial superoxide; however, CR did not reduce the oxidative damage in proteins and DNA. Subsequently, calorie-restricted yeast had higher mitochondrial membrane potential (MMP), and it sustained consistent ATP levels during the process of chronological aging. Our results suggest that CR extends the survival of the chronologically aged cells by improving the efficiency of energy metabolism for the maintenance of the ATP level rather than reducing the global oxidative damage of proteins and DNA.

  19. Translation Factors Specify Cellular Metabolic State

    Directory of Open Access Journals (Sweden)

    Juan Mata

    2016-08-01

    Full Text Available In this issue of Cell Reports, Shah et al. present evidence that a subcomplex of the eIF3 translation initiation factor regulates translation of mRNAs encoding components of the mitochondrial electron transport chain and glycolytic enzymes, thus linking translational control with energy metabolism.

  20. Cellular localization of rheumatoid factor idiotypes.

    OpenAIRE

    Bonagura, V R; Kunkel, H. G.; Pernis, B

    1982-01-01

    the stimulation of lymphocytes from rheumatoid arthritis patients with pokeweed mitogen produces a large number of plasma cells that express the dominant cross-reactive idiotype previously found on monoclonal IgM anti-gamma-globulins from patients with mixed cryoglobulinemia. Similar experiments with the cells of normal individuals show a much lower percentage of these cells with a lower intensity of staining with the fluorescent reagents utilized. Efforts to demonstrate rheumatoid factor in ...

  1. Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys.

    Science.gov (United States)

    McKiernan, Susan H; Colman, Ricki J; Aiken, Erik; Evans, Trent D; Beasley, T Mark; Aiken, Judd M; Weindruch, Richard; Anderson, Rozalyn M

    2012-03-01

    We have previously shown that a 30% reduced calorie intake diet delayed the onset of muscle mass loss in adult monkeys between ~16 and ~22 years of age and prevented multiple cellular phenotypes of aging. In the present study we show the impact of long term (~17 years) calorie restriction (CR) on muscle aging in very old monkeys (27-33 yrs) compared to age-matched Control monkeys fed ad libitum, and describe these data in the context of the whole longitudinal study. Muscle mass was preserved in very old calorie restricted (CR) monkeys compared to age-matched Controls. Immunohistochemical analysis revealed an age-associated increase in the proportion of Type I fibers in the VL from Control animals that was prevented with CR. The cross sectional area (CSA) of Type II fibers was reduced in old CR animals compared to earlier time points (16-22 years of age); however, the total loss in CSA was only 15% in CR animals compared to 36% in old Controls at ~27 years of age. Atrophy was not detected in Type I fibers from either group. Notably, Type I fiber CSA was ~1.6 fold greater in VL from CR animals compared to Control animals at ~27 years of age. The frequency of VL muscle fibers with defects in mitochondrial electron transport system enzymes (ETS(ab)), the absence of cytochrome c oxidase and hyper-reactive succinate dehydrogenase, were identical between Control and CR. We describe changes in ETS(ab) fiber CSA and determined that CR fibers respond differently to the challenge of mitochondrial deficiency. Fiber counts of intact rectus femoris muscles revealed that muscle fiber density was preserved in old CR animals. We suggest that muscle fibers from CR animals are better poised to endure and adapt to changes in muscle mass than those of Control animals. PMID:22226624

  2. KAP1 is a host restriction factor that promotes HAdV E1B-55K SUMO modification

    DEFF Research Database (Denmark)

    Bürck, Carolin; Mund, Andreas; Berscheminski, Julia; Kieweg, Lisa; Müncheberg, Sarah; Dobner, Thomas; Schreiner, Sabrina

    2016-01-01

    minimize epigenetic gene silencing and to promote SUMO modification of E1B-55K by a so far unknown mechanism. IMPORTANCE: Here we describe a novel cellular restriction factor for Human Adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin...

  3. Tombusvirus-yeast interactions identify conserved cell-intrinsic viral restriction factors

    Directory of Open Access Journals (Sweden)

    Zsuzsanna eSasvari

    2014-08-01

    Full Text Available To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae, which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast reveals that TBSV replication is limited by a wide variety of host gene functions. Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5’-3’ exoribonuclease, Act1p actin protein and Cse4p centromere protein. The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones, and possibly key roles for the ribosomal or ribosome-associated factors. We discuss the antiviral functions of selected CIRFs, such as the RNA binding nucleolin, ribonucleases, WW-domain proteins, single- and multi-domain cyclophilins, TPR-domain co-chaperones and cellular ion pumps. These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase. Although many of the characterized CIRFs act directly against TBSV, we propose that the TPR-domain co-chaperones function as guardians of the cellular Hsp70 chaperone system, which is subverted efficiently by TBSV for viral replicase assembly in the absence of the TPR-domain co-chaperones.

  4. p16(INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Li

    Full Text Available Although caloric restriction (CR has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellular proliferation of normal WI-38, IMR-90 and MRC-5 human lung fibroblasts and found that glucose restriction (GR can inhibit cellular senescence and significantly extend cellular lifespan compared with cells receiving normal glucose (NG in the culture medium. Moreover, GR decreased expression of p16(INK4a (p16, a well-known senescence-related gene, in all of the tested cell lines. Over-expressed p16 resulted in early replicative senescence in glucose-restricted cells suggesting a crucial role of p16 regulation in GR-induced cellular lifespan extension. The decreased expression of p16 was partly due to GR-induced chromatin remodeling through effects on histone acetylation and methylation of the p16 promoter. GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity. The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR. Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. Collectively, these results provide new insights into interactions between epigenetic and genetic mechanisms on CR-induced longevity that may contribute to anti-aging approaches and also provide a general molecular model for studying CR in vitro in mammalian systems.

  5. Dietary Restriction Mitigates Cocaine-Induced Alterations of Olfactory Bulb Cellular Plasticity and Gene Expression, and Behavior

    OpenAIRE

    Xu, Xiangru; Mughal, Mohamed R.; Hall, F. Scott; Perona, Maria T. G.; Pistell, Paul J.; Lathia, Justin D.; Chigurupati, Srinivasulu; Becker, Kevin G.; Ladenheim, Bruce; Niklason, Laura E.; Uhl, George R; Cadet, Jean Lud; Mattson, Mark P.

    2010-01-01

    Because the olfactory system plays a major role in food consumption, and because “food addiction” and associated morbidities have reached epidemic proportions, we tested the hypothesis that dietary energy restriction can modify adverse effects of cocaine on behavior and olfactory cellular and molecular plasticity. Mice maintained on an alternate day fasting (ADF) diet exhibited increased baseline locomotion and increased cocaine-sensitized locomotion during cocaine conditioning, despite no ch...

  6. Growth restriction factor in Al-Si-Mg-Cu alloys

    International Nuclear Information System (INIS)

    The Growth Restriction Factor, Q, proved to be useful to analyse and control grain refinement during solidification of alloys. It is known that in multicomponent alloys a simple summation of the Qi values of the individual constituents taken from the binary phase diagrams can lead to grossly wrong results and that the ternary or higher-level phase diagram needs to be evaluated. This work demonstrates that the actual evaluation of Q using the liquidus gradient and partition coefficients of the multicomponent phase diagram requires some precautions and may be cumbersome. More importantly, this approach entirely fails if an intermetallic phase turns out to be the primary solidifying phase even in tiny amount. A very simple and general solution of this problem is illustrated for Al-Si-Mg-Cu alloys.

  7. Cellular Reprogramming Using Defined Factors and MicroRNAs

    Directory of Open Access Journals (Sweden)

    Takanori Eguchi

    2016-01-01

    Full Text Available Development of human bodies, organs, and tissues contains numerous steps of cellular differentiation including an initial zygote, embryonic stem (ES cells, three germ layers, and multiple expertized lineages of cells. Induced pluripotent stem (iPS cells have been recently developed using defined reprogramming factors such as Nanog, Klf5, Oct3/4 (Pou5f1, Sox2, and Myc. This outstanding innovation is largely changing life science and medicine. Methods of direct reprogramming of cells into myocytes, neurons, chondrocytes, and osteoblasts have been further developed using modified combination of factors such as N-myc, L-myc, Sox9, and microRNAs in defined cell/tissue culture conditions. Mesenchymal stem cells (MSCs and dental pulp stem cells (DPSCs are also emerging multipotent stem cells with particular microRNA expression signatures. It was shown that miRNA-720 had a role in cellular reprogramming through targeting the pluripotency factor Nanog and induction of DNA methyltransferases (DNMTs. This review reports histories, topics, and idea of cellular reprogramming.

  8. Cellular Reprogramming Using Defined Factors and MicroRNAs.

    Science.gov (United States)

    Eguchi, Takanori; Kuboki, Takuo

    2016-01-01

    Development of human bodies, organs, and tissues contains numerous steps of cellular differentiation including an initial zygote, embryonic stem (ES) cells, three germ layers, and multiple expertized lineages of cells. Induced pluripotent stem (iPS) cells have been recently developed using defined reprogramming factors such as Nanog, Klf5, Oct3/4 (Pou5f1), Sox2, and Myc. This outstanding innovation is largely changing life science and medicine. Methods of direct reprogramming of cells into myocytes, neurons, chondrocytes, and osteoblasts have been further developed using modified combination of factors such as N-myc, L-myc, Sox9, and microRNAs in defined cell/tissue culture conditions. Mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) are also emerging multipotent stem cells with particular microRNA expression signatures. It was shown that miRNA-720 had a role in cellular reprogramming through targeting the pluripotency factor Nanog and induction of DNA methyltransferases (DNMTs). This review reports histories, topics, and idea of cellular reprogramming. PMID:27382371

  9. Fast cellular automata with restricted inter-cell communication: computational capacity

    OpenAIRE

    Kutrib, Martin; Malcher, Andreas

    2006-01-01

    A d-dimensional cellular automaton with sequential input mode is a d-dimensional grid of interconnected interacting finite automata. The distinguished automaton at the origin, the communication cell, is connected to the outside world and fetches the input sequentially. Often in the literature this model is referred to as iterative array. We investigate d-dimensional iterative arrays and one-dimensional cellular automata operating in real and linear time, whose inter-cell communicati...

  10. BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection

    OpenAIRE

    Lee, Song Hee; Kalejta, Robert F; Kerry, Julie; Semmes, Oliver John; O’Connor, Christine M.; Khan, Zia; Garcia, Benjamin A.; Shenk, Thomas; Murphy, Eain

    2012-01-01

    Cell proteins can restrict the replication of viruses. Here, we identify the cellular BclAF1 protein as a human cytomegalovirus restriction factor and describe two independent mechanisms the virus uses to decrease its steady-state levels. Immediately following infection, the viral pp71 and UL35 proteins, which are delivered to cells within virions, direct the proteasomal degradation of BclAF1. Although BclAF1 reaccumulates through the middle stages of infection, it is subsequently down-regula...

  11. Robust Template Decomposition without Weight Restriction for Cellular Neural Networks Implementing Arbitrary Boolean Functions Using Support Vector Classifiers

    Directory of Open Access Journals (Sweden)

    Yih-Lon Lin

    2013-01-01

    Full Text Available If the given Boolean function is linearly separable, a robust uncoupled cellular neural network can be designed as a maximal margin classifier. On the other hand, if the given Boolean function is linearly separable but has a small geometric margin or it is not linearly separable, a popular approach is to find a sequence of robust uncoupled cellular neural networks implementing the given Boolean function. In the past research works using this approach, the control template parameters and thresholds are restricted to assume only a given finite set of integers, and this is certainly unnecessary for the template design. In this study, we try to remove this restriction. Minterm- and maxterm-based decomposition algorithms utilizing the soft margin and maximal margin support vector classifiers are proposed to design a sequence of robust templates implementing an arbitrary Boolean function. Several illustrative examples are simulated to demonstrate the efficiency of the proposed method by comparing our results with those produced by other decomposition methods with restricted weights.

  12. Deficiency of the homologous restriction factor in paroxysmal nocturnal hemoglobinuria.

    Science.gov (United States)

    Zalman, L S; Wood, L M; Frank, M M; Müller-Eberhard, H J

    1987-02-01

    The affected E of two patients with paroxysmal nocturnal hemoglobinuria (PNH) were enriched by lysing the unaffected, normal E with anti-human decay-accelerating factor (DAF) and guinea pig serum. The membranes of the unlysed, DAF-deficient cells (PNH-E) were dissolved and examined by SDS-PAGE and immunoblotting using an antiserum to homologous restriction factor (HRF). Whereas the 65 kD complement regulatory protein was readily detectable in the normal controls, it was completely lacking in both samples of PNH-E membranes. Functional studies likewise indicated the absence of HRF activity from PNH-E. When radiolabeled, isolated HRF protein was offered to PNH-E, it became firmly attached to the cell. Approximately 1,000 molecules of HRF per cell reduced the characteristic susceptibility of these cells to reactive lysis by C5b-9 to nearly normal levels. The results suggest that HRF, which is known to control the action of C8 and C9 on normal human E membranes, is deficient in PNH, as well as acetylcholinesterase and DAF. PMID:2434597

  13. Influence of physical and biological factors in cellular radiosensitivity

    International Nuclear Information System (INIS)

    The use of therapeutic radiopharmaceuticals is associated with radiation damage, and this at-nuclear physical properties of radionuclides used and the characteristics of the irradiated cells. The work deals with the damage caused by radiation to DNA, factors that condition and tools that can be used to measure it. It presents current concepts of death and cellular radiosensitivity, based on the pioneering work in this field. Enter the neighborhood effect and adaptive response and evaluates the influence of the same in the paradigms of classical radiobiology. (author)

  14. Caloric restriction delays aging-induced cellular phenotypes in rhesus monkey skeletal muscle

    OpenAIRE

    McKiernan, Susan H.; Colman, Ricki J; Lopez, Marisol; Beasley, T. Mark; Aiken, Judd M.; Anderson, Rozalyn M; Weindruch, Richard

    2010-01-01

    Sarcopenia is the age-related loss of skeletal muscle mass and function and is characterized by a reduction in muscle mass and fiber cross-sectional area, alterations in muscle fiber type and mitochondrial functional changes. In rhesus monkeys, calorie restriction (CR) without malnutrition improves survival and delays the onset of age-associated diseases and disorders including sarcopenia. We present a longitudinal study on the impact of CR on early stage sarcopenia in the upper leg of monkey...

  15. Multiscale characterization of cardiac remodeling induced by intrauterine growth restriction, at organ, cellular and subcellular level

    OpenAIRE

    González Tendero, Anna

    2014-01-01

    Tesi realitzada a l'Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) INTRODUCTION: Intrauterine growth restriction (IUGR) due to placental insufficiency affects up to 7-10% of pregnancies and is a major cause of perinatal mortality and long term morbidity. IUGR results in low birth weight, which is associated with increased risk of cardiovascular mortality in adulthood, and is thought to be mediated by fetal cardiovascular programming. IUGR fetuses show signs of cardiac s...

  16. Metabolic and cellular effects of calorie restriction and whey proteins in experimental obesity

    OpenAIRE

    Kurki, Eveliina

    2013-01-01

    Obesity, an epidemic problem in the world, is associated with higher mortality and increase in the risk of diabetes, cardiovascular diseases, and certain forms of cancer. Calorie restriction (CR) with adequate nutrition is the most effective method to induce weight loss, though compliance with low-caloric diets is often poor among obese individuals. Compounds capable of mimicking the effects of CR therefore hold great promise as novel anti-obesity drugs. The main aim of the present study was ...

  17. Cellular & Molecular Immunology receives its first Impact Factor

    Institute of Scientific and Technical Information of China (English)

    Zhigang Tian

    2010-01-01

    @@ The 2009 edition of the JCR, in which Cellular (c) Molecular Immunology (CMI) is listed for the first time, reveals an Impact Factor of 2.765, placing CMI 63rd out of 128 in the Immunology subject category. According to ISI's ranking this also places the journal 5th out of 114 journals published in China and 23rd out of 587 journals published in the Asia-Pacific region. This is an excellent first Impact Factor for a young journal like CMI and,together with our publishing partner Nature Publishing Group and the continued support of our readers and authors, we hope to further build on this into the future. We are delighted that CMI can be internationally recognized as important in the field of immunology.

  18. Restricting Factors at Modification of Parameters of Associative Engineering Objects

    Science.gov (United States)

    Horváth, László

    Advancements in product development have reached full integration of engineering activities and processes in product lifecycle management (PLM) systems. PLM systems are based on high-level modeling, simulation and data management. Despite significant development of modeling in PLM systems, a strong demand was recognized for improved decision assistance in product development. Decision assistance can be improved by application of methods from the area of computer intelligence. In order for a product development company to stay competitive, it is important for its modeling system to be relied on local even personal knowledge. The authors analyzed current PLM systems for shortcomings and possibilities for extended intelligence at decision-making during product development. They propose methods in order to increase suitability of current modeling systems to accommodate knowledge based IT at definition of sets of parameters of modeled objects and in the management of frequent changes of modeled objects. In the center of the proposed methodology, constrained parameters act as restricting factors at definition and modification of parameters of associative engineering objects. Paper starts with an outlook to modeling in current engineering systems and preliminary results by the authors. Following this, groups of essential information as handled by he proposed modeling are summarized and procedures for processing of that groups of information are detailed. Next, management of chains of changes along chains of associa-tive product objects and a new style of decision assistance in modeling systems are explained. Changes are created or verified by behavior analysis. Finally, behavior analysis, human intent combination, product data view creation, and change management are discussed as the proposed integrated and coordinated methodology for enhanced support of decision-making in product development.

  19. Viroid Intercellular Trafficking: RNA Motifs, Cellular Factors and Broad Impacts

    Directory of Open Access Journals (Sweden)

    Ryuta Takeda

    2009-09-01

    Full Text Available Viroids are noncoding RNAs that infect plants. In order to establish systemic infection, these RNAs must traffic from an initially infected host cell into neighboring cells and ultimately throughout a whole plant. Recent studies have identified structural motifs in a viroid that are required for trafficking, enabling further studies on the mechanisms of their function. Some cellular proteins interact with viroids in vivo and may play a role in viroid trafficking, which can now be directly tested by using a virus-induced gene silencing system that functions efficiently in plant species from which these factors were identified. This review discusses these recent advances, unanswered questions and the use of viroid infection as an highly productive model to elucidate mechanisms of RNA trafficking that is of broad biological significance.

  20. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

    Energy Technology Data Exchange (ETDEWEB)

    Salaita, Khalid; Nair, Pradeep M; Petit, Rebecca S; Neve, Richard M; Das, Debopriya; Gray, Joe W; Groves, Jay T

    2009-09-09

    Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.

  1. Gene Therapy Strategies to Exploit TRIM Derived Restriction Factors against HIV-1.

    OpenAIRE

    Emma Chan; Towers, Greg J; Waseem Qasim

    2014-01-01

    Restriction factors are a collection of antiviral proteins that form an important aspect of the innate immune system. Their constitutive expression allows immediate response to viral infection, ahead of other innate or adaptive immune responses. We review the molecular mechanism of restriction for four categories of restriction factors; TRIM5, tetherin, APOBEC3G and SAMHD1 and go on to consider how the TRIM5 and TRIMCyp proteins in particular, show promise for exploitation using gene therapy ...

  2. Variability of Butyrivibrio fibrosolvens estimated with cellular fatty acids content, DNA restriction analysis and fermentation patterns

    Czech Academy of Sciences Publication Activity Database

    Marníšek, L. R.; Kopečný, Jan

    2000-01-01

    Roč. 40, č. 2 (2000), s. 182-183. ISSN 0926-5287 R&D Projects: GA ČR GA524/99/0602 Institutional research plan: CEZ:AV0Z5045916 Keywords : butyrivibrio fibrosolvens Subject RIV: ED - Physiology Impact factor: 1.351, year: 2000

  3. A Study of Evaluation System of Restricting Factors in Training Students' Qualities

    Institute of Scientific and Technical Information of China (English)

    MA Xiao-yan

    2002-01-01

    This paper studies evaluation system of restricting factors in training students' qualities by modern mathematical method of analysis hierarchy process and principal factor analysis, and to build up a mathematical model of evaluation system.

  4. Serum factors in older individuals change cellular clock properties

    Science.gov (United States)

    Pagani, Lucia; Schmitt, Karen; Meier, Fides; Izakovic, Jan; Roemer, Konstanze; Viola, Antoine; Cajochen, Christian; Wirz-Justice, Anna; Brown, Steven A.; Eckert, Anne

    2011-01-01

    Human aging is accompanied by dramatic changes in daily sleep–wake behavior: Activity shifts to an earlier phase, and the consolidation of sleep and wake is disturbed. Although this daily circadian rhythm is brain-controlled, its mechanism is encoded by cell-autonomous circadian clocks functioning in nearly every cell of the body. In fact, human clock properties measured in peripheral cells such as fibroblasts closely mimic those measured physiologically and behaviorally in the same subjects. To understand better the molecular mechanisms by which human aging affects circadian clocks, we characterized the clock properties of fibroblasts cultivated from dermal biopsies of young and older subjects. Fibroblast period length, amplitude, and phase were identical in the two groups even though behavior was not, thereby suggesting that basic clock properties of peripheral cells do not change during aging. Interestingly, measurement of the same cells in the presence of human serum from older donors shortened period length and advanced the phase of cellular circadian rhythms compared with treatment with serum from young subjects, indicating that a circulating factor might alter human chronotype. Further experiments demonstrated that this effect is caused by a thermolabile factor present in serum of older individuals. Thus, even though the molecular machinery of peripheral circadian clocks does not change with age, some age-related circadian dysfunction observed in vivo might be of hormonal origin and therefore might be pharmacologically remediable. PMID:21482780

  5. Cellular localization of Type I restriction-modification enzymes is family dependent

    Czech Academy of Sciences Publication Activity Database

    Holubová, Inge; Vejsadová, Štěpánka; Firman, K.; Weiserová, Marie

    2004-01-01

    Roč. 319, - (2004), s. 375-380. ISSN 0006-291X R&D Projects: GA ČR GA204/96/1365; GA ČR GA204/03/1011 Institutional research plan: CEZ:AV0Z5020903 Keywords : membrane-associated proteins * protein localization * spheroplast Subject RIV: EE - Microbiology, Virology Impact factor: 2.904, year: 2004

  6. Humoral and cellular factors of maternal immunity in swine.

    Science.gov (United States)

    Salmon, Henri; Berri, Mustapha; Gerdts, Volker; Meurens, François

    2009-03-01

    Immunoglobulins cannot cross the placenta in pregnant sows. Neonatal pigs are therefore agammaglobulinemic at birth and, although immunocompetent, they cannot mount rapid immune responses at systemic and mucosal sites. Their survival depends directly on the acquisition of maternal immunity via colostrum and milk. Protection by maternal immunity is mediated by a number of factors, including specific systemic humoral immunity, involving mostly maternal IgG transferred from blood to colostrum and typically absorbed within the first 36 h of life. Passive mucosal immunity involves local humoral immunity, including the production of secretory IgA (sIgA), which is transferred principally via milk until weaning. The mammary gland (MG) produces sIgA, which is, then secreted into the milk via the poly-Ig receptor (pIgR) of epithelial cells. These antibodies are produced in response to intestinal and respiratory antigens, including pathogens and commensal organisms. Protection is also mediated by cellular immunity, which is transferred via maternal cells present in mammary secretions. The mechanisms underlying the various immunological links between MG and the mucosal surfaces involve hormonally regulated addressins and chemokines specific to these compartments. The enhancement of colostrogenic immunity depends on the stimulation of systemic immunity, whereas the enhancement of lactogenic immunity depends on appropriate stimulation at induction sites, an increase in cell trafficking from the gut and upper respiratory tract to the MG and, possibly, enhanced immunoglobulin production at the effector site and secretion in milk. In addition, mammary secretions provide factors other than immunoglobulins that protect the neonate and regulate the development of mucosal immunity--a key element of postnatal adaptation to environmental antigens. PMID:18761034

  7. Instability restricts signaling of multiple fibroblast growth factors

    Czech Academy of Sciences Publication Activity Database

    Buchtová, Marcela; Chaloupková, R.; Zakrzewska, M.; Veselá, I.; Celá, Petra; Barathová, J.; Gudernová, I.; Zajíčková, R.; Trantírek, L.; Martin, J.; Kostas, M.; Otlewski, J.; Damborský, J.; Kozubík, Alois; Wiedlocha, A.; Krejčí, P.

    2015-01-01

    Roč. 72, č. 12 (2015), s. 2445-2459. ISSN 1420-682X R&D Projects: GA ČR(CZ) GA14-31540S; GA ČR GBP302/12/G157 Institutional support: RVO:67985904 ; RVO:68081707 Keywords : fibroblast growth factor * FGF * unstable Subject RIV: EA - Cell Biology Impact factor: 5.808, year: 2014

  8. Modeling mechanical restriction differences between car and heavy truck in two-lane cellular automata traffic flow model

    Science.gov (United States)

    Li, Xin; Li, Xingang; Xiao, Yao; Jia, Bin

    2016-06-01

    Real traffic is heterogeneous with car and truck. Due to mechanical restrictions, the car and the truck have different limited deceleration capabilities, which are important factors in safety driving. This paper extends the single lane safety driving (SD) model with limited deceleration capability to two-lane SD model, in which car-truck heterogeneous traffic is considered. A car has a larger limited deceleration capability while a heavy truck has a smaller limited deceleration capability as a result of loaded goods. Then the safety driving conditions are different as the types of the following and the leading vehicles vary. In order to eliminate the well-known plug in heterogeneous two-lane traffic, it is assumed that heavy truck has active deceleration behavior when the heavy truck perceives the forming plug. The lane-changing decisions are also determined by the safety driving conditions. The fundamental diagram, spatiotemporal diagram, and lane-changing frequency were investigated to show the effect of mechanical restriction on heterogeneous traffic flow. It was shown that there would be still three traffic phases in heterogeneous traffic condition; the active deceleration of the heavy truck could well eliminate the plug; the lane-changing frequency was low in synchronized flow; the flow and velocity would decrease as the proportion of heavy truck grows or the limited deceleration capability of heavy truck drops; and the flow could be improved with lane control measures.

  9. Effects of selenium supply and dietary restriction on maternal and fetal body weight, visceral organ mass, cellularity estimates, and jejeunal vascularity in pregnant ewe lambs.

    Science.gov (United States)

    To examine effects of nutrient restriction and dietary Se on maternal and fetal visceral tissues, 36 pregnant Targhee-cross ewe lambs were allotted randomly to one of four treatments in a 2 x 2 factorial design. Factors were nutrition [control nutrition (CON, 100% of requirements) vs. restricted nu...

  10. Alveologenesis: key cellular players and fibroblast growth factor 10 signaling

    OpenAIRE

    Chao, Cho-Ming; Moiseenko, Alena; Zimmer, Klaus-Peter; Bellusci, Saverio

    2016-01-01

    Background Alveologenesis is the last stage in lung development and is essential for building the gas-exchanging units called alveoli. Despite intensive lung research, the intricate crosstalk between mesenchymal and epithelial cell lineages during alveologenesis is poorly understood. This crosstalk contributes to the formation of the secondary septae, which are key structures of healthy alveoli. Conclusions A better understanding of the cellular and molecular processes underlying the formatio...

  11. Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression

    International Nuclear Information System (INIS)

    Transcription factors are frequently involved in the process of cellular transformation, and many malignancies are characterized by a distinct genetic event affecting a specific transcription factor. This probably reflects a tissue specific ability of transcription factors to contribute to the generation of cancer but very little is known about the precise mechanisms that governs these restricted effects. To investigate this selectivity in target gene activation we compared the overall gene expression patterns by micro-array analysis and expression of target genes for the transcription factor EBF in lymphoma and neuroblastoma cells by RT-PCR. The presence of transcription factors in the different model cell lines was further investigated by EMSA analysis. In pre-B cells mb-1 and CD19 are regulate by EBF-1 in collaboration with Pax-5 and E-proteins. We here show that neuroblastoma cells express these three, for B cell development crucial transcription factors, but nevertheless fail to express detectable levels of their known target genes. Expression of mb-1 could, however, be induced in neuroblastoma cells after disruption of the chromatin structure by treatment with 5-azacytidine and Trichostatin A. These data suggest that transcription factors are able to selectively activate target genes in different tissues and that chromatin structure plays a key role in the regulation of this activity

  12. Cellular origin and procoagulant activity of tissue factor-exposing microparticles in cancer patients

    NARCIS (Netherlands)

    Kleinjan, A.; Berckmans, R.J.; Böing, A.N.; Sturk, A.; Büller, H.R.; Kamphuisen, P.W.; Nieuwland, R.

    2012-01-01

    Background: In patients with cancer, tissue factor-exposing microparticles (TF-exposing MP) have been associated with disease progression and thrombosis. The cellular origin and coagulant activity of TF-exposing MP, however, remain disputed. Therefore, we investigated the cellular origin of the TF-e

  13. Depletion of Cellular Pre-Replication Complex Factors Results in Increased Human Cytomegalovirus DNA Replication

    OpenAIRE

    Tamara Evans Braun; Emma Poole; John Sinclair

    2012-01-01

    Although HCMV encodes many genes required for the replication of its DNA genome, no HCMV-encoded orthologue of the origin binding protein, which has been identified in other herpesviruses, has been identified. This has led to speculation that HCMV may use other viral proteins or possibly cellular factors for the initiation of DNA synthesis. It is also unclear whether cellular replication factors are required for efficient replication of viral DNA during or after viral replication origin recog...

  14. Restrictive Factors of Vocational Education Development in Cultivation of Rural Practical Skilled Personnel and Countermeasures

    OpenAIRE

    Wang, Ning; Liu, Fang

    2014-01-01

    Kunming City is accelerating the process of agricultural modernization, industrialization, informationization and ecological development. In this process, it needs speeding up building new high level and advanced rural practical skilled personnel team suitable for development demand. By empirical analysis method, this paper discussed the factors restricting vocational education in cultivation of rural practical skilled personnel. Then, it came up with countermeasures in cultivation objective ...

  15. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor

    OpenAIRE

    Stremlau, Matthew; Perron, Michel; Lee, Mark; Li, Yuan; Song, Byeongwoon; Javanbakht, Hassan; Diaz-Griffero, Felipe; Anderson, Donovan J.; Sundquist, Wesley I.; Sodroski, Joseph

    2006-01-01

    The host restriction factor TRIM5α mediates species-specific, early blocks to retrovirus infection; susceptibility to these blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5α variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5α B30.2 domain. Human and New World monkey TRIM5α proteins associated less efficiently with the HIV-1 capsid, accounting for the lack of restriction in cells...

  16. The Cellular Antiviral Restriction Factor Tetherin Does Not Inhibit Poxviral Replication

    OpenAIRE

    Sliva, Katja; Resch, Theresa; Kraus, Benjamin; Goffinet, Christine; Keppler, Oliver T.; Schnierle, Barbara S.

    2012-01-01

    Interferon-stimulated genes fulfill innate antiviral effector functions. Among them, tetherin (THN) blocks the release of many enveloped viruses from infected cells. Vaccinia virus (VACV) encodes immune modulators interfering with antiviral host responses. Therefore, it was tempting to study a potential VACV-THN interaction. Remarkably, THN expression did not inhibit VACV release and replication. VACV infection did not diminish THN surface levels or impair its function on retroviral release. ...

  17. Automobile Driving in Older Adults: Factors Affecting Driving Restriction in Men and Women

    OpenAIRE

    MARIE-DIT-ASSE, Laetitia; Fabrigoule, Colette; Helmer, Catherine; Laumon, Bernard; Lafont, Sylviane

    2014-01-01

    OBJECTIVES: To identify factors associated with driving restriction in elderly men and women. DESIGN: Prospective cohort study of French drivers from 2003 to 2009. SETTING: The Three-City Cohort of Bordeaux, a prospective study of 2,104 people aged 65 and older. PARTICIPANTS: Five hundred twenty-three drivers with a mean age of 76 (273 male, 250 female). MEASUREMENTS: Sociodemographic characteristics, driving habits, health variables, cognitive evaluation and dementia diagnosis. Predementia w...

  18. Macrophage Migration Inhibitory Factor in Fetoplacental Tissues from Preeclamptic Pregnancies with or without Fetal Growth Restriction

    OpenAIRE

    Roberta Romagnoli; Tullia Todros; Ettore Piccoli; Alessandro Rolfo; Elena Vasario; Mario Castellucci; Francesca Ietta; Daniela Marzioni; Simona Cardaropoli; Luana Paulesu

    2012-01-01

    The proinflammatory cytokine MIF (macrophage migration inhibitory factor) is involved in physiological and pathological processes in pregnancy. MIF maternal serum levels are increased in preeclampsia (PE). We hypothesize that pregnancy tissues are the source of MIF overexpression in PE. MIF protein was studied in maternal sera, placental tissues, fetal membranes, and umbilical cord of 8 control and 20 PE pregnancies: 10 with normal fetal growth (PE-AGA) and 10 with fetal growth restriction (P...

  19. Tumor Necrosis Factor Receptor 2: Its Contribution to Acute Cellular Rejection and Clear Cell Renal Carcinoma

    OpenAIRE

    Jun Wang; Al-Lamki, Rafia S.

    2013-01-01

    Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein and one of the two receptors that orchestrate the complex biological functions of tumor necrosis factor (TNF, also designed TNF- α ). Accumulating experimental evidence suggests that TNFR2 plays an important role in renal disorders associated with acute cellular rejection and clear cell renal carcinoma but its exact role in these settings is still not completely understood. This papers reviews the factors that may...

  20. Sequestration of Vascular Endothelial Growth Factor (VEGF) Induces Late Restrictive Lung Disease

    Science.gov (United States)

    Wieck, Minna M.; Spurrier, Ryan G.; Levin, Daniel E.; Mojica, Salvador Garcia; Hiatt, Michael J.; Reddy, Raghava; Hou, Xiaogang; Navarro, Sonia; Lee, Jooeun; Lundin, Amber; Driscoll, Barbara; Grikscheit, Tracy C.

    2016-01-01

    Rationale Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF), which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function. Objectives To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function. Methods Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1) were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model. Measurements and Main Results Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes. Conclusions These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions. PMID:26863115

  1. Sequestration of Vascular Endothelial Growth Factor (VEGF Induces Late Restrictive Lung Disease.

    Directory of Open Access Journals (Sweden)

    Minna M Wieck

    Full Text Available Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF, which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function.To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function.Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1 were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model.Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes.These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions.

  2. Quantification and control of restrictive ecological factors in acidogenic de-sulfate bioreactor

    Institute of Scientific and Technical Information of China (English)

    王爱杰; 任南琪

    2002-01-01

    As an artificial microbial ecosystem, acidogenic de-sulfate bioreactor has high efficiency of sulfate removal. The restrictive ecological factors, including causing ecological factors, such as COD/SO42- ratio and sulfate loading rate (Ns), and following ecological factors, such as pH value, oxidation reduction potential (ORP) and alkalinity (ALK) have significant effect on the ability and stability of acidogenic de-sulfate bio-reactor. Continuous flow and batch test were carried out to investigate the quantification and control of COD/SO42- ratio, Ns, pH value, ORP and ALK in acidogenic de-sulfate bioreactor supplied with molasses wastewater as sole organic carbon source and sodium sulfate as electron donor. It was demonstrated that In order to maintain high sulfate removal rate (SRR) of 80% to 90%, the restrictive factors should meet all the requirement as follows: kCOD/ SO42- ratio≥2.0, Ns≤7.5 kg (m3·d)-1,pH=5.7~6.2,ORP=-320~-420 mV and ALK=1 500~2 000 mg/L.

  3. Inhibition of in vitro myogenic differentiation by cellular transcription factor E2F1

    DEFF Research Database (Denmark)

    Wang, J; Helin, K; Jin, P;

    1995-01-01

    Terminal differentiation of cultured myocytes requires withdrawal of the cells from the cell cycle. Constitutive overexpression of several oncogenes in myoblasts can inhibit in vitro myogenesis. Here we studied the role of the cellular transcription factor E2F1 on myogenic differentiation. E2F1...

  4. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

    Directory of Open Access Journals (Sweden)

    Debrah A Fine

    Full Text Available The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT.

  5. Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

    Science.gov (United States)

    Padi, Megha; Korkhin, Anna; James, Robert L.; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A.; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A.; Hill, David E.; Cusick, Michael E.; Vidal, Marc; Florens, Laurence; Washburn, Michael P.; Litovchick, Larisa; DeCaprio, James A.

    2012-01-01

    The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. PMID:23093934

  6. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

    Science.gov (United States)

    Fine, Debrah A; Rozenblatt-Rosen, Orit; Padi, Megha; Korkhin, Anna; James, Robert L; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A; Hill, David E; Cusick, Michael E; Vidal, Marc; Florens, Laurence; Washburn, Michael P; Litovchick, Larisa; DeCaprio, James A

    2012-01-01

    The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. PMID:23093934

  7. Restrictive Factors of Vocational Education Development in Cultivation of Rural Practical Skilled Personnel and Countermeasures

    Institute of Scientific and Technical Information of China (English)

    Ning; WANG; Fang; LIU

    2014-01-01

    Kunming City is accelerating the process of agricultural modernization,industrialization,informationization and ecological development. In this process,it needs speeding up building new high level and advanced rural practical skilled personnel team suitable for development demand. By empirical analysis method,this paper discussed the factors restricting vocational education in cultivation of rural practical skilled personnel. Then,it came up with countermeasures in cultivation objective of rural vocational education,arrangement of specialized disciplines,key development tasks,and establishment of diversified investment system.

  8. Model identification with BPNN on restrictive ecological factors of SRB for sulfate-reduction

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The model of back-propagation neural network(BPNN)was presented to demonstrate the effect of restrictive ecological factors,COD/SO42-ratio,pH value,alkalinity(ALK)and SO42-loading rate(Ns),on sulfate-reduction of Sulfate Reducing Bacteria(SRB)in an acidogenic sulfate-reducing reactor supplied with molasses as sole organic carbon source and sodium sulfate as electron acceptor.The compare of experimental results and computer simulation was also discussed.It was shown that the method of BPNN had a powerful ability to analyze the ecological characteristic of acidogenic sulfate-reducing ecosystem quantitatively.

  9. Food restriction beginning at lactation interferes with the cellular dynamics of the mucosa and colonic myenteric innervation in adult rats

    Directory of Open Access Journals (Sweden)

    JOÃO PAULO F. SCHOFFEN

    2014-12-01

    Full Text Available The effects of food restriction (FR on the morphoquantitative aspects of the wall and myenteric neurons of the proximal colon in adult rats were analysed. FR was imposed by duplication of the experimental brood size in relation to the control brood during lactation. The FR group received a 50% reduction of food from weaning until 90 days of age. Samples of the colon underwent histological processing to morphometrically analyze the crypts, muscularis mucosae, tunica mucosa, and muscularis externa. We determined the number of goblet cells and serotoninergic enteroendocrine cells, and morphoquantitatively studied the myenteric neuronal population. FR caused hypertrophy in the tunica mucosa, increase in crypt depth and in the muscular layer of the mucosa, a decrease in the thickness of the tunica muscularis and in the number of goblet cells and an increase in serotoninergic cells. A higher neuronal density in the ganglia and a reduction of the cell profile area were observed in the FR group. FR imposed since lactation led to hypertrophy of the tunica mucosa, a reduction of neutral mucin production, atrophy of the tunica muscularis, and an increase in the survival neuronal in adult rats, attributable to an increase in the number of serotoninergic enteroendocrine cells in mucosa.

  10. Immunochemical determination of cellular content of translation release factor RF4 in Escherichia coli

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Manuel Palacios Moreno, Juan; Clark, Brian F. C.;

    1999-01-01

    The biosynthesis of proteins in prokaryotes is terminated when a stop codon is present in the A-site of the 70S ribosomal complex. Four different translation termination factors are known to participate in the termination process. Release factor RF1 and RF2 are responsible for the recognition of...... the stop codons, and RF3 is known to accelerate the overall termination process. Release factor RF4 is a protein involved in the release of the mRNA and tRNA from the ribosomal complex. Furthermore, RF4 is involved in the proofreading in the elongation step of protein biosynthesis. The cellular...... contents of RF1, RF2, and RF3 were determined earlier. Here we report the cellular content of RF4 in Escherichia coli to be approximately 16,500 molecules per cell. The cells were grown in a rich medium and harvested in the beginning of the exponential growth phase. The quantifications were performed by...

  11. CryoEM analysis of capsid assembly and structural changes upon interactions with a host restriction factor, TRIM5α.

    Science.gov (United States)

    Zhao, Gongpu; Zhang, Peijun

    2014-01-01

    After virus fusion with a target cell, the viral core is released into the host cell cytoplasm and undergoes a controlled disassembly process, termed uncoating, before or as reverse transcription takes place. The cellular protein TRIM5α is a host cell restriction factor that blocks HIV-1 infection in rhesus macaque cells by targeting the viral capsid and inducing premature uncoating. The molecular mechanism of the interaction between capsid and TRIM5α remains unclear. Here, we describe an approach that utilizes cryo-electron microscopy (cryoEM) to examine the structural changes exerted on HIV-1 capsid (CA) assembly by TRIM5α binding. The TRIM5α interaction sites on CA assembly were further dissected by combining cryoEM with pair-wise cysteine mutations that crosslink CA either within a CA hexamer or between CA hexamers. Based on the structural information from cryoEM and crosslinking results from in vitro CA assemblies and purified intact HIV-1 cores, we demonstrate that direct binding of TRIM5α CC-SPRY domains to the viral capsid results in disruption and fragmentation of the surface lattice of HIV-1 capsid, specifically at inter-hexamer interfaces. The method described here can be easily adopted to study other important interactions in multi-protein complexes. PMID:24158810

  12. Demand Forecasting at Low Aggregation Levels using Factored Conditional Restricted Boltzmann Machine

    DEFF Research Database (Denmark)

    Mocanu, Elena; Nguyen, Phuong H.; Gibescu, Madeleine;

    2016-01-01

    approaches have been proposed in the literature. As an evolution of neural network-based prediction methods, deep learning techniques are expected to increase the prediction accuracy by allowing stochastic formulations and bi-directional connections between neurons. In this paper, we investigate a newly...... developed deep learning model for time series prediction, namely Factored Conditional Restricted Boltzmann Machine (FCRBM), and extend it for electrical demand forecasting. The assessment is made on the EcoGrid dataset, originating from the Bornholm island experiment in Denmark, consisting of aggregated......The electrical demand forecasting problem can be regarded as a nonlinear time series prediction problem depending on many complex factors since it is required at various aggregation levels and at high temporal resolution. To solve this challenging problem, various time series and machine learning...

  13. Evolution of the antiretroviral restriction factor TRIMCyp in Old World primates.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Dietrich

    Full Text Available The retroviral restriction factor TRIMCyp, which is a fusion protein derived from the TRIM5 gene, blocks replication at a post-entry step. Among Old World primates, TRIMCyp has been found in four species of Asian macaques, but not in African monkeys. To further define the evolutionary origin of Old World TRIMCyp, we examined two species of baboons (genus Papio and three additional macaque species, including M. sylvanus, which is the only macaque species found outside Asia, and represents the earliest diverging branch of the macaque lineage. None of four P. cynocephalus anubis, one P. hamadryas, and 36 M. sylvanus had either TRIMCyp mRNA or the genetic features required for its expression. M. sylvanus genomic sequences indicated that the lack of TRIMCyp in this species was not due to genetic homogeneity among specimens studied and revealed the existence of four TRIM5α alleles, all distinct from M. mulatta and Papio counterparts. Together with existing data on macaque evolution, our findings indicate that TRIMCyp evolved in the ancestors of Asian macaques approximately 5-6 million years before present (ybp, likely as a result of a retroviral threat. TRIMCyp then became fixed in the M. nemestrina lineage after it diverged from M. nigra, approximately 2 million ybp. The macaque lineage is unique among primates studied so far due to the presence and diversity of both TRIM5 and TRIMCyp restriction factors. Studies of these antiviral proteins may provide valuable information about natural antiviral mechanisms, and give further insight into the factors that shaped the evolution of macaque species.

  14. Feed-borne Outbreak of Salmonella Cubana in Swedish Pig Farms: Risk Factors and Factors Affecting the Restriction Period in Infected Farms

    OpenAIRE

    Österberg J; Vågsholm I; Boqvist S; Lewerin S Sternberg

    2006-01-01

    In 2003, a feed-borne outbreak of Salmonella Cubana occurred in Sweden as a result of contamination in a feed plant. Salmonella Cubana was detected in 49 out of 77 pig farms having received possibly contaminated feed. In this study, potential risk factors for farms being salmonella positive were examined, and a survival analysis was performed to investigate risk factors affecting the restriction period for salmonella positive farms. The median restriction time for all 49 farms was 17 weeks. ...

  15. Interacting factors and cellular localization of SR protein-specific kinase Dsk1

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Zhaohua, E-mail: ztang@jsd.claremont.edu [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Luca, Maria; Taggart-Murphy, Laura; Portillio, Jessica; Chang, Cathey; Guven, Ayse [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Lin, Ren-Jang [Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010 (United States); Murray, Johanne; Carr, Antony [Genome Damage and Stability Center, University of Sussex, Falmer, BN1 9RQ (United Kingdom)

    2012-10-01

    Schizosaccharomyces pombe Dsk1 is an SR protein-specific kinase (SRPK), whose homologs have been identified in every eukaryotic organism examined. Although discovered as a mitotic regulator with protein kinase activity toward SR splicing factors, it remains largely unknown about what and how Dsk1 contributes to cell cycle and pre-mRNA splicing. In this study, we investigated the Dsk1 function by determining interacting factors and cellular localization of the kinase. Consistent with its reported functions, we found that pre-mRNA processing and cell cycle factors are prominent among the proteins co-purified with Dsk1. The identification of these factors led us to find Rsd1 as a novel Dsk1 substrate, as well as the involvement of Dsk1 in cellular distribution of poly(A){sup +} RNA. In agreement with its role in nuclear events, we also found that Dsk1 is mainly localized in the nucleus during G{sub 2} phase and at mitosis. Furthermore, we revealed the oscillation of Dsk1 protein in a cell cycle-dependent manner. This paper marks the first comprehensive analysis of in vivo Dsk1-associated proteins in fission yeast. Our results reflect the conserved role of SRPK family in eukaryotic organisms, and provide information about how Dsk1 functions in pre-mRNA processing and cell-division cycle.

  16. Interacting factors and cellular localization of SR protein-specific kinase Dsk1

    International Nuclear Information System (INIS)

    Schizosaccharomyces pombe Dsk1 is an SR protein-specific kinase (SRPK), whose homologs have been identified in every eukaryotic organism examined. Although discovered as a mitotic regulator with protein kinase activity toward SR splicing factors, it remains largely unknown about what and how Dsk1 contributes to cell cycle and pre-mRNA splicing. In this study, we investigated the Dsk1 function by determining interacting factors and cellular localization of the kinase. Consistent with its reported functions, we found that pre-mRNA processing and cell cycle factors are prominent among the proteins co-purified with Dsk1. The identification of these factors led us to find Rsd1 as a novel Dsk1 substrate, as well as the involvement of Dsk1 in cellular distribution of poly(A)+ RNA. In agreement with its role in nuclear events, we also found that Dsk1 is mainly localized in the nucleus during G2 phase and at mitosis. Furthermore, we revealed the oscillation of Dsk1 protein in a cell cycle-dependent manner. This paper marks the first comprehensive analysis of in vivo Dsk1-associated proteins in fission yeast. Our results reflect the conserved role of SRPK family in eukaryotic organisms, and provide information about how Dsk1 functions in pre-mRNA processing and cell-division cycle.

  17. Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone

    Institute of Scientific and Technical Information of China (English)

    Julie L Frey; David P Stonko; Marie-Claude Faugere; Ryan C Riddle

    2014-01-01

    The hypoxia inducible factors (Hifs) are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone (PTH). Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of b-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.

  18. Studies on determining the cellular factors in pediatric mycoplasma pneumonia patients

    International Nuclear Information System (INIS)

    Objective: To study the interrelation between the degree of infection and changes in cellular factors in pediatrics mycoplasma pneumonia patients. Methods: 91 cases of pediatric mycoplasma pneumonia were divided into a serious group and a lighter group according to the serum IgM levels. The fast serum levels of tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6) were determined with ratio-immunoassay (RIA) in those patients as well as 35 controls. Results: The levels of serum TNF-α and IL-6 in both groups of patients were significantly higher than those in the controls (P < 0.01). The levels in the serious group were also significantly higher than those in the lighter group (P < 0.05). The data in patient groups were analysed with linear correlation. The correlative coefficient of TNF-α was r = 0.49 and that of IL-6 was r = 0.95, Suggesting positive correlation with the seriousness of infection. Conclusion: The cellular factors TNF-α and IL-6 might participate in the whole process of mycoplasma infection and their serum levels were positively correlated with the seriousness of the disease

  19. Evaluation of Arable Land Reserve Resources and Analysis of Restrictive Factors: A Case Study of Hangjin Banner in Inner Mongolia

    Institute of Scientific and Technical Information of China (English)

    Xia; YANG; Xiangjun; YUN

    2015-01-01

    Taking land available for cultivation and mining land available for reclamation in Hangjin Banner of Inner Mongolia Autonomous Region,using land use database of 2012 as evaluation base,it made evaluation of arability of 677 021. 40 hm2 reserve land resources by the restrictive factor evaluation method. Besides,it analyzed main restrictive factors of arable land reserve resources in Hangjin Banner. Results indicate that the total area arable land reserve resources is 52 200. 02 hm2,accounting for 7. 71% of total area evaluated. Irrigation condition and soil thickness are major factors restricting development of arable land reserve resources in the study area. It is expected to provide reference for development of arable land reserve resources and land consolidation project in Hangjin Banner.

  20. The role of nuclear factor κB in the cellular response to different radiation qualities

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Kristina

    2013-04-11

    Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

  1. The role of nuclear factor κB in the cellular response to different radiation qualities

    International Nuclear Information System (INIS)

    Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

  2. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

    Science.gov (United States)

    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  3. Using restricted factor analysis with latent moderated structures to detect uniform and nonuniform measurement bias; a simulation study

    OpenAIRE

    Barendse, M. T.; Oort, F. J.; Garst, G.J.A.

    2010-01-01

    Factor analysis is an established technique for the detection of measurement bias. Multigroup factor analysis (MGFA) can detect both uniform and nonuniform bias. Restricted factor analysis (RFA) can also be used to detect measurement bias, albeit only uniform measurement bias. Latent moderated structural equations (LMS) enable the estimation of nonlinear interaction effects in structural equation modelling. By extending the RFA method with LMS, the RFA method should be suited to detect nonuni...

  4. Interaction of alpha particles at the cellular level - Implications for the radiation weighting factor

    International Nuclear Information System (INIS)

    Since low dose effects of alpha particles are produced by cellular hits in a relatively small fraction of exposed cells, the present study focuses on alpha particle interactions in bronchial epithelial cells following exposure to inhaled radon progeny. A computer code was developed for the calculation of microdosimetric spectra, dose and hit probabilities for alpha particles emitted from uniform and non-uniform source distributions in cylindrical and Y-shaped bronchial airway geometries. Activity accumulations at the dividing spur of bronchial airway bifurcations produce hot spots of cellular hits, indicating that a small fraction of cells located at such sites may receive substantially higher doses. While presently available data on in vitro transformation frequencies suggest that the relative biological effectiveness for alpha particles ranges from about 3 to 10, the effect of inhomogeneous activity distributions of radon progeny may slightly increase the radiation weighting factor relative to a uniform distribution. Thus a radiation weighting factor of about 10 may be more realistic than the current value of 20, at least for lung cancer risk following inhalation of short-lived radon progeny. (authors)

  5. A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev

    International Nuclear Information System (INIS)

    HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative DEAD box (Asp-Glu-Ala-Asp) RNA helicase, DDX1, as a cellular co-factor of Rev, through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev as 'bait'. DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)-containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev(-) cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as to the RRE, strongly suggest that DDX1 affects Rev function through the Rev-RRE axis. Moreover, down-regulation of DDX1 altered the steady state subcellular distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These findings indicate that DDX1 is a critical cellular co-factor for Rev function, which maintains the proper subcellular distribution of this lentiviral regulatory protein. Therefore, alterations in DDX1-Rev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics

  6. Is abnormal vaginal microflora a risk factor for intrauterine fetal growth restriction?

    Institute of Scientific and Technical Information of China (English)

    NatalijaVedmedovska; Dace Rezeberga; GilbertG G Donders

    2015-01-01

    Objective:To conduct a literature review in search of possible preventable causes for fetal growth restriction.Methods:We performed a systematic literature search regarding abnormal vaginal microflora and fetal growth encompassing the last 27-year (starting from 1986) in PubMed, Embase, and Cochrane Central to study the evidence that abnormal vaginal microflora is may be related to diminished fetal growth or small for date birth.Results:Most of the 14 studies suggested a significant role of vaginal organisms in impaired fetal growth, unrelated to preterm birth. The neonatal outcome has shown to be largely linked to the preventable or foreseeable fetal factors, such as genetic abnormalities, but also ascending intrauterine infections. Our previous work suggested a role of vaginal organisms in adverse pregnancy outcome, not only preterm birth, but also impaired fetal growth.Conclusions:There is a need for cohort studies designed to unravel this link between abnormal microflora and FGR, in order to enable preventive actions to protect these small babies from severe damage and death by early screening and treatment.

  7. Intrauterine growth restriction: distribution, risk factors, management of labour and outcome

    Directory of Open Access Journals (Sweden)

    Diana Andzane

    2015-08-01

    Full Text Available Background: The development of Intrauterine growth restriction (IUGR determines maternal, fetal and placental factors. Many of these factors are preventable. There is still no enough developed effective pregnancy and labour management tactics that could protect both mother and child from the unintended consequences. Methods: The research was made in Riga Maternity Hospital. In the research there were included pregnant women who gave birth neonates with weight under 10th percentile (IUGR group as well there was compiled the control group. The weight of neonates was evaluated using the percentile scales - Intrauterine Growth Curves based on US data. Results: According to the criteria, in the IUGR group were included 209 pregnant women and in the control group was the same number of patients. In the IUGR group mothers discharged from the hospital one day later than it was in the control group both after vaginal delivery (4.0 +/- 1.5 vs. 3.3 +/- 1.0, p and #706;0.0001 and after caesarean (5.6 +/- 1.5 vs. 4.5 +/- 1.0, p=0.0001. Comparing the evaluations after Apgar scale after spontaneous birth, induced labour and caesarean it was discovered that there is no statistically significant difference. Conclusions: IUGR negatively affect not just the fetus but also the mother and this is the reason why she should stay in the hospital for a longer period due to the child or experience the caesarean. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1117-1121

  8. Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary.

    Science.gov (United States)

    Bristol, Sarah K; Woodruff, Teresa K

    2004-03-01

    Ovarian follicular development, follicle selection, and the process of ovulation remain poorly understood in most species. Throughout reproductive life, follicle fate is balanced between growth and apoptosis. These opposing forces are controlled by numerous endocrine, paracrine, and autocrine factors, including the ligands represented by the transforming growth factor beta (TGFbeta) superfamily. TGFbeta, activin, inhibin, bone morphometric protein (BMP), and growth differentiation factor 9 (GDF-9) are present in the ovary of many animals; however, no comprehensive analysis of the localization of each ligand or its receptors and intracellular signaling molecules during folliculogenesis has been done. The domestic cat is an ideal model for studying ovarian follicle dynamics due to an abundance of all follicle populations, including primordial stage, and the amount of readily available tissue following routine animal spaying. Additionally, knowledge of the factors involved in feline follicular development could make an important impact on in vitro maturation/in vitro fertilization (IVM/IVF) success for endangered feline species. Thus, the presence and position of TGFbeta superfamily members within the feline ovary have been evaluated in all stages of follicular development by immunolocalization. The cat inhibin alpha subunit protein is present in all follicle stages but increases in intensity within the mural granulosa cells in large antral follicles. The inhibin betaA and betaB subunit proteins, in addition to the activin type I (ActRIB) and activin type II receptor (ActRIIB), are produced in primordial and primary follicle granulosa cells. Additionally, inhibin betaA subunit is detected in the theca cells from secondary through large antral follicle size classes. GDF-9 is restricted to the oocyte of preantral and antral follicles, whereas the type II BMP receptor (BMP-RII) protein is predominantly localized to primordial- and primary-stage follicles. TGFbeta1, 2

  9. Quantifying colocalization of a conditionally active transcription factor FOXP3 in three-dimensional cellular space

    Science.gov (United States)

    Abraham, Thomas; Allan, Sarah E.; Levings, Megan K.

    2009-02-01

    Biological macromolecular interactions between proteins, transcription factors, DNA and other types of biomolecules, are fundamentally important to several cellular and biological processes. 3D Multi-channel confocal microscopy and colocalization analysis of fluorescent signals have proven to be invaluable tools for detecting such molecular interactions. The aim of this work was to quantify colocalization of the FOXP3 transcription factor in 3D cellular space generated from the confocal 3D image sets. 293T cells transfected with a conditionally active form of FOXP3 were stained for nuclei with Hoechst, for FOXP3 with anti-FOXP3 conjugated to PE, and 4-hydroxytamoxifen used as protein translocation and activation agent. Since the protein signal was weak and nonspecific intensity contributions were strong, it was difficult to perform colocalization analysis and estimate colocalization quantities. We performed 3D restoration by deconvolution method on the confocal images using experimentally measured point spread functions (PSFs) and subsequently a color shift correction. The deconvolution method eliminated nonspecific intensity contributions originating from PSF imposed by optical microscopy diffraction resolution limits and noise since these factors significantly affected colocalization analysis and quantification. Visual inspection of the deconvolved 3D image suggested that the FOXP3 molecules are predominantly colocalized within the nuclei although the fluorescent signals from FOXP3 molecules were also present in the cytoplasm. A close inspection of the scatter plot (colocalization map) and correlation quantities such as the Pearsons and colocalization coefficients showed that the fluorescent signals from the FOXP3 molecules and DNA are strongly correlated. In conclusion, our colocalization quantification approach confirms the preferential association of the FOXP3 molecules with the DNA despite the presence of fluorescent signals from the former one both in the

  10. No Effect of the Transforming Growth Factor {beta}1 Promoter Polymorphism C-509T on TGFB1 Gene Expression, Protein Secretion, or Cellular Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Reuther, Sebastian; Metzke, Elisabeth [Laboratory of Radiobiology and Experimental Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Bonin, Michael [Department of Medical Genetics, University of Tuebingen (Germany); Petersen, Cordula [Clinic of Radiotherapy and Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Dikomey, Ekkehard, E-mail: dikomey@uke.de [Laboratory of Radiobiology and Experimental Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Raabe, Annette [Laboratory of Radiobiology and Experimental Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany)

    2013-02-01

    Purpose: To study whether the promoter polymorphism (C-509T) affects transforming growth factor {beta}1 gene (TGFB1) expression, protein secretion, and/or cellular radiosensitivity for both human lymphocytes and fibroblasts. Methods and Materials: Experiments were performed with lymphocytes taken either from 124 breast cancer patients or 59 pairs of normal monozygotic twins. We used 15 normal human primary fibroblast strains as controls. The C-509T genotype was determined by polymerase chain reaction-restriction fragment length polymorphism or TaqMan single nucleotide polymorphism (SNP) genotyping assay. The cellular radiosensitivity of lymphocytes was measured by G0/1 assay and that of fibroblasts by colony assay. The amount of extracellular TGFB1 protein was determined by enzyme-linked immunosorbent assay, and TGFB1 expression was assessed via microarray analysis or reverse transcription-polymerase chain reaction. Results: The C-509T genotype was found not to be associated with cellular radiosensitivity, neither for lymphocytes (breast cancer patients, P=.811; healthy donors, P=.181) nor for fibroblasts (P=.589). Both TGFB1 expression and TGFB1 protein secretion showed considerable variation, which, however, did not depend on the C-509T genotype (protein secretion: P=.879; gene expression: lymphocytes, P=.134, fibroblasts, P=.605). There was also no general correlation between TGFB1 expression and cellular radiosensitivity (lymphocytes, P=.632; fibroblasts, P=.573). Conclusion: Our data indicate that any association between the SNP C-509T of TGFB1 and risk of normal tissue toxicity cannot be ascribed to a functional consequence of this SNP, either on the level of gene expression, protein secretion, or cellular radiosensitivity.

  11. Cellular Homeostasis and Aging.

    Science.gov (United States)

    Hartl, F Ulrich

    2016-06-01

    Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans. PMID:27050288

  12. Repression of the human papillomavirus type 18 enhancer by the cellular transcription factor Oct-1.

    Science.gov (United States)

    Hoppe-Seyler, F; Butz, K; zur Hausen, H

    1991-01-01

    The role of cellular factors involved in the transcriptional regulation of the cancer-associated human papillomavirus type 18 (HPV18) is yet poorly understood. The presence of an Oct-1-binding site within the HPV18 upstream regulatory region led us to investigate the influence of Oct-1 on viral transcription. Cotransfection of Oct-1 expression plasmids together with luciferase reporter constructs containing HPV18 regulatory sequences indicated that Oct-1 can transcriptionally repress the HPV18 upstream regulatory region. In contrast, heterologous control regions were not affected by Oct-1. HPV18 cis elements that can be repressed by Oct-1 mapped to a 135-bp subregion of the viral constitutive enhancer. Analysis of an Oct-1 mutant defective in DNA binding suggested that HPV18 down-modulation does not require direct binding of Oct-1 to DNA. These results make Oct-1 a candidate factor involved in the intracellular surveillance of HPV18 transcription and support the notion of a host cell mechanism that can specifically repress HPV E6-E7 transforming gene expression. Images PMID:1654457

  13. Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signalling in the mouse hypothalamus

    OpenAIRE

    AntonioGiordano; SaverioCinti

    2013-01-01

    In the mouse hypothalamus, ciliary neurotrophic factor (CNTF) is mainly expressed by ependymal cells and tanycytes of the ependymal layer covering the third ventricle. Since exogenously administered CNTF causes reduced food intake and weight loss, we tested whether endogenous CNTF might be involved in energy balance regulation. We thus evaluated CNTF production and responsiveness in the hypothalamus of mice fed a high-fat diet (HFD), of ob/ob obese mice, and of mice fed a calorie restriction ...

  14. Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signaling in the mouse hypothalamus

    OpenAIRE

    Severi, Ilenia; Perugini, Jessica; Mondini, Eleonora; Smorlesi, Arianna; Frontini, Andrea; Cinti, Saverio; Giordano, Antonio

    2013-01-01

    In the mouse hypothalamus, ciliary neurotrophic factor (CNTF) is mainly expressed by ependymal cells and tanycytes of the ependymal layer covering the third ventricle. Since exogenously administered CNTF causes reduced food intake and weight loss, we tested whether endogenous CNTF might be involved in energy balance regulation. We thus evaluated CNTF production and responsiveness in the hypothalamus of mice fed a high-fat diet (HFD), of ob/ob obese mice, and of mice fed a calorie restriction ...

  15. Retroviral restriction factors TRIM5α: therapeutic strategy to inhibit HIV-1 replication.

    Science.gov (United States)

    Zhang, Jing; Ge, Weiying; Zhan, Peng; De Clercq, Erik; Liu, Xinyong

    2011-01-01

    Tripartite motif protein 5-alpha (TRIM5α) is a cytoplasmic protein that efficiently recognizes the incoming capsid (CA) protein of retroviruses and potently inhibits virus infection in a species-specific manner. Through directly recognizing and interacting with HIV CA, TRIM5α is capable of disrupting the ordered process of viral uncoating, eventually interfering with HIV-1 reverse transcription and virus replication. TRIM5α protein contains four domains: RING domain, B-box 2 domain, coiled-coil domain, and B30.2 domain (SPRY) domain. All of the domains are necessary for efficient retrovirus restriction and the B30.2 domain has been shown to be the determinant of the specificity of restriction. Species-specific innate resistance against viral infections offers novel avenues for antiviral therapeutics. Various mutants of TRIM5α have been described which differently affect the HIV-1 reverse transcription process. This makes the establishment of new and improved models for HIV replication and AIDS pathogenesis by monitoring endogenous TRIM5α an attractive approach. TRIM5α-mediated restriction is modulated by the host protein Cyclophilin A (Cyp A) which could effectively interact with the CA of HIV-1. Here we will review the structure and roles of TRIM5α protein, the interaction between Cyp A and TRIM5α, as well as gene therapy strategies associated with TRIM5α to inhibit HIV-1 infection. PMID:21568899

  16. Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

    Science.gov (United States)

    Bertazzoni, Umberto; Turci, Marco; Avesani, Francesca; Di Gennaro, Gianfranco; Bidoia, Carlo; Romanelli, Maria Grazia

    2011-01-01

    Human T-lymphotropic viruses type 1 (HTLV-1) and type 2 (HTLV-2) present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity. PMID:21994745

  17. Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

    Directory of Open Access Journals (Sweden)

    Maria Grazia Romanelli

    2011-05-01

    Full Text Available Human T-lymphotropic viruses type 1 (HTLV-1 and type 2 (HTLV-2 present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity.

  18. Knowledge-based matrix factorization temporally resolves the cellular responses to IL-6 stimulation

    Directory of Open Access Journals (Sweden)

    Gretz Norbert

    2010-11-01

    Full Text Available Abstract Background External stimulations of cells by hormones, cytokines or growth factors activate signal transduction pathways that subsequently induce a re-arrangement of cellular gene expression. The analysis of such changes is complicated, as they consist of multi-layered temporal responses. While classical analyses based on clustering or gene set enrichment only partly reveal this information, matrix factorization techniques are well suited for a detailed temporal analysis. In signal processing, factorization techniques incorporating data properties like spatial and temporal correlation structure have shown to be robust and computationally efficient. However, such correlation-based methods have so far not be applied in bioinformatics, because large scale biological data rarely imply a natural order that allows the definition of a delayed correlation function. Results We therefore develop the concept of graph-decorrelation. We encode prior knowledge like transcriptional regulation, protein interactions or metabolic pathways in a weighted directed graph. By linking features along this underlying graph, we introduce a partial ordering of the features (e.g. genes and are thus able to define a graph-delayed correlation function. Using this framework as constraint to the matrix factorization task allows us to set up the fast and robust graph-decorrelation algorithm (GraDe. To analyze alterations in the gene response in IL-6 stimulated primary mouse hepatocytes, we performed a time-course microarray experiment and applied GraDe. In contrast to standard techniques, the extracted time-resolved gene expression profiles showed that IL-6 activates genes involved in cell cycle progression and cell division. Genes linked to metabolic and apoptotic processes are down-regulated indicating that IL-6 mediated priming renders hepatocytes more responsive towards cell proliferation and reduces expenditures for the energy metabolism. Conclusions GraDe provides

  19. Cellular Levels of Signaling Factors Are Sensed by β-actin Alleles to Modulate Transcriptional Pulse Intensity

    Directory of Open Access Journals (Sweden)

    Alon Kalo

    2015-04-01

    Full Text Available The transcriptional response of β-actin to extra-cellular stimuli is a paradigm for transcription factor complex assembly and regulation. Serum induction leads to a precisely timed pulse of β-actin transcription in the cell population. Actin protein is proposed to be involved in this response, but it is not known whether cellular actin levels affect nuclear β-actin transcription. We perturbed the levels of key signaling factors and examined the effect on the induced transcriptional pulse by following endogenous β-actin alleles in single living cells. Lowering serum response factor (SRF protein levels leads to loss of pulse integrity, whereas reducing actin protein levels reveals positive feedback regulation, resulting in elevated gene activation and a prolonged transcriptional response. Thus, transcriptional pulse fidelity requires regulated amounts of signaling proteins, and perturbations in factor levels eliminate the physiological response, resulting in either tuning down or exaggeration of the transcriptional pulse.

  20. Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape

    Science.gov (United States)

    Landolfo, Santo; De Andrea, Marco; Dell’Oste, Valentina; Gugliesi, Francesca

    2016-01-01

    Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed “restriction factors” (RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus (HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell’s intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16 (IFI16) (a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and hDaxx; the latter three being the keys elements of nuclear domain 10 (ND10). IFI16 inhibits the synthesis of virus DNA by down-regulating UL54 transcription - a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65 (pUL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents. PMID:27563536

  1. Endogenous Murine BST-2/Tetherin Is Not a Major Restriction Factor of Influenza A Virus Infection.

    Directory of Open Access Journals (Sweden)

    Sarah L Londrigan

    Full Text Available BST-2 (tetherin, CD317, HM1.24 restricts virus growth by tethering enveloped viruses to the cell surface. The role of BST-2 during influenza A virus infection (IAV is controversial. Here, we assessed the capacity of endogenous BST-2 to restrict IAV in primary murine cells. IAV infection increased BST-2 surface expression by primary macrophages, but not alveolar epithelial cells (AEC. BST-2-deficient AEC and macrophages displayed no difference in susceptibility to IAV infection relative to wild type cells. Furthermore, BST-2 played little role in infectious IAV release from either AEC or macrophages. To examine BST-2 during IAV infection in vivo, we infected BST-2-deficient mice. No difference in weight loss or in viral loads in the lungs and/or nasal tissues were detected between BST-2-deficient and wild type animals. This study rules out a major role for endogenous BST-2 in modulating IAV in the mouse model of infection.

  2. Feed-borne Outbreak of Salmonella Cubana in Swedish Pig Farms: Risk Factors and Factors Affecting the Restriction Period in Infected Farms

    Directory of Open Access Journals (Sweden)

    Österberg J

    2006-03-01

    Full Text Available In 2003, a feed-borne outbreak of Salmonella Cubana occurred in Sweden as a result of contamination in a feed plant. Salmonella Cubana was detected in 49 out of 77 pig farms having received possibly contaminated feed. In this study, potential risk factors for farms being salmonella positive were examined, and a survival analysis was performed to investigate risk factors affecting the restriction period for salmonella positive farms. The median restriction time for all 49 farms was 17 weeks. An increased risk for farms being salmonella infected (positive in feed and/or faeces was seen for fattening farms and farms feeding soy. The survival analysis showed that herds with a low level of infection and farms with a high hygiene level had shorter restriction times. This study is unique as it investigates a real outbreak of feed-borne salmonella, where the source of infection was reliably identified, the period of exposure could be defined and data were collected from all exposed farms.

  3. Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G.

    OpenAIRE

    Stanley, David J.; Koen Bartholomeeusen; Crosby, David C; Dong Young Kim; Eunju Kwon; Linda Yen; Nathalie Caretta Cartozo; Ming Li; Stefanie Jäger; Jeremy Mason-Herr; Fumiaki Hayashi; Shigeyuki Yokoyama; Krogan, Nevan J; Harris, Reuben S.; Boris Matija Peterlin

    2012-01-01

    Cellular restriction factors help to defend humans against human immunodeficiency virus (HIV). HIV accessory proteins hijack at least three different Cullin-RING ubiquitin ligases, which must be activated by the small ubiquitin-like protein NEDD8, in order to counteract host cellular restriction factors. We found that conjugation of NEDD8 to Cullin-5 by the NEDD8-conjugating enzyme UBE2F is required for HIV Vif-mediated degradation of the host restriction factor APOBEC3G (A3G). Pharmacologica...

  4. On the Restricting Factors & System Arrangements of Chinese Land Tenure Marketization

    Institute of Scientific and Technical Information of China (English)

    YU Peng-yi; ZHANG Wei-dong

    2003-01-01

    As a general rule of Economics of Development,economic growth and development require rational institution guarantee.Land Tenure.As a main institution factor in agricultural development,closely relates to the reform of Chinese agriculture.Based on the relevant theories of Economics of Institution and Economics of Development,and combined with the marketization process of Chinese Land Tenure of Property Rights,the article studied the effects of institutional factors and put forward some choices in the development of agriculture,which is of both significant and practical importance.

  5. Cellular Localization of the Molecular Forms of Acetylcholinesterase in rat Pheochromocytoma Pc12 Cells Treated with Nerve Growth Factor1

    OpenAIRE

    Inestrosa, Nibaldo C; Reiness, C. Gary; Reichardt, Louis F.; Hall, Zach W

    1981-01-01

    In rat pheochromocytoma (PC12) cells treated with nerve growth factor (NGF), there are several molecular forms of the enzyme acetylcholinesterase (AChE) which sediment on sucrose density gradients at 4 to 6, 10, and 16 S, respectively. We have investigated the cellular localization of these forms in PC12 cells. In order to determine which forms are soluble and which are membrane bound, we extracted PC12 cells in buffers of various ionic strengths and detergent compositions. To distinguish int...

  6. H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s)

    International Nuclear Information System (INIS)

    To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented

  7. Enhanced CD4+ cellular apoptosis by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with progressive HIV-1 infection

    International Nuclear Information System (INIS)

    CCR5-using (R5) human immunodeficiency virus type 1 (HIV-1) strains cause CD4+ T-cell loss in most infected individuals, but mechanisms underlying cytopathicity of R5 viruses are poorly understood. We investigated mechanisms contributing to R5 envelope glycoprotein (Env)-mediated cellular apoptosis by constructing a panel of retroviral vectors engineered to co-express GFP and R5 Envs derived from two HIV-1-infected subjects spanning asymptomatic (Early, E-R5 Envs) to late stages of infection (Late, L-R5 Envs). The L-R5 Envs induced significantly more cellular apoptosis than E-R5 Envs, but only in Env-expressing (GFP-positive) cells, and only in cells where CD4 and CCR5 levels were limiting. Studies with fusion-defective Env mutants showed induction of apoptosis required membrane-fusing events. Our results provide evidence for an intracellular mechanism of R5 Env-induced apoptosis of CD4+ cells that requires membrane fusion. Furthermore, they contribute to a better understanding of mechanisms involved in CD4+ T-cell loss in subjects experiencing progressive R5 HIV-1 infection.

  8. Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse

    Directory of Open Access Journals (Sweden)

    Chunjun Sheng

    2016-01-01

    Full Text Available Type 2 diabetes (T2D is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs and functional factors with long-term caloric restriction (CR. Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies.

  9. A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus.

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

    Influenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for IAV rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type IAV by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited IAV infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds. PMID:27375580

  10. A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

    Influenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for IAV rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type IAV by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited IAV infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds. PMID:27375580

  11. Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer's Disease.

    Science.gov (United States)

    McGinley, Lisa M; Sims, Erika; Lunn, J Simon; Kashlan, Osama N; Chen, Kevin S; Bruno, Elizabeth S; Pacut, Crystal M; Hazel, Tom; Johe, Karl; Sakowski, Stacey A; Feldman, Eva L

    2016-03-01

    Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder and a leading cause of dementia. Current treatment fails to modify underlying disease pathologies and very little progress has been made to develop effective drug treatments. Cellular therapies impact disease by multiple mechanisms, providing increased efficacy compared with traditional single-target approaches. In amyotrophic lateral sclerosis, we have shown that transplanted spinal neural stem cells (NSCs) integrate into the spinal cord, form synapses with the host, improve inflammation, and reduce disease-associated pathologies. Our current goal is to develop a similar "best in class" cellular therapy for AD. Here, we characterize a novel human cortex-derived NSC line modified to express insulin-like growth factor-I (IGF-I), HK532-IGF-I. Because IGF-I promotes neurogenesis and synaptogenesis in vivo, this enhanced NSC line offers additional environmental enrichment, enhanced neuroprotection, and a multifaceted approach to treating complex AD pathologies. We show that autocrine IGF-I production does not impact the cell secretome or normal cellular functions, including proliferation, migration, or maintenance of progenitor status. However, HK532-IGF-I cells preferentially differentiate into gamma-aminobutyric acid-ergic neurons, a subtype dysregulated in AD; produce increased vascular endothelial growth factor levels; and display an increased neuroprotective capacity in vitro. We also demonstrate that HK532-IGF-I cells survive peri-hippocampal transplantation in a murine AD model and exhibit long-term persistence in targeted brain areas. In conclusion, we believe that harnessing the benefits of cellular and IGF-I therapies together will provide the optimal therapeutic benefit to patients, and our findings support further preclinical development of HK532-IGF-I cells into a disease-modifying intervention for AD. PMID:26744412

  12. In Vivo Accumulation of Cyclin A and Cellular Replication Factors in Autonomous Parvovirus Minute Virus of Mice-Associated Replication Bodies

    OpenAIRE

    Bashir, Tarig; Rommelaere, Jean; Cziepluch, Celina

    2001-01-01

    Autonomous parvovirus minute virus of mice (MVM) DNA replication is strictly dependent on cellular factors expressed during the S phase of the cell cycle. Here we report that MVM DNA replication proceeds in specific nuclear structures termed autonomous parvovirus-associated replication bodies, where components of the basic cellular replication machinery accumulate. The presence of DNA polymerases α and δ in these bodies suggests that MVM utilizes partially preformed cellular replication compl...

  13. The expression level of the transcription factor Aryl hydrocarbon receptor nuclear translocator (ARNT) determines cellular survival after radiation treatment

    International Nuclear Information System (INIS)

    Tumour hypoxia promotes radioresistance and is associated with poor prognosis. The transcription factor Aryl hydrocarbon receptor nuclear translocator (ARNT), also designated as Hypoxia-inducible factor (HIF)-1β, is part of the HIF pathway which mediates cellular adaptations to oxygen deprivation and facilitates tumour progression. The subunits HIF-1α and ARNT are key players within this pathway. HIF-1α is regulated in an oxygen-dependent manner whereas ARNT is considered to be constitutively expressed. However, there is mounting evidence that certain tumour cells are capable to elevate ARNT in hypoxia which suggests a survival benefit. Therefore the objective of this study was to elucidate effects of an altered ARNT expression level on the cellular response to radiation. Different human cell lines (Hep3B, MCF-7, 786-Owt, 786-Ovhl, RCC4wt and RCC4vhl) originating from various tumour entities (Hepatocellular carcinoma, breast cancer and renal cell carcinoma respectively) were X-irradiated using a conventional linear accelerator. Knockdown of ARNT expression was achieved by transient siRNA transfection. Complementary experiments were performed by forced ARNT overexpression using appropriate plasmids. Presence/absence of ARNT protein was confirmed by Western blot analysis. Clonogenic survival assays were performed in order to determine cellular survival post irradiation. Statistical comparison of two groups was achieved by the unpaired t-test. The results of this study indicate that ARNT depletion renders tumour cells susceptible to radiation whereas overexpression of this transcription factor confers radioresistance. These findings provide evidence to consider ARNT as a drug target and as a predictive marker in clinical applications concerning the response to radiation. The online version of this article (doi:10.1186/s13014-015-0539-9) contains supplementary material, which is available to authorized users

  14. Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis

    Directory of Open Access Journals (Sweden)

    Eckard Jonathan

    2010-08-01

    Full Text Available Abstract Background Young women diagnosed with breast cancer are known to have a higher mortality rate from the disease than older patients. Specific risk factors leading to this poorer outcome have not been identified. In the present study, we hypothesized that iron deficiency, a common ailment in young women, contributes to the poor outcome by promoting the hypoxia inducible factor-1α (HIF-1α and vascular endothelial growth factor (VEGF formation. This hypothesis was tested in an in vitro cell culture model system. Results Human breast cancer MDA-MB-231 cells were transfected with transferrin receptor-1 (TfR1 shRNA to constitutively impair iron uptake. Cellular iron status was determined by a set of iron proteins and angiogenesis was evaluated by levels of VEGF in cells as well as by a mouse xenograft model. Significant decreases in ferritin with concomitant increases in VEGF were observed in TfR1 knockdown MDA-MB-231 cells when compared to the parental cells. TfR1 shRNA transfectants also evoked a stronger angiogenic response after the cells were injected subcutaneously into nude mice. The molecular mechanism appears that cellular iron deficiency elevates VEGF formation by stabilizing HIF-1α. This mechanism is also true in human breast cancer MCF-7 and liver cancer HepG2 cells. Conclusions Cellular iron deficiency increased HIF-1α, VEGF, and angiogenesis, suggesting that systemic iron deficiency might play an important part in the tumor angiogenesis and recurrence in this young age group of breast cancer patients.

  15. Low neural exosomal levels of cellular survival factors in Alzheimer’s disease

    OpenAIRE

    Goetzl, Edward J.; Boxer, Adam; Schwartz, Janice B.; Abner, Erin L; Petersen, Ronald C.; Miller, Bruce L.; Carlson, Olga D.; Mustapic, Maja; Kapogiannis, Dimitrios

    2015-01-01

    Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer’s disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer’s disease patients than controls (P 

  16. Transcriptional control of fungal cell cycle and cellular events by Fkh2, a forkhead transcription factor in an insect pathogen

    OpenAIRE

    Wang, Juan-juan; Qiu, Lei; Cai, Qing; Ying, Sheng-Hua; Feng, Ming-Guang

    2015-01-01

    Transcriptional control of the cell cycle by forkhead (Fkh) transcription factors is likely associated with fungal adaptation to host and environment. Here we show that Fkh2, an ortholog of yeast Fkh1/2, orchestrates cell cycle and many cellular events of Beauveria bassiana, a filamentous fungal insect pathogen. Deletion of Fkh2 in B. bassiana resulted in dramatic down-regulation of the cyclin-B gene cluster and hence altered cell cycle (longer G2/M and S, but shorter G0/G1, phases) in unicel...

  17. Repressor element-1 silencing transcription factor/neuronal restrictive silencer factor (REST/NRSF can regulate HSV-1 immediate-early transcription via histone modification

    Directory of Open Access Journals (Sweden)

    Hill James M

    2007-06-01

    Full Text Available Abstract Background During primary infection of its human host, Herpes Simplex Virus Type-1 (HSV-1 establishes latency in neurons where the viral genome is maintained in a circular form associated with nucleosomes in a chromatin configration. During latency, most viral genes are silenced, although the molecular mechanisms responsible for this are unclear. We hypothesized that neuronal factors repress HSV-1 gene expression during latency. A search of the HSV-1 DNA sequence for potential regulatory elements identified a Repressor Element-1/Neuronal Restrictive Silencer Element (RE-1/NRSE located between HSV-1 genes ICP22 and ICP4. We predicted that the Repressor Element Silencing Transcription Factor/Neuronal Restrictive Silencer Factor (REST/NRSF regulates expression of ICP22 and ICP4. Results Transient cotransfection indicated that REST/NRSF inhibited the activity of both promoters. In contrast, cotransfection of a mutant form of REST/NRSF encoding only the DNA-binding domain of the protein resulted in less inhibition. Stably transformed cell lines containing episomal reporter plasmids with a chromatin structure showed that REST/NRSF specifically inhibited the ICP4 promoter, but not the ICP22 promoter. REST/NRSF inhibition of the ICP4 promoter was reversed by histone deacetylase (HDAC inhibitor Trichostatin A (TSA. Additionally, chromatin immuno-precipitation (ChIP assays indicated that the corepressor CoREST was recruited to the proximity of ICP4 promoter and that acetylation of histone H4 was reduced in the presence of REST/NRSF. Conclusion Since the ICP4 protein is a key transactivator of HSV-1 lytic cycle genes, these results suggest that REST/NRSF may have an important role in the establishment and/or maintenance of HSV-1 gene silencing during latency by targeting ICP4 expression.

  18. Nuclear epidermal growth factor receptor modulates cellular radio-sensitivity by regulation of chromatin access

    International Nuclear Information System (INIS)

    Purpose: Nuclear EGFR is involved in cellular stress management and regulation of cellular radio-sensitivity. The aim of this study was to elucidate the molecular mode of nuclear EGFR action. Methods: Radiation induced nuclear EGFR-shuttling and EGFR-foci formation was analyzed with immunohistochemistry and confocal microscopy. Composition of γH2AX-protein complexes was analyzed by western-blotting after immuno-precipitation. Functional relevance of nuclear EGFR was analyzed after siRNA mediated depletion of EGFR with respect to activation of ATM, histone H3 acetylation, residual DNA-damage and cell survival after irradiation. Results: Following radiation nuclear EGFR was localized in foci similar to γH2AX. EGFR co-localized in a sub-fraction of γH2AX-foci. Analysis of composition of γH2AX-complexes revealed presence of EGFR, ATM, promyelocytic leukemia protein (PML), histone H3 and hetero-chromatin binding protein (HP1) in response to radiation. Depletion of EGFR protein inhibited ATM activation due to inhibition of acetylase TIP60 activity following irradiation. Consequently, histone H3 acetylation and phosphorylation was blocked and chromatin could not be opened for repair. Thus, residual DNA-damage was increased 24 h after irradiation and cells were radio-sensitized. Comparable results were obtained when cells were treated with EGFR-NLS-peptide, which blocks EGFR nuclear shuttling specifically. Conclusions: Nuclear EGFR is part of DNA-damage repair complex and is involved in regulation of TIP60-acetylase activity. TIP60 is essential for ATM activation and chromatin relaxation which is a prerequisite for DNA-repair in heterochromatic DNA. Thus interventional EGFR strategies during tumor treatment may also interact with DNA-repair by blocking access to damaged DNA.

  19. Alphavirus Restriction by IFITM Proteins.

    Science.gov (United States)

    Weston, Stuart; Czieso, Stephanie; White, Ian J; Smith, Sarah E; Wash, Rachael S; Diaz-Soria, Carmen; Kellam, Paul; Marsh, Mark

    2016-09-01

    Interferon inducible transmembrane proteins (IFITMs) are broad-spectrum antiviral factors. In cell culture the entry of many enveloped viruses, including orthomyxo-, flavi-, and filoviruses, is inhibited by IFITMs, though the mechanism(s) involved remain unclear and may vary between viruses. We demonstrate that Sindbis and Semliki Forest virus (SFV), which both use endocytosis and acid-induced membrane fusion in early endosomes to infect cells, are restricted by the early endosomal IFITM3. The late endosomal IFITM2 is less restrictive and the plasma membrane IFITM1 does not inhibit normal infection by either virus. IFITM3 inhibits release of the SFV capsid into the cytosol, without inhibiting binding, internalization, trafficking to endosomes or low pH-induced conformational changes in the envelope glycoprotein. Infection by SFV fusion at the cell surface was inhibited by IFITM1, but was equally inhibited by IFITM3. Furthermore, an IFITM3 mutant (Y20A) that is localized to the plasma membrane inhibited infection by cell surface fusion more potently than IFITM1. Together, these results indicate that IFITMs, in particular IFITM3, can restrict alphavirus infection by inhibiting viral fusion with cellular membranes. That IFITM3 can restrict SFV infection by fusion at the cell surface equivalently to IFITM1 suggests that IFITM3 has greater antiviral potency against SFV. PMID:27219333

  20. Study Design for a Case Control Investigation of Cellular Telephones and Other Risk Factors for Brain Tumors in Adults

    International Nuclear Information System (INIS)

    The aetiology of brain tumours is poorly understood. Due, in part, to public concern about a postulated relationship between the use of cellular telephones or other increasingly prevalent environmental exposures and the incidence of brain cancer in adults, the National Cancer Institute is collaborating with three US hospitals in a comprehensive case control study of malignant and benign brain tumours. Factors under consideration include use of cellular phones and other wireless communication devices, workplace exposures to chemical agents and electromagnetic fields, dietary factors, family history of tumours, genetic determinants of susceptibility, home appliance use, reproductive history and hormonal exposures, viruses, medical and dental exposure to ionising radiation, and other aspects of medical history. Approximately 800 newly diagnosed brain tumour cases and 800 controls were enrolled at hospitals in Boston, Phoenix and Pittsburgh from 1994 to 1998. Cases include all adults (age ≥ 18 y) newly diagnosed with a histologically confirmed intracranial glioma, histologically confirmed intracranial meningioma or acoustic neuroma. Controls are patients admitted to the same hospitals as the cases, and treated for any of a variety of non-malignant conditions. Key features of the study include its large size, the emphasis on rapid ascertainment of incident cases and interview of study subjects rather than surrogate respondents, the use of detailed, job-specific questions developed by industrial hygienists to ascertain occupational exposures, and the storage of blood samples for future evaluation of inherited susceptibility, biomarkers of exposure and gene environment interactions. (author)

  1. Study Design for a Case Control Investigation of Cellular Telephones and Other Risk Factors for Brain Tumors in Adults

    Energy Technology Data Exchange (ETDEWEB)

    Inskip, P.D.; Hatch, E.E.; Stewart, P.A.; Heineman, E.F.; Ziegler, R.G.; Dosemeci, M.; Parry, D.; Rothman, N.; Boice, J.D. Jr.; Wilcosky, T.C.; Watson, D.J.; Shapiro, W.R.; Selker, R.G.; Fine, H.A.; Black, P. McL.; Loeffler, J.S.; Linet, M.S

    1999-07-01

    The aetiology of brain tumours is poorly understood. Due, in part, to public concern about a postulated relationship between the use of cellular telephones or other increasingly prevalent environmental exposures and the incidence of brain cancer in adults, the National Cancer Institute is collaborating with three US hospitals in a comprehensive case control study of malignant and benign brain tumours. Factors under consideration include use of cellular phones and other wireless communication devices, workplace exposures to chemical agents and electromagnetic fields, dietary factors, family history of tumours, genetic determinants of susceptibility, home appliance use, reproductive history and hormonal exposures, viruses, medical and dental exposure to ionising radiation, and other aspects of medical history. Approximately 800 newly diagnosed brain tumour cases and 800 controls were enrolled at hospitals in Boston, Phoenix and Pittsburgh from 1994 to 1998. Cases include all adults (age {>=} 18 y) newly diagnosed with a histologically confirmed intracranial glioma, histologically confirmed intracranial meningioma or acoustic neuroma. Controls are patients admitted to the same hospitals as the cases, and treated for any of a variety of non-malignant conditions. Key features of the study include its large size, the emphasis on rapid ascertainment of incident cases and interview of study subjects rather than surrogate respondents, the use of detailed, job-specific questions developed by industrial hygienists to ascertain occupational exposures, and the storage of blood samples for future evaluation of inherited susceptibility, biomarkers of exposure and gene environment interactions. (author)

  2. Epigenetic and genetic factors in the cellular response to radiations and DNA-damaging chemicals

    International Nuclear Information System (INIS)

    DNA-damaging agents are widely used as therapeutic tools for a variety of disease states. Many such agents are considered to produce detrimental side effects. Thus, it is important to evaluate both therapeutic efficacy and potential risk. DNA-damaging agents can be so evaluated by comparison to agents whose therapeutic benefit and potential hazards are better known. We propose a framework for such comparison, demonstrating that a simple transformation of cytotoxicity-dose response patterns permits a facile comparison of variation between cells exposed to a single DNA-damaging agent or to different cytotoxic agents. Further, by transforming data from experiments which compare responses of 2 cell populations to an effects ratio, different patterns for the changes in cytotoxicity produced by epigenetic and genetic factors were compared. Using these transformations, we found that there is a wide variation (a factor of 4) between laboratories for a single agent (UVC) and only a slightly larger variation (factor of 6) between normal cell response for different types of DNA-damaging agents (x-ray, UVC, alkylating agents, crosslinking agents). Epigenetic factors such as repair and recovery appear to be a factor only at higher dose levels. Comparison in the cytotoxic effect of a spectrum of DNA-damaging agents in xeroderma pigmentosum, ataxia telangiectasia, and Fanconi's anemia cells indicates significantly different patterns, implying that the effect, and perhaps the nature, of these genetic conditions are quite different

  3. RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro.

    Science.gov (United States)

    Soldati, Chiara; Caramanica, Pasquale; Burney, Matthew J; Toselli, Camilla; Bithell, Angela; Augusti-Tocco, Gabriella; Stanton, Lawrence W; Biagioni, Stefano; Buckley, Noel J; Cacci, Emanuele

    2015-08-01

    Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate. PMID:25691247

  4. Dopaminergic and brain-derived neurotrophic factor signalling in inbred mice exposed to a restricted feeding schedule.

    Science.gov (United States)

    Gelegen, C; van den Heuvel, J; Collier, D A; Campbell, I C; Oppelaar, H; Hessel, E; Kas, M J H

    2008-07-01

    Increased physical activity and decreased motivation to eat are common features in anorexia nervosa. We investigated the development of these features and the potential implication of brain-derived neurotrophic factor (BDNF) and dopaminergic signalling in their development in C57BL/6J and A/J inbred mice, using the 'activity-based anorexia' model. In this model, mice on a restricted-feeding schedule are given unlimited access to running wheels. We measured dopamine receptor D2 and BDNF expression levels in the caudate putamen and the hippocampus, respectively, using in situ hybridization. We found that in response to scheduled feeding, C57BL/6J mice reduced their running wheel activity and displayed food anticipatory activity prior to food intake from day 2 of scheduled feeding as an indication of motivation to eat. In contrast, A/J mice increased running wheel activity during scheduled feeding and lacked food anticipatory activity. These were accompanied by increased dopamine receptor D2 expression in the caudate putamen and reduced BDNF expression in the hippocampus. Consistent with human linkage and association studies on BDNF and dopamine receptor D2 in anorexia nervosa, our study shows that dopaminergic and BDNF signalling are altered as a function of susceptibility to activity-based anorexia. Differences in gene expression and behaviour between A/J and C57BL/6J mice indicate that mouse genetic mapping populations based on these progenitor lines are valuable for identifying molecular determinants of anorexia-related traits. PMID:18363853

  5. Identification of class II ADP-ribosylation factors as cellular factors required for hepatitis C virus replication.

    Science.gov (United States)

    Farhat, Rayan; Séron, Karin; Ferlin, Juliette; Fénéant, Lucie; Belouzard, Sandrine; Goueslain, Lucie; Jackson, Catherine L; Dubuisson, Jean; Rouillé, Yves

    2016-08-01

    GBF1 is a host factor required for hepatitis C virus (HCV) replication. GBF1 functions as a guanine nucleotide exchange factor for G-proteins of the Arf family, which regulate membrane dynamics in the early secretory pathway and the metabolism of cytoplasmic lipid droplets. Here we established that the Arf-guanine nucleotide exchange factor activity of GBF1 is critical for its function in HCV replication, indicating that it promotes viral replication by activating one or more Arf family members. Arf involvement was confirmed with the use of two dominant negative Arf1 mutants. However, siRNA-mediated depletion of Arf1, Arf3 (class I Arfs), Arf4 or Arf5 (class II Arfs), which potentially interact with GBF1, did not significantly inhibit HCV infection. In contrast, the simultaneous depletion of both Arf4 and Arf5, but not of any other Arf pair, imposed a significant inhibition of HCV infection. Interestingly, the simultaneous depletion of both Arf4 and Arf5 had no impact on the activity of the secretory pathway and induced a compaction of the Golgi and an accumulation of lipid droplets. A similar phenotype of lipid droplet accumulation was also observed when GBF1 was inhibited by brefeldin A. In contrast, the simultaneous depletion of both Arf1 and Arf4 resulted in secretion inhibition and Golgi scattering, two actions reminiscent of GBF1 inhibition. We conclude that GBF1 could regulate different metabolic pathways through the activation of different pairs of Arf proteins. PMID:26814617

  6. Wnt inhibitory factor 1 suppresses cancer stemness and induces cellular senescence

    OpenAIRE

    Ramachandran, I; Ganapathy, V.; Gillies, E; Fonseca, I.; Sureban, S M; Houchen, C.W.; A. Reis; Queimado, L

    2014-01-01

    Hyperactivation of the Wingless-type (Wnt)/β-catenin pathway promotes tumor initiation, tumor growth and metastasis in various tissues. Although there is evidence for the involvement of Wnt/β-catenin pathway activation in salivary gland tumors, the precise mechanisms are unknown. Here we report for the first time that downregulation of the Wnt inhibitory factor 1 (WIF1) is a widespread event in salivary gland carcinoma ex-pleomorphic adenoma (CaExPA). We also show that WIF1 downregulation occ...

  7. Caloric restriction.

    Science.gov (United States)

    Speakman, John R; Mitchell, Sharon E

    2011-06-01

    generalized shift from carbohydrate to fat metabolism. Four pathways have been implicated in mediating the CR effect. These are the insulin like growth factor (IGF-1)/insulin signaling pathway, the sirtuin pathway, the adenosine monophosphate (AMP) activated protein kinase (AMPK) pathway and the target of rapamycin (TOR) pathway. These different pathways may interact and may all play important roles mediating different aspects of the response. Exactly how they generate the health benefits remains open for debate, however CR results in reduced oxidative stress and enhanced autophagy, both of which could be essential components of the beneficial effects. Most data about the effects of CR in mammals comes from work on rodents. There is limited work on non-human primates that shows promising effects and one randomized controlled trial in humans where physiological markers of the CR response are consistent with the responses in mice and rats. There are also populations of humans voluntarily restricting themselves. Humans on long term restriction report similar negative side effects to those observed in animals - perpetual hunger, reduced body temperature leading to a feeling of being cold, and diminished libido. Considerable effort has been directed in recent years to find drugs that mimic the CR response. Promising candidates are those that intersect with the critical signaling pathways identified above and include biguanides such as metformin that target the insulin signaling pathway, stilbenes (e.g. resveratrol) that affect sirtuin activity and drugs such as rapamycin that interact with mTOR signaling. Whether it will ever be possible to find drugs that capture the health benefits of CR without the negative side-effects remains unclear. Moreover, even if such drugs are developed how the current licensing system for drug use in western societies would cope with them may be a further obstacle to their use. PMID:21840335

  8. Restrictive cardiomyopathy

    Science.gov (United States)

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy ... In a case of restrictive cardiomyopathy, the heart muscle is normal size or slightly enlarged. Most of the time, it also pumps normally. However, it does not ...

  9. Aiolos transcription factor controls cell death in T cells by regulating Bcl-2 expression and its cellular localization.

    Science.gov (United States)

    Romero, F; Martínez-A, C; Camonis, J; Rebollo, A

    1999-01-01

    We searched for proteins that interact with Ras in interleukin (IL)-2-stimulated or IL-2-deprived cells, and found that the transcription factor Aiolos interacts with Ras. The Ras-Aiolos interaction was confirmed in vitro and in vivo by co-immunoprecipitation. Indirect immunofluorescence shows that IL-2 controls the cellular distribution of Aiolos and induces its tyrosine phosphorylation, required for dissociation from Ras. We also identified functional Aiolos-binding sites in the Bcl-2 promoter, which are able to activate the luciferase reporter gene. Mutation of Aiolos-binding sites within the Bcl-2 promoter inhibits transactivation of the reporter gene luciferase, suggesting direct control of Bcl-2 expression by Aiolos. Co-transfection experiments confirm that Aiolos induces Bcl-2 expression and prevents apoptosis in IL-2-deprived cells. We propose a model for the regulation of Bcl-2 expression via Aiolos. PMID:10369681

  10. Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1

    DEFF Research Database (Denmark)

    Burton, C.M.; Iversen, M.; Carlsen, J.;

    2009-01-01

    BACKGROUND: Post-transplant baseline forced expiratory volume in 1 second (FEV(1)) constitutes a systematic bias in analyses of bronchiolitis obliterans syndrome (BOS). This retrospective study evaluates risk factors for BOS adjusting for the confounding of post-transplant baseline FEV(1). METHODS......: A multivariate survival and competing risk analysis of a large consecutive series of patients (n = 389) from a national center 1992 to 2004. Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and no available lung function measurements (n = 4). RESULTS......: The first maximum FEV(1) occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an...

  11. Cellular Effects of Pyocyanin, a Secreted Virulence Factor of Pseudomonas aeruginosa.

    Science.gov (United States)

    Hall, Susan; McDermott, Catherine; Anoopkumar-Dukie, Shailendra; McFarland, Amelia J; Forbes, Amanda; Perkins, Anthony V; Davey, Andrew K; Chess-Williams, Russ; Kiefel, Milton J; Arora, Devinder; Grant, Gary D

    2016-01-01

    Pyocyanin has recently emerged as an important virulence factor produced by Pseudomonas aeruginosa. The redox-active tricyclic zwitterion has been shown to have a number of potential effects on various organ systems in vitro, including the respiratory, cardiovascular, urological, and central nervous systems. It has been shown that a large number of the effects to these systems are via the formation of reactive oxygen species. The limitations of studies are, to date, focused on the localized effect of the release of pyocyanin (PCN). It has been postulated that, given its chemical properties, PCN is able to readily cross biological membranes, however studies have yet to be undertaken to evaluate this effect. This review highlights the possible manifestations of PCN exposure; however, most studies to date are in vitro. Further high quality in vivo studies are needed to fully assess the physiological manifestations of PCN exposure on the various body systems. PMID:27517959

  12. Cellular Effects of Pyocyanin, a Secreted Virulence Factor of Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Susan Hall

    2016-08-01

    Full Text Available Pyocyanin has recently emerged as an important virulence factor produced by Pseudomonas aeruginosa. The redox-active tricyclic zwitterion has been shown to have a number of potential effects on various organ systems in vitro, including the respiratory, cardiovascular, urological, and central nervous systems. It has been shown that a large number of the effects to these systems are via the formation of reactive oxygen species. The limitations of studies are, to date, focused on the localized effect of the release of pyocyanin (PCN. It has been postulated that, given its chemical properties, PCN is able to readily cross biological membranes, however studies have yet to be undertaken to evaluate this effect. This review highlights the possible manifestations of PCN exposure; however, most studies to date are in vitro. Further high quality in vivo studies are needed to fully assess the physiological manifestations of PCN exposure on the various body systems.

  13. Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo

    OpenAIRE

    Paquette, Alice J.; Perez, Sharon E.; Anderson, David J.

    2000-01-01

    The neuron-restrictive silencer factor (NRSF; also known as REST for repressor element-1 silencing transcription factor) is a transcriptional repressor of multiple neuronal genes, but little is known about its function in vivo. NRSF is normally down-regulated upon neuronal differentiation. Constitutive expression of NRSF in the developing spinal cord of chicken embryos caused repression of two endogenous target genes, N-tubulin and Ng-CAM, but did not prevent overt...

  14. Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signalling in the mouse hypothalamus

    Directory of Open Access Journals (Sweden)

    AntonioGiordano

    2013-12-01

    Full Text Available In the mouse hypothalamus, ciliary neurotrophic factor (CNTF is mainly expressed by ependymal cells and tanycytes of the ependymal layer covering the third ventricle. Since exogenously administered CNTF causes reduced food intake and weight loss, we tested whether endogenous CNTF might be involved in energy balance regulation. We thus evaluated CNTF production and responsiveness in the hypothalamus of mice fed a high-fat diet (HFD, of ob/ob obese mice, and of mice fed a calorie restriction (CR regimen. RT-PCR showed that CNTF mRNA increased significantly in HFD mice and decreased significantly in CR animals. Western blotting confirmed that CNTF expression was higher in HFD mice and reduced in CR mice, but high interindividual variability blunted the significance of these differences. By immunohistochemistry, hypothalamic tuberal and mammillary region tanycytes stained strongly for CNTF in HFD mice, whereas CR mice exhibited markedly reduced staining. RT-PCR and Western blotting disclosed that changes in CNTF expression were paralleled by changes in the expression of its specific receptor, CNTF receptor α (CNTFRα. Injection of recombinant CNTF and detection of phospho-signal transducer and activator of transcription 3 (P-STAT3 showed that CNTF responsiveness by the ependymal layer, mainly by tanycytes, was higher in HFD than CR mice. In addition, in HFD mice CNTF administration induced distinctive STAT3 signalling in a large neuron population located in the dorsomedial and ventromedial nuclei, perifornical area and mammillary body. The hypothalamic expression of CNTF and CNTFRα did not change in the hyperphagic, leptin-deficient ob/ob obese mice; accordingly, P-STAT3 immunoreactivity in CNTF-treated ob/ob mice was confined to ependymal layer and arcuate neurons. Collectively, these data suggest that hypothalamic CNTF is involved in controlling the energy balance and that CNTF signalling plays a role in HFD obese mice at specific sites.

  15. In vitro and in vivo analyses of a genetically—restricted antigen specific factor from mixed cell cultures of macrophage,T and B lymphocytes

    Institute of Scientific and Technical Information of China (English)

    CHAURMW; LAUASK

    1990-01-01

    An immunostimulatory factor was identified to be secreted by antigen-pulsed macrophages.This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo.Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a geneticallyrestricted antigen specific factor (ASF).The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-qulsed macrophages with T lymphocytes,and then spleen cells,and finally the TNP-coated sheep red blood cells.

  16. Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC-3G and APOBEC-3F restriction factors.

    Science.gov (United States)

    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-06-01

    The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive cells, possess strong anti-HIV-1 activity and are sufficient to confer a nonpermissive phenotype. Vif induces the degradation of hA3G and hA3F, suggesting that its main function is to counteract these cellular factors. Most studies focused on the hypermutation induced by the cytidine deaminase activity of hA3G and hA3F and on their Vif-induced degradation by the proteasome. However, recent studies suggested that several mechanisms are involved both in the antiviral activity of hA3G and hA3F and in the way Vif counteracts these antiviral factors. Attempts to reconcile the studies involving Vif in virus assembly and stability with these recent findings suggest that hA3G and hA3F partially exert their antiviral activity independently of their catalytic activity by destabilizing the viral core and the reverse transcription complex, possibly by interfering with the assembly and/or maturation of the viral particles. Vif could then counteract hA3G and hA3F by excluding them from the viral assembly intermediates through competition for the viral genomic RNA, by regulating the proteolytic processing of Pr55(Gag), by enhancing the efficiency of the reverse transcription process, and by inhibiting the enzymatic activities of hA3G and hA3F. PMID:19487726

  17. Sleep Loss as a Factor to Induce Cellular and Molecular Inflammatory Variations

    Directory of Open Access Journals (Sweden)

    Gabriela Hurtado-Alvarado

    2013-01-01

    Full Text Available A reduction in the amount of time spent sleeping occurs chronically in modern society. Clinical and experimental studies in humans and animal models have shown that immune function is impaired when sleep loss is experienced. Sleep loss exerts a strong regulatory influence on peripheral levels of inflammatory mediators of the immune response. An increasing number of research projects support the existence of reciprocal regulation between sleep and low-intensity inflammatory response. Recent studies show that sleep deficient humans and rodents exhibit a proinflammatory component; therefore, sleep loss is considered as a risk factor for developing cardiovascular, metabolic, and neurodegenerative diseases (e.g., diabetes, Alzheimer's disease, and multiple sclerosis. Circulating levels of proinflammatory mediators depend on the intensity and duration of the method employed to induce sleep loss. Recognizing the fact that the concentration of proinflammatory mediators is different between acute and chronic sleep-loss may expand the understanding of the relationship between sleep and the immune response. The aim of this review is to integrate data from recent published reports (2002–2013 on the effects of sleep loss on the immune response. This review may allow readers to have an integrated view of the mechanisms involved in central and peripheral deficits induced by sleep loss.

  18. Measurement of immunotargeted plasmonic nanoparticles' cellular binding: a key factor in optimizing diagnostic efficacy

    International Nuclear Information System (INIS)

    In this study, we use polarized light scattering to study immunotargeted plasmonic nanoparticles which bind to live SK-BR-3 human breast carcinoma cells. Gold nanoparticles can be conjugated to various biomolecules in order to target specific molecular signatures of disease. This specific targeting provides enhanced contrast in scattering-based optical imaging techniques. While there are papers which report the number of antibodies that bind per nanoparticle, there are almost no reports of the key factor which influences diagnostic or therapeutic efficacy using nanoparticles: the number of targeted nanoparticles that bind per cell. To achieve this goal, we have developed a 'negative' method of determining the binding concentration of those antibody/nanoparticle bioconjugates which are targeted specifically to breast cancer cells. Unlike previously reported methods, we collected unbound nanoparticle bioconjugates and measured the light scattering from dilute solutions of these particles so that quantitative binding information can be obtained. By following this process, the interaction effects of adjacent bound nanoparticles on the cell membrane can be avoided simply by measuring the light scattering from the unbound nanoparticles. Specifically, using nanoshells of two different sizes, we compared the binding concentrations of anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates targeted to HER2-positive SK-BR-3 breast cancer cells. The results indicate that, for anti-HER2/nanoshell bioconjugates, there are approximately 800-1600 nanoshells bound per cell; for anti-IgG/nanoshell bioconjugates, the binding concentration is significantly lower at nearly 100 nanoshells bound per cell. These results are also supported by dark-field microscopy images of the cells labeled with anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates

  19. SAMHD1: a new insight into HIV-1 restriction in myeloid cells

    OpenAIRE

    Wu Li; St Gelais Corine

    2011-01-01

    Abstract Human myeloid-lineage cells are refractory to HIV-1 infection. The Vpx proteins from HIV-2 and sooty mangabey SIV render these cells permissive to HIV-1 infection through proteasomal degradation of a putative restriction factor. Two recent studies discovered the cellular protein SAMHD1 to be this restriction factor, demonstrating that Vpx induces proteasomal degradation of SAMHD1 and enhances HIV-1 infection in myeloid-lineage cells. SAMHD1 functions as a myeloid-cell-specific HIV-1 ...

  20. Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade

    International Nuclear Information System (INIS)

    Tissue factor (TF) is the high-affinity receptor for plasma factors VII and VIIa. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade. outside the vasculature, TF expression is highly dependent upon cell type. TF can also be induced by inflammatory mediators to appear on monocytes and vascular endothelial cells as a component of cellular immune responses. As an initial step toward elucidating the regulatory regions involved in control of TF gene expression, we have established the organization of the 12.4 kbp human TF gene and its complete DNA sequence. There are six exons separated by five introns. Within intron 5, we have mapped the single nucleotide difference which leads to the previously described MspI polymorphism; the same intron also contains an apparently polymorphic PstI site. The TF gene also contains three full-length Alu repeats and one partial Alu repeat. A single major transcription start site was identified 26 bp downstream from a TATA consensus promoter element. The putative promoter and first exon are located within a 1.2 kbp region of very high G + C content which fits the criteria of an HTF island. A cluster of predicted binding sites for a number of known transcription factors was found to coincide with this putative promoter region. These factors included AP-1 and AP-2 which can mediate the effects of phorbol esters, agonists known to induce TF expression in monocytes and vascular endothelial cells

  1. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    International Nuclear Information System (INIS)

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: ► Endothelial cells mount a stress response under conditions of low serum. ► Endothelial VEGFR levels are

  2. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    Energy Technology Data Exchange (ETDEWEB)

    Latham, Antony M.; Odell, Adam F. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Mughal, Nadeem A. [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Issitt, Theo; Ulyatt, Clare; Walker, John H. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Homer-Vanniasinkam, Shervanthi [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Ponnambalam, Sreenivasan, E-mail: s.ponnambalam@leeds.ac.uk [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom)

    2012-11-01

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black

  3. Identification of multiple cellular uptake pathways of polystyrene nanoparticles and factors affecting the uptake: relevance for drug delivery systems.

    Science.gov (United States)

    Firdessa, Rebuma; Oelschlaeger, Tobias A; Moll, Heidrun

    2014-01-01

    Nanoparticles may address challenges by human diseases through improving diagnosis, vaccination and treatment. The uptake mechanism regulates the type of threat a particle poses on the host cells and how a cell responds to it. Hence, understanding the uptake mechanisms and cellular interactions of nanoparticles at the cellular and subcellular level is a prerequisite for their effective biomedical applications. The present study shows the uptake mechanisms of polystyrene nanoparticles and factors affecting their uptake in bone marrow-derived macrophages, 293T kidney epithelial cells and L929 fibroblasts. Labeling with the endocytic marker FM4-64 and transmission electron microscopy studies show that the nanoparticles were internalized rapidly via endocytosis and accumulated in intracellular vesicles. Soon after their internalizations, nanoparticles trafficked to organelles with acidic pH. Analysis of the ultrastructural morphology of the plasma membrane invaginations or extravasations provides clear evidence for the involvement of several uptake routes in parallel to internalize a given type of nanoparticles by mammalian cells, highlighting the complexity of the nanoparticle-cell interactions. Blocking the specific endocytic pathways by different pharmacological inhibitors shows similar outcomes. The potential to take up nanoparticles varies highly among different cell types in a particle sizes-, time- and energy-dependent manner. Furthermore, infection and the activation status of bone marrow-derived macrophages significantly affect the uptake potential of the cells, indicating the need to understand the diseases' pathogenesis to establish effective and rational drug-delivery systems. This study enhances our understanding of the application of nanotechnology in biomedical sciences. PMID:25224362

  4. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21

    OpenAIRE

    Lees, Emma K.; Król, Elżbieta; Grant, Louise; Shearer, Kirsty; Wyse, Cathy; Moncur, Eleanor; Bykowska, Aleksandra S; Mody, Nimesh; Gettys, Thomas W.; Delibegovic, Mirela

    2014-01-01

    Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) o...

  5. Behavioural changes are a major contributing factor in the reduction of sarcopenia in caloric-restricted ageing mice

    NARCIS (Netherlands)

    Norren, van K.; Rusli, F.; Dijk, van M.; Lute, C.; Nagel, J.C.; Dijk, F.J.; Dwarkasing, J.T.; Boekschoten, M.V.; Luiking, Y.; Witkamp, R.F.; Müller, M.R.; Steegenga, W.T.

    2015-01-01

    Background - In rodent models, caloric restriction (CR) with maintenance of adequate micronutrient supply has been reported to increase lifespan and to reduce age-induced muscle loss (sarcopenia) during ageing. In the present study, we further investigated effects of CR on the onset and severity of

  6. 农村群众体育活动的制约因素发展对策%Study on Restricting Factors of Rural Mass Sports

    Institute of Scientific and Technical Information of China (English)

    高小爱; 陈巧弟

    2011-01-01

    采用问卷调查法,数理统计法等分析研究,认为制约农村群众体育活动的因素主要有:经济因素、社会因素、农民自身因素及自然环境因素。针对这些因素,提出相应的发展对策与建议。%Through using the method of literature review and mathematical statistics,this paper finds out the factors restricting the rural mass sports development including economic factors,social factors,natural factors and farmer factors.Based on existing factors

  7. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21.

    Science.gov (United States)

    Lees, Emma K; Król, Elżbieta; Grant, Louise; Shearer, Kirsty; Wyse, Cathy; Moncur, Eleanor; Bykowska, Aleksandra S; Mody, Nimesh; Gettys, Thomas W; Delibegovic, Mirela

    2014-10-01

    Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) or control diet (0.86% methionine) for 8 weeks or 48 h. Food intake and whole-body physiology were assessed and serum/tissues analyzed biochemically. Methionine restriction in 12-month-old mice completely reversed age-induced alterations in body weight, adiposity, physical activity, and glucose tolerance to the levels measured in healthy 2-month-old control-fed mice. This was despite a significant increase in food intake in 12-month-old MR-fed mice. Methionine restriction decreased hepatic lipogenic gene expression and caused a remodeling of lipid metabolism in white adipose tissue, alongside increased insulin-induced phosphorylation of the insulin receptor (IR) and Akt in peripheral tissues. Mice restricted of methionine exhibited increased circulating and hepatic gene expression levels of FGF21, phosphorylation of eIF2a, and expression of ATF4, with a concomitant decrease in IRE1α phosphorylation. Short-term 48-h MR treatment increased hepatic FGF21 expression/secretion and insulin signaling and improved whole-body glucose homeostasis without affecting body weight. Our findings suggest that MR feeding can reverse the negative effects of aging on body mass, adiposity, and insulin resistance through an FGF21 mechanism. These findings implicate MR dietary intervention as a viable therapy for age-induced metabolic syndrome in adult humans. PMID:24935677

  8. 甘孜州畜牧业发展的制约因素及对策%Restrictive Factors and Countermeasures of Animal Husbandry Development in Ganzi Prefecture

    Institute of Scientific and Technical Information of China (English)

    邓竹佳

    2012-01-01

    介绍了甘孜州畜牧业发展的优势,分析了其发展畜牧业的制约因素,并提出了相应的对策,以供参考。%The advantages of animal husbandry development were introduced,the restrictive factors of animal husbandry development were analyzed.Countermeasures were proposed for reference.

  9. SAMHD1, the Aicardi-Goutières syndrome gene and retroviral restriction factor, is a phosphorolytic ribonuclease rather than a hydrolytic ribonuclease.

    Science.gov (United States)

    Ryoo, Jeongmin; Hwang, Sung-Yeon; Choi, Jongsu; Oh, Changhoon; Ahn, Kwangseog

    2016-09-01

    SAMHD1 plays diverse roles in innate immunity, autoimmune diseases and HIV restriction, but the mechanisms involved are still unclear. SAMHD1 has been reported to have both dNTPase and RNase activities. However, whether SAMHD1 possesses RNase activity remains highly controversial. Here, we found that, unlike conventional hydrolytic exoribonucleases, SAMHD1 requires inorganic phosphate to degrade RNA substrates and produces nucleotide diphosphates rather than nucleoside monophosphates, which indicated that SAMHD1 is a phosphorolytic but not hydrolytic 3'-5' exoribonuclease. Furthermore, SAMHD1 preferentially cleaved single-stranded RNAs comprising A20 or U20, whereas neither C20 nor G20 was susceptible to SAMHD1-mediated degradation. Our findings will facilitate more advanced studies into the role of the SAMHD1 RNase function in the cellular pathogenesis implicated in nucleic acid-triggered inflammatory responses and the anti-retroviral function of SAMHD1. PMID:27387229

  10. Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.

    Directory of Open Access Journals (Sweden)

    Hanna Björkelund

    Full Text Available The interaction of the epidermal growth factor (EGF with its receptor (EGFR is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of (125I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®.Highly repeatable and precise measurements show that the overall apparent affinity of the (125I-EGF - EGFR interaction is greatly dependent on cell line at normal culturing conditions, ranging from K(D ≈ 200 pM on SKBR3 cells to K(D≈8 nM on A431 cells. The (125I-EGF - EGFR binding curves (irrespective of cell line have strong signs of multiple simultaneous interactions. Furthermore, for the cell lines A431 and SKOV3, gefitinib treatment increases the (125I-EGF - EGFR affinity, in particular when the cells are starved. The (125I-EGF - EGFR interaction on cell line U343 is sensitive to starvation while as on SKBR3 it is insensitive to gefitinib and starvation.The intriguing pattern of the binding characteristics proves that the cellular context is important when deciphering how EGF interacts with EGFR. From a general perspective, care is advisable when generalizing ligand-receptor interaction results across multiple cell-lines.

  11. Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Yasuda, Takeshi [Radiation Emergency Medicine Research Program, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Fujita, Mayumi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Asada, Masahiro [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Meineke, Viktor [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany); Imamura, Toru [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan)

    2014-02-01

    Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation with γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the

  12. Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

    International Nuclear Information System (INIS)

    Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation with γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the

  13. Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1.

    Science.gov (United States)

    Jeong, Gi Uk; Park, Il-Hyun; Ahn, Kwangseog; Ahn, Byung-Yoon

    2016-08-01

    SAMHD1 is a cellular protein that possesses dNTPase activity and inhibits retroviruses and DNA viruses through the depletion of cellular dNTPs. However, recent evidence suggests the existence of alternative or additional mechanisms that involve novel nuclease activities. Hepatitis B virus is a DNA virus but resembles retroviruses in that its DNA genome is synthesized via reverse transcription of an RNA transcript. SAMHD1 was shown to inhibit the expression and replication of a transfected HBV DNA. We further investigated the antiviral mechanisms in a newly developed infection assay. Our data indicated that SAMHD1 exerts a profound antiviral effect. In addition, unlike previous findings, our results demonstrate the essential role of SAMHD1 dNTPase. SAMHD1 did not affect virion-derived cccDNA and gene expression but specifically inhibited viral DNA synthesis. These results indicate that SAMHD1 inhibits HBV replication at the reverse transcription step, most likely through the depletion of cellular dNTPs. PMID:27179347

  14. Restricted Airspace

    Data.gov (United States)

    Federal Laboratory Consortium — Redstone Technical Test Center has restricted airspace up to 30,000 feet ASL. Airspace encompasses R-2104 (Redstone). Airspace is used extensively for airborne/UAV...

  15. Effects of the breed, sex and age on cellular content and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel

    OpenAIRE

    Giraldo Carlos E; López Catalina; Álvarez María E; Samudio Ismael J; Prades Marta; Carmona Jorge U

    2013-01-01

    Abstract Background There is no information on the effects of the breed, gender and age on the cellular content and growth factor (GF) release from equine pure-platelet rich plasma (P-PRP) and pure-platelet rich gel (P-PRG). The objectives of this study were: 1) to compare the cellular composition of P-PRP with whole blood and platelet poor plasma (PPP); 2) to compare the concentration of transforming GF beta 1 (TGF-β1) and platelet derived GF isoform BB (PDGF-BB) between P-PRP treated with n...

  16. Regulation of Ras exchange factors and cellular localization of Ras activation by lipid messengers in T cells

    Directory of Open Access Journals (Sweden)

    Jesse E. Jun

    2013-09-01

    Full Text Available The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and SOS-family GEFs.Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood.One large group of biomolecules critically involved in the control of Ras-GEFs´functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells.

  17. Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene.

    OpenAIRE

    Ho, I C; Vorhees, P; Marin, N; Oakley, B K; Tsai, S F; Orkin, S H; Leiden, J. M.

    1991-01-01

    In addition to its role in the recognition of foreign antigens, the T cell receptor (TCR) alpha gene serves as a model system for studies of developmentally-regulated, lineage-specific gene expression in T cells. TCR alpha gene expression is restricted to cells of the TCR alpha/beta+ lineage, and is controlled by a T cell-specific transcriptional enhancer located 4.5 kb 3' to the C alpha gene segment. The TCR alpha enhancer contains four nuclear protein binding sites called T alpha 1-T alpha ...

  18. Effects of chloroquine and hepatic stimulator substance on cellular accumulation and nuclear binding of 125I-epidermal growth factor in primary culture of adult rat hepatocytes

    International Nuclear Information System (INIS)

    The effects of chloroquine and hepatic stimulator substance (HSS) on cellular accumulation and nuclear binding of 125I-epidermal growth factor (EGF) were examined in primary culture of adult rat hepatocytes. When intact hepatocytes were incubated at 37 degrees C with 125I-EGF, the cellular accumulation and the nuclear binding reached a peak at 1 h and declined thereafter, where the nuclear binding was 2.49% at 1 h and 2.53% at 2 h. Chloroquine resulted in a time-dependent increase in the cellular accumulation and the nuclear binding was 3.37% at 1 h and 3.72% at 2 h. In contrast, HSS produced no change in each value, suggesting that HSS does not modulate EGF receptors in plasma membrane and nucleus

  19. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations

    Directory of Open Access Journals (Sweden)

    Kroeger Cynthia M

    2012-10-01

    Full Text Available Abstract Background The ability of an intermittent fasting (IF-calorie restriction (CR regimen (with or without liquid meals to modulate adipokines in a way that is protective against coronary heart disease (CHD has yet to be tested. Objective Accordingly, we examined the effects of an IFCR diet on adipokine profile, body composition, and markers of CHD risk in obese women. Methods Subjects (n = 54 were randomized to either the IFCR-liquid (IFCR-L or IFCR-food based (IFCR-F diet for 10 weeks. Results Greater decreases in body weight and waist circumference were noted in the IFCR-L group (4 ± 1 kg; 6 ± 1 cm versus the IFCR-F group (3 ± 1 kg; 4 ± 1 cm. Similar reductions (P Conclusion These findings suggest that IFCR with a liquid diet favorably modulates visceral fat and adipokines in a way that may confer protection against CHD.

  20. Differential binding of the Bombyx silk gland-specific factor SGFB to its target DNA sequence drives posterior-cell-restricted expression.

    OpenAIRE

    Horard, B; Julien, E; Nony, P; Garel, A; Couble, P

    1997-01-01

    The gene encoding the silk protein P25 in Bombyx mori is expressed in the posterior silk gland (PSG) cells and repressed in the middle silk gland (MSG) cells. To identify the factors involved in this transcription-dependent spatial restriction, we examined the P25 chromatin in PSG and MSG nuclei by DNase I-aided ligation-mediated PCR and analyzed the expression of various P25-lacZ constructs in biolistically treated silk glands. P25 promoter activation depends on two cis-acting elements. One ...

  1. Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells

    OpenAIRE

    Laich, A; Matscheski, A.; Mück, C.; Ferrando-May, E.; H. Pircher; Ebner, H L; Micutkova, L.; Huber, L A; M. Hermann; Offerdinger, M.; Hess, M. W.; Jansen-Dürr, P; Zwerschke, W.

    2010-01-01

    Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) is an important regulator of cell proliferation and survival, which plays an important role in a variety of epithelial cancers, including prostate cancer, cervical cancer and breast cancer. IGFBP-3 was described as a tumor suppressor in the prostate and identified as a functional cellular target for the E7 oncoprotein of human papillomaviruses. IGFBP-3 interacts with IGF-I outside the cell; however, IGF-independent actions of IGFBP...

  2. Increased expression and dysregulated association of restriction factors and type I interferon in HIV, HCV mono- and co-infected patients.

    Science.gov (United States)

    Zhu, Jia-Wu; Liu, Feng-Liang; Mu, Dan; Deng, De-Yao; Zheng, Yong-Tang

    2016-06-01

    Host restriction factors and type I interferon are important in limiting HIV and HCV infections, yet the role of HIV, HCV mono- and co-infection in regulating these antiviral genes expression is not clear. In this study, we measured the levels of TRIM5α, TRIM22, APOBEC3G, and IFN-α, -β mRNA expression in peripheral blood mononuclear cells of 43 HIV mono-infected, 70 HCV mono-infected and 64 HIV/HCV co-infected patients along with 98 healthy controls. We also quantified HIV and HCV viral loads in mono- and co-infected patients. The results showed that HCV, HIV mono- and co-infection differentially increased TRIM22, APOBEC3G, and IFN-α, -β mRNA expression while the mRNA expression of TRIMα was upregulated only by HCV-mono infection. HIV/HCV co-infection was associated with higher viral load, compared to either HIV or HCV mono-infection. Additionally, we showed TRIMα and TRIM22 positively correlated with IFN-α, -β, which could be dysregulated by HIV, HCV mono- and co-infection. Furthermore, we found TRIM22 negatively correlated with HCV viral load in mono-infected patients and APOBEC3G positively correlated with HCV viral load in co-infected patients. Collectively, our findings suggest the potential role of restriction factors in restricting HIV, HCV mono- and co-infection in vivo, which appears to be a therapeutic target for potential drug discovery. J. Med. Virol. 88:987-995, 2016. © 2015 Wiley Periodicals, Inc. PMID:26519943

  3. Elevated circulating insulin-like growth factor binding protein-1 is sufficient to cause fetal growth restriction.

    Science.gov (United States)

    Watson, Carole S; Bialek, Peter; Anzo, Makoto; Khosravi, Javad; Yee, Siu-Pok; Han, Victor K M

    2006-03-01

    IGF binding protein-1 (IGFBP-1) inhibits the mitogenic actions of the IGFs. Circulating IGFBP-1 is elevated in newborns and experimental animals with fetal growth restriction (FGR). To establish a causal relationship between high circulating IGFBP-1 and FGR, we have generated transgenic mice using the mouse alpha-fetoprotein gene promoter to target overexpression of human IGFBP-1 (hIGFBP-1) in the fetal liver. These transgenic mice (AFP-BP1) expressed hIGFBP-1 mainly in the fetal hepatocytes, starting at embryonic d 14.5 (E14.5), with lower levels in the gut. The expression peaked at 1 wk postnatally (plasma concentration, 474 +/- 34 ng/ml). At birth, AFP-BP1 pups were 18% smaller [weighed 1.34 +/- 0.02 g compared with 1.62 +/- 0.04 g for wild type (WT); P catch-up growth. The placentas of the AFP-BP1 mice were larger than WT from E16.5 onwards (150 +/- 12 for AFP-BP1 vs. 100 +/- 5 mg for WT at E16.5; P catch-up growth. Overall, these data clearly demonstrate that high concentrations of circulating IGFBP-1 are sufficient to cause FGR. PMID:16293667

  4. Epigenetic regulation of caloric restriction in aging

    Directory of Open Access Journals (Sweden)

    Daniel Michael

    2011-08-01

    Full Text Available Abstract The molecular mechanisms of aging are the subject of much research and have facilitated potential interventions to delay aging and aging-related degenerative diseases in humans. The aging process is frequently affected by environmental factors, and caloric restriction is by far the most effective and established environmental manipulation for extending lifespan in various animal models. However, the precise mechanisms by which caloric restriction affects lifespan are still not clear. Epigenetic mechanisms have recently been recognized as major contributors to nutrition-related longevity and aging control. Two primary epigenetic codes, DNA methylation and histone modification, are believed to dynamically influence chromatin structure, resulting in expression changes of relevant genes. In this review, we assess the current advances in epigenetic regulation in response to caloric restriction and how this affects cellular senescence, aging and potential extension of a healthy lifespan in humans. Enhanced understanding of the important role of epigenetics in the control of the aging process through caloric restriction may lead to clinical advances in the prevention and therapy of human aging-associated diseases.

  5. Placental Adaptations in Growth Restriction

    Directory of Open Access Journals (Sweden)

    Song Zhang

    2015-01-01

    Full Text Available The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions.

  6. Cellular responses induced by environmental stress factors in Arctic Seabird chicks : Responses of the antioxidant defense system and autophagic lysosomal processes related to contaminant exposure and food restriction

    OpenAIRE

    Hegseth, Marit Nøst

    2011-01-01

    The papers of this thesis are not available in Munin: 1. Marit Nøst Hegseth, Lionel Camus, Lisa Bjørnsdatter Helgason, Raffaella Bocchetti, Geir Wing Gabrielsen and Francesco Regoli: 'Hepatic antioxidant responses related to levels of PCBs and metals in chicks of three Arctic seabird species', Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology (2011) 154: 28-35. Available at http://dx.doi.org/10.1016/j.cbpc.2011.02.008 2. Marit Nøst Hegseth, Lionel Camus, Stefania Go...

  7. Both viral E2 protein and the cellular factor PEBP2 regulate transcription via E2 consensus sites within the bovine papillomavirus type 4 long control region.

    OpenAIRE

    Jackson, M E; Campo, M. S.

    1995-01-01

    The bovine papillomavirus type 4 (BPV4) long control region (LCR) contains three consensus binding sites, E2(1), E2(2), and E2(3) (ACCN6GGT), for the viral E2 transcription factor and a fourth degenerate site, dE2 (ATCN6GGT), which lies 3 bp upstream of E2(3). The E2(2) site was found to bind the cellular transcription factor PEBP2, and mutations at this site reduced basal promoter activity by as much as 60%, indicating an important role for PEBP2 in LCR function. Mutation of the E2(3) or dE2...

  8. Cellular and humoral responses to Leishmania major virulence factors in healed cutaneous leishmaniasis and Mediterranean visceral leishmaniasis patients.

    OpenAIRE

    Lakhal-Naouar, Inès; Boussoffara, Thouraya; Meddeb-Garnaoui, Amel; Ben Achour-Chenik, Yosser; Louzir, Hechmi; Chenik, Mehdi

    2009-01-01

    Cellular and humoral immune responses of healed cutaneous leishmaniasis and Mediterranean visceral leishmaniasis patients were evaluated against results for Leishmania major virulence proteins L. major protein disulfide isomerase (LmPDI) and mitogen-activated protein kinase kinase (MAPKK). Only MAPKK induces significant peripheral blood mononuclear cell proliferation with gamma interferon production as well as antibody responses. Thus, MAPKK may be of interest in Leishmania vaccination and se...

  9. Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats

    Institute of Scientific and Technical Information of China (English)

    In(ě)s Tomada; Nuno Tomada; Henrique Almeida; Delminda Neves

    2012-01-01

    The purpose of the current study was to evaluate the effect of a high-fat (HF) diet,energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF),angiopoietin (Ang) 1 and 2,and their receptors in rat corpus cavernosum (CC).Male Wistar rats were fed adlibitum with an HF diet for 8 or 16 weeks.After 8 weeks of the HF diet,a group of rats was subjected to energy restriction with or without exercise for 8 weeks.Control animals had free access to standard diet for the same period.After euthanasia,blood was collected and the penises removed for immunofluorescence assays (VEGF,VEGF receptor (VEGFR) 1 and 2,Ang1,Ang2 and Tie2) and semiquantification of VEGF,VEGFR1,VEGFR2,Ang1,Ang2,Tie2,endothelial nitric oxide synthase (eNOS) and Akt/phospho-Akt by Western blotting.HF diet-fed rats exhibited lower high-density lipoprotein cholesterol (HDL-c) levels,higher systolic blood pressure and an increased atherogenic index.A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs.The Akt pathway was activated by the HF diet.Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression.These results emphasize the role of diet on vascular function regulation,demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/rie2 systems occurs before serum lipid changes and obesity onset,antedating structural atherosclerotic features.

  10. The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.

    Directory of Open Access Journals (Sweden)

    Jyh-Ming Liou

    Full Text Available The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.The defined daily dose (DDD of antibiotics was analyzed using the Taiwan National Health Insurance (NHI research database. H. pylori strains isolated from treatment naïve (N=1395 and failure from prior eradication therapies (N=360 from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001. The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001, which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

  11. HIV-1 Vif versus the APOBEC3 cytidine deaminases: an intracellular duel between pathogen and host restriction factors.

    Science.gov (United States)

    Wissing, Silke; Galloway, Nicole L K; Greene, Warner C

    2010-10-01

    The Vif protein of HIV is essential for the effective propagation of this pathogenic retrovirus in vivo. Vif acts by preventing virion encapsidation of two potent antiviral factors, the APOBEC3G and APOBEC3F cytidine deaminases. Decreased encapsidation in part involves Vif-mediated recruitment of a ubiquitin E3 ligase complex that promotes polyubiquitylation and proteasome-mediated degradation of APOBEC3G/F. The resultant decline in intracellular levels of these enzymes leads to decreased encapsidation of APOBECG/F into budding virions. This review discusses recent advances in our understanding of the dynamic interplay of Vif with the antiviral APOBEC3 enzymes. PMID:20538015

  12. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  13. IN SUBJECTS ALLERGIC TO GRASS POLLEN, BASOPHIL SENSITIVITY DECREASES DURING SUBCUTANEOUS IMMUNOTHERAPY DUE TO BOTH HUMORAL FACTORS AND CELLULAR DESENSITIZATION

    DEFF Research Database (Denmark)

    Schmid, Johannes Martin; Dahl, Ronald; Hoffmann, Hans Jürgen

    2011-01-01

    allergic rhino-conjunctivitis with basophil activation tests (BAT). Methods: We have randomized 24 patients to a treatment (18) and an open control group (6). Repeated BAT were performed at baseline and througout treatment. Heparinized blood was centrifuged, plasma was removed, the cells washed twice, then...... be a cellular desensitisation after 1 year. Selected for presentation during the Poster Walk on Friday. (2011), Abstracts of the 11th Euroconference on Clinical Cell Analysis. Dublin, Ireland, 14–17 September 2011. Cytometry, 80B: 390–429. doi: 10.1002/cyto.b.20619...

  14. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.

    Directory of Open Access Journals (Sweden)

    I-Chueh Huang

    Full Text Available Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3 are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV hemagglutinin (HA protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2 of Marburg and Ebola filoviruses (MARV, EBOV. Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV and entry mediated by the SARS-CoV spike (S protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

  15. Hepatic insulin-like growth-factor binding protein (igfbp) responses to food restriction in Atlantic salmon smolts.

    Science.gov (United States)

    Breves, Jason P; Phipps-Costin, Silas K; Fujimoto, Chelsea K; Einarsdottir, Ingibjörg E; Regish, Amy M; Björnsson, Björn Thrandur; McCormick, Stephen D

    2016-07-01

    The growth hormone (Gh)/insulin-like growth-factor (Igf) system plays a central role in the regulation of growth in fishes. However, the roles of Igf binding proteins (Igfbps) in coordinating responses to food availability are unresolved, especially in anadromous fishes preparing for seaward migration. We assayed plasma Gh, Igf1, thyroid hormones and cortisol along with igfbp mRNA levels in fasted and fed Atlantic salmon (Salmo salar). Fish were fasted for 3 or 10days near the peak of smoltification (late April to early May). Fasting reduced plasma glucose by 3days and condition factor by 10days. Plasma Gh, cortisol, and thyroxine (T4) were not altered in response to fasting, whereas Igf1 and 3,5,3'-triiodo-l-thyronine (T3) were slightly higher and lower than controls, respectively. Hepatic igfbp1b1, -1b2, -2a, -2b1 and -2b2 mRNA levels were not responsive to fasting, but there were marked increases in igfbp1a1 following 3 and 10days of fasting. Fasting did not alter hepatic igf1 or igf2; however, muscle igf1 was diminished by 10days of fasting. There were no signs that fasting compromised branchial ionoregulatory functions, as indicated by unchanged Na(+)/K(+)-ATPase activity and ion pump/transporter mRNA levels. We conclude that dynamic hepatic igfbp1a1 and muscle igf1 expression participate in the modulation of Gh/Igf signaling in smolts undergoing catabolism. PMID:27210270

  16. Hepatic insulin-like growth-factor binding protein (igfbp) responses tofood restriction in Atlantic salmon smolts

    Science.gov (United States)

    Breves, Jason P.; Phipps-Costin, Silas K.; Fujimoto, Chelsea K.; Einarsdottir, Ingibjörg E.; Regish, Amy M.; Björnsson, Björn Thrandur; McCormick, Stephen

    2016-01-01

    The growth hormone (Gh)/insulin-like growth-factor (Igf) system plays a central role in the regulation of growth in fishes. However, the roles of Igf binding proteins (Igfbps) in coordinating responses to food availability are unresolved, especially in anadromous fishes preparing for seaward migration. We assayed plasma Gh, Igf1, thyroid hormones and cortisol along with igfbp mRNA levels in fasted and fed Atlantic salmon ( Salmo salar ). Fish were fasted for 3 or 10 days near the peak of smoltification (late April to early May). Fasting reduced plasma glucose by 3 days and condition factor by 10 days. Plasma Gh, cortisol, and thyroxine (T 4 ) were not altered in response to fasting, whereas Igf1 and 3,5,3′-triiodo- l -thyronine (T 3 ) were slightly higher and lower than controls, respectively. Hepatic igfbp1b1 , - 1b2 , - 2a , - 2b1 and - 2b2 mRNA levels were not responsive to fasting, but there were marked increases in igfbp1a1 following 3 and 10 days of fasting. Fasting did not alter hepatic igf1or igf2 ; however, muscle igf1 was diminished by 10 days of fasting. There were no signs that fasting compromised branchial ionoregulatory functions, as indicated by unchanged Na + /K + -ATPase activity and ion pump/transporter mRNA levels. We conclude that dynamic hepatic igfbp1a1 and muscle igf1 expression participate in the modulation of Gh/Igf signaling in smolts undergoing catabolism.

  17. Molecular features of cellular reprogramming and development.

    Science.gov (United States)

    Smith, Zachary D; Sindhu, Camille; Meissner, Alexander

    2016-03-01

    Differentiating somatic cells are progressively restricted to specialized functions during ontogeny, but they can be experimentally directed to form other cell types, including those with complete embryonic potential. Early nuclear reprogramming methods, such as somatic cell nuclear transfer (SCNT) and cell fusion, posed significant technical hurdles to precise dissection of the regulatory programmes governing cell identity. However, the discovery of reprogramming by ectopic expression of a defined set of transcription factors, known as direct reprogramming, provided a tractable platform to uncover molecular characteristics of cellular specification and differentiation, cell type stability and pluripotency. We discuss the control and maintenance of cellular identity during developmental transitions as they have been studied using direct reprogramming, with an emphasis on transcriptional and epigenetic regulation. PMID:26883001

  18. Study on the Factors Restricting the Development of Rural Specialized Cooperatives%农村专业合作社发展制约因素研究

    Institute of Scientific and Technical Information of China (English)

    张建宁

    2012-01-01

    As an organization carrier of new rural economic order, the rural specialized cooperatives could not only promote the development of rural economic, but could also play a positive role in standardization of rural social management. Factors restricting the development of rural specialized cooperatives were analyzed; and suggestions were proposed accordingly, which could help improving and solving problems of agriculture, rural areas and farmers.%农村专业合作社作为农村经济新秩序中的一个组织载体,不仅能推动农村经济的繁荣发展,而且对农村的社会管理也有规范作用.分析制约农村专业合作社发展的因素,提出建议,对改进并解决“三农”问题具有现实意义.

  19. The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone

    DEFF Research Database (Denmark)

    Rasmussen, M H; Frystyk, Jan; Andersen, T; Breum, Leif; Christiansen, J S; Hilsted, J

    1994-01-01

    The aim of this study was to characterize the association between serum insulin-like growth factor-1 (IGF-1) and obesity, as well as fat distribution, before and during moderate energy restriction (1,200 kcal/d). In 51 females and nine males having a body mass index (BMI) between 27 and 39 kg/m2......, relationships between serum IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, growth hormone (GH), blood glucose, and anthropometric measurements of body fat were examined. The patients were studied before treatment and again after 8 and 16 weeks of dieting. Visceral adipose tissue (AT) was estimated by...... anthropometric computed tomography (CT)-calibrated equations. In females, IGF-1 was inversely associated with the abdominal sagittal diameter (SagD) and with the visceral AT (r = -.41, P = .006). No significant correlations were found between IGF-1 and BMI or other indices of adiposity. Weight loss caused a...

  20. Phloem restriction of viroids in three citrus hosts is overcome by grafting with Etrog citron: potential involvement of a translocatable factor.

    Science.gov (United States)

    Bani-Hashemian, Seyed Mehdi; Pensabene-Bellavia, Giovanni; Duran-Vila, Nuria; Serra, Pedro

    2015-08-01

    Viroid systemic spread involves cell-to-cell movement from initially infected cells via plasmodesmata, long-distance movement within the phloem and again cell-to-cell movement to invade distal tissues including the mesophyll. Citrus exocortis viroid (CEVd), hop stunt viroid, citrus bent leaf viroid, citrus dwarfing viroid, citrus bark cracking viroid and citrus viroid V remained phloem restricted when singly infecting Citrus karna, Citrus aurantium and Poncirus trifoliata, but not Etrog citron, where they were additionally detected in mesophyll protoplasts. However, when CEVd-infected C. karna was side-grafted with Etrog citron--with the resulting plants being composed of a C. karna stock and an Etrog citron branch--the viroid was detected in mesophyll protoplasts of the former, thus indicating that the ability of Etrog citron to support viroid invasion of non-vascular tissues was transferred to the stock. Further results suggest that a translocatable factor from Etrog citron mediates this viroid trafficking. PMID:25888624

  1. Restriction of Retroviral Replication by Tetherin/BST-2

    Directory of Open Access Journals (Sweden)

    Jason Hammonds

    2012-01-01

    Full Text Available Tetherin/BST-2 is an important host restriction factor that limits the replication of HIV and other enveloped viruses. Tetherin is a type II membrane glycoprotein with a very unusual domain structure that allows it to engage budding virions and retain them on the plasma membrane of infected cells. Following the initial report identifying tetherin as the host cell factor targeted by the HIV-1 Vpu gene, knowledge of the molecular, structural, and cellular biology of tetherin has rapidly advanced. This paper summarizes the discovery and impact of tetherin biology on the HIV field, with a focus on recent advances in understanding its structure and function. The relevance of tetherin to replication and spread of other retroviruses is also reviewed. Tetherin is a unique host restriction factor that is likely to continue to provide new insights into host-virus interactions and illustrates well the varied ways by which host organisms defend against viral pathogens.

  2. Off the shelf cellular therapeutics: Factors to consider during cryopreservation and storage of human cells for clinical use.

    Science.gov (United States)

    Woods, Erik J; Thirumala, Sreedhar; Badhe-Buchanan, Sandhya S; Clarke, Dominic; Mathew, Aby J

    2016-06-01

    The field of cellular therapeutics has immense potential, affording an exciting array of applications in unmet medical needs. One of several key issues is an emphasis on getting these therapies from bench to bedside without compromising safety and efficacy. The successful commercialization of cellular therapeutics will require many to extend the shelf-life of these therapies beyond shipping "fresh" at ambient or chilled temperatures for "just in time" infusion. Cryopreservation is an attractive option and offers potential advantages, such as storing and retaining patient samples in case of a relapse, banking large quantities of allogeneic cells for broader distribution and use and retaining testing samples for leukocyte antigen typing and matching. However, cryopreservation is only useful if cells can be reanimated to physiological life with negligible loss of viability and functionality. Also critical is the logistics of storing, processing and transporting cells in clinically appropriate packaging systems and storage devices consistent with quality and regulatory standards. Rationalized approaches to develop commercial-scale cell therapies require an efficient cryopreservation system that provides the ability to inventory standardized products with maximized shelf life for later on-demand distribution and use, as well as a method that is scientifically sound and optimized for the cell of interest. The objective of this review is to bridge this gap between the basic science of cryobiology and its application in this context by identifying several key aspects of cryopreservation science in a format that may be easily integrated into mainstream cell therapy manufacture. PMID:27173747

  3. Cellular Injury of Cardiomyocytes during Hepatocyte Growth Factor Gene Transfection with Ultrasound-Triggered Bubble Liposome Destruction

    Directory of Open Access Journals (Sweden)

    Kazuo Komamura

    2011-01-01

    Full Text Available We transfected naked HGF plasmid DNA into cultured cardiomyocytes using a sonoporation method consisting of ultrasound-triggered bubble liposome destruction. We examined the effects on transfection efficiency of three concentrations of bubble liposome (1×106, 1×107, 1×108/mL, three concentrations of HGF DNA (60, 120, 180 μg/mL, two insonification times (30, 60 sec, and three incubation times (15, 60, 120 min. We found that low concentrations of bubble liposome and low concentrations of DNA provided the largest amount of the HGF protein expression by the sonoporated cardiomyocytes. Variation of insonification and incubation times did not affect the amount of product. Following insonification, cardiomyocytes showed cellular injury, as determined by a dye exclusion test. The extent of injury was most severe with the highest concentration of bubble liposome. In conclusion, there are some trade-offs between gene transfection efficiency and cellular injury using ultrasound-triggered bubble liposome destruction as a method for gene transfection.

  4. 宿主细胞对HIV-1复制的限制性%The host restriction factors targeted HIV-1 replication

    Institute of Scientific and Technical Information of China (English)

    贾彦辉; 徐庆刚

    2013-01-01

    HIV-1感染的主要靶细胞是宿主的CD4+T淋巴细胞,使宿主的免疫机能下降.在HIV-1与宿主的长期进化中,它们之间逐渐形成了复杂的入侵与反入侵关系.人类已经进化出多种机制来抵制HIV-1的感染和复制.宿主细胞内的限制性因子是抑制HIV-1复制的主要机制之一,也是研究人员比较关注的一类机制.SAMHD1作为最新发现的一个限制性因子,成为一个研究热点.通过阐述SAMHD1,APOBEC3G/F,TRIM5α及Tetherin在HIV-1复制中的关键作用,了解宿主细胞对病毒感染的限制性,有助于理解宿主与病毒之间的抗衡关系,宿主抗病毒机制,为治疗HIV-1寻找新的靶点.%The CD4 + T cells are the most important targeted cells of HIV-1 infection leading to immunity dysfunction.A long history of human infection by HIV-1 has resulted in complicated relationship between human and HIV-1.Among the many mechanisms to inhibit HIV-1 infection and replication in human,the host restriction factors are an attentive mechanism.Recently,researchers pay much attention to SAMHD1 which is a new discovered restriction factor.This review mainly discussed the effect of SAMHD1,APOBEC3G/ F,TRIM5α and Tetherin on HIV-1 life cycle.Description of HIV-1 restriction in host cells helps us to understand viral pathogenesis and searching for a new antiviral strategy.

  5. Calorie restriction and stroke

    Directory of Open Access Journals (Sweden)

    Manzanero Silvia

    2011-09-01

    Full Text Available Abstract Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR or intermittent fasting (IF, extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF and basic fibroblast growth factor (bFGF; protein chaperones, including heat shock protein 70 (Hsp70 and glucose regulated protein 78 (GRP78; antioxidant enzymes, such as superoxide dismutases (SOD and heme oxygenase-1 (HO-1, silent information regulator T1 (SIRT1, uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke.

  6. Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis

    OpenAIRE

    Eckard Jonathan; Dai Jisen; Wu Jing; Jian Jinlong; Yang Qing; Chen Haobin; Costa Max; Frenkel Krystyna; Huang Xi

    2010-01-01

    Abstract Background Young women diagnosed with breast cancer are known to have a higher mortality rate from the disease than older patients. Specific risk factors leading to this poorer outcome have not been identified. In the present study, we hypothesized that iron deficiency, a common ailment in young women, contributes to the poor outcome by promoting the hypoxia inducible factor-1α (HIF-1α and vascular endothelial growth factor (VEGF) formation. This hypothesis was tested in an in vitro ...

  7. Cellular processing of 125I- and 111in-labeled epidermal growth factor (EGF) bound to cultured A431 tumor cells

    International Nuclear Information System (INIS)

    Low molecular weight of epidermal growth factor (EGF) enables better intratumoral penetration in comparison with larger targeting proteins, but the cellular retention of EGF-associated radioactivity is poor for directly iodinated EGF. An attempt was made to improve intracellular retention by the use of metal-diethylenetriaminepentaacetic acid or nonphenolic linker (N-succinimidyl-para-iodobenzoate) as labeling agents. The use of nonphenolic linker did not improve retention of the radioactivity in A431 carcinoma cell line. The use of the radiometal label provided an appreciable prolongation of radioactivity residence inside the cell

  8. Restricted Mobilities

    DEFF Research Database (Denmark)

    Nielsen, Mette; Lassen, Claus

    2012-01-01

    exclusion and stratification mechanisms. In conclusion the article therefore suggests that future urban research and planning also needs a mobile understanding of spaces in the cities and how different mobility systems play an important role to sustain the exclusiveness that often characterises the private......Privatisation of public spaces in the contemporary city has increased during the last decades but only few studies have approached this field from a mobility perspective. Therefore the article seeks to rectify this by exploring two Australian examples of private spaces in the city; gated...... communities and shopping centres through mobility lenses. The article shows how different mobility systems enable and restrict the public access to private-public spaces, and it points out that proprietary communities create an unequal potential for human movement and access in the city. The main argument in...

  9. Detection of Polymorphism at the Insulin Like Growth Factor-I Gene in Mazandaran Native Chicken using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Method

    Directory of Open Access Journals (Sweden)

    Hossein A. Abbasi

    2011-01-01

    Full Text Available Problem statement: Molecular genetics selection on individual genes is a promising method to genetically improve economically important traits in chickens. The Insulin like Growth Factor-I (IGF1 gene may play important roles in growth of multiple tissues, including muscle cells, cartilage and bone. Approach: In the present study polymorphism of the promoter and 5' untranslated region of IGF-1 gene of Mazandaran native fowls was investigated. In order to evaluate the IGF-1 gene polymorphism we have used a Restriction Fragment Length Polymorphism (RFLP method. Blood samples were collected from randomly chosen 100 Mazandaran native fowls. Genomic DNA was extracted using modified salting-out method and used amplified polymerase chain reaction technique. The promoter and 5' untranslated region of the fowl IGF-1 gene was amplified to produce a 621 bp fragment. The PCR products were electrophoresed on 2.5% agarose gel and stained by etidium bromide. Results: Then, they were digested of amplicon with PstI and revealed two alleles A and B. Data were analyzed using Pop Gene 32 package. In this population, AA, AB, BB genotype have been identified with the 25.88, 50.23, 23.89% frequencies. A and B alleles frequencies were 0.51, 0.49, respectively. The Chi-square (÷2 test was significant and the population was in Hardy-Weinberg equilibrium (pConclusion: The PCR technique amplified a DNA fragment of IGF-1 with 621 bp. The results of the RFLP analysis showed two fragment 257 and 354bp after restriction with enzyme with PstI that identify changes in 5' untranslated region. In according to action modes and importance of IGF-1, its polymorphisms can be related to economical traits such as body weight, muscle cells and bone.

  10. Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues.

    OpenAIRE

    J.A. Takahashi; Mori, H.; Fukumoto, M; Igarashi, K; Jaye, M; Oda, Y.; Kikuchi, H; Hatanaka, M

    1990-01-01

    The growth autonomy of human tumor cells is considered due to the endogenous production of growth factors. Transcriptional expression of candidates for autocrine stimulatory factors such as basic fibroblast growth factor (FGF), acidic FGF, and transforming growth factor type beta were determined in human brain tumors. Basic FGF was expressed abundantly in 17 of 18 gliomas, 20 of 22 meninglomas, and 0 of 5 metastatic brain tumors. The level of mRNA expression of acidic FGF in gliomas was signi...

  11. Factors influencing the transfection efficiency and cellular uptake mechanisms of Pluronic P123-modified polypropyleneimine/pDNA polyplexes in multidrug resistant breast cancer cells.

    Science.gov (United States)

    Gu, Jijin; Hao, Junguo; Fang, Xiaoling; Sha, Xianyi

    2016-04-01

    Generally, the major obstacles for efficient gene delivery are cellular internalization and endosomal escape of nucleic acid such as plasmid DNA (pDNA) or small interfering RNA (siRNA). We previously developed Pluronic P123 modified polypropyleneimine (PPI)/pDNA (P123-PPI/pDNA) polyplexes as a gene delivery system. The results showed that P123-PPI/pDNA polyplexes revealed higher transfection efficiency than PPI/pDNA polyplexes in multidrug resistant breast cancer cells. As a continued effort, the present investigation on the factors influencing the transfection efficiency, cellular uptake mechanisms, and intracellular fate of P123-PPI/pDNA polyplexes is reported. The presence of P123 was the main factor influencing the transfection efficiency of P123-PPI/pDNA polyplexes in MCF-7/ADR cells, but other parameters, such as N/P ratio, FBS concentration, incubation time and temperature were important as well. The endocytic inhibitors against clathrin-mediated endocytosis (CME), caveolae-mediated endocytosis (CvME), and macropinocytosis were involved in the internalization to investigate their effects on the cellular uptake and transfection efficiency of P123-PPI/pDNA polyplexes in vitro. The data showed that the internalization of P123-PPI/pDNA polyplexes was obtained from both CME and CvME. Colocalization experiments with TRITC-transferrin (CME indicator), Alexa Fluor 555-CTB (CvME indicator), monoclonal anti-α-tubulin (microtubule indicator), and LysoTracker Green (Endosome/lysosome indicator) were carried out to confirm the internalization routes. The results showed that both CME and CvME played vital roles in the effective transfection of P123-PPI/pDNA polyplexes. Endosome/lysosome system and skeleton, including actin filament and microtubule, were necessary for the transportation after internalization. PMID:26741268

  12. Tumultuous Relationship between the Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) and the Human APOBEC-3G and APOBEC-3F Restriction Factors

    OpenAIRE

    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-01-01

    Summary: The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive c...

  13. EXTERIOR PRESSURE OF THE GASEOUS MEDIUM AS AN ADDITIONAL TECHNOLOGICAL FACTOR FOR OPTIMIZING THE VAPORIZATION PROCESS IN THE PRODUCTION OF CELLULAR SILICATE CONCRETE

    Directory of Open Access Journals (Sweden)

    A. A. Rezanov

    2012-11-01

    Full Text Available Statement of the problem. The quality of silicate porous concrete is largely determined by vapor-ization processes at the stage of the formation of the macrostructure of the obtained material. In the production of cellular concrete with the use of injection molding, the existing manufacturing technologies do not enable the expeditious handling of the vaporization process. This is why there is a growing need to develop additional efficient methods of handling the vaporization process thus improving cellular silicate concrete.Results. Based on modelling and detailed examination of the balance of pressure affecting devel-oping gas pores, mechanisms and factors governing a defect-free structure are found. An additional governing factor, which is a pressure of the external gaseous medium, was discovered. The approaches to handling the vaporization process have been developed and a plant fitted with a system of automatic control of vaporization process by conscious operative pressuring effect from the external gaseous phase on a poring mixture has been designed.Conclusions. Theoretical validation along with the results of the experimental study help to arrive at the conclusion about the efficiency of the suggested system in controlling vaporization that could provide a good addition to the traditional injection molding and make it more susceptible against varying characteristics of raw materials.

  14. Suppression of cellular immunity by head and neck irradiation. Precipitating factors and reparative mechanisms in an experimental model

    International Nuclear Information System (INIS)

    A model was developed in C3H mice to investigate the immunosuppressive effects of head and neck irradiation and to explore mechanisms for repair of the defects. Mice receiving 1200 rad (12 Gy) of head and neck irradiation showed significant depression of delayed-type hypersensitivity, peripheral blood lymphocyte counts, spleen cell counts, and spleen cell production of interleukin-2. Treatment with optimal dosages of thymosin alpha 1 (T alpha-1) produced significant increases in all of these values, in some instances to levels higher than in the nonirradiated controls. In identical experiments with mice irradiated to a portal limited to the pelvic region, T alpha-1 induced only partial remission of the abnormalities. The dose response of T alpha-1 with head and neck irradiation showed a relatively limited dose range for immune restoration, a finding that warrants similar determinations in clinical trials with immunomodulating agents. The results suggest a potential clinical usefulness of T alpha-1 and also interleukin-2 in restoring cellular immunity after irradiation for head and neck cancers. The model appears to be useful for investigating immunomodulating agents before they are clinically evaluated as adjuvants with head and neck irradiation regimens

  15. The role of nutritional factors in cellular protection against DNA damage, altered gene expression and malignant transformation

    International Nuclear Information System (INIS)

    In recent years data from epidemiological studies and laboratory experiments have revealed numerous links between diet and cancer. The complex role of nutritional factors in modifying cancer incidence may be attributed in part to dietary agents acting as potentiators or promoters of cancer, serving as auxilliary agents to other environmental factors; as causes of cancer, or as cancer preventive agents. Studies can be carried on in vitro, in cell culture systems, where malignant transformation serves as an end point. These systems afford the opportunity to study the direct effect of nutrition in oncogenesis and the role of dietary factors in modulating the frequency and course of neoplastic development in its various stages. 20 refs., 1 fig., 3 tabs

  16. Effects of the breed, sex and age on cellular content and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel

    Directory of Open Access Journals (Sweden)

    Giraldo Carlos E

    2013-02-01

    Full Text Available Abstract Background There is no information on the effects of the breed, gender and age on the cellular content and growth factor (GF release from equine pure-platelet rich plasma (P-PRP and pure-platelet rich gel (P-PRG. The objectives of this study were: 1 to compare the cellular composition of P-PRP with whole blood and platelet poor plasma (PPP; 2 to compare the concentration of transforming GF beta 1 (TGF-β1 and platelet derived GF isoform BB (PDGF-BB between P-PRP treated with non-ionic detergent (P-PRP+NID, P-PRG (activated with calcium gluconate -CG-, PPP+NID, PPP gel (PPG, and plasma and; 3 to evaluate and to correlate the effect of the breed, gender and age on the cellular and GF concentration for each blood component. Forty adult horses, 20 Argentinean Creole Horses (ACH and, 20 Colombian Creole Horses (CCH were included. Data were analyzed by parametric (i.e.: t-test, one way ANOVA and non parametric (Kruskal-Wallis test, Wilcoxon test tests. Correlation analysis was also performed by using the Spearman and Pearson tests. A p ≤ 0.05 was set as significant for all tests. All the blood components were compared for platelet (PLT, leukocyte (WBC, TGF-β1 and PDGF-BB concentrations. The effect of the breed, gender and age on these variables was analyzed. A P ≤ 0.05 was accepted as significant for all the tests. Results PLT counts were 1.8 and 0.6 times higher in P-PRP than in whole blood and PPP, respectively; WBC counts were 0.5 and 0.1 times lower in P-PRP, in comparison with whole blood and PPP, respectively. TGF-β1 and PDGF-BB concentrations were 2.3 and 262 times higher, respectively, in P-PRG than in plasma, and 0.59 and 0.48 times higher, respectively, in P-PRG than in PPG. P-PRG derived from CCH females or young horses presented significantly (P Conclusions Our results indicated that P-PRP obtained by a manual method was affected by intrinsic factors such as the breed, gender and age. Equine practitioners should be

  17. Fat-specific protein 27 modulates nuclear factor of activated T cells 5 and the cellular response to stress

    Science.gov (United States)

    Fat-specific protein 27 (FSP27), a member of the cell death-inducing DNA fragmentation factor a-like effector (Cide) family, is highly expressed in adipose tissues and is a lipid droplet (LD)-associated protein that induces the accumulation of LDs. Using a yeast two-hybrid system to examine potentia...

  18. Evaluation of udder health parameters and risk factors for clinical mastitis in Dutch dairy herds in the context of a restricted antimicrobial usage policy.

    Science.gov (United States)

    Santman-Berends, I M G A; Swinkels, J M; Lam, T J G M; Keurentjes, J; van Schaik, G

    2016-04-01

    study indicated that udder health had not deteriorated compared with udder health in previous Dutch studies where herd sizes were somewhat smaller and before the restrictions in antimicrobial use. Several of the risk factors that were found can be influenced by the farmer and can prevent the occurrence of CMI. Still, when cases of CM occur, treatment with antimicrobials might be necessary to cure the CM case and is beneficial for the overall udder health in the herd. PMID:26874413

  19. Multiuser Cellular Network

    CERN Document Server

    Bao, Yi; Chen, Ming

    2011-01-01

    Modern radio communication is faced with a problem about how to distribute restricted frequency to users in a certain space. Since our task is to minimize the number of repeaters, a natural idea is enlarging coverage area. However, coverage has restrictions. First, service area has to be divided economically as repeater's coverage is limited. In this paper, our fundamental method is to adopt seamless cellular network division. Second, underlying physics content in frequency distribution problem is interference between two close frequencies. Consequently, we choose a proper frequency width of 0.1MHz and a relevantly reliable setting to apply one frequency several times. We make a few general assumptions to simplify real situation. For instance, immobile users yield to homogenous distribution; repeaters can receive and transmit information in any given frequency in duplex operation; coverage is mainly decided by antenna height. Two models are built up to solve 1000 users and 10000 users situations respectively....

  20. Improved restriction landmark cDNA scanning and its application to global analysis of genes regulated by nerve growth factor in PC12 cells.

    Science.gov (United States)

    Mayumi, K; Yaoi, T; Kawai, J; Kojima, S; Watanabe, S; Suzuki, H

    1998-07-30

    Restriction landmark cDNA scanning (RLCS) is a novel method by which more than 1000 genes can be simultaneously and quantitatively displayed as two-dimensional gel spots. Here we present an adaptation that allows an individual spot to correspond to a unique gene species without redundancy in more than two gel patterns. Using this improved RLCS, we examined global changes on the gene expression of PC12 cells before and after treatment with nerve growth factor. Among a total of 3000 spots, 21 (0.70%) and 91 (3.03%) spots newly appeared and became more intense with treatment. On the other hand, 15 (0.50%) and 44 (1.47%) spots disappeared, becoming less intense with treatment. These observations suggest that approx. 6% of the detected PC12 genes are up-(3.73%) or down-(1.97%) regulated when the cells differentiate to neuronal cells. In comparison with the results obtained using the expressed-sequence-tag approach, previously reported by Lee et al. (Proc. Natl. Acad. Sci. USA 92 (1995) 8303-8307), RLCS should be useful for quantitatively examining the global change of differentially expressed genes of various expression levels. PMID:9714711

  1. The effects of the calcium-restricted diet of urolithiasis patients with absorptive hypercalciuria type II on risk factors for kidney stones and osteopenia

    NARCIS (Netherlands)

    Faassen, A. van; Ploeg, E.M.C. van der; Habets, H.M.L.; Meer, R. van der; Hermus, R.J.J.; Janknegt, R.A.

    1998-01-01

    The calcium (Ca)-restricted diet of urolithiasis patients with absorptive hypercalciuria type II may decrease Ca excretion but increase biochemical markers of risk for osteopenia. We randomly allocated 25 patients from six hospitals into an experimental group (Ca restriction to 500 mg/day, oxalate-r

  2. The "occlusis" model of cell fate restriction.

    Science.gov (United States)

    Lahn, Bruce T

    2011-01-01

    A simple model, termed "occlusis", is presented here to account for both cell fate restriction during somatic development and reestablishment of pluripotency during reproduction. The model makes three assertions: (1) A gene's transcriptional potential can assume one of two states: the "competent" state, wherein the gene is responsive to, and can be activated by, trans-acting factors in the cellular milieu, and the "occluded" state, wherein the gene is blocked by cis-acting, chromatin-based mechanisms from responding to trans-acting factors such that it remains silent irrespective of whether transcriptional activators are present in the milieu. (2) As differentiation proceeds in somatic lineages, lineage-inappropriate genes shift progressively and irreversibly from competent to occluded state, thereby leading to the restriction of cell fate. (3) During reproduction, global deocclusion takes place in the germline and/or early zygotic cells to reset the genome to the competent state in order to facilitate a new round of organismal development. PMID:20954221

  3. Cellular Automata

    OpenAIRE

    Bagnoli, Franco

    1998-01-01

    An introduction to cellular automata (both deterministic and probabilistic) with examples. Definition of deterministic automata, dynamical properties, damage spreading and Lyapunov exponents; probabilistic automata and Markov processes, nonequilibrium phase transitions, directed percolation, diffusion; simulation techniques, mean field. Investigation themes: life, epidemics, forest fires, percolation, modeling of ecosystems and speciation. They represent my notes for the school "Dynamical Mod...

  4. Interaction of cellular factors related to the Jun oncoprotein with the promoter of a replication-dependent hamster histone H3.2 gene

    International Nuclear Information System (INIS)

    The promoter region of a replication-dependent histone H3.2 gene contains a putative DNA binding site for the Jun oncoprotein within a 32-nucleotide regulatory domain. The hamster sequence differs by one nucleotide from the AP-1 consensus sequence found in several promoters responsive to phorbol 12-myristate 13-acetate. The authors have identified the factors interacting with this region as 42- and 45-kDa proteins by DNA affinity chromatography, immunoblotting, and UV crosslinking. These proteins, which are candidates for conferring high-level expression to the histone promoter, share an antigenic epitope with the DNA-binding domain of Jun but diverge from it at the amino terminus. The interaction of these proteins with the promoter of a replication-dependent cellular gene provides evidence that members of the Jun oncoprotein family may play specific roles in the expression of genes essential for progression of the cell cycle

  5. Effects of calorie restriction and diet-induced obesity on murine colon carcinogenesis, growth and inflammatory factors, and microRNA expression.

    Directory of Open Access Journals (Sweden)

    Susan E Olivo-Marston

    Full Text Available Obesity is an established colon cancer risk factor, while preventing or reversing obesity via a calorie restriction (CR diet regimen decreases colon cancer risk. Unfortunately, the biological mechanisms underlying these associations are poorly understood, hampering development of mechanism-based approaches for preventing obesity-related colon cancer. We tested the hypotheses that diet-induced obesity (DIO would increase (and CR would decrease colon tumorigenesis in the mouse azoxymethane (AOM model. In addition, we established that changes in inflammatory cytokines, growth factors, and microRNAs are associated with these energy balance-colon cancer links, and thus represent mechanism-based targets for colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and randomized to: 1 control diet; 2 30% CR diet; or 3 DIO diet. Mice were euthanized at week 5 (n = 12/group, 10 (n = 12/group, and 20 (n = 20/group after the last AOM injection. Colon tumors were counted, and cytokines, insulin-like growth factor 1 (IGF-1, IGF binding protein 3 (IGFBP-3, adipokines, proliferation, apoptosis, and expression of microRNAs (miRs were measured. The DIO diet regimen induced an obese phenotype (∼36% body fat, while CR induced a lean phenotype (∼14% body fat; controls were intermediate (∼26% body fat. Relative to controls, DIO increased (and CR decreased the number of colon tumors (p = 0.01, cytokines (p<0.001, IGF-1 (p = 0.01, and proliferation (p<0.001. DIO decreased (and CR increased IGFBP-3 and apoptosis (p<0.001. miRs including mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and mir-138 were differentially expressed between the dietary groups. We conclude that the enhancing effects of DIO and suppressive effects of CR on colon carcinogenesis are associated with alterations in several biological pathways, including inflammation, IGF-1, and microRNAs.

  6. Epidermal Growth Factor Receptor mediated cellular and subcellular targeted delivery of Iron oxide core-Titanium dioxide shell nanoparticles

    Science.gov (United States)

    Yuan, Ye

    TiO2 nanomaterials can carry a multitude of therapeutic and diagnostic agents and the semiconductor properties of TiO2 allow for the production of cytotoxic reactive oxygen species following photoactivation. However, the delivery of these nanomaterials to specific cancer cells and specific subcellular organelles within these cells can have a substantial impact on the efficacy and safety of TiO2 nanoparticle therapeutics. Targeting cell surface receptors that are overexpressed by cancer cells is one strategy to improve the specificity of nanoparticle delivery. Therefore we decided to target the Epidermal Growth Factor Receptor (EGFR) because ligand- binding induces rapid receptor endocytosis and ligand-bound EGFR can translocate to the nucleus of cancer cells. To create NPs that can bind EGFR, we identified a peptide derived from the B-loop of Epidermal Growth Factor (EGF) that has been shown to bind and activate EGFR and conjugated it to the surface of Fe3O4 core-TiO2 shell NPs to produce B-loop NCs. We then devised a pulldown assay to show that B-loop NCs, but not bare NPs or NCs carrying a scrambled B-loop peptide, can bind and extract EGFR from HeLa cell protein extracts. Interestingly, B-loop NCs can also pulldown importin-beta, a protein that can transport EGFR to the nucleus. Furthermore, we used flow cytometry and fluorescently labeled NPs to show that B-loop peptides can significantly improve the internalization of NPs by EGFR-expressing HeLa cells. We determined that B-loop NCs can bind EGFR on the membrane of HeLa cells and that these NCs can be transported to the nucleus, by using a combination of confocal microscopy and X-ray Fluorescence Microscopy (XFM) to indirectly and directly track the subcellular distribution of NCs. Finally, we demonstrate how the Bionanoprobe, a novel high-resolution XFM apparatus that can scan whole-mounted, frozen-hydrated cells at multiple angles can be used to verify the subcellular distribution of B-loop NCs.

  7. Cellular and molecular evidence for a role of tumor necrosis factor alpha in the ovulatory mechanism of trout

    Directory of Open Access Journals (Sweden)

    Bobe Julien

    2010-04-01

    Full Text Available Abstract Background The relevance of immune-endocrine interactions to the regulation of ovarian function in teleosts is virtually unexplored. As part of the innate immune response during infection, a number of cytokines such as tumor necrosis factor alpha (TNF alpha and other immune factors, are produced and act on the reproductive system. However, TNF alpha is also an important physiological player in the ovulatory process in mammals. In the present study, we have examined for the first time the effects of TNF alpha in vitro in preovulatory ovarian follicles of a teleost fish, the brown trout (Salmo trutta. Methods To determine the in vivo regulation of TNF alpha expression in the ovary, preovulatory brook trout (Salvelinus fontinalis were injected intraperitoneally with either saline or bacterial lipopolysaccharide (LPS. In control and recombinant trout TNF alpha (rtTNF alpha-treated brown trout granulosa cells, we examined the percentage of apoptosis by flow cytometry analysis and cell viability by propidium iodide (PI staining. Furthermore, we determined the in vitro effects of rtTNF alpha on follicle contraction and testosterone production in preovulatory brown trout ovarian follicles. In addition, we analyzed the gene expression profiles of control and rtTNF alpha-treated ovarian tissue by microarray and real-time PCR (qPCR analyses. Results LPS administration in vivo causes a significant induction of the ovarian expression of TNF alpha. Treatment with rtTNF alpha induces granulosa cell apoptosis, decreases granulosa cell viability and stimulates the expression of genes known to be involved in the normal ovulatory process in trout. In addition, rtTNF alpha causes a significant increase in follicle contraction and testosterone production. Also, using a salmonid-specific microarray platform (SFA2.0 immunochip we observed that rtTNF alpha induces the expression of genes known to be involved in inflammation, proteolysis and tissue remodeling

  8. Cellular receptor for 125I-labeled tumor necrosis factor: specific binding, affinity labeling, and relationship to sensitivity

    International Nuclear Information System (INIS)

    Tumor necrosis factor (TNF) is a proteinaceous toxin shed by stimulated myeloid cells. Murine TNF was radioiodinated to a specific activity of 1 mCi/nmol (1 Ci = 37 GBq) of monomer. 125I-labeled TNF (125-TNF) retained complete cytotoxic activity and it was immunochemically identical to the native toxin in a quantitative immunoprecipitation assay. It could be shown by competition binding that 125I-TNF bound to intact L929 cells with a specificity equal to that of native toxin. The conditions of time, temperature, and concentration involved in equilibrium specific binding to intact cells were studied in detail. J774.1 cells, the source of the toxin, demonstrated similar binding but were not sensitive to 125I-TNF cytotoxicity. Normal lymphoid organ cell suspensions and two human tumorigenic cell lines were not sensitive and failed to demonstrate specific binding. 125I-TNF, covalently cross-linked to its receptor on sensitive L-M cells with disuccinimidyl suberate, was isolated and analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and autoradiography. Two specific bands were identified. The presence of the binding site appears to be necessary but not sufficient to explain the sensitivity of cells to the cytotoxic action of TNF

  9. Hypoxia-inducible factors in T lymphocyte differentiation and function. A Review in the Theme: Cellular Responses to Hypoxia.

    Science.gov (United States)

    Tao, Jin-Hui; Barbi, Joseph; Pan, Fan

    2015-11-01

    Low oxygen concentrations or hypoxia is a trait common to inflamed tissues. Therefore it is not surprising that pathways of hypoxic stress response, largely governed by hypoxia-inducible factors (HIF), are highly relevant to the proper function of immune cells. HIF expression and stabilization in immune cells can be triggered not only by hypoxia, but also by a variety of stimuli and pathological stresses associated with leukocyte activation and inflammation. In addition to its role as a sensor of oxygen scarcity, HIF is also a major regulator of immune cell metabolic function. Rapid progress is being made in elucidating the roles played by HIF in diverse aspects of both innate and adaptive immunity. Here we discuss a number of breakthroughs that have shed light on how HIF expression and activity impact the differentiation and function of diverse T cell populations. The insights gained from these findings may serve as the foundation for future therapies aimed at fine-tuning the immune response. PMID:26354751

  10. HIV-1 infection induces changes in expression of cellular splicing factors that regulate alternative viral splicing and virus production in macrophages

    Directory of Open Access Journals (Sweden)

    Purcell Damian FJ

    2008-02-01

    Full Text Available Abstract Background Macrophages are important targets and long-lived reservoirs of HIV-1, which are not cleared of infection by currently available treatments. In the primary monocyte-derived macrophage model of infection, replication is initially productive followed by a decline in virion output over ensuing weeks, coincident with a decrease in the levels of the essential viral transactivator protein Tat. We investigated two possible mechanisms in macrophages for regulation of viral replication, which appears to be primarily regulated at the level of tat mRNA: 1 differential mRNA stability, used by cells and some viruses for the rapid regulation of gene expression and 2 control of HIV-1 alternative splicing, which is essential for optimal viral replication. Results Following termination of transcription at increasing times after infection in macrophages, we found that tat mRNA did indeed decay more rapidly than rev or nef mRNA, but with similar kinetics throughout infection. In addition, tat mRNA decayed at least as rapidly in peripheral blood lymphocytes. Expression of cellular splicing factors in uninfected and infected macrophage cultures from the same donor showed an inverse pattern over time between enhancing factors (members of the SR family of RNA binding proteins and inhibitory factors (members of the hnRNP family. While levels of the SR protein SC35 were greatly up-regulated in the first week or two after infection, hnRNPs of the A/B and H groups were down-regulated. Around the peak of virus production in each culture, SC35 expression declined to levels in uninfected cells or lower, while the hnRNPs increased to control levels or above. We also found evidence for increased cytoplasmic expression of SC35 following long-term infection. Conclusion While no evidence of differential regulation of tat mRNA decay was found in macrophages following HIV-1 infection, changes in the balance of cellular splicing factors which regulate alternative

  11. Cultured fibroblast monolayers secrete a protein that alters the cellular binding of somatomedin-C/insulinlike growth factor I

    International Nuclear Information System (INIS)

    We studied somatomedin-C/insulinlike growth factor (Sm-C/IGF-I) binding to human fibroblasts in both adherent monolayers and in suspension cultures. The addition of Sm-C/IGF-I in concentrations between 0.5 and 10 ng/ml to monolayers cultures resulted in a paradoxical increase in 125I-Sm-C/IGF-I binding and concentrations between 25 and 300 ng/ml were required to displace the labeled peptide. The addition of unlabeled insulin resulted in no displacement of labeled Sm-C/IGF-I from the adherent cells. When fibroblast suspensions were used Sm-C/IGF-I concentrations between 1 and 10 ng/ml caused displacement, the paradoxical increase in 125I-Sm-C/IGF-I binding was not detected, and insulin displaced 60% of the labeled peptide. Affinity cross-linking to fibroblast monolayers revealed a 43,000-mol wt 125I-Sm-C-binding-protein complex that was not detected after cross-linking to suspended cells. The 43,000-mol wt complex was not detected after cross-linking to smooth muscle cell monolayers, and binding studies showed that 125I-Sm-C/IGF-I was displaced greater than 90% by Sm-C/IGF-I using concentrations between 0.5 and 10 ng/ml. Because fibroblast-conditioned medium contains the 43,000-mol wt complex, smooth muscle cells were incubated with conditioned medium for 24 h prior to initiation of the binding studies. 125I-Sm-C/IGF-I-binding increased 1.6-fold compared to control cultures and after cross-linking the 43,000-mol wt complex could be detected on the smooth muscle cell surface. Human fibroblast monolayers secrete a protein that binds 125I-Sm-C/IGF-I which can be transferred to the smooth muscle cell surface and alters 125I-Sm-C/IGF-I binding

  12. Identification of major factors influencing ELISpot-based monitoring of cellular responses to antigens from Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Steven G Smith

    Full Text Available A number of different interferon-gamma ELISpot protocols are in use in laboratories studying antigen-specific immune responses. It is therefore unclear how results from different assays compare, and what factors most significantly influence assay outcome. One such difference is that some laboratories use a short in vitro stimulation period of cells before they are transferred to the ELISpot plate; this is commonly done in the case of frozen cells, in order to enhance assay sensitivity. Other differences that may be significant include antibody coating of plates, the use of media with or without serum, the serum source and the number of cells added to the wells. The aim of this paper was to identify which components of the different ELISpot protocols influenced assay sensitivity and inter-laboratory variation. Four laboratories provided protocols for quantifying numbers of interferon-gamma spot forming cells in human peripheral blood mononuclear cells stimulated with Mycobacterium tuberculosis derived antigens. The differences in the protocols were compared directly. We found that several sources of variation in assay protocols can be eliminated, for example by avoiding serum supplementation and using AIM-V serum free medium. In addition, the number of cells added to ELISpot wells should also be standardised. Importantly, delays in peripheral blood mononuclear cell processing before stimulation had a marked effect on the number of detectable spot forming cells; processing delay thus should be minimised as well as standardised. Finally, a pre-stimulation culture period improved the sensitivity of the assay, however this effect may be both antigen and donor dependent. In conclusion, small differences in ELISpot protocols in routine use can affect the results obtained and care should be given to conditions selected for use in a given study. A pre-stimulation step may improve the sensitivity of the assay, particularly when cells have been previously

  13. Prognostic significance of cellular vascular endothelial growth factor (VEGF expression in the course of chronic myeloid leukaemia

    Directory of Open Access Journals (Sweden)

    Vidović Ana

    2009-01-01

    Full Text Available Introduction. Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML, a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown. Objective. The aim of this study was the follow-up of VEGF expression during the course of CML. Methods. We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years. At the commencement of the study, 29 patients were in chronic phase (CP, 25 in an accelerated phase (AP, and 31 in the blast crisis (BC. The temporal expression (percentage positivity per 1000 analysed cells VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts and clinical parameters (organomegaly, duration of CP, AP, and BC of disease progression. Results. The expression of VEGF protein was most pronounced in AP (ANOVA, p=0.033. The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011. High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042. Conclusion. Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.

  14. Cellular mechanisms regulating activity-dependent release of native brain-derived neurotrophic factor from hippocampal neurons.

    Science.gov (United States)

    Balkowiec, Agnieszka; Katz, David M

    2002-12-01

    Brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent modifications of neuronal connectivity and synaptic strength, including establishment of hippocampal long-term potentiation (LTP). To shed light on mechanisms underlying BDNF-dependent synaptic plasticity, the present study was undertaken to characterize release of native BDNF from newborn rat hippocampal neurons in response to physiologically relevant patterns of electrical field stimulation in culture, including tonic stimulation at 5 Hz, bursting stimulation at 25 and 100 Hz, and theta-burst stimulation (TBS). Release was measured using the ELISA in situ technique, developed in our laboratory to quantify secretion of native BDNF without the need to first overexpress the protein to nonphysiological levels. Each stimulation protocol resulted in a significant increase in BDNF release that was tetrodotoxin sensitive and occurred in the absence of glutamate receptor activation. However, 100 Hz tetanus and TBS, stimulus patterns that are most effective in inducing hippocampal LTP, were significantly more effective in releasing native BDNF than lower-frequency stimulation. For all stimulation protocols tested, removal of extracellular calcium, or blockade of N-type calcium channels, prevented BDNF release. Similarly, depletion of intracellular calcium stores with thapsigargin and treatment with dantrolene, an inhibitor of calcium release from caffeine-ryanodine-sensitive stores, markedly inhibited activity-dependent BDNF release. Our results indicate that BDNF release can encode temporal features of hippocampal neuronal activity. The dual requirement for calcium influx through N-type calcium channels and calcium mobilization from intracellular stores strongly implicates a role for calcium-induced calcium release in activity-dependent BDNF secretion. PMID:12451139

  15. Increases in mature brain-derived neurotrophic factor protein in the frontal cortex and basal forebrain during chronic sleep restriction in rats: possible role in initiating allostatic adaptation.

    Science.gov (United States)

    Wallingford, J K; Deurveilher, S; Currie, R W; Fawcett, J P; Semba, K

    2014-09-26

    Chronic sleep restriction (CSR) has various negative consequences on cognitive performance and health. Using a rat model of CSR that uses alternating cycles of 3h of sleep deprivation (using slowly rotating activity wheels) and 1h of sleep opportunity continuously for 4 days ('3/1' protocol), we previously observed not only homeostatic but also allostatic (adaptive) sleep responses to CSR. In particular, non-rapid eye movement sleep (NREMS) electroencephalogram (EEG) delta power, an index of sleep intensity, increased initially and then declined gradually during CSR, with no rebound during a 2-day recovery period. To study underlying mechanisms of these allostatic responses, we examined the levels of brain-derived neurotrophic factor (BDNF), which is known to regulate NREMS EEG delta activity, during the same CSR protocol. Mature BDNF protein levels were measured in the frontal cortex and basal forebrain, two brain regions involved in sleep and EEG regulation, and the hippocampus, using Western blot analysis. Adult male Wistar rats were housed in motorized activity wheels, and underwent the 3/1 CSR protocol for 27 h, for 99 h, or for 99 h followed by 24h of recovery. Additional rats were housed in either locked wheels (locked wheel controls [LWCs]) or unlocked wheels that rats could rotate freely (wheel-running controls [WRCs]). BDNF levels did not differ between WRC and LWC groups. BDNF levels were increased, compared to the control levels, in all three brain regions after 27 h, and were increased less strongly after 99 h, of CSR. After 24h of recovery, BDNF levels were at the control levels. This time course of BDNF levels parallels the previously reported changes in NREMS delta power during the same CSR protocol. Changes in BDNF protein levels in the cortex and basal forebrain may be part of the molecular mechanisms underlying allostatic sleep responses to CSR. PMID:25010399

  16. Calorie restriction decreases murine and human pancreatic tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression in an insulin-like growth factor-1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Alison E Harvey

    Full Text Available Calorie restriction (CR prevents obesity and has potent anticancer effects that may be mediated through its ability to reduce serum growth and inflammatory factors, particularly insulin-like growth factor (IGF-1 and protumorigenic cytokines. IGF-1 is a nutrient-responsive growth factor that activates the inflammatory regulator nuclear factor (NF-κB, which is linked to many types of cancers, including pancreatic cancer. We hypothesized that CR would inhibit pancreatic tumor growth through modulation of IGF-1-stimulated NF-κB activation and protumorigenic gene expression. To test this, 30 male C57BL/6 mice were randomized to either a control diet consumed ad libitum or a 30% CR diet administered in daily aliquots for 21 weeks, then were subcutaneously injected with syngeneic mouse pancreatic cancer cells (Panc02 and tumor growth was monitored for 5 weeks. Relative to controls, CR mice weighed less and had decreased serum IGF-1 levels and smaller tumors. Also, CR tumors demonstrated a 70% decrease in the expression of genes encoding the pro-inflammatory factors S100a9 and F4/80, and a 56% decrease in the macrophage chemoattractant, Ccl2. Similar CR effects on tumor growth and NF-κB-related gene expression were observed in a separate study of transplanted MiaPaCa-2 human pancreatic tumor cell growth in nude mice. In vitro analyses in Panc02 cells showed that IGF-1 treatment promoted NF-κB nuclear localization, increased DNA-binding of p65 and transcriptional activation, and increased expression of NF-κB downstream genes. Finally, the IGF-1-induced increase in expression of genes downstream of NF-κB (Ccdn1, Vegf, Birc5, and Ptgs2 was decreased significantly in the context of silenced p65. These findings suggest that the inhibitory effects of CR on Panc02 pancreatic tumor growth are associated with reduced IGF-1-dependent NF-κB activation.

  17. Cellular Uptake and Cytotoxic Effect of Epidermal Growth Factor Receptor Targeted and Plitidepsin Loaded Co-Polymeric Polymersomes on Colorectal Cancer Cell Lines.

    Science.gov (United States)

    Goñi-de-Cerio, Felipe; Thevenot, Julie; Oliveira, Hugo; Pérez-Andrés, Encarnación; Berra, Edurne; Masa, Marc; Suárez-Merino, Blanca; Lecommandoux, Sébastien; Heredia, Pedro

    2015-11-01

    Encapsulating chemotherapy drugs in targeted nanodelivery systems is one of the most promising approaches to tackle cancer disease, avoiding side effects of common treatment. In the last decade, several nanocarriers with different nature have been tested, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as their low toxicity. In this work, we synthesized, characterized and evaluated poly(trimethylene carbonate)-bock-poly(L-glutamic acid) derived polymersomes, targeted to epidermal growth factor receptor (EGFR), loaded with plitidepsin and ultimately tested in HT29 and LS174T colorectal cancer cell lines for specificity and efficacy. Furthermore, morphology, physico-chemical properties and plitidepsin loading were carefully investigated. A thorough in vitro cytotoxicity analysis of the unloaded polymersomes was carried out for biocompatibility check, studying viability, cell membrane asymmetry and reactive oxygen species levels. Those cytotoxicity assays showed good biocompatibility for plitidepsin-unloaded polymersomes. Cellular uptake and cytotoxic effect of EGFR targeted and plitidepsin loaded polymersome indicated that colorectal cancer cell lines were.more sensitive to anti-EGFR-drug-loaded than untargeted drug-loaded polymersomes. Also, in both cell lines, the use of untargeted polymersomes greatly reduced plitidepsin cytotoxicity as well as the cellular uptake, indicating that the use of this targeted nanocarrier is a promising approach to tackle colorectal cancer disease and avoid the undesired effects of the usual treatment. Furthermore, in vivo assays support the in vitro conclusions that EGFR targeted polymersomes could be a good drug delivery system. This work provides a proof of concept for the use of encapsulated targeted drugs as future therapeutic treatments for cancer. PMID:26554161

  18. Research on the Factors of Class A Lightweight Cellular Concrete%A级轻质蜂窝水泥混凝土影响因素探索

    Institute of Scientific and Technical Information of China (English)

    陈建波; 马红宵; 穆琰; 任晓林; 张志国; 赵风清

    2014-01-01

    A kind of soap powder,interface agent N as the main component of the composite foaming agent was de-veloped.Factors affecting the light honeycomb cement concrete were researched.They are the foam,water feed ratio, cement,fly ash,and the impact of the amount of fiber pilot.The ratio has been optimized.By adj usting the ratio of ce-mentitious materials different density levels of cellular concrete blocks were got.By industrial test and optimize the production process parameters,class A Lightweight cellular concrete optimization ratio was got.The product has been tested to achieve JC 1062-2007"foam concrete block"FCB A0.5 B03 product rating,fire rating to A-level.%开发出一种以皂粉、界面剂 N等为主要组分的复合发泡剂,在其基础上开展轻质蜂窝水泥混凝土影响因素试验,对泡沫、水料比、水泥、粉煤灰、纤维的用量及影响进行试验研究,得到优化的配比,通过调整胶凝材料的配比可以得到不同密度等级的蜂窝混凝土砌块。通过工业化试验,优化生产工艺参数,得到 A 级轻质蜂窝水泥混凝土优化配比。产品经检测达到JC 1062-2007《泡沫混凝土砌块》FCB A0.5 B03产品等级,防火等级达到 A级。

  19. Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin transcription.

    Science.gov (United States)

    Cartier, Jessy; Berthelet, Jean; Marivin, Arthur; Gemble, Simon; Edmond, Valérie; Plenchette, Stéphanie; Lagrange, Brice; Hammann, Arlette; Dupoux, Alban; Delva, Laurent; Eymin, Béatrice; Solary, Eric; Dubrez, Laurence

    2011-07-29

    The inhibitor of apoptosis protein cIAP1 (cellular inhibitor of apoptosis protein-1) is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-κB signaling pathways in the cytoplasm. However, in some primary cells and tumor cell lines, cIAP1 is expressed in the nucleus, and its nuclear function remains poorly understood. Here, we show that the N-terminal part of cIAP1 directly interacts with the DNA binding domain of the E2F1 transcription factor. cIAP1 dramatically increases the transcriptional activity of E2F1 on synthetic and CCNE promoters. This function is not conserved for cIAP2 and XIAP, which are cytoplasmic proteins. Chromatin immunoprecipitation experiments demonstrate that cIAP1 is recruited on E2F binding sites of the CCNE and CCNA promoters in a cell cycle- and differentiation-dependent manner. cIAP1 silencing inhibits E2F1 DNA binding and E2F1-mediated transcriptional activation of the CCNE gene. In cells that express a nuclear cIAP1 such as HeLa, THP1 cells and primary human mammary epithelial cells, down-regulation of cIAP1 inhibits cyclin E and A expression and cell proliferation. We conclude that one of the functions of cIAP1 when localized in the nucleus is to regulate E2F1 transcriptional activity. PMID:21653699

  20. Cellular resilience.

    Science.gov (United States)

    Smirnova, Lena; Harris, Georgina; Leist, Marcel; Hartung, Thomas

    2015-01-01

    Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after the hit or end in programmed cell death, the ensuing stress responses promote a new homeostasis under stress. The processes of reverting "back to normal" and reversal of apoptosis ("anastasis") have been studied little at the cellular level. Cell types show astonishingly similar vulnerability to most toxicants, except for those that require a very specific target, metabolism or mechanism present only in specific cell types. The majority of chemicals triggers "general cytotoxicity" in any cell at similar concentrations. We hypothesize that cells differ less in their vulnerability to a given toxicant than in their resilience (coping with the "hit"). In many cases, cells do not return to the naive state after a toxic insult. The phenomena of "pre-conditioning", "tolerance" and "hormesis" describe this for low-dose exposures to toxicants that render the cell more resistant to subsequent hits. The defense and resilience programs include epigenetic changes that leave a "memory/scar" - an alteration as a consequence of the stress the cell has experienced. These memories might have long-term consequences, both positive (resistance) and negative, that contribute to chronic and delayed manifestations of hazard and, ultimately, disease. This article calls for more systematic analyses of how cells cope with toxic perturbations in the long-term after stressor withdrawal. A technical prerequisite for these are stable (organotypic) cultures and a characterization of stress response molecular networks. PMID:26536287

  1. Achieving Salt Restriction in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Emma J. McMahon

    2012-01-01

    Full Text Available There is consistent evidence linking excessive dietary sodium intake to risk factors for cardiovascular disease and chronic kidney disease (CKD progression in CKD patients; however, additional research is needed. In research trials and clinical practice, implementing and monitoring sodium intake present significant challenges. Epidemiological studies have shown that sodium intake remains high, and intervention studies have reported varied success with participant adherence to a sodium-restricted diet. Examining barriers to sodium restriction, as well as factors that predict adherence to a low sodium diet, can aid researchers and clinicians in implementing a sodium-restricted diet. In this paper, we critically review methods for measuring sodium intake with a specific focus on CKD patients, appraise dietary adherence, and factors that have optimized sodium restriction in key research trials and discuss barriers to sodium restriction and factors that must be considered when recommending a sodium-restricted diet.

  2. Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G.

    Directory of Open Access Journals (Sweden)

    David J Stanley

    2012-12-01

    Full Text Available Cellular restriction factors help to defend humans against human immunodeficiency virus (HIV. HIV accessory proteins hijack at least three different Cullin-RING ubiquitin ligases, which must be activated by the small ubiquitin-like protein NEDD8, in order to counteract host cellular restriction factors. We found that conjugation of NEDD8 to Cullin-5 by the NEDD8-conjugating enzyme UBE2F is required for HIV Vif-mediated degradation of the host restriction factor APOBEC3G (A3G. Pharmacological inhibition of the NEDD8 E1 by MLN4924 or knockdown of either UBE2F or its RING-protein binding partner RBX2 bypasses the effect of Vif, restoring the restriction of HIV by A3G. NMR mapping and mutational analyses define specificity determinants of the UBE2F NEDD8 cascade. These studies demonstrate that disrupting host NEDD8 cascades presents a novel antiretroviral therapeutic approach enhancing the ability of the immune system to combat HIV.

  3. Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag

    Directory of Open Access Journals (Sweden)

    Woods Matthew W

    2011-11-01

    Full Text Available Abstract Background The identification and characterization of several interferon (IFN-induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta-induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5 that blocks a unique late stage of the HIV-1 life cycle. Results HERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production. The E3 ligase activity of HERC5 was required for blocking HIV-1 Gag particle production and correlated with the post-translational modification of Gag with ISG15. HERC5 interacted with HIV-1 Gag and did not alter trafficking of HIV-1 Gag to the plasma membrane. Electron microscopy revealed that the assembly of HIV-1 Gag particles was arrested at the plasma membrane, at an early stage of assembly. The mechanism of HERC5-induced restriction of HIV-1 particle production is distinct from the mechanism underlying HIV-1 restriction by the expression of ISG15 alone, which acts at a later step in particle release. Moreover, HERC5 restricted murine leukemia virus (MLV Gag particle production, showing that HERC5 is effective in restricting Gag particle production of an evolutionarily divergent retrovirus. Conclusions HERC5 represents a potential new host factor that blocks an early stage of retroviral Gag particle assembly. With no apparent HIV-1 protein that directly counteracts it, HERC5 may represent a new candidate for HIV/AIDS therapy.

  4. A Mechanism to Enhance Cellular Responsivity to Hormone Action: Krüppel-Like Factor 9 Promotes Thyroid Hormone Receptor-β Autoinduction During Postembryonic Brain Development.

    Science.gov (United States)

    Hu, Fang; Knoedler, Joseph R; Denver, Robert J

    2016-04-01

    Thyroid hormone (TH) receptor (TR)-β (trb) is induced by TH (autoinduced) in Xenopus tadpoles during metamorphosis. We previously showed that Krüppel-like factor 9 (Klf9) is rapidly induced by TH in the tadpole brain, associates in chromatin with the trb upstream region in a developmental stage and TH-dependent manner, and forced expression of Klf9 in the Xenopus laevis cell line XTC-2 accelerates and enhances trb autoinduction. Here we investigated whether Klf9 can promote trb autoinduction in tadpole brain in vivo. Using electroporation-mediated gene transfer, we transfected plasmids into premetamorphic tadpole brain to express wild-type or mutant forms of Klf9. Forced expression of Klf9 increased baseline trb mRNA levels in thyroid-intact but not in goitrogen-treated tadpoles, supporting that Klf9 enhances liganded TR action. As in XTC-2 cells, forced expression of Klf9 enhanced trb autoinduction in tadpole brain in vivo and also increased TH-dependent induction of the TR target genes klf9 and thbzip. Consistent with our previous mutagenesis experiments conducted in XTC-2 cells, the actions of Klf9 in vivo required an intact N-terminal region but not a functional DNA binding domain. Forced expression of TRβ in tadpole brain by electroporation-mediated gene transfer increased baseline and TH-induced TR target gene transcription, supporting a role for trb autoinduction during metamorphosis. Our findings support that Klf9 acts as an accessory transcription factor for TR at the trb locus during tadpole metamorphosis, enhancing trb autoinduction and transcription of other TR target genes, which increases cellular responsivity to further TH action on developmental gene regulation programs. PMID:26886257

  5. Potentiation of nerve growth factor-induced neurite outgrowth by fluvoxamine: role of sigma-1 receptors, IP3 receptors and cellular signaling pathways.

    Directory of Open Access Journals (Sweden)

    Tomoko Nishimura

    Full Text Available BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs have been widely used and are a major therapeutic advance in psychopharmacology. However, their pharmacology is quite heterogeneous. The SSRI fluvoxamine, with sigma-1 receptor agonism, is shown to potentiate nerve-growth factor (NGF-induced neurite outgrowth in PC 12 cells. However, the precise cellular and molecular mechanisms underlying potentiation by fluvoxamine are not fully understood. In this study, we examined the roles of cellular signaling pathways in the potentiation of NGF-induced neurite outgrowth by fluvoxamine and sigma-1 receptor agonists. METHODS AND FINDINGS: The effects of three SSRIs (fluvoxamine, sertraline, paroxetine and three sigma-1 receptor agonists (SA4503, 4-phenyl-1-(4-phenylbutyl piperidine (PPBP, and dehydroepiandrosterone (DHEA-sulfate on NGF-induced neurite outgrowth in PC12 cells were examined. Also examined were the effects of the sigma-1 receptor antagonist NE-100, inositol 1,4,5-triphosphate (IP(3 receptor antagonist, and specific inhibitors of signaling pathways in the potentiation of NGF-induced neurite outgrowth by selective sigma-1 receptor agonist SA4503. Fluvoxamine (but not sertraline or paroxetine and the sigma-1 receptor agonists SA4503, PPBP, and DHEA-sulfate significantly potentiated NGF-induced neurite outgrowth in PC12 cells in a concentration-dependent manner. The potentiation by fluvoxamine and the three sigma-1 receptor agonists was blocked by co-administration of the selective sigma-1 receptor antagonist NE-100, suggesting that sigma-1 receptors play a role in blocking the enhancement of NGF-induced neurite outgrowth. Moreover, the potentiation by SA4503 was blocked by co-administration of the IP(3 receptor antagonist xestospongin C. In addition, the specific inhibitors of phospholipase C (PLC-gamma, phosphatidylinositol 3-kinase (PI3K, p38MAPK, c-Jun N-terminal kinase (JNK, and the Ras/Raf/mitogen-activated protein kinase (MAPK

  6. Electromagnetic cellular interactions

    Czech Academy of Sciences Publication Activity Database

    Cifra, Michal; Fields, J. S.; Farhadi, A.

    2011-01-01

    Roč. 105, č. 3 (2011), 223-246. ISSN 0079-6107. [36th International Congress of Physiological Sciences (IUPS2009). Kyoto, 27.07.2009-01.08.2009] R&D Projects: GA ČR(CZ) GPP102/10/P454 Institutional research plan: CEZ:AV0Z20670512 Keywords : bioelectric phenomena * cellular biophysics Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 3.203, year: 2011

  7. Measuring the Restrictiveness of Living Environments for Children and Youth: Reconceptualizing Restriction

    Science.gov (United States)

    Rauktis, Mary E.; Huefner, Jonathan C.; O'Brien, Kirk; Pecora, Peter J.; Doucette, Ann; Thompson, Ronald W.

    2009-01-01

    The "Restrictiveness of Living Environment Scale" has long been the primary way to conceptualize the "restrictiveness" of a child's living situation. However, changes in systems of care and other factors have created a need to revisit how restrictiveness is conceptualized and measured. A measure was created to assess an environment's level of…

  8. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1

    OpenAIRE

    Csiszar, Anna; Labinskyy, Nazar; Jimenez, Rosario; Pinto, John T.; Ballabh, Praveen; Losonczy, Gyorgy; Pearson, Kevin J.; de Cabo, Rafael; Ungvari, Zoltan

    2009-01-01

    Endothelial-dysfunction, oxidative stress and inflammation are associated with vascular aging and promote the development of cardiovascular-disease. Caloric restriction (CR) mitigates conditions associated with aging, but its effects on vascular dysfunction during aging remain poorly defined. To determine whether CR exerts vasoprotective effects in aging, aortas of ad libitum (AL) fed young and aged and CR-aged F344 rats were compared. Aging in AL-rats was associated with impaired acetylcholi...

  9. Reduced Insulin/Insulin-like Growth Factor-1 Signaling and Dietary Restriction Inhibit Translation but Preserve Muscle Mass in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Shanmugam, Nilesh; Smolders, Arne; Dhondt, Ineke; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

    2013-09-03

    Reduced signaling through the C. elegans insulin/IGF1 like tyrosine kinase receptor daf2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LCMS/MS quantitative proteomics we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction as well as in the daf2(e1370) insulin/IGF1 receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that posttranscriptional regulation determines ribosome content. Proteomics also revealed increased presence of many structural muscle cell components in long-lived worms, which appears to result from prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF16, but not diet-restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf2 specific proteome changes include overexpression of aerobic metabolism enzymes and a general activation of stress responsive and immune defense systems, while increased abundance of many protein subunits of the proteasome core complex is a DR-specific characteristic.

  10. CTCF and Rad21 Act as Host Cell Restriction Factors for Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Lytic Replication by Modulating Viral Gene Transcription

    OpenAIRE

    Da-Jiang Li; Dinesh Verma; Tim Mosbruger; Sankar Swaminathan

    2014-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a human herpesvirus that causes Kaposi's sarcoma and is associated with the development of lymphoproliferative diseases. KSHV reactivation from latency and virion production is dependent on efficient transcription of over eighty lytic cycle genes and viral DNA replication. CTCF and cohesin, cellular proteins that cooperatively regulate gene expression and mediate long-range DNA interactions, have been shown to bind at specific sites in herpesv...

  11. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains.

    Directory of Open Access Journals (Sweden)

    Marlène Dreux

    2009-02-01

    Full Text Available HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI, a major receptor of high-density lipoprotein (HDL, the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection.

  12. Mechanism of Laser/light beam interaction at cellular and tissue level and study of the influential factors for the application of low level laser therapy

    OpenAIRE

    Khalid, Muhammad Zeeshan

    2016-01-01

    After the discovery of laser therapy it was realized it has useful application of wound healing and reduce pain, but due to the poor understanding of the mechanism and dose response this technique remained to be controversial for therapeutic applications. In order to understand the working and effectiveness different experiments were performed to determine the laser beam effect at the cellular and tissue level. This article discusses the mechanism of beam interaction at tissues and cellular l...

  13. Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles

    OpenAIRE

    Singh Jagbir; Michel Deborah; Chitanda Jackson M; Verrall Ronald E; Badea Ildiko

    2012-01-01

    Abstract Background Gene transfer using non-viral vectors offers a non-immunogenic and safe method of gene delivery. Cellular uptake and intracellular trafficking of the nanoparticles can impact on the transfection efficiency of these vectors. Therefore, understanding the physicochemical properties that may influence the cellular uptake and the intracellular trafficking can aid the design of more efficient non-viral gene delivery systems. Recently, we developed novel amino acid-substituted ge...

  14. Selectional Restrictions in HPSG

    OpenAIRE

    Androutsopoulos, Ion; Dale, Robert

    2000-01-01

    Selectional restrictions are semantic sortal constraints imposed on the participants of linguistic constructions to capture contextually-dependent constraints on interpretation. Despite their limitations, selectional restrictions have proven very useful in natural language applications, where they have been used frequently in word sense disambiguation, syntactic disambiguation, and anaphora resolution. Given their practical value, we explore two methods to incorporate selectional restrictions...

  15. Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice

    International Nuclear Information System (INIS)

    The authors have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, the author analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that were provided by the thymuses of the recipient mice

  16. Massively parallel characterization of restriction endonucleases

    OpenAIRE

    Kamps-Hughes, Nick; Quimby, Aine; Zhu, Zhenyu; Johnson, Eric A.

    2013-01-01

    Restriction endonucleases are highly specific in recognizing the particular DNA sequence they act on. However, their activity is affected by sequence context, enzyme concentration and buffer composition. Changes in these factors may lead to either ineffective cleavage at the cognate restriction site or relaxed specificity allowing cleavage of degenerate ‘star’ sites. Additionally, uncharacterized restriction endonucleases and engineered variants present novel activities. Traditionally, restri...

  17. Mechanism of Laser/light beam interaction at cellular and tissue level and study of the influential factors for the application of low level laser therapy

    CERN Document Server

    Khalid, Muhammad Zeeshan

    2016-01-01

    After the discovery of laser therapy it was realized it has useful application of wound healing and reduce pain, but due to the poor understanding of the mechanism and dose response this technique remained to be controversial for therapeutic applications. In order to understand the working and effectiveness different experiments were performed to determine the laser beam effect at the cellular and tissue level. This article discusses the mechanism of beam interaction at tissues and cellular level with different light sources and dosimetry principles for clinical application of low level laser therapy. Different application techniques and methods currently in use for clinical treatment has also been reviewed.

  18. Investigation Analysis of the City Inhabitants Participate Community Sports Motivation and Its Restrictive Factors%城市居民参加社区体育动机及其制约因素的调查分析

    Institute of Scientific and Technical Information of China (English)

    葛冰

    2012-01-01

    Take the Jilin Province partial city community inhabitants as the sample,investigate the motivation and the restrictive factors from the questionnaire that city inhabitants participates in the community sports,using the mathematical statistic method,discussion the difference of the motivation and the restrictive factors that community inhabitants participates in community sports.Result show:24.1% city inhabitants participate in community sports above 3 time/week;The first three motivation that inhabitants participates in the community sports is the enhance physical,the leisure and entertainment,the fitness and loses weight;The restriction factors existence significant differences that the city inhabitants participate in community sports in physiology,psychology,facilities,society and so on.%以吉林省部分城市社区居民为样本,对城市居民参加社区体育动机及其制约因素进行问卷调查,运用数理统计方法探讨城市居民参加社区体育动机和制约因素的差异。结果显示:有24.1%的城市居民参加3次/周以上的社区体育活动;参加社区体育动机前三位的是增强体质、休闲娱乐、健美减肥;城市居民参加社区体育的制约因素在生理、心理、设施和社会等层面存在显著差异。

  19. SAMHD1——A HIV-1 restriction factor derived from myeloid lineage monocytes%髓系单核细胞来源的HIV-1限制性因子——SAMHD1

    Institute of Scientific and Technical Information of China (English)

    李佩璐; 陈倩倩; 张驰宇

    2012-01-01

    天然抗病毒限制因子是HIV-1研究最热点的领域.继APOBEC3G、Trim5α、Tetherin被发现之后,SAMHD1于2011年被发现为新的抗HIV-1限制因子.它主要在髓系来源的单核细胞中表达,如巨噬细胞和树突状细胞.该文对SAMHD1的结构、抗病毒机制、与Vpx的相互作用以及进化等方面的研究进行了综述.SAMHD1的发现为深入研究SAMHD1在慢病毒致病机理中作用打开了一扇门.%HIV-1 restriction factors have became one of the hottest fields of AIDS researches. In 2011, SAMHD1 was demonstrated to be a novel HIV-1 restriction factor, adding to a list of HIV-1 restriction factors that include APOBEC3G, TRIM5a and Tetherin. SAMHD1 is highly expressed in myeloid-lineage monocytes, such as macrophages and dendritic cells. In this paper, we review the current research progress on the structure of SAMHD1, its antiviral mechanism, interaction with the lentivirus Vpx, and evolution. The identification of SAMHD1 opens the door towards understanding the role of SAMHD1 in lentiviral pathogenesis.

  20. Fasting and Caloric Restriction in Cancer Prevention and Treatment.

    Science.gov (United States)

    Brandhorst, Sebastian; Longo, Valter D

    2016-01-01

    Cancer is the second leading cause of death in the USA and among the leading major diseases in the world. It is anticipated to continue to increase because of the growth of the aging population and prevalence of risk factors such as obesity, smoking, and/or poor dietary habits. Cancer treatment has remained relatively similar during the past 30 years with chemotherapy and/or radiotherapy in combination with surgery remaining the standard therapies although novel therapies are slowly replacing or complementing the standard ones. According to the American Cancer Society, the dietary recommendation for cancer patients receiving chemotherapy is to increase calorie and protein intake. In addition, there are no clear guidelines on the type of nutrition that could have a major impact on cancer incidence. Yet, various forms of reduced caloric intake such as calorie restriction (CR) or fasting demonstrate a wide range of beneficial effects able to help prevent malignancies and increase the efficacy of cancer therapies. Whereas chronic CR provides both beneficial and detrimental effects as well as major compliance challenges, periodic fasting (PF), fasting-mimicking diets (FMDs), and dietary restriction (DR) without a reduction in calories are emerging as interventions with the potential to be widely used to prevent and treat cancer. Here, we review preclinical and preliminary clinical studies on dietary restriction and fasting and their role in inducing cellular protection and chemotherapy resistance. PMID:27557543

  1. Caloric restriction-associated remodeling of rat white adipose tissue: effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration

    OpenAIRE

    Chujo, Yoshikazu; Fujii, Namiki; Okita, Naoyuki; Konishi, Tomokazu; Narita, Takumi; Yamada, Atsushi; Haruyama, Yushi; Tashiro, Kosuke; Chiba, Takuya; Shimokawa, Isao; Higami, Yoshikazu

    2012-01-01

    The role of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis in the lifelong caloric restriction (CR)-associated remodeling of white adipose tissue (WAT), adipocyte size, and gene expression profiles was explored in this study. We analyzed the WAT morphology of 6–7-month-old wild-type Wistar rats fed ad libitum (WdAL) or subjected to CR (WdCR), and of heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (TgAL) or subjected to CR (TgCR). Although ...

  2. Change in prevalence of restrictive lung impairment in the U.S. population and associated risk factors: the National Health and Nutrition Examination Survey (NHANES) 1988–1994 and 2007–2010

    OpenAIRE

    Kurth, Laura; Hnizdo, Eva

    2015-01-01

    Background Data for the U.S adult population from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate risk factors for a restrictive pattern on spirometry and estimate the change in its prevalence from the 1988–1994 to 2007–2010 sampling periods. Several previous epidemiologic studies used the Global Initiative for Chronic Obstructive Lung Disease fixed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.70 criteria for classifying restr...

  3. Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures

    Directory of Open Access Journals (Sweden)

    Murugan K

    2015-03-01

    Full Text Available Karmani Murugan, Yahya E Choonara, Pradeep Kumar, Divya Bijukumar, Lisa C du Toit, Viness Pillay Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Abstract: Cellular internalization and trans-barrier transport of nanoparticles can be manipulated on the basis of the physicochemical and mechanical characteristics of nanoparticles. Research has shown that these factors significantly influence the uptake of nanoparticles. Dictating these characteristics allows for the control of the rate and extent of cellular uptake, as well as delivering the drug-loaded nanosystem intra-cellularly, which is imperative for drugs that require a specific cellular level to exert their effects. Additionally, physicochemical characteristics of the nanoparticles should be optimal for the nanosystem to bypass the natural restricting phenomena of the body and act therapeutically at the targeted site. The factors at the focal point of emerging smart nanomedicines include nanoparticle size, surface charge, shape, hydrophobicity, surface chemistry, and even protein and ligand conjugates. Hence, this review discusses the mechanism of internalization of nanoparticles and ideal nanoparticle characteristics that allow them to evade the biological barriers in order to achieve optimal cellular uptake in different organ systems. Identifying these parameters assists with the progression of nanomedicine as an outstanding vector of pharmaceuticals. Keywords: nanoparticles, transport mechanisms, cellular uptake, size, shape, charge

  4. Restricting retrotransposons: a review.

    Science.gov (United States)

    Goodier, John L

    2016-01-01

    Retrotransposons have generated about 40 % of the human genome. This review examines the strategies the cell has evolved to coexist with these genomic "parasites", focussing on the non-long terminal repeat retrotransposons of humans and mice. Some of the restriction factors for retrotransposition, including the APOBECs, MOV10, RNASEL, SAMHD1, TREX1, and ZAP, also limit replication of retroviruses, including HIV, and are part of the intrinsic immune system of the cell. Many of these proteins act in the cytoplasm to degrade retroelement RNA or inhibit its translation. Some factors act in the nucleus and involve DNA repair enzymes or epigenetic processes of DNA methylation and histone modification. RISC and piRNA pathway proteins protect the germline. Retrotransposon control is relaxed in some cell types, such as neurons in the brain, stem cells, and in certain types of disease and cancer, with implications for human health and disease. This review also considers potential pitfalls in interpreting retrotransposon-related data, as well as issues to consider for future research. PMID:27525044

  5. Cellular therapy in Tuberculosis

    Directory of Open Access Journals (Sweden)

    Shreemanta K. Parida

    2015-03-01

    Full Text Available Cellular therapy now offer promise of potential adjunct therapeutic options for treatment of drug-resistant tuberculosis (TB. We review here the role of Mesenchymal stromal cells, (MSCs, as well as other immune effector cells in the therapy of infectious diseases with a focus on TB. MSCs represent a population of tissue-resident non-hematopoietic adult progenitor cells which home into injured tissues increase the proliferative potential of broncho-alveolar stem cells and restore lung epithelium. MSCs have been shown to be immune-modulatory and anti-inflammatory mediated via cell-cell contacts as well as soluble factors. We discuss the functional profile of MSCs and their potential use for adjunct cellular therapy of multi-drug resistant TB, with the aim of limiting tissue damage, and to convert unproductive inflammatory responses into effective anti-pathogen directed immune responses. Adjunct cellular therapy could potentially offer salvage therapy options for patients with drug-resistant TB, increase clinically relevant anti-M.tuberculosis directed immune responses and possibly shorten the duration of anti-TB therapy.

  6. Cellular therapy in tuberculosis.

    Science.gov (United States)

    Parida, Shreemanta K; Madansein, Rajhmun; Singh, Nalini; Padayatchi, Nesri; Master, Iqbal; Naidu, Kantharuben; Zumla, Alimuddin; Maeurer, Markus

    2015-03-01

    Cellular therapy now offer promise of potential adjunct therapeutic options for treatment of drug-resistant tuberculosis (TB). We review here the role of Mesenchymal stromal cells, (MSCs), as well as other immune effector cells in the therapy of infectious diseases with a focus on TB. MSCs represent a population of tissue-resident non-hematopoietic adult progenitor cells which home into injured tissues increase the proliferative potential of broncho-alveolar stem cells and restore lung epithelium. MSCs have been shown to be immune-modulatory and anti-inflammatory mediated via cell-cell contacts as well as soluble factors. We discuss the functional profile of MSCs and their potential use for adjunct cellular therapy of multi-drug resistant TB, with the aim of limiting tissue damage, and to convert unproductive inflammatory responses into effective anti-pathogen directed immune responses. Adjunct cellular therapy could potentially offer salvage therapy options for patients with drug-resistant TB, increase clinically relevant anti-M.tuberculosis directed immune responses and possibly shorten the duration of anti-TB therapy. PMID:25809753

  7. Cellular-scale hydrodynamics

    DEFF Research Database (Denmark)

    Abkarian, Manouk; Faivre, Magalie; Horton, Renita; Smistrup, Kristian; Best-Popescu, Catherine A; Stone, Howard A.

    2008-01-01

    Microfluidic tools are providing many new insights into the chemical, physical and physicochemical responses of cells. Both suspension-level and single-cell measurements have been studied. We review our studies of these kinds of problems for red blood cells with particular focus on the shapes of ...... mechanical effects on suspended cells can be studied systematically in small devices, and how these features can be exploited to develop methods for characterizing physicochemical responses and possibly for the diagnosis of cellular-scale changes to environmental factors....

  8. Effect of Vitamin D Receptor Gene Foki Restriction Sites and Gastric Factors%维生素D受体基因FokI酶切位点与胃癌的影响因素研究

    Institute of Scientific and Technical Information of China (English)

    方法; 高洁; 王海江

    2016-01-01

    目的:探讨维生素D受体基因 Fok I酶切位点多态性与胃癌的影响因素。方法随机选取2013年5月—2015年5月该院就诊的维吾尔族胃癌患者143例(A组)及维吾尔族健康对照者147例(B组),采用多聚酶链反应-限制性酶切片段长度多态性(Polymerase Chain Reaction-Restriction Fragment Length Polymorphism,PCR-RFLP)方法测定维生素D受体基因Fok I酶切位点多态性,进行两组间比较。结果单因素Logistic回归分析显示:胃癌患者的f等位基因频率高于对照组(58.0%vs 47.3%,P<0.05)。多因素Logistic回归分析显示:带有f等位基因(Ff+ ff)的受试者表现出较高的患胃癌的风险(OR值2.87)。结论 VDR的FokI酶切位点多态性是胃癌易感性影响因素。 f等位基因可能是胃癌发生的危险因素之一,而F等位基因可能是胃癌的保护因素。%Objective Discussion of vitamin D receptor gene Fok I restriction site polymorphism influencing factors and gastric cancer. Methods 143 cases of Uygur patients with gastric cancer treated in our hospital from May 2013 to May 2015 were randomly selected as the group A, 147 cases of Uygur healthy people treated in our hospital at the same period were selected as the group B (control group ), the polymorphism of vitamin D acceptor gene FokI restriction enzyme cutting site was measured by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method,PCR-RFLP and com-pared between the two groups. Results The single factor Logistic regression analysis showed that F allele frequency in the gastric cancer group was higher than that in the control group (58.0% vs 47.3%,P<0.05), multi-factor Logistic regression analysis showed that the subjects with F allele(Ff + ff)had a higher risk of gastric cancer(OR value was 2.87). Conclusion VDR FokI restriction site polymorphisms are susceptibility factors in gastric cancer. F allele may be one of the risk factors of occurrence of gastric cancer, however, F allele

  9. Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles

    Science.gov (United States)

    2012-01-01

    Background Gene transfer using non-viral vectors offers a non-immunogenic and safe method of gene delivery. Cellular uptake and intracellular trafficking of the nanoparticles can impact on the transfection efficiency of these vectors. Therefore, understanding the physicochemical properties that may influence the cellular uptake and the intracellular trafficking can aid the design of more efficient non-viral gene delivery systems. Recently, we developed novel amino acid-substituted gemini surfactants that showed higher transfection efficiency than their parent compound. In this study, we evaluated the mechanism of cellular uptake of the plasmid/gemini surfactant/helper lipid nanoparticles and their effect on the transfection efficiency. Results Nanoparticles were incubated with Sf 1 Ep cells in the presence of different endocytic inhibitors and gene expression (interferon-γ) was measured using ELISA. Clathrin-mediated and caveolae-mediated uptake were found to be equally contributing to cellular internalization of both P/12-7NH-12/L (parent gemini surfactant) and P/12-7NGK-12/L (amino acid-substituted gemini surfactant) nanoparticles. The plasmid and the helper lipid were fluorescently tagged to track the nanoparticles inside the cells, using confocal laser scanning microscopy. Transmission electron microscopy images showed that the P/12-7NGK-12/L particles were cylindrical while the P/12-7NH-12/L particles were spherical which may influence the cellular uptake behaviour of these particles. Dye exclusion assay and pH-titration of the nanoparticles suggested that high buffering capacity, pH-dependent increase in particle size and balanced DNA binding properties may be contributing to a more efficient endosomal escape of P/12-7NGK-12/L compared to the P/12-7NH-12/L nanoparticles, leading to higher gene expression. Conclusion Amino-acid substitution in the spacer of gemini surfactant did not alter the cellular uptake pathway, showing similar pattern to the

  10. Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles

    Directory of Open Access Journals (Sweden)

    Singh Jagbir

    2012-02-01

    Full Text Available Abstract Background Gene transfer using non-viral vectors offers a non-immunogenic and safe method of gene delivery. Cellular uptake and intracellular trafficking of the nanoparticles can impact on the transfection efficiency of these vectors. Therefore, understanding the physicochemical properties that may influence the cellular uptake and the intracellular trafficking can aid the design of more efficient non-viral gene delivery systems. Recently, we developed novel amino acid-substituted gemini surfactants that showed higher transfection efficiency than their parent compound. In this study, we evaluated the mechanism of cellular uptake of the plasmid/gemini surfactant/helper lipid nanoparticles and their effect on the transfection efficiency. Results Nanoparticles were incubated with Sf 1 Ep cells in the presence of different endocytic inhibitors and gene expression (interferon-γ was measured using ELISA. Clathrin-mediated and caveolae-mediated uptake were found to be equally contributing to cellular internalization of both P/12-7NH-12/L (parent gemini surfactant and P/12-7NGK-12/L (amino acid-substituted gemini surfactant nanoparticles. The plasmid and the helper lipid were fluorescently tagged to track the nanoparticles inside the cells, using confocal laser scanning microscopy. Transmission electron microscopy images showed that the P/12-7NGK-12/L particles were cylindrical while the P/12-7NH-12/L particles were spherical which may influence the cellular uptake behaviour of these particles. Dye exclusion assay and pH-titration of the nanoparticles suggested that high buffering capacity, pH-dependent increase in particle size and balanced DNA binding properties may be contributing to a more efficient endosomal escape of P/12-7NGK-12/L compared to the P/12-7NH-12/L nanoparticles, leading to higher gene expression. Conclusion Amino-acid substitution in the spacer of gemini surfactant did not alter the cellular uptake pathway, showing similar

  11. Purification by DNA affinity precipitation of the cellular factors HEB1-p67 and HEB1-p94 which bind specifically to the human T-cell leukemia virus type-I 21 bp enhancer.

    OpenAIRE

    Lombard-Platet, G; Jalinot, P

    1993-01-01

    Transcription driven by the proviral promoter of the Human T-cell Leukemia Virus type I (HTLV-I) is tightly regulated by the Tax1 transactivator. This viral protein potently induces the enhancer activity of a 21 bp motif repeated three times in the promoter. We have previously shown that this induction results from the binding of Tax1 to this enhancer sequence and that this association is mediated by the cellular factor HEB1. In this paper we report the purification of this factor by chromato...

  12. The induction of cellular senescence in dental follicle cells inhibits the osteogenic differentiation.

    Science.gov (United States)

    Morsczeck, Christian; Gresser, Jan; Ettl, Tobias

    2016-06-01

    Dental stem cells such as human dental follicle cells (DFCs) have opened new promising treatment alternatives for today's dental health issues such as periodontal tissue regeneration. However, cellular senescence represents a restricting factor to cultured stem cells, resulting in limited lifespan and reduced cell differentiation potential. Therefore, this study evaluated if and how DFCs exhibit features of cellular senescence after being expanded in cell culture. The cell proliferation of DFCs decreased, while the cell size increased during prolonged cell culture. Moreover, DFCs expressed the senescence-associated β-galactosidase after a prolonged cell culture. The onset of senescence inhibited both the induction of osteoblast markers RUNX2 and osteopontin and the biomineralization of DFCs after stimulation of the osteogenic differentiation. In conclusion, we showed that a prolonged cell culture induces cellular senescence and inhibits the osteogenic differentiation in DFCs. PMID:27165403

  13. CD8+-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription

    OpenAIRE

    Le Borgne, Sylvie; Février, Michèle; Callebaut, Christian; Lee, Steven P.; Rivière, Yves

    2000-01-01

    CD8+ lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4+ T cells by a noncytolytic mechanism involving secreted CD8+-cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4+ T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the presence of the specific antigen during the effector pha...

  14. Expression of HIV-1 Vpu leads to loss of the viral restriction factor CD317/Tetherin from lipid rafts and its enhanced lysosomal degradation.

    Directory of Open Access Journals (Sweden)

    Ruth Rollason

    Full Text Available CD317/tetherin (aka BST2 or HM1.24 antigen is an interferon inducible membrane protein present in regions of the lipid bilayer enriched in sphingolipids and cholesterol (often termed lipid rafts. It has been implicated in an eclectic mix of cellular processes including, most notably, the retention of fully formed viral particles at the surface of cells infected with HIV and other enveloped viruses. Expression of the HIV viral accessory protein Vpu has been shown to lead to intracellular sequestration and degradation of tetherin, thereby counteracting the inhibition of viral release. There is evidence that tetherin interacts directly with Vpu, but it remains unclear where in the cell this interaction occurs or if Vpu expression affects the lipid raft localisation of tetherin. We have addressed these points using biochemical and cell imaging approaches focused on endogenous rather than ectopically over-expressed tetherin. We find i no evidence for an interaction between Vpu and endogenous tetherin at the cell surface, ii the vast majority of endogenous tetherin that is at the cell surface in control cells is in lipid rafts, iii internalised tetherin is present in non-raft fractions, iv expression of Vpu in cells expressing endogenous tetherin leads to the loss of tetherin from lipid rafts, v internalised tetherin enters early endosomes, and late endosomes, in both control cells and cells expressing Vpu, but the proportion of tetherin molecules destined for degradation rather than recycling is increased in cells expressing Vpu vi lysosomes are the primary site for degradation of endogenous tetherin in cells expressing Vpu. Our studies underlie the importance of studying endogenous tetherin and let us propose a model in which Vpu intercepts newly internalised tetherin and diverts it for lysosomal destruction rather than recycling to the cell surface.

  15. RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG

    NARCIS (Netherlands)

    Yuan, Lei; Sacharidou, Anastasia; Stratman, Amber N.; Le Bras, Alexandra; Zwiers, Peter J.; Spokes, Katherine; Bhasin, Manoj; Shih, Shou-ching; Nagy, Janice A.; Molema, Grietje; Aird, William C.; Davis, George E.; Oettgen, Peter

    2011-01-01

    ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). To further define the role of ERG in regulating EC function, we evaluated the effect of ERG knockdown on EC lumen formation in 3D collagen matrices. Blockade of ERG using siRNA completely inter

  16. Psychological factors in analogous thinking and their restriction%类比思维的心理因素及其制约

    Institute of Scientific and Technical Information of China (English)

    张晓芒

    2006-01-01

    AIM: To investigate the role of certain psychological factors in the process of new analogous combination on the basis of complete perceptual materials.METHODS: By means of evaluation of critical thinking, the psychological factors in the process of analogous thinking were investigated.RESULTS: In the process of analogous thinking, how to choose and reflect the analogous objects has its proper use of analogous mode of thinking. At the same time, it is also influenced by certain psychological factors.CONCLUSION: Analogous thinking plays an important role as thinking tool in the process of recognizing new things and solving new problems, or explaining abstract affair with simple reasons.%目的:探讨一定的心理因素在完整的知觉材料基础上进行新的类比组合过程中的作用.方法:以批判性思维的评价方法,对类比思维过程中心理因素进行研究.结果:在类比思维的过程中,如何选择、映射类比事物,不但有着正确的类比思维方法的运用,同时它也受到一定的心理因素的影响.结论:类比思维在认识新事物、解决新问题的过程中,或者以简单的道理说明抽象事理的过程中,都发挥着重要的思维工具作用.

  17. Are cellular phone blocking applications effective for novice teen drivers?

    OpenAIRE

    Creaser, J.

    2014-01-01

    Distracted driving is a significant concern for novice teen drivers. Although cellular phone bans are applied in many jurisdictions to restrict cellular phone use, teen drivers often report making calls and texts while driving. Method The Minnesota Teen Driver Study incorporated cellular phone blocking functions via a software application for 182 novice teen drivers in two treatment conditions. The first condition included 92 teens who ran a driver support application on a smartphone that als...

  18. Temperature based Restricted Boltzmann Machines

    Science.gov (United States)

    Li, Guoqi; Deng, Lei; Xu, Yi; Wen, Changyun; Wang, Wei; Pei, Jing; Shi, Luping

    2016-01-01

    Restricted Boltzmann machines (RBMs), which apply graphical models to learning probability distribution over a set of inputs, have attracted much attention recently since being proposed as building blocks of multi-layer learning systems called deep belief networks (DBNs). Note that temperature is a key factor of the Boltzmann distribution that RBMs originate from. However, none of existing schemes have considered the impact of temperature in the graphical model of DBNs. In this work, we propose temperature based restricted Boltzmann machines (TRBMs) which reveals that temperature is an essential parameter controlling the selectivity of the firing neurons in the hidden layers. We theoretically prove that the effect of temperature can be adjusted by setting the parameter of the sharpness of the logistic function in the proposed TRBMs. The performance of RBMs can be improved by adjusting the temperature parameter of TRBMs. This work provides a comprehensive insights into the deep belief networks and deep learning architectures from a physical point of view.

  19. Change in proportional protein intake in a 10-week energy-restricted low- or high-fat diet, in relation to changes in body size and metabolic factors

    DEFF Research Database (Denmark)

    Stocks, Tanja; Taylor, Moira A; Ängquist, Lars;

    2013-01-01

    Objective: To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. Methods: Obese adults (n = 771) were randomised to a 600 kcal...... increased the percentage energy intake from protein showed the greatest reduction in weight and cholesterol, and a triglyceride reduction equally large to that of participants on a high-fat diet. Copyright © 2013 S. Karger GmbH, Freiburg....... energy-deficient low-fat (20-25 fat%) or high-fat (40-45 fat%) diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (2) on outcomes...

  20. Restrictions of stable bundles

    CERN Document Server

    Balaji, V

    2011-01-01

    The Mehta-Ramanathan theorem ensures that the restriction of a stable vector bundle to a sufficiently high degree complete intersection curve is again stable. We improve the bounds for the "sufficiently high degree" and propose a possibly optimal conjecture.

  1. The Affecting Factors to Restrict Increasing Convert Ratio of Fluid Catalytic Cracking Unit%制约提高催化裂化转化率的影响因素分析

    Institute of Scientific and Technical Information of China (English)

    曹小伟

    2012-01-01

    通过运用催化裂化相关理论并结合惠州炼油分公司催化裂化装置的实际生产情况,对影响催化裂化转化率的因素进行了分析,通过分析各操作参数间的相互关系,确定在装置掺炼加氢尾油后,油浆系统是制约提高转化率的关键因素。%On the basis of the fluid catalytic cracking theory,the main process parameters of FCC unit in Huizhou Oil Refining Company were analyzed,that the slurry oil system was the important restrict factor to increase the convert ratio when FCC unit process the feed mixed with hydro-cracking unconverted oil.

  2. Intermediation under Trade Restrictions.

    OpenAIRE

    Winkler, G Michael

    1989-01-01

    Intermediation is the activity of buying and selling simultaneously in one market. In this paper, intermediation in the market for an arbitrary good is derived from trade restrictions in a general equilibrium exchange model. The trade restrictions are given by a trade feasibility relation defined on the set of households, and they necessitate dropping the one price assumption of standard general equilibrium theory. It is shown that, in this setting, equilibria need not exist in spite of well-...

  3. Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology.

    Science.gov (United States)

    Hu, C; Cao, H; Pan, X; Li, J; He, J; Pan, Q; Xin, J; Yu, X; Li, J; Wang, Y; Zhu, D; Li, L

    2016-01-01

    Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated. PMID:26986509

  4. Antagonism of CD317 Restriction of Human Immunodeficiency Virus Type 1 (HIV-1) Particle Release and Depletion of CD317 Are Separable Activities of HIV-1 Vpu▿

    OpenAIRE

    Goffinet, Christine; Homann, Stefanie; Ambiel, Ina; Tibroni, Nadine; Rupp, Daniel; Keppler, Oliver T.; Fackler, Oliver T.

    2010-01-01

    Vpu antagonizes human immunodeficiency virus type 1 (HIV-1) particle release inhibition by CD317/BST-2/Tetherin. Whether this Vpu activity strictly requires cellular depletion of the restriction factor is unclear. Here, we characterized CD317 variants with mutations in putative sorting or ubiquitination motifs. All mutants still potently impaired release of Vpu-defective HIV-1 and remained sensitive to Vpu-mediated release enhancement. Importantly, this virological antagonism correlated with ...

  5. Serum factors modify the cellular requirement for Ca2+, K+, Mg2+, phosphate ions, and 2-oxocarboxylic acids for multiplication of normal human fibroblasts

    OpenAIRE

    McKeehan, W. L.; McKeehan, K A

    1980-01-01

    The rate of multiplication of a population of cultured human lung fibroblasts is determined by the level of common nutrients and serum factors in the medium. By application of the principles of Henri--Michaelis--Menten kinetic analysis to cell growth in vitro, the relationship between the level of a macromolecular fraction of serum that contains growth factors and the concentration of individual nutrient that is required to support a half-maximal rate of cell multiplication was explored. The ...

  6. Membrane properties and lipid peroxidation in food restricted animals

    OpenAIRE

    Pieri, C.

    1997-01-01

    Food restriction (FR) is a well-recognized method of extending mean and maximum longevity of rodents, but the mode of its action remains to be uncovered. This article reviews the effect of FR on the physical-chemical properties and lipid peroxidizability of cellular membranes. FR prevents the age-dependent increase in microviscosity and peroxidizability of cellular membranes. It has been suggested that a decrease in the body temperature occurring in undernourished animals may play a fundament...

  7. Proteomic Analysis of Unbounded Cellular Compartments: Synaptic Clefts.

    Science.gov (United States)

    Loh, Ken H; Stawski, Philipp S; Draycott, Austin S; Udeshi, Namrata D; Lehrman, Emily K; Wilton, Daniel K; Svinkina, Tanya; Deerinck, Thomas J; Ellisman, Mark H; Stevens, Beth; Carr, Steven A; Ting, Alice Y

    2016-08-25

    Cellular compartments that cannot be biochemically isolated are challenging to characterize. Here we demonstrate the proteomic characterization of the synaptic clefts that exist at both excitatory and inhibitory synapses. Normal brain function relies on the careful balance of these opposing neural connections, and understanding how this balance is achieved relies on knowledge of their protein compositions. Using a spatially restricted enzymatic tagging strategy, we mapped the proteomes of two of the most common excitatory and inhibitory synaptic clefts in living neurons. These proteomes reveal dozens of synaptic candidates and assign numerous known synaptic proteins to a specific cleft type. The molecular differentiation of each cleft allowed us to identify Mdga2 as a potential specificity factor influencing Neuroligin-2's recruitment of presynaptic neurotransmitters at inhibitory synapses. PMID:27565350

  8. Mechanistic insight into Type I restriction endonucleases.

    Science.gov (United States)

    Youell, James; Firman, Keith

    2012-01-01

    Restriction and modification are two opposing activities that are used to protect bacteria from cellular invasion by DNA (e.g. bacteriophage infection). Restriction activity involves cleavage of the DNA; while modification activity is the mechanism used to "mark" host DNA and involves DNA methylation. The study of Type I restriction enzymes has often been seen as an esoteric exercise and this reflects some of their more unusual properties - non-stoichiometric (non-catalytic) cleavage of the DNA substrate, random cleavage of DNA, a massive ATPase activity, and the ability to both cleave DNA and methylate DNA. Yet these enzymes have been found in many bacteria and are very efficient as a means of protecting bacteria against bacteriophage infection, indicating they are successful enzymes. In this review, we summarise recent work on the mechanisms of action, describe switching of function and review their mechanism of action. We also discuss structural rearrangements and cellular localisation, which provide powerful mechanisms for controlling the enzyme activity. Finally, we speculate as to their involvement in recombination and discuss their relationship to helicase enzymes. PMID:22652768

  9. Oxidative stress action in cellular aging

    Directory of Open Access Journals (Sweden)

    Monique Cristine de Oliveira

    2010-12-01

    Full Text Available Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the factors such as cellular oxidative damage, its consequences and the main protective measures taken to prevent or delay this process. Tests with antioxidants: vitamins A, E and C, flavonoids, carotenoids and minerals, the practice of caloric restriction and physical exercise, seeking the beneficial effects on human health, increasing longevity, reducing the level of oxidative stress, slowing the cellular senescence and origin of certain diseases, are discussed.Diferentes teorias tentam explicar o envelhecimento biológico através da alteração das funções e estrutura dos sistemas orgânicos e células. Ao longo da vida, os radicais livres presentes no estresse oxidativo conduzem à peroxidação dos lipídios das membranas celulares, desequilíbrio da homeostase, formação de resíduos químicos, mutações gênicas no DNA, disfunção de certas organelas, bem como ao surgimento de doenças devido à lesão e/ou morte celular. Nesta revisão descreve-se a ação do estresse oxidativo no processo de envelhecimento das células, enfatizando fatores como os danos oxidativos celulares, suas conseqüências e as principais medidas protetoras adotadas para se prevenir ou retardar este processo. Testes com antioxidantes: vitaminas A, E e C, flavonóides, carotenóides e minerais; a prática de restrição calórica e exercícios físicos, que buscam efeitos benéficos sobre a saúde humana, aumentando a longevidade, reduzindo o nível de estresse oxidativo

  10. Bilinear Fourier restriction theorems

    CERN Document Server

    Demeter, Ciprian

    2012-01-01

    We provide a general scheme for proving $L^p$ estimates for certain bilinear Fourier restrictions outside the locally $L^2$ setting. As an application, we show how such estimates follow for the lacunary polygon. In contrast with prior approaches, our argument avoids any use of the Rubio de Francia Littlewood--Paley inequality.

  11. Neuroaesthetics: range and restrictions.

    Science.gov (United States)

    Chatterjee, Anjan

    2013-04-01

    Bullot & Reber (B&R) should be commended for highlighting tensions between scientific aesthetics and art history. The question of how each tradition can learn from the other is timely. While I am sympathetic to their views, their diagnosis of the problem appears exaggerated and their solution partial. They underestimate the reach of scientific aesthetics while failing to identify its inherent restrictions. PMID:23507092

  12. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

    Restricted Boltzmann machines (RBMs) are probabilistic graphical models that can also be interpreted as stochastic neural networks. Training RBMs is known to be challenging. Computing the likelihood of the model parameters or its gradient is in general computationally intensive. Thus, training...

  13. A major binding protein for leukemia inhibitory factor in normal mouse serum: identification as a soluble form of the cellular receptor.

    OpenAIRE

    Layton, M. J.; Cross, B. A.; Metcalf, D; Ward, L. D.; Simpson, R. J.; Nicola, N A

    1992-01-01

    A protein that specifically binds leukemia inhibitory factor (LIF) has been isolated from normal mouse serum by using four successive fractionation steps: chromatography on a LIF affinity matrix, anion-exchange chromatography, size-exclusion chromatography, and preparative native gel electrophoresis. The purified LIF-binding protein (LBP) is a glycoprotein with an apparent molecular mass of 90 kDa that specifically binds 125I-labeled murine LIF with an affinity comparable to that of the low-a...

  14. Dietary restriction: could it be considered as speed bump on tumor progression road?

    Science.gov (United States)

    Cangemi, Antonina; Fanale, Daniele; Rinaldi, Gaetana; Bazan, Viviana; Galvano, Antonio; Perez, Alessandro; Barraco, Nadia; Massihnia, Daniela; Castiglia, Marta; Vieni, Salvatore; Bronte, Giuseppe; Mirisola, Mario; Russo, Antonio

    2016-06-01

    Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long- and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models. However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes. PMID:27043958

  15. 海洋无脊椎动物细胞培养的制约因素及改进方法%Restrictive Factor and Improved Strategy of Cell Culture from Marine Invertebrates

    Institute of Scientific and Technical Information of China (English)

    张晓燕; 王昌留; 李琳

    2015-01-01

    Attempts to development cell culture from marine invertebrates dated back to 1970s. The cell culture from marine invertebrates lags far behind that from vertebrates,there is no single immortal cell line available from marine invertebrates yet. This review outlines the progress of marine invertebrates’ cell culture,points out restrictive factor,and proposes improved strategy. This article provides the reference on the establishment of im-mortal cell lines from marine invertebrates.%海洋无脊椎动物细胞培养的研究始于20世纪70年代,至今未得到永生化细胞系,远远落后于脊椎动物细胞培养的研究。本文概述了海洋无脊椎动物细胞培养的进展,指出了制约因素,参考脊椎动物的研究成果进而提出了海洋无脊椎动物细胞培养的改进方法,为进一步建立起海洋无脊椎动物的永生化细胞系提供参考。

  16. 高校网络法制教育效果的制约因素研究%On the Restrictive Factors of Internet Legal Education in Colleges and Universities

    Institute of Scientific and Technical Information of China (English)

    何庆江; 石浩旭

    2015-01-01

    目前很多高校陆续对大学生开展了网络法制教育,但教育效果不佳。制约高校网络法制教育效果的因素主要包括教育者的观念、受教育者的心理、教育的内容与方法、教育环境等。只有针对这些因素提出相应的改进措施,才能提高高校网络法制教育的效果。%Now many colleges and universities have carried out internet legal education for their students in suc-cession, but the effectiveness is poor. There are many factors restricting internet legal education, which mainly in-clude idea of educators, psychology of educatee, content and methods of education, educational environment, etc. In order to improve the effectiveness of internet legal education in colleges and universities, corresponding measures must be put forward.

  17. The Examination of China’s New Medical Reform Based on Restrictive Factors in British Medical Reform%基于英国医改制约性因素审视我国新医改

    Institute of Scientific and Technical Information of China (English)

    王演艺

    2014-01-01

    As the first country established universal health insurance in the world, UK has been devoted to construct the fairness and welfare of National Health Service(NHS) with constant development and improvement. It focuses on the reform process of NHS since the beginning of this century and studies the deep factors restricted the reform, compared with the current situation of health care system under China’s new medical reform since 2006, putting forward enlightenment to China’s reform.%作为世界上最早建立全民医疗保障的国家,英国一直致力于其医疗服务系统(NHS)公平性与福利性的构建,不断进行发展与完善。文章重点关注本世纪以来NHS 的改革历程,研究影响其改革成效的深层次制约性因素,同时对照我国2006年启动新医疗改革后国内卫生医疗服务体系的现状,提出其对我国新医改的启示。

  18. Restriction of Helmholtz Model

    Directory of Open Access Journals (Sweden)

    V.M. Polunin

    2014-07-01

    Full Text Available The results of the experimental studies of physical mechanisms of energy dissipation in the oscillating system in which air cavity held by the forces of magnetic levitation is used as the elastic element, and magnetic fluid prepared on the basis of dispersing media with different viscosity level is used as the inertial element are considered in the article. Based on the obtained results the conclusion on the restriction of the applicability of Helmholtz equation, caused by boundary effects is made.

  19. License restrictions at Barnwell

    Energy Technology Data Exchange (ETDEWEB)

    Autry, V.R. [S.C. Dept. of Health and Environmental Control, Columbia, SC (United States). Bureau of Radiological Health

    1991-12-31

    The State of South Carolina was delegated the authority by the US Nuclear Regulatory Commission to regulate the receipt, possession, use and disposal of radioactive material as an Agreement State. Since 1970, the state has been the principal regulatory authority for the Barnwell Low-Level Waste Disposal Facility operated by Chem-Nuclear Systems, Inc. The radioactive material license issued authorizing the receipt and disposal of low-level waste contains numerous restrictions to ensure environmental protection and compliance with shallow land disposal performance criteria. Low-level waste has evolved from minimally contaminated items to complex waste streams containing high concentrations of radionuclides and processing chemicals which necessitated these restrictions. Additionally, some waste with their specific radionuclides and concentration levels, many classified as low-level radioactive waste, are not appropriate for shallow land disposal unless additional precautions are taken. This paper will represent a number of these restrictions, the rationale for them, and how they are being dealt with at the Barnwell disposal facility.

  20. 中国职业经理人市场发展的制约因素分析%On the Restricting Factors in the Development of Professional Manager Market in China

    Institute of Scientific and Technical Information of China (English)

    张金艳; 张帆

    2013-01-01

    职业经理人市场是为适应市场经济发展的内在需求而产生的一种新的人力资源配置方式。职业经理人市场的建立和完善涉及到一系列有关因素。相对而言,中国市场经济的建设时期较短,并且具有特殊国情。这决定了不完善的职业经理人价值评价体系、企业主和职业经理人之间的信息不对称、企业主和职业经理人相互信任的缺失、公司治理结构的缺陷和职业经理人市场法律制度的不健全等成为中国职业经理人市场发展的制约因素。%As a new way of human resource allocation, the professional manager market is created to meet the internal demand of the development of market economy. The creation and improvement of professional manager market involves a se-ries of relevant factors. Relatively, China, with special national condition, has established the market economy for a short time period. This determines that the restricting factors for the development of professional manager market in China include the non-perfect value evaluation system for professional managers, asymmetry of information, mutual trust deficiencies between enterprise owners and professional managers, drawback in corporate governance structure and imperfection of relevant legal system and so on.

  1. Problems and Restricting Factor Analysis of Leisure Sports Industry in Shaanxi Province%陕西省休闲体育产业面临的问题及制约因素分析

    Institute of Scientific and Technical Information of China (English)

    姜健

    2012-01-01

    通过对陕西省休闲体育产业面临的问题及制约因素进行深入细致的分析,认为目前面临的主要问题有休闲体育消费市场城乡差别较明显;现有体育场馆设施面向休闲体育市场的开放不够;经营性休闲健身场所与竞赛表演产业发展较成熟,休闲体育培训服务产业较滞后;休闲体育文化产业市场尚待开发。制约陕西省休闲体育产业发展的主要因素包括经济、体制、政策、场地设施、人才等方面。%Through the analysis of problems and factors of Shaanxi leisure sports industry, the paper concludes that the main prob- lem facing leisure sports consumer market gap between urban and rural areas is obvious; Existing sports facilities for leisure sports market opening up enough; Business leisure fitness place and competition demonstration industry development are more mature, leisure sports training service industry is lag; Leisure sports culture industry market is yet to be developed. Restriction of the de- velopment of leisure sports industry of shaanxi province, the main factors including economy, system, policy, the ground equip- ment, personnel, etc.

  2. Modelling cellular behaviour

    Science.gov (United States)

    Endy, Drew; Brent, Roger

    2001-01-01

    Representations of cellular processes that can be used to compute their future behaviour would be of general scientific and practical value. But past attempts to construct such representations have been disappointing. This is now changing. Increases in biological understanding combined with advances in computational methods and in computer power make it possible to foresee construction of useful and predictive simulations of cellular processes.

  3. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  4. Cellular Reflectarray Antenna

    Science.gov (United States)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  5. Do Economic Restrictions Improve Forecasts?

    OpenAIRE

    Murphy, Elizabeth A.; Norwood, F. Bailey; Wohlgenant, Michael K.

    2003-01-01

    A previous study showed that imposing economic restrictions improves the forecasting ability of food demand systems, thus warranting their use even when they are rejected in-sample. This article evaluates whether this result is due to economic restrictions enhancing degrees of freedom or containing nonsample information. Results indicate that restrictions improve forecasting ability even when they are not derived from economic theory, but theoretical restrictions forecast best.

  6. 制约大学生体育能力发展的因素分析与对策研究%The Factor Analysis and Countermeasure Research of Restricting the University Students Sports Ability

    Institute of Scientific and Technical Information of China (English)

    余丁友

    2011-01-01

    运用问卷和建模等方法,对制约大学生体育能力发展的因素进行了分析讨论。结果表明:在高中阶段,切勿随意调停体育课,学校和家长要积极鼓动他们体育锻炼,努力营造良好的体育氛围;大学阶段,优化教师队伍,大力发展体育社团,加强身体健康的重要性教育;临近毕业阶段,通过各种途径积极提高大学生自我认知能力。同时也提出了针对性的发展对策。%This paper analyzes and disscusses the factors of the restrict on the university sports ability development by the the methods of questionnaire and modeling.The results show that:In the high school stage,PE class can not be stop.Teachers and students parents should actively encouraged student to exercise body and tried to create a fine sports atmosphere.At University phase,optimizing the teachers team,devotes to developing sports organization and strengthen health education of exercising.During the graduation stages,improves the university students' selfcognitive ability by some actively means.Finally,the paper also puts forward corresponding develope countermeasures of how to improve the university students ablity of sports.

  7. 我国公共政策参与中公民层面的制约因素分析%AN ANALYSIS OF FACTORS RESTRICTING CITIZENS FROM PARTICIPATING IN PUBLIC POLICIES

    Institute of Scientific and Technical Information of China (English)

    李占乐

    2011-01-01

    在现代社会,公民积极主动地参与政府的公共政策,除了基于自身利益追求的参与动机外,实现和促进与全体社会成员相联系的公共利益也是一个重要动机。改革开放以后,在公民个体的政策参与逐渐增多的同时,我国以民间组织为主体的各种利益团体参与政府公共政策的活动也逐渐增多。同时在我国公民的公共政策参与过程中存在的问题也十分突出。公共政策参与中公民层面的制约因素主要包括参与意识不强、参与能力不足和参与的组织化程度不高3个方面。%In modern society, citizens actively participate in the government' s public policies. In addition to participation based on the pursuit of self-interests, the achieving and promoting of the public interest involving all members of society can be another important motivation. After the reform and opening up, an increasing number of individual citizens participate in policies and meanwhile more various interest groups in China take part in more policy-related activities with civil organizations as the main body. There exist some prominent problems in the participating process. The factors restricting citizens from participating in public policy include weak sense of participation, lack of capacity for involvement and participation and low degree of organization.

  8. 贫困地区民营经济发展的制约因素及对策分析%Restricting Factors for the Growth of Private Economy in Poverty-Stricken Areas and the Strategy

    Institute of Scientific and Technical Information of China (English)

    彭贞贞; 马骥

    2014-01-01

    民营经济发展水平低是贫困地区经济发展不发达的重要原因。制约贫困地区民营经济发展的因素有脱贫致富的思想、人力资源状况、金融生态环境和技术创新水平等。促进贫困地区民营经济发展与脱贫致富必须根据民营经济产业发展需求,大力发展职业教育;优化环境,承接产业转移;创新贫困地区新型城镇化发展机制,推动地区民营经济发展;大力发展交通基础设施,破解民营经济发展瓶颈;创新民营企业管理,做大做强民营经济。%Inadequate development of the private economy is a major reason of economic underdevelopment in poverty-driven areas. Fac-tors restricting the growth of the private economy in these areas include people's lack of eagerness for creating a fortune, human resource shortage, and the poor financial environment and technological innovation ability. To shake off poverty, the areas must develop the private economy by proactively develop vocational education, improve environment for carrying on industry transfer, innovate new-type urbaniza-tion mechanism, enhance the transportation infrastructure construction, and innovate the management of private enterprises.

  9. Deconfinement from action restriction

    International Nuclear Information System (INIS)

    The effect of restricting the plaquette to be greater than a certain cutoff value is studied. The action considered is the standard Wilson action with the addition of a plaquette restriction, which should not affect the continuum limit of the theory. In this investigation, the strong coupling limit is also taken. It is found that a deconfining phase transition occurs as the cutoff is increased, on all lattices studied (up to 204). The critical cutoff on the infinite lattice appears to be around 0.55. For cutoffs above this, a fixed point behavior is observed in the normalized fourth cumulant of the Polyakov loop, suggesting the existence of a line of critical points corresponding to a massless gluon phase, not unlike the situation in compact U(1). The Polyakov loop susceptibility also appears to be diverging with lattice size at these cutoffs. A strong finite volume behavior is observed in the pseudo-specific heat. It is discussed whether these results could still be consistent with the standard crossover picture which precludes the existence of a deconfining phase transition on an infinite symmetric lattice. (orig.)

  10. Cellular and molecular mechanisms in kidney fibrosis

    Science.gov (United States)

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution. PMID:24892703

  11. Cellular and molecular mechanisms in kidney fibrosis

    OpenAIRE

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progressi...

  12. Factoring

    OpenAIRE

    Lenstra, Arjen K.

    1994-01-01

    Factoring, finding a non-trivial factorization of a composite positive integer, is believed to be a hard problem. How hard we think it is, however, changes almost on a daily basis. Predicting how hard factoring will be in the future, an important issue for cryptographic applications of composite numbers, is therefore a challenging task. The author presents a brief survey of general purpose integer factoring algorithms and their implementations

  13. Cellular oncogenes in neoplasia.

    OpenAIRE

    Chan, V T; McGee, J O

    1987-01-01

    In recent years cellular homologues of many viral oncogenes have been identified. As these genes are partially homologous to viral oncogenes and are activated in some tumour cell lines they are termed "proto-oncogenes". In tumour cell lines proto-oncogenes are activated by either quantitative or qualitative changes in gene structure: activation of these genes was originally thought to be a necessary primary event in carcinogenesis, but activated cellular oncogenes, unlike viral oncogenes, do ...

  14. Cellular Cardiomyoplasty: Clinical Application

    OpenAIRE

    Chachques, J. (J.); Acar, C; J. Herreros; Trainini, J. (Jorge); Prosper, F.; D’Attellis, N. (N.); Fabiani, J. N.; Carpentier, A

    2004-01-01

    Myocardial regeneration can be induced with the implantation of a variety of myogenic and angiogenic cell types. More than 150 patients have been treated with cellular cardiomyoplasty worldwide, 18 patients have been treated by our group. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit postischemic remodelling, and restore regional myocardial contractility. Techniques for skeletal myoblasts culture and ex vivo expansion using auto...

  15. MRI of restrictive cardiomyopathy

    International Nuclear Information System (INIS)

    Objective: To evaluate the diagnostic value of MRI in combination of delayed gadolinium-enhanced MR imaging for the identification of restrictive cardiomyopathy (RCM). Methods: One hundred sixteen patients with RCM underwent ECG, thoracic radiography, echocardiography and MRI. The final diagnosis was made on comprehensive evaluation in consideration of patient history, clinical symptoms and imaging appearances. Fifty-five normal subjects were used as the controls. All patients were divided into two groups according to contrast-enhanced MRI patterns: RCM with delayed enhancement (RCM with DE, n=35) and RCM without delayed enhancement (RCM without DE, n=81). Bi-atrial and bi-ventricular size, ventricular septal and left free wall thickness were measured. A paired t-test was used for statistic analysis. Results: Bi-atrial size, right ventricular diastolic diameter (RVDD), ventricular septal and left free wall thickness were significantly larger in RCM patients than in normal subjects (P0.05). Visual observation showed mild mitral regurgitation (50 cases), moderate mitral regurgitation (24 cases ), mild tricuspid regurgitation (32 cases) and severe tricuspid regurgitation (46 cases). Thirty-five RCMs with DE presented diffuse (15 cases) or segmental (20 cases) enhancement. Twelve RCMs with diffuse delayed enhancement showed powdery, enhancement, and 3 showed petaline enhancement. Three cases with powdery enhancement were histologically proven as myocardial amyloidosis. Ventricular septum was the most vulnerable segment in patients with segmental enhancement. Six cases presented subendocardial enhancement that corresponded to apical obliteration, of which one case was confirmed as hypereosinophilia by bone marrow biopsy and the other 14 cases didn't present any regular enhancement. In 81 RCMs without DE, marked bi-atrial dilation, near-normal ventricular chambers and near-normal ventricular thickness were presented. Conclusion: MRI is an excellent imaging modality for

  16. Differences between disease-associated endoplasmic reticulum aminopeptidase 1 (ERAP1) isoforms in cellular expression, interactions with tumour necrosis factor receptor 1 (TNF-R1) and regulation by cytokines.

    Science.gov (United States)

    Yousaf, N; Low, W Y; Onipinla, A; Mein, C; Caulfield, M; Munroe, P B; Chernajovsky, Y

    2015-05-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) processes peptides for major histocompatibility complex (MHC) class I presentation and promotes cytokine receptor ectodomain shedding. These known functions of ERAP1 may explain its genetic association with several autoimmune inflammatory diseases. In this study, we identified four novel alternatively spliced variants of ERAP1 mRNA, designated as ΔExon-11, ΔExon-13, ΔExon-14 and ΔExon-15. We also observed a rapid and differential modulation of ERAP1 mRNA levels and spliced variants in different cell types pretreated with lipopolysaccharide (LPS). We have studied three full-length allelic forms of ERAP1 (R127-K528, P127-K528, P127-R528) and one spliced variant (ΔExon-11) and assessed their interactions with tumour necrosis factor receptor 1 (TNF-R1) in transfected cells. We observed variation in cellular expression of different ERAP1 isoforms, with R127-K528 being expressed at a much lower level. Furthermore, the cellular expression of full-length P127-K528 and ΔExon-11 spliced variant was enhanced significantly when co-transfected with TNF-R1. Isoforms P127-K528, P127-R528 and ΔExon-11 spliced variant associated with TNF-R1, and this interaction occurred in a region within the first 10 exons of ERAP1. Supernatant-derived vesicles from transfected cells contained the full-length and ectodomain form of soluble TNF-R1, as well as carrying the full-length ERAP1 isoforms. We observed marginal differences between TNF-R1 ectodomain levels when co-expressed with individual ERAP1 isoforms, and treatment of transfected cells with tumour necrosis factor (TNF), interleukin (IL)-1β and IL-10 exerted variable effects on TNF-R1 ectodomain cleavage. Our data suggest that ERAP1 isoforms may exhibit differential biological properties and inflammatory mediators could play critical roles in modulating ERAP1 expression, leading to altered functional activities of this enzyme. PMID:25545008

  17. Modulation of Cellular Transcription Factor Activity

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  18. Cellular Factors Implicated in Filovirus Entry

    OpenAIRE

    Suchita Bhattacharyya; Hope, Thomas J.

    2013-01-01

    Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replica...

  19. Restrictions to HIV-1 replication in resting CD4+T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Xiaoyu Pan; Hanna-Mari Baldauf; Oliver T Keppler; Oliver T Fackler

    2013-01-01

    CD4+ T lymphocytes represent the main target cell population of human immunodeficiency virus (HIV).In an activated state,CD4+ T cells residing in lymphoid organs are a major reservoir of ongoing HIV-1 replication in infected individuals.In contrast,resting CD4+ T cells are highly resistant to productive HIV-1 infection,yet are massively depleted during disease progression and represent a substantial latent reservoir for the virus in vivo.Barriers preventing replication of HIV-1 in resting CD4+ T cells include a rigid layer of cortical actin and,early after HIV-1entry,a block that limits reverse transcription of incoming viral RNA genomes.Defining the molecular bases of these restrictions has remained one of the central open questions in HIV research.Recent advances unraveled mechanisms by which HIV-1 bypasses the entry block and established the host cell restriction factor SAMHD1,a deoxynucleoside triphosphate triphosphohydrolase,as a central determinant of the cellular restriction to HIV-1 reverse transcription in resting CD4+ T cells.This review summarizes our current molecular and pathophysiological understanding of the multi-faceted interactions of HIV-1 with resting CD4+ T lymphocytes.

  20. Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms.

    LENUS (Irish Health Repository)

    Corvin, Aiden P

    2012-06-27

    Insulin-like growth factor-1 (IGF1) and its active peptide (1-3)IGF1 modulate brain growth and plasticity and are candidate molecules for treatment of brain disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri-peptide (1-3)IGF1 (glycine-praline-glutamate). IGF1 and (1-3)IGF have been proposed as treatment for neuropathologies, yet their effect on nerve cells has not been directly compared. In this study we examine the effects of IGF1 and (1-3)IGF1 in primary cortical cultures and measure the expression levels of markers for intracellular pathways and synaptic function. We find that both treatments activate the IGF1 receptor and enhance the expression of synaptic markers, however, they activate different intracellular pathways. Furthermore, (1-3)IGF1 administration increases the expression of endogenous IGF1, suggesting a direct interaction between the two molecules. The results show that the two molecules increase the expression of synaptic proteins through activating different cellular mechanisms.

  1. Cellular events and biomarkers of wound healing

    OpenAIRE

    Shah Jumaat Mohd Yussof; Effat Omar; Pai, Dinker R.; Suneet Sood

    2012-01-01

    Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth f...

  2. Irregular Cellular Learning Automata.

    Science.gov (United States)

    Esnaashari, Mehdi; Meybodi, Mohammad Reza

    2015-08-01

    Cellular learning automaton (CLA) is a recently introduced model that combines cellular automaton (CA) and learning automaton (LA). The basic idea of CLA is to use LA to adjust the state transition probability of stochastic CA. This model has been used to solve problems in areas such as channel assignment in cellular networks, call admission control, image processing, and very large scale integration placement. In this paper, an extension of CLA called irregular CLA (ICLA) is introduced. This extension is obtained by removing the structure regularity assumption in CLA. Irregularity in the structure of ICLA is needed in some applications, such as computer networks, web mining, and grid computing. The concept of expediency has been introduced for ICLA and then, conditions under which an ICLA becomes expedient are analytically found. PMID:25291810

  3. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  4. Effect of cellular mobility on immune response

    Science.gov (United States)

    Pandey, R. B.; Mannion, R.; Ruskin, H. J.

    2000-08-01

    Mobility of cell types in our HIV immune response model is subject to an intrinsic mobility and an explicit directed mobility, which is governed by Pmob. We investigate how restricting the explicit mobility, while maintaining the innate mobility of a viral-infected cell, affects the model's results. We find that increasing the explicit mobility of the immune system cells leads to viral dominance for certain levels of viral mutation. We conclude that increasing immune system cellular mobility indirectly increases the virus’ inherent mobility.

  5. Wireless Cellular Mobile Communications

    Directory of Open Access Journals (Sweden)

    V. Zalud

    2002-12-01

    Full Text Available In this article is briefly reviewed the history of wireless cellularmobile communications, examined the progress in current secondgeneration (2G cellular standards and discussed their migration to thethird generation (3G. The European 2G cellular standard GSM and itsevolution phases GPRS and EDGE are described somewhat in detail. Thethird generation standard UMTS taking up on GSM/GPRS core network andequipped with a new advanced access network on the basis of codedivision multiple access (CDMA is investigated too. A sketch of theperspective of mobile communication beyond 3G concludes this article.

  6. Property Rights, Restrictions and Responsibilities

    DEFF Research Database (Denmark)

    Enemark, Stig

    more to a social, ethical commitment or attitude to environmental sustainability and good husbandry. This paper provides an overall understanding of the concept of land administration systems for dealing with rights, restrictions and responsibilities in future spatially enabled government. Finally the......Land Administration Systems are the basis for conceptualizing rights, restrictions and responsibilities related to people, policies and places. Property rights are normally concerned with ownership and tenure whereas restrictions usually control use and activities on land. Responsibilities relate...

  7. Translating partitioned cellular automata into classical type cellular automata

    OpenAIRE

    Poupet, Victor

    2008-01-01

    Partitioned cellular automata are a variant of cellular automata that was defined in order to make it very simple to create complex automata having strong properties such as number conservation and reversibility (which are often difficult to obtain on cellular automata). In this article we show how a partitioned cellular automaton can be translated into a regular cellular automaton in such a way that these properties are conserved.

  8. Genetic Dominance & Cellular Processes

    Science.gov (United States)

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  9. Radioactivity of cellular concrete

    International Nuclear Information System (INIS)

    The natural radioactivity of cellular concrete is discussed. Some data on the concentrations of 40K, 226Ra and 232Th in building materials in Poland are given. The results of dose rates measurements in living quarters as well as outside are presented. (A.S.)

  10. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  11. Geometry of the restricted Boltzmann machine

    OpenAIRE

    Cueto, Maria Angelica; Morton, Jason; Sturmfels, Bernd

    2009-01-01

    The restricted Boltzmann machine is a graphical model for binary random variables. Based on a complete bipartite graph separating hidden and observed variables, it is the binary analog to the factor analysis model. We study this graphical model from the perspectives of algebraic statistics and tropical geometry, starting with the observation that its Zariski closure is a Hadamard power of the first secant variety of the Segre variety of projective lines. We derive a dimension formula for the ...

  12. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

    Science.gov (United States)

    Pietrocola, Federico; Pol, Jonathan; Vacchelli, Erika; Rao, Shuan; Enot, David P; Baracco, Elisa E; Levesque, Sarah; Castoldi, Francesca; Jacquelot, Nicolas; Yamazaki, Takahiro; Senovilla, Laura; Marino, Guillermo; Aranda, Fernando; Durand, Sylvère; Sica, Valentina; Chery, Alexis; Lachkar, Sylvie; Sigl, Verena; Bloy, Norma; Buque, Aitziber; Falzoni, Simonetta; Ryffel, Bernhard; Apetoh, Lionel; Di Virgilio, Francesco; Madeo, Frank; Maiuri, Maria Chiara; Zitvogel, Laurence; Levine, Beth; Penninger, Josef M; Kroemer, Guido

    2016-07-11

    Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. PMID:27411589

  13. Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/ T helper 2 balance in humans.

    Directory of Open Access Journals (Sweden)

    John Axelsson

    Full Text Available BACKGROUND: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. METHODS: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00-07.00 h followed by 5 days with restricted sleep (03.00-07.00 h. On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α, interleukin (IL -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1 after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA. Also leukocyte numbers, mononuclear cells and cortisol were analysed. RESULTS: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05. A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05. In addition, all variables varied across the 24 h day. CONCLUSIONS: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

  14. Hepatic autophagy contributes to the metabolic response to dietary protein restriction.

    Science.gov (United States)

    Henagan, Tara M; Laeger, Thomas; Navard, Alexandra M; Albarado, Diana; Noland, Robert C; Stadler, Krisztian; Elks, Carrie M; Burk, David; Morrison, Christopher D

    2016-06-01

    Autophagy is an essential cellular response which acts to release stored cellular substrates during nutrient restriction, and particularly plays a key role in the cellular response to amino acid restriction. However, there has been limited work testing whether the induction of autophagy is required for adaptive metabolic responses to dietary protein restriction in the whole animal. Here, we found that moderate dietary protein restriction led to a series of metabolic changes in rats, including increases in food intake and energy expenditure, the downregulation of hepatic fatty acid synthesis gene expression and reduced markers of hepatic mitochondrial number. Importantly, these effects were also associated with an induction of hepatic autophagy. To determine if the induction of autophagy contributes to these metabolic effects, we tested the metabolic response to dietary protein restriction in BCL2-AAA mice, which bear a genetic mutation that impairs autophagy induction. Interestingly, BCL2-AAA mice exhibit exaggerated responses in terms of both food intake and energy expenditure, whereas the effects of protein restriction on hepatic metabolism were significantly blunted. These data demonstrate that restriction of dietary protein is sufficient to trigger hepatic autophagy, and that disruption of autophagy significantly alters both hepatic and whole animal metabolic response to dietary protein restriction. PMID:27173459

  15. Stroke and restricted sensory syndromes

    International Nuclear Information System (INIS)

    There have been sporadic case reports of a restricted sensory syndrome caused by stroke, most often as a cheiro-oral syndrome. We describe 14 patients with stroke who showed various restricted sensory syndromes and correlated their symptoms with the radiological findings. (orig./MG)

  16. Factores asociados a la infección celular por el virus de la necrosis pancreática infecciosa (IPNV Factors associated with cellular infection by the infectious pancreatic necrosis virus (IPNV

    Directory of Open Access Journals (Sweden)

    C Ortega

    2007-01-01

    Full Text Available El virus de la necrosis pancreática infecciosa (IPNV es una de las principales causas de pérdidas económicas en salmónidos de cultivo; la expresión temporal y las características de sus componentes han sido descritas en varios trabajos; sin embargo, el papel de las distintas proteínas en la patogénesis viral no ha sido completamente determinado. En este artículo se presenta una revisión bibliográfica de los procesos que permiten establecer la relación virus-célula, la replicación y diseminación de la infección, destacando el papel de los componentes virales en tales mecanismos y los efectos de su variabilidad sobre la virulencia viral, describiendo también los mecanismos moleculares que son característicos de los Birnavirusen relación a su replicación, traducción y maduración. Las respuestas y mecanismos de defensa del hospedero en contra de la infección viral son abordadas resaltando la importancia de la inmunidad inespecífica a través de la vía interferón como estimulador de la síntesis de proteínas antivirales y la implicancia de la apoptosis también como un mecanismo de defensa, pero que puede ser modulado por las proteínas del virus. El desarrollo del estado portador, considerado uno de los aspectos más importantes en la diseminación de IPNV, se aborda describiendo la participación de factores virales y celulares.The infectious pancreatic necrosis virus (IPNV is one of the main causes of economic losses in salmon farms. Its temporal expression and the characteristics of its components have been described in many studies, however, the role of proteins in viral pathogenesis has not been completely determined. The aim of this review is to detail the processes that allow the establishment of a virus-cell relationship, replication and dissemination of the infection, highlighting the role of the viral components in such mechanisms and the effect of their variability on viral virulence. The molecular mechanisms

  17. The RNA helicase DDX1 is involved in restricted HIV-1 Rev function in human astrocytes

    International Nuclear Information System (INIS)

    Productive infection by human immunodeficiency virus type I (HIV-1) in the central nervous system (CNS) involves mainly macrophages and microglial cells. A frequency of less than 10% of human astrocytes is estimated to be infectable with HIV-1. Nonetheless, this relatively low percentage of infected astrocytes, but associated with a large total number of astrocytic cells in the CNS, makes human astrocytes a critical part in the analyses of potential HIV-1 reservoirs in vivo. Investigations in astrocytic cell lines and primary human fetal astrocytes revealed that limited HIV-1 replication in these cells resulted from low-level viral entry, transcription, viral protein processing, and virion maturation. Of note, a low ratio of unspliced versus spliced HIV-1-specific RNA was also investigated, as Rev appeared to act aberrantly in astrocytes, via loss of nuclear and/or nucleolar localization and diminished Rev-mediated function. Host cellular machinery enabling Rev function has become critical for elucidation of diminished Rev activity, especially for those factors leading to RNA metabolism. We have recently identified a DEAD-box protein, DDX1, as a Rev cellular co-factor and now have explored its potential importance in astrocytes. Cells were infected with HIV-1 pseudotyped with envelope glycoproteins of amphotropic murine leukemia viruses (MLV). Semi-quantitative reverse transcriptase-polymerase chain reactions (RT-PCR) for unspliced, singly-spliced, and multiply-spliced RNA clearly showed a lower ratio of unspliced/singly-spliced over multiply-spliced HIV-1-specific RNA in human astrocytes as compared to Rev-permissive, non-glial control cells. As well, the cellular localization of Rev in astrocytes was cytoplasmically dominant as compared to that of Rev-permissive, non-glial controls. This endogenous level of DDX1 expression in astrocytes was demonstrated directly to lead to a shift of Rev sub-cellular distribution dominance from nuclear and/or nucleolar to

  18. Weighted Centroid Correction Localization in Cellular Systems

    Directory of Open Access Journals (Sweden)

    Rong-Zheng Li

    2011-01-01

    Full Text Available Problem statement: There is a large demand for wireless Location-Based Service (LBS and it is provided by many wireless cellular systems. In process of positioning a Mobile Station (MS, the computing speed is as important as the positioning accuracy and the algorithm should also be resistant to environmental influences. Approach: A new positioning method based on Weighted Centroid Correction Localization (WCCL for wireless cellular systems is introduced in this article. Firstly, referring to the receiving-state of an MS in cellular systems, it computes a weighted centroid of surrounding Base Stations (BSs as a rough approximate position of the MS. Then, according to the distances between the MS and the BSs being less or bigger than the computed distances between the BSs and the weighted centroid, it corrects the coordinate of the weighted centroid towards the directions of the BSs by moving it closer or farther in turn. Results: According to our experiments, WCCL improves the positioning accuracy, as well as to provide a better resistance to environmental influences. Conclusion: As a modified centroid-based localization algorithm, WCCL obtains weighting factors from the receiving-state of MS in multi-cells structured cellular systems and obtains a better positioning result in cellular systems without updating the network equipment. Therefore, for the cellular positioning problem, WCCL algorithm can be an alternate solution.

  19. Cellular host responses to gliomas.

    Directory of Open Access Journals (Sweden)

    Joseph Najbauer

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. METHODOLOGY/PRINCIPAL FINDINGS: Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a 'network' with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a 'pair-wise' manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a low-generation tumors (first in vivo passage in rats were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b high-generation xenografts (fifth passage had pronounced cellularity, were angiogenic with 'glomerulus-like' microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  20. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  1. Magnetic Cellular Switches

    OpenAIRE

    Overby, Darryl R.; Alenghat, Francis J.; Montoya-Zavala, Martín; Bei, HuCheng; Oh, Philmo; Karavitis, John; Ingber, Donald E.

    2004-01-01

    This paper focuses on the development of magnetic cellular switches to enable magnetic control of intracellular functions in living mammalian cells, including receptor signal transduction and gene transcription. Our approach takes advantage of the mechanosensitivity of adenosine 3′,5′-monophosphate (cAMP) induction and downstream transcription controlled by the cAMP regulatory element (CRE) to engineer gene constructs that optically report gene expression in living cells. We activate transcri...

  2. Quantum cellular automata

    Science.gov (United States)

    Porod, Wolfgang; Lent, Craig S.; Bernstein, Gary H.

    1994-06-01

    The Notre Dame group has developed a new paradigm for ultra-dense and ultra-fast information processing in nanoelectronic systems. These Quantum Cellular Automata (QCA's) are the first concrete proposal for a technology based on arrays of coupled quantum dots. The basic building block of these cellular arrays is the Notre Dame Logic Cell, as it has been called in the literature. The phenomenon of Coulomb exclusion, which is a synergistic interplay of quantum confinement and Coulomb interaction, leads to a bistable behavior of each cell which makes possible their use in large-scale cellular arrays. The physical interaction between neighboring cells has been exploited to implement logic functions. New functionality may be achieved in this fashion, and the Notre Dame group invented a versatile majority logic gate. In a series of papers, the feasibility of QCA wires, wire crossing, inverters, and Boolean logic gates was demonstrated. A major finding is that all logic functions may be integrated in a hierarchial fashion which allows the design of complicated QCA structures. The most complicated system which was simulated to date is a one-bit full adder consisting of some 200 cells. In addition to exploring these new concepts, efforts are under way to physically realize such structures both in semiconductor and metal systems. Extensive modeling work of semiconductor quantum dot structures has helped identify optimum design parameters for QCA experimental implementations.

  3. [Glycotoxins and cellular dysfunction. A new mechanism for understanding the preventive effects of lifestyle modifications].

    Science.gov (United States)

    Michalsen, A; Bierhaus, A; Nawroth, P P; Dobos, G J

    2006-08-01

    Recently the AGE-RAGE interaction was identified as a potential mechanism underlying chronic and inflammatory diseases like atherosclerosis, diabetes mellitus and kidney disease. Advanced glycation end products (AGEs) are the derivatives of glucose-protein or glucose-lipid reactions and are mainly generated from the diet (depending on intensity of heating, cooking time and oxygenation). Binding of AGEs or other ligands to the AGE receptor (RAGE) results in cellular activation, i.e. increased expression of inflammatory mediators and oxidative stress. Diet-derived AGEs thus induce deleterious effects on tissues and the cardiovascular system. Recent research also found that other lifestyle factors are associated with pronounced inflammatory activation, e.g. psychosocial stress and smoking. In addition, each intake of meals is associated with proinflammatory cellular changes. The AGE-RAGE model and investigations of the underlying cellular mechanisms thus may lead to a better understanding of the health benefits of diets (Mediterranean diet, uncooked vegetarian diets), caloric restriction and intermittent fasting. The clinical impact of low-AGE diets and fasting and the interaction between stress and food intake should be further investigated in controlled trials. PMID:16897151

  4. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

    The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

  5. How harmful are adaptation restrictions

    OpenAIRE

    Bruin, de, B.; Dellink, R.B.

    2009-01-01

    The dominant assumption in economic models of climate policy remains that adaptation will be implemented in an optimal manner. There are, however, several reasons why optimal levels of adaptation may not be attainable. This paper investigates the effects of suboptimal levels of adaptation, i.e. adaptation restrictions, on the composition and level of climate change costs and on welfare. Several adaptation restrictions are identified and then simulated in a revised DICE model, extended with ad...

  6. Failover in cellular automata

    CERN Document Server

    Kumar, Shailesh

    2010-01-01

    A cellular automata (CA) configuration is constructed that exhibits emergent failover. The configuration is based on standard Game of Life rules. Gliders and glider-guns form the core messaging structure in the configuration. The blinker is represented as the basic computational unit, and it is shown how it can be recreated in case of a failure. Stateless failover using primary-backup mechanism is demonstrated. The details of the CA components used in the configuration and its working are described, and a simulation of the complete configuration is also presented.

  7. Cellular mechanics and motility

    Science.gov (United States)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  8. Radiolabelled Cellular Blood Elements

    International Nuclear Information System (INIS)

    This volume contains the abstracts of the 5th International Symposion on Radiolabelling of Cellular Blood Elements to be held in Vienna, Austria, September 10-14, 1989. The Meeting is the fifth in a series of meetings designed to discuss the basics and clinical application of radiolabelling techniques. In these days, beside the search for new labelling agents and extending the knowledge in clinical use, the use of monoclonal antibodies is a big new challenge. All reviewed contributions that have been accepted for presentation are contained in this volume. (authors) 58 of them are of INIS scope

  9. Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin

    Directory of Open Access Journals (Sweden)

    Masarudin MJ

    2015-12-01

    Full Text Available Mas Jaffri Masarudin,1 Suzanne M Cutts,2 Benny J Evison,3 Don R Phillips,2 Paul J Pigram4 1Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2Department of Biochemistry, La Trobe University, Melbourne, Victoria, Australia; 3Department of Chemical Biology and Therapeutics, St Jude Children's Hospital, Memphis, TN, USA; 4Department of Physics, La Trobe University, Melbourne, Victoria, Australia Abstract: Development of parameters for the fabrication of nanosized vectors is pivotal for its successful administration in therapeutic applications. In this study, homogeneously distributed chitosan nanoparticles (CNPs with diameters as small as 62 nm and a polydispersity index (PDI of 0.15 were synthesized and purified using a simple, robust method that was highly reproducible. Nanoparticles were synthesized using modified ionic gelation of the chitosan polymer with sodium tripolyphosphate. Using this method, larger aggregates were mechanically isolated from single particles in the nanoparticle population by selective efficient centrifugation. The presence of disaggregated monodisperse nanoparticles was confirmed using atomic force microscopy. Factors such as anions, pH, and concentration were found to affect the size and stability of nanoparticles directly. The smallest nanoparticle population was ~62 nm in hydrodynamic size, with a low PDI of 0.15, indicating high particle homogeneity. CNPs were highly stable and retained their monodisperse morphology in serum-supplemented media in cell culture conditions for up to 72 hours, before slowly degrading over 6 days. Cell viability assays demonstrated that cells remained viable following a 72-hour exposure to 1 mg/mL CNPs, suggesting that the nanoparticles are well tolerated and highly suited for biomedical applications. Cellular uptake studies using fluorescein isothiocyanate-labeled CNPs showed that cancer cells

  10. A novel envelope mediated post entry restriction of murine leukaemia virus in human cells is Ref1/TRIM5α independent

    Directory of Open Access Journals (Sweden)

    McKnight Áine

    2010-10-01

    Full Text Available Abstract Background 'Intrinsic' resistance to retroviral infection was first recognised with the Friend virus susceptibility gene (Fv1, which determines susceptibility to murine leukaemia virus (MLV infection in different murine species. Similarly, the tripartite motif (TRIM family of proteins determine lentiviral restriction in a primate host-species specific manner. For example rhesus TRIM5α (rhTRIM5α can potently restrict HIV-1 infection while human TRIM5α (huTRIM5α only has a mild effect on SIVmac and HIV-1 infectivity (Lv1. Human TRIM5α is able to restrict MLV-N virus replication, but is ineffective against MLV-B or MLV-NB virus infection. Lv2 restriction of some HIV-2 viruses is seen in human cells. Like Lv1, Lv2 is a post-entry restriction factor, whose viral determinants have been mapped to the viral capsid (CA. Unlike Lv1, however, Lv2 is determined by envelope (Env in addition to CA. Here we present evidence of a novel Env determined post entry restriction to infection in human cells of pseudotyped MLV-B and MLV-NB cores. Results We generated retroviral vectors pseudotyped with various gamma and lentiviral Envs on MLV-B and -NB CAs containing a green fluorescent protein (GFP reporter. Flow cytometry was used to determine transduction efficiencies in NP2/CD4/CXCR4 (glioma cell line stably transduced with the HIV receptors and HeLa/CD4 cell lines. The HeLa/CD4 cell line restricted both MLV CAs in an Env dependent manner, compared to NP2/CD4/CXCR4 cells. Quantitative polymerase chain reaction (QT-PCR analysis of reverse transcription (RT transcripts demonstrates that this restriction occurs at a post entry and RT level. siRNA knockdown of huTRIM5α ruled out a direct role for this cellular component in mediating this restriction. We describe a previously unobserved Env determined restriction of MLV-B and MLV-NB CAs in HeLa/CD4 cells when pseudotyped with HIV-2 and RD114 Envs, but not gibbon ape leukaemia virus (GALV, HIV-1 or

  11. Photoperiod interacts with food restriction on performance in the Barnes maze in female California mice

    OpenAIRE

    Steinman, Michael Q.; Crean, Katie K.; Trainor, Brian C.

    2010-01-01

    Food restriction has been reported to have positive effects on cognition. This study examines how another environmental factor, daylength, can alter the impact of food restriction on the brain and behavior. Female California mice (Peromyscus californicus), housed on either long days (16L:8D) or short days (8L:16D) were restricted to 80% of their normal baseline food intake or provided food ad libitum. Testing in a Barnes maze revealed that the effects of food restriction depend on photoperiod...

  12. The Ability of Multimerized Cyclophilin A to Restrict Retrovirus Infection

    OpenAIRE

    Javanbakht, Hassan; Diaz-Griffero, Felipe; Yuan, Wen; Yeung, Darwin F.; Li, Xing; Song, Byeongwoon; Sodroski, Joseph

    2007-01-01

    In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cycl...

  13. Neutron inelastic scattering from {sup 4}He in restricted geometries

    Energy Technology Data Exchange (ETDEWEB)

    Gibbs, M.R. [Keele Univ. (United Kingdom). Dept. of Physics; Sokol, P.E. [Dept. of Physics, Pennsylvania State Univ., University Park, PA (United States); Azuah, R.T. [Keele Univ. (United Kingdom). Dept. of Physics]|[Rutherford Appleton Lab., Chilton, Didcot (United Kingdom); Stirling, W.G. [Keele Univ. (United Kingdom). Dept. of Physics; Adams, M.A. [Rutherford Appleton Lab., Chilton, Didcot (United Kingdom)

    1995-08-01

    When liquid {sup 4}He is condensed in porous aerogel glass (typical pore size {approx}5000 A), many of the superfluid properties are significantly altered. Measurements have been made of the dynamic structure factor S(Q,{omega}) of liquid {sup 4}He in restricted geometries. The collective phonon-roton excitations are shown to have an intrinsic broadening associated with the restricted geometry. The temperature dependence of the excitation spectrum is discussed. (orig.).

  14. Genetics Home Reference: familial restrictive cardiomyopathy

    Science.gov (United States)

    ... Home Health Conditions familial restrictive cardiomyopathy familial restrictive cardiomyopathy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Familial restrictive cardiomyopathy is a genetic form of heart disease. For ...

  15. Integrated cellular systems

    Science.gov (United States)

    Harper, Jason C.

    The generation of new three-dimensional (3D) matrices that enable integration of biomolecular components and whole cells into device architectures, without adversely altering their morphology or activity, continues to be an expanding and challenging field of research. This research is driven by the promise that encapsulated biomolecules and cells can significantly impact areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, photonics, smart prosthetics, advanced physiological sensors, portable medical diagnostic devices, and tissue/organ replacement. This work focuses on the development of a fundamental understanding of the biochemical and nanomaterial mechanisms that govern the cell directed assembly and integration process. It was shown that this integration process relies on the ability of cells to actively develop a pH gradient in response to evaporation induced osmotic stress, which catalyzes silica condensation within a thin 3D volume surrounding the cells, creating a functional bio/nano interface. The mechanism responsible for introducing functional foreign membrane-bound proteins via proteoliposome addition to the silica-lipid-cell matrix was also determined. Utilizing this new understanding, 3D cellular immobilization capabilities were extended using sol-gel matrices endowed with glycerol, trehalose, and media components. The effects of these additives, and the metabolic phase of encapsulated S. cerivisiase cells, on long-term viability and the rate of inducible gene expression was studied. This enabled the entrapment of cells within a novel microfluidic platform capable of simultaneous colorimetric, fluorescent, and electrochemical detection of a single analyte, significantly improving confidence in the biosensor output. As a complementary approach, multiphoton protein lithography was utilized to engineer 3D protein matrices in which to

  16. Entanglement with restricted measurement setups

    CERN Document Server

    Meznaric, Sebastian

    2010-01-01

    We consider what is the effective amount of entanglement when the measurement operators one has at their disposal are restricted. Such a scenario occurs when superselection rules are in effect or when there are imperfections in our measurement setup. Given a quantum state and the restrictions on measurements, we consider the following scenario. Imagine we have an ideal, or non-restricted, measurement setup and a state $\\rho_1$ and a non-ideal, or restricted, measurement setup and a state $\\rho_2$. Then the minimum amount of entanglement in $\\rho_1$ so that all quantum communication protocols still perform with the same fidelity as with $\\rho_2$ is effectively the entanglement with restricted measurement setup. For indistinguishable particles, we find that any quantum communication protocol that can be performed with indistinguishable particles, can thus be performed with a ``normal'' state of no more than $E_P$ of entanglement. For the imperfect measurement apparatus we find an upper bound for the effective e...

  17. Numerical investigation on evolution of cylindrical cellular detonation

    Institute of Scientific and Technical Information of China (English)

    WANG Chun; JIANG Zong-lin; HU Zong-min; HAN Gui-lai

    2008-01-01

    Cylindrical cellular detonation is numerically investigated by solving twodimensional reactive Euler equations with a finite volume method on a two-dimensional self-adaptive unstructured mesh.The one-step reversible chemical reaction model is applied to simplify the control parameters of chemical reaction.Numerical results demonstrate the evolution of cellular cell splitting of cylindrical cellular detonation explored in experimentas.Split of cellular structures shows different features in the near-field and far-field from the initiation zone.Variation of the local curvature is a key factor in the behavior of cell split of cylindrical cellular detonation in propagation.Numerical results show that split of cellular structures comes from the self-organization of transverse waves corresponding to the development of small disturbances along the detonation front related to detonation instability.

  18. Cellular basis of memory for addiction.

    Science.gov (United States)

    Nestler, Eric J

    2013-12-01

    DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. Here, we review the types of molecular and cellular adaptations that occur in specific brain regions to mediate addiction-associated behavioral abnormalities. These include alterations in gene expression achieved in part via epigenetic mechanisms, plasticity in the neurophysiological functioning of neurons and synapses, and associated plasticity in neuronal and synaptic morphology mediated in part by altered neurotrophic factor signaling. Each of these types of drug-induced modifications can be viewed as a form of "cellular or molecular memory." Moreover, it is striking that most addiction-related forms of plasticity are very similar to the types of plasticity that have been associated with more classic forms of "behavioral memory," perhaps reflecting the finite repertoire of adaptive mechanisms available to neurons when faced with environmental challenges. Finally, addiction-related molecular and cellular adaptations involve most of the same brain regions that mediate more classic forms of memory, consistent with the view that abnormal memories are important drivers of addiction syndromes. The goal of these studies which aim to explicate the molecular and cellular basis of drug addiction is to eventually develop biologically based diagnostic tests, as well as more effective treatments for addiction disorders. PMID:24459410

  19. Modeling and cellular studies

    International Nuclear Information System (INIS)

    Testing the applicability of mathematical models with carefully designed experiments is a powerful tool in the investigations of the effects of ionizing radiation on cells. The modeling and cellular studies complement each other, for modeling provides guidance for designing critical experiments which must provide definitive results, while the experiments themselves provide new input to the model. Based on previous experimental results the model for the accumulation of damage in Chlamydomonas reinhardi has been extended to include various multiple two-event combinations. Split dose survival experiments have shown that models tested to date predict most but not all the observed behavior. Stationary-phase mammalian cells, required for tests of other aspects of the model, have been shown to be at different points in the cell cycle depending on how they were forced to stop proliferating. These cultures also demonstrate different capacities for repair of sublethal radiation damage

  20. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds......, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  1. Anticancer agent CHS-828 inhibits cellular synthesis of NAD

    DEFF Research Database (Denmark)

    Olesen, U.H.; Christensen, M.K.; Bjorkling, F.;

    2008-01-01

    Malignant cells display increased demands for energy production and DNA repair. Nicotinamide adenine dinucleotide (NAD) is required for both processes and is also continuously degraded by cellular enzymes. Nicotinamide phosphoribosyltransferase (Nampt) is a crucial factor in the resynthesis of NA...

  2. Eukaryotic protein domains as functional units of cellular evolution

    DEFF Research Database (Denmark)

    Jin, Jing; Xie, Xueying; Chen, Chen;

    2009-01-01

    of different domain types to assess the molecular compartment occupied by each domain. This reveals that specific subsets of domains demarcate particular cellular processes, such as growth factor signaling, chromatin remodeling, apoptotic and inflammatory responses, or vesicular trafficking. We suggest...

  3. Molecular motion in restricted geometries

    Indian Academy of Sciences (India)

    Siddharth Gautam; S Mitra; R Mukhopadhyay

    2008-10-01

    Molecular dynamics in restricted geometries is known to exhibit anomalous behaviour. Diffusion, translational or rotational, of molecules is altered significantly on confinement in restricted geometries. Quasielastic neutron scattering (QENS) offers a unique possibility of studying molecular motion in such systems. Both time scales involved in the motion and the geometry of motion can be studied using QENS. Molecular dynamics (MD) simulation not only provides insight into the details of the different types of motion possible but also does not suffer limitations of the experimental set-up. Here we report the effect of confinement on molecular dynamics in various restricted geometries as studied by QENS and MD simulations: An example where the QENS technique provided direct evidence of phase transition associated with change in the dynamical behaviour of the molecules is also discussed.

  4. Bridge Decomposition of Restriction Measures

    CERN Document Server

    Alberts, Tom

    2009-01-01

    Motivated by Kesten's bridge decomposition for two-dimensional self-avoiding walks in the upper half plane, we show that the conjectured scaling limit of the half-plane SAW, the SLE(8/3) process, also has an appropriately defined bridge decomposition. This continuum decomposition turns out to entirely be a consequence of the restriction property of SLE(8/3), and as a result can be generalized to the wider class of restriction measures. Specifically we show that the restriction hulls with index less than one can be decomposed into a Poisson Point Process of irreducible bridges in a way that is similar to Ito's excursion decomposition of a Brownian motion according to its zeros.

  5. Telomere Restriction Fragment (TRF) Analysis

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W.

    2016-01-01

    While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al., 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al., 1990; Ouellette et al., 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

  6. CDRL - company dose restriction level

    International Nuclear Information System (INIS)

    For a number of year's close constraints and controls have been used as effective measures in aiding restricting exposure to ionising radiation. Predecessor companies to British Energy Generation (BEG) originally established the Company Dose Restriction Level (CDRL) as a consequence of the revision of risk estimates, then with the revised Ionising Radiations Regulations 1999 (IRR99) the CDRL for BEG was also revised. The background, influences and consequences of CDRL appliance in a commercial organisation in calendar year 2000/1 are presented below. (author)

  7. HFB in a restricted space

    International Nuclear Information System (INIS)

    A restricted Hartree-Fock-Bogoliubov method is developed with a restriction on the angular momenta of the Cooper pairs that conform the vacuum (SD or SDG). The method is applied to 176Yb. The quadrupole moment in the SD subspace is found to be 80% for neutrons and 91% for protons of its value in the full space. The inclusion of the G part of the Cooper pairs improves that agreement. The descriptions in terms of boson condensate and coherent states are discussed. (author)

  8. Simulation of earthquakes with cellular automata

    Directory of Open Access Journals (Sweden)

    P. G. Akishin

    1998-01-01

    Full Text Available The relation between cellular automata (CA models of earthquakes and the Burridge–Knopoff (BK model is studied. It is shown that the CA proposed by P. Bak and C. Tang,although they have rather realistic power spectra, do not correspond to the BK model. We present a modification of the CA which establishes the correspondence with the BK model.An analytical method of studying the evolution of the BK-like CA is proposed. By this method a functional quadratic in stress release, which can be regarded as an analog of the event energy, is constructed. The distribution of seismic events with respect to this “energy” shows rather realistic behavior, even in two dimensions. Special attention is paid to two-dimensional automata; the physical restrictions on compression and shear stiffnesses are imposed.

  9. Cellular mechanisms of nociception in the frog

    Czech Academy of Sciences Publication Activity Database

    Kuffler, D. P.; Lyfenko, Alla; Vyklický st., Ladislav; Vlachová, Viktorie

    2002-01-01

    Roč. 88, č. 4 (2002), s. 1843-1850. ISSN 0022-3077 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Grant ostatní: NATO(XX) Grant 977062 Institutional research plan: CEZ:AV0Z5011922 Keywords : cellular mechanisms of nociception * frog Subject RIV: FH - Neurology Impact factor: 3.743, year: 2002

  10. Cellular phones: are they detrimental?

    Science.gov (United States)

    Salama, Osama E; Abou El Naga, Randa M

    2004-01-01

    The issue of possible health effects of cellular phones is very much alive in the public's mind where the rapid increase in the number of the users of cell phones in the last decade has increased the exposure of people to the electromagnetic fields (EMFs). Health consequences of long term use of mobile phones are not known in detail but available data indicates the development of non specific annoying symptoms on acute exposure to mobile phone radiations. In an attempt to determine the prevalence of such cell phones associated health manifestations and the factors affecting their occurrence, a cross sectional study was conducted in five randomly selected faculties of Alexandria University. Where, 300 individuals including teaching staff, students and literate employee were equally allocated and randomly selected among the five faculties. Data about mobile phone's users and their medical history, their pattern of mobile usage and the possible deleterious health manifestations associated with cellular phone use was collected. The results revealed 68% prevalence of mobile phone usage, nearly three quarters of them (72.5%) were complainers of the health manifestations. They suffered from headache (43%), earache (38.3%), sense of fatigue (31.6%), sleep disturbance (29.5%), concentration difficulty (28.5%) and face burning sensation (19.2%). Both univariate and multivariate analysis were consistent in their findings. Symptomatic users were found to have significantly higher frequency of calls/day, longer call duration and longer total duration of mobile phone usage/day than non symptomatic users. For headache both call duration and frequency of calls/day were the significant predicting factors for its occurrence (chi2 = 18.208, p = 0.0001). For earache, in addition to call duration, the longer period of owning the mobile phone were significant predictors (chi2 = 16.996, p = 0.0002). Sense of fatigue was significantly affected by both call duration and age of the user

  11. The State of Cellular Probes

    OpenAIRE

    Yim, Youngbin

    2003-01-01

    Cellular probe technology is one of several potentially promising technologies for obtaining accurate travel time information. In 1996, the Federal Communications Commission (FCC) mandated E911 requirements that cellular location be provided when 911 emergency calls come in to emergency management authorities. The E911 requirements allow 50 -300 meters from the emergency call location, depending on the type of cellular phone technology used and whether handset-based or network-based solutions...

  12. Never-ageing cellular senescence

    OpenAIRE

    Ogrunc, Müge; d’Adda di Fagagna, Fabrizio

    2011-01-01

    Cellular senescence was historically discovered as a form of cellular ageing of in vitro cultured cells. It has been under the spotlight following the evidence of oncogene-induced senescence in vivo and its role as a potent tumour suppressor mechanism. Presently, a PubMed search using keywords ‘cellular senescence and cancer’ reveals 8398 number of references (by April 2011) showing that while our knowledge of senescence keeps expanding, the complexity of the phenomenon keeps us – researchers...

  13. Caloric restriction leads to high marrow adiposity and low bone mass in growing mice.

    Science.gov (United States)

    Devlin, Maureen J; Cloutier, Alison M; Thomas, Nishina A; Panus, David A; Lotinun, Sutada; Pinz, Ilka; Baron, Roland; Rosen, Clifford J; Bouxsein, Mary L

    2010-09-01

    The effects of caloric restriction (CR) on the skeleton are well studied in adult rodents and include lower cortical bone mass but higher trabecular bone volume. Much less is known about how CR affects bone mass in young, rapidly growing animals. This is an important problem because low caloric intake during skeletal acquisition in humans, as in anorexia nervosa, is associated with low bone mass, increased fracture risk, and osteoporosis in adulthood. To explore this question, we tested the effect of caloric restriction on bone mass and microarchitecture during rapid skeletal growth in young mice. At 3 weeks of age, we weaned male C57Bl/6J mice onto 30% caloric restriction (10% kcal/fat) or normal diet (10% kcal/fat). Outcomes at 6 (n = 4/group) and 12 weeks of age (n = 8/group) included body mass, femur length, serum leptin and insulin-like growth factor 1 (IGF-1) values, whole-body bone mineral density (WBBMD, g/cm(2)), cortical and trabecular bone architecture at the midshaft and distal femur, bone formation and cellularity, and marrow fat measurement. Compared with the normal diet, CR mice had 52% and 88% lower serum leptin and 33% and 39% lower serum IGF-1 at 6 and 12 weeks of age (p < .05 for all). CR mice were smaller, with lower bone mineral density, trabecular, and cortical bone properties. Bone-formation indices were lower, whereas bone-resorption indices were higher (p < .01 for all) in CR versus normal diet mice. Despite having lower percent of body fat, bone marrow adiposity was elevated dramatically in CR versus normal diet mice (p < .05). Thus we conclude that caloric restriction in young, growing mice is associated with impaired skeletal acquisition, low leptin and IGF-1 levels, and high marrow adiposity. These results support the hypothesis that caloric restriction during rapid skeletal growth is deleterious to cortical and trabecular bone mass and architecture, in contrast to potential skeletal benefits of CR in aging animals

  14. Space-restricted attribute grammars

    DEFF Research Database (Denmark)

    Schmidt, Erik Meineche

    1980-01-01

    Restricting the size of attribute values, relative to the length of the string under consideration, leads to a model of attribute grammars in which grammars with both inherited and synthesized attributes can be significantly more economical than grammars with synthesized attributes only....

  15. Restrictive dermopathy and fetal behaviour

    NARCIS (Netherlands)

    Mulder, EJH; Beemer, FA; Stoutenbeek, P

    2001-01-01

    We report three siblings from consecutive pregnancies affected with restrictive dermopathy (RD). During the second pregnancy, fetal behavioural development and growth were studied extensively using ultrasound at 1-4 week intervals. Dramatic and sudden changes occurred in fetal body movements and gro

  16. Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

    Directory of Open Access Journals (Sweden)

    Wood Richard J

    2006-05-01

    Full Text Available Abstract Background Diets that restrict carbohydrate (CHO have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. Methods We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy. A total of 27 single nucleotide polymorphisms (SNPs were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. Results Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF, hepatic glycogen synthase (GYS2, cholesteryl ester transfer protein (CETP and galanin (GAL genes were significantly associated with weight loss. Conclusion A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction.

  17. 制约少数民族生态移民可持续发展的因素探究%Probing into the Factors Restricting the Sustainable Development of the Minority Ecological Migration

    Institute of Scientific and Technical Information of China (English)

    金莲; 王永平; 周丕东; 黄海燕

    2012-01-01

    To realize the sustainable development of the minority ecological migration, we must consider four constraints that are social factors, economical factors, ecological factors and own factors. Social factors involve the constraints of government, community, enterprise and NGO. Economic factors mainly include three aspects that are economic development foundation, the development level of the industry and the urbanization level. Ecological factors are considered from the angle of natural conditions, such as land and water. Economic conditions, cultural quality, ideology and family structure of eco-migrants themselves also affect the sustainable development of the minority ecological migration.%实现可持续发展受到社会、经济、生态及移民自身方面因素的制约,其中社会因素,涉及政府、社区、企业及民间组织四个方面;经济因素主要包括经济发展基础、产业发展水平和城镇化水平三个方面;生态因素主要是从自然条件(如土地、水等资源)的角度去考虑其制约因素;移民自身的经济条件、文化素质、思想观念和家庭结构也是影响少数民族生态移民可持续发展的因素.

  18. Active Cellular Nematics

    Science.gov (United States)

    Duclos, Guillaume; Erlenkaemper, Christoph; Garcia, Simon; Yevick, Hannah; Joanny, Jean-François; Silberzan, Pascal; Biology inspired physics at mesoscales Team; Physical approach of biological problems Team

    We study the emergence of a nematic order in a two-dimensional tissue of apolar elongated fibroblast cells. Initially, these cells are very motile and the monolayer is characterized by giant density fluctuations, a signature of far-from-equilibrium systems. As the cell density increases because of proliferation, the cells align with each other forming large perfectly oriented domains while the cellular movements slow down and eventually freeze. Therefore topological defects characteristic of nematic phases remain trapped at long times, preventing the development of infinite domains. By analogy with classical non-active nematics, we have investigated the role of boundaries and we have shown that cells confined in stripes of width smaller than typically 500 µm are perfectly aligned in the stripe direction. Experiments performed in cross-shaped patterns show that both the number of cells and the degree of alignment impact the final orientation. Reference: Duclos G., Garcia S., Yevick H.G. and Silberzan P., ''Perfect nematic order in confined monolayers of spindle-shaped cells'', Soft Matter, 10, 14, 2014

  19. 49 CFR 215.203 - Restricted cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than...

  20. 47 CFR 22.909 - Cellular markets.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  1. Material and mechanical factors:new strategy in cellular neurogenesis

    Institute of Scientific and Technical Information of China (English)

    Hillary Stoll; Il Keun Kwon; Jung Yul Lim

    2014-01-01

    Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharma-cological factors on the cellular neurogenesis. On the other hand, it is now recognized that the other extracellular factors, including material and mechanical cues, also have a strong potential to induce cellular neurogenesis. This article will review recent data on the material (chemical patterning, micro/nano-topography, carbon nanotube, graphene) and mechanical (static cue from substrate stiffness, dynamic cue from stretch and lfow shear) stimulations of cellular neuro-genesis. These approaches may provide new neural regenerative medicine protocols. Scaffolding material templates capable of triggering cellular neurogenesis can be explored in the presence of neurogenesis-stimulatory mechanical environments, and also with conventional soluble factors, to enhance axonal growth and neural network formation in neural tissue engineering.

  2. Restrictions to cross-species transmission of lentiviral infection gleaned from studies of FIV.

    Science.gov (United States)

    VandeWoude, Sue; Troyer, Jennifer; Poss, Mary

    2010-03-15

    new host sufficiently divergent from the primary host to support viral replication (i.e. passive unfacilitated viral replication); (4) Intracellular restriction mechanisms present in the new host that is able to limit viral replication (i.e. active interrupted viral replication. These include factors that limit uncoating, replication, packaging, and virion release); (5) Unique ability of new host to raise sterilizing adaptive immunity, resulting in aborted infection and inability to spread infections among con-specifics; or (6) Production of defective or non-infectious viral progeny that lack cellular cofactors to render them infectious to con-specifics (i.e. particles lacking appropriate cellular components in viral Env to render them infectious to other animals of the same species). Data to support or refute the relative importance of each of these possibilities is described in this review. Insights based on our in vivo cross-species model suggest intracellular restriction mechanisms effectively inhibit rapid inter-specific transmission of lentiviruses. Further, limited contact both within and between species in natural populations is highly relevant to limiting the opportunity for spread of FIV strains. Studies of naturally occurring SIV and innate host restriction systems suggest these same two mechanisms are significant factors inhibiting widespread cross-species transmission of lentiviruses among primate species as well. PMID:19896218

  3. Study on the Restricting Factors and Countermeasures in Resource - based Industries Green Development of Poyang Lake Ecological Economic Zone%鄱阳湖生态经济区资源型产业绿色发展制约因素及对策研究

    Institute of Scientific and Technical Information of China (English)

    李胜连

    2014-01-01

    鄱阳湖生态经济区作为国家的战略发展区域,应该具有超前思维,大力发展绿色产业,而资源型产业容易造成外部不经济,因此更需要健康、绿色发展。本文利用 AHP 方法对环鄱区资源型产业绿色发展的制约因素进行分层排序,得到如下结论:技术因素和生态因素是主要制约因素;制约因素排名前5位的分别是:空气质量、政府及社会第三方的技术监督、水资源质量、外部不经济补救成本、绿色检测技术的推广与应用。%As a strategic development areas of the country ,Poyang Lake Ecological Economic Zone should have advanced thinking ,to vigorously develop the green industry .But the resources industry is easy to cause the external diseconomy , therefore it need more healthy and green development .In this paper ,by using the AHP method ,hierarchical ranking con-straints of Poyang Lake Ecological Economic Zone is conducted and conclusion is as follows :technical factors and ecological factors are the main restricting factors and the top five restricting factors should be air quality ,the technological supervision of the third party government and society ,the quality of water resources ,external non economic recovery cost ,promotion and application of green detection technology .

  4. Nullity Restrictions and Comparative Static Analysis.

    OpenAIRE

    Chavas, Jean-Paul; Pope, Rulon

    1992-01-01

    While homogeneity restrictions of optimal choice functions are well known in the context of neoclassical economic theory, the existence and implications of "homogeneity-like" restrictions in more general optimization models have not received much attention in the literature. The authors call such restrictions "nullity" restrictions since they involve the null space of the matrix of slopes of choice functions. The existence, nature, and implications of nullity restrictions are investigated in ...

  5. HIV restriction by APOBEC3 in humanized mice.

    Directory of Open Access Journals (Sweden)

    John F Krisko

    2013-03-01

    Full Text Available Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses. Significant consideration has been given to their possible use for therapeutic benefit. The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3 family of cytidine deaminases are potent immune defense molecules capable of efficiently restricting endogenous retroelements as well as a broad range of viruses including Human Immunodeficiency virus (HIV, Hepatitis B virus (HBV, Human Papilloma virus (HPV, and Human T Cell Leukemia virus (HTLV. The best characterized members of this family are APOBEC3G (A3G and APOBEC3F (A3F and their restriction of HIV. HIV has evolved to counteract these powerful restriction factors by encoding an accessory gene designated viral infectivity factor (vif. Here we demonstrate that APOBEC3 efficiently restricts CCR5-tropic HIV in the absence of Vif. However, our results also show that CXCR4-tropic HIV can escape from APOBEC3 restriction and replicate in vivo independent of Vif. Molecular analysis identified thymocytes as cells with reduced A3G and A3F expression. Direct injection of vif-defective HIV into the thymus resulted in viral replication and dissemination detected by plasma viral load analysis; however, vif-defective viruses remained sensitive to APOBEC3 restriction as extensive G to A mutation was observed in proviral DNA recovered from other organs. Remarkably, HIV replication persisted despite the inability of HIV to develop resistance to APOBEC3 in the absence of Vif. Our results provide novel insight into a highly specific subset of cells that potentially circumvent the action of APOBEC3; however our results also demonstrate the massive inactivation of CCR5-tropic HIV in the absence of Vif.

  6. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  7. Decision Making and Cooperation Restrictions.

    OpenAIRE

    2000-01-01

    Decision making by various individuals can result in conflicts or cooperation between these individuals. Game theory deals with both the mathematical modeling of these situations of conflict and cooperation and with the analysis of these models using math atical techniques. This thesis focuses on decision making and cooperation restrictions and can roughly be divided into two parts. The first part provides an analysis of cooperative games with exogenously given cooperation structures. Three t...

  8. Decision making and cooperation restrictions

    OpenAIRE

    Slikker, M.

    2000-01-01

    Decision making by various individuals can result in conflicts or cooperation between these individuals. Game theory deals with both the mathematical modeling of these situations of conflict and cooperation and with the analysis of these models using math atical techniques. This thesis focuses on decision making and cooperation restrictions and can roughly be divided into two parts. The first part provides an analysis of cooperative games with exogenously given cooperation structures. Three t...

  9. Management of fetal growth restriction

    OpenAIRE

    Alberry, M; Soothill, P

    2007-01-01

    Fetal growth restriction (FGR) is challenging because of the difficulties in reaching a definitive diagnosis of the cause and planning management. FGR is associated not only with a marked increased risk in perinatal mortality and morbidity but also with long‐term outcome risks. Combinations of fetal biometry, amniotic fluid volume, heart rate patterns, arterial and venous Doppler, and biophysical variables allow a comprehensive fetal evaluation of FGR. However, no evidence supports that the u...

  10. Judgment aggregation on restricted domains

    OpenAIRE

    Dietrich Franz; List Christian

    2006-01-01

    We show that, when a group takes independent majority votes on interconnected propositions, the outcome is consistent once the profile of individual judgment sets respects appropriate structural conditions. We introduce several such conditions on profiles, based on ordering the propositions or ordering the individuals, and we clarify the relations between these conditions. By restricting the conditions to appropriate subagendas, we obtain local conditions that are less demanding but still gua...

  11. HIV-related travel restrictions: trends and country characteristics

    Directory of Open Access Journals (Sweden)

    Felicia Chang

    2013-06-01

    a finding that is relevant to migrant populations and travel medicine providers alike. Despite international pressure to remove travel restrictions, many countries continue to implement these restrictions for HIV-positive individuals on entry and stay. Since 2010, the United States and China have engaged in high profile removals. This may be indicative of an increasing trend, facilitated by various factors, including international advocacy and the setting of a UNAIDS goal to halve the number of countries with restrictions by 2015.

  12. 制约我国地方性国有资产证券化的因素与对策研究%The Research on the Restrict Factors to Local State- owned Assets Securitization and Countermeasure

    Institute of Scientific and Technical Information of China (English)

    李国义; 杨果

    2012-01-01

    Securitization is the local state - owned assets important means for increment. But some factors exist in the local state - owned asset securitization process, including the subjective and objective factors, the subjective factors are enor of understanding in state - owned asset function, efficiency of public ownership theory. In order to promote the local state- owned asset securitizafion, it is necessary to undertake an analysis to these elements, put forward according to these factors the countermeasures to solve the problems, to further promote the local state - owned assets securitization. We can take the induction, inference analysis method to study. Securitization of state - owned assets, should from the dynamic asset expanded to static asset, from artificial assets expanded to natural assets.%证券化是地方性国有资产保值增值的重要手段。但是在地方性国有资产证券化过程中存在一些制约因素,包括主观因素和客观因素,其中主观因素主要是在国有资产功能、公有制效率等理论方面存在认识偏差。为了顺利推进地方性国有资产证券化工作,有必要对这些因素进行分析,针对这些因素提出解决问题的对策,进一步推进地方性国有资产证券化。可以采取归纳、推理分析方法进行研究。可证券化的国有资产范围,应该从动态资产扩大到静态资产,从人工资产扩大到自然资产。

  13. Reversibility of cellular aging by reprogramming through an embryonic-like state : a new paradigm for human cell rejuvenation

    Directory of Open Access Journals (Sweden)

    Jean-Marc Lemaitre

    2014-01-01

    Full Text Available Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs provides a unique opportunity to derive patient-specific stem cells with potential application in autologous tissue replacement therapies and without the ethical concerns of Embryonic Stem Cells (hESC. However, this strategy still suffers from several hurdles that need to be overcome before clinical applications. Among them, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. This suggests that aging might be an important limitation for therapeutic purposes for elderly individuals. Senescence is characterized by an irreversible cell cycle arrest in response to various forms of stress, including activation of oncogenes, shortened telomeres, DNA damage, oxidative stress, and mitochondrial dysfunction. To overcome this barrier, we developed an optimized 6-factor-based reprogramming protocol that is able to cause efficient reversing of cellular senescence and reprogramming into iPSCs. We demonstrated that iPSCs derived from senescent and centenarian fibroblasts have reset telomere size, gene expression profiles, oxidative stress, and mitochondrial metabolism, and are indistinguishable from hESC. Finally, we demonstrate that re-differentiation led to rejuvenated cells with a reset cellular physiology, defining a new paradigm for human cell rejuvenation. We discuss the molecular mechanisms involved in cell reprogramming of senescent cells. 

  14. Cyclin A degradation by primate cytomegalovirus protein pUL21a counters its innate restriction of virus replication.

    Directory of Open Access Journals (Sweden)

    Nicolas Caffarelli

    Full Text Available Cyclin A is critical for cellular DNA synthesis and S phase progression of the cell cycle. Human cytomegalovirus (HCMV can reduce cyclin A levels and block cellular DNA synthesis, and cyclin A overexpression can repress HCMV replication. This interaction has only been previously observed in HCMV as murine CMV does not downregulate cyclin A, and the responsible viral factor has not been identified. We previously reported that the HCMV protein pUL21a disrupted the anaphase-promoting complex (APC, but a point mutant abrogating this activity did not phenocopy a UL21a-deficient virus, suggesting that pUL21a has an additional function. Here we identified a conserved arginine-x-leucine (RxL cyclin-binding domain within pUL21a, which allowed pUL21a to interact with cyclin A and target it for proteasome degradation. Homologous pUL21a proteins from both chimpanzee and rhesus CMVs also contained the RxL domain and similarly degraded cyclin A, indicating that this function is conserved in primate CMVs. The RxL point mutation disabled the virus' ability to block cellular DNA synthesis and resulted in a growth defect similar to pUL21a-deficient virus. Importantly, knockdown of cyclin A rescued growth of UL21a-deficient virus. Together, these data show that during evolution, the pUL21a family proteins of primate CMVs have acquired a cyclin-binding domain that targets cyclin A for degradation, thus neutralizing its restriction on virus replication. Finally, the combined proteasome-dependent degradation of pUL21a and its cellular targets suggests that pUL21a may act as a novel suicide protein, targeting its protein cargos for destruction.

  15. Quantifying a cellular automata simulation of electric vehicles

    Science.gov (United States)

    Hill, Graeme; Bell, Margaret; Blythe, Phil

    2014-12-01

    Within this work the Nagel-Schreckenberg (NS) cellular automata is used to simulate a basic cyclic road network. Results from SwitchEV, a real world Electric Vehicle trial which has collected more than two years of detailed electric vehicle data, are used to quantify the results of the NS automata, demonstrating similar power consumption behavior to that observed in the experimental results. In particular the efficiency of the electric vehicles reduces as the vehicle density increases, due in part to the reduced efficiency of EVs at low speeds, but also due to the energy consumption inherent in changing speeds. Further work shows the results from introducing spatially restricted speed restriction. In general it can be seen that induced congestion from spatially transient events propagates back through the road network and alters the energy and efficiency profile of the simulated vehicles, both before and after the speed restriction. Vehicles upstream from the restriction show a reduced energy usage and an increased efficiency, and vehicles downstream show an initial large increase in energy usage as they accelerate away from the speed restriction.

  16. Cellular and molecular basis of cerebellar development

    Science.gov (United States)

    Martinez, Salvador; Andreu, Abraham; Mecklenburg, Nora; Echevarria, Diego

    2013-01-01

    Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering, and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification, and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function. PMID:23805080

  17. Cellular and Molecular Basis of Cerebellar Development

    Directory of Open Access Journals (Sweden)

    Salvador eMartinez

    2013-06-01

    Full Text Available Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function.

  18. Actual problems of cellular cardiomyoplasty

    Directory of Open Access Journals (Sweden)

    Bulat Kaupov

    2010-04-01

    Full Text Available The paper provides review of cellular technologies used incardiology, describes types of cellular preparations depending onsources of cells and types of compounding cells. The generalmechanisms of therapies with stem cells applications are described.Use of cellular preparations for treatment of cardiovascular diseasesand is improvement of the forecast at patients with heartinsufficiency of various genesis is considered as alternative topractice with organ transplantations. Efforts of biotechnologicallaboratories are directed on search of optimum population of cellsfor application in cardiology and studying of mechanisms andfactors regulating function of cardiac stem cells.

  19. Influence of cell size on cellular uptake of gold nanoparticles.

    Science.gov (United States)

    Wang, Xinlong; Hu, Xiaohong; Li, Jingchao; Russe, Adriana C Mulero; Kawazoe, Naoki; Yang, Yingnan; Chen, Guoping

    2016-06-24

    Nanoparticles (NPs) have shown great potential for biomedical applications because of their unique physical and structural properties. A critical aspect for their clinical applications is cellular uptake that depends on both particle properties and the cell mechanical state. Despite the numerous studies trying to disclose the influencing factors, the role of cell size on cellular uptake remains unclear. In this study, poly(vinyl alcohol) was micropatterned on tissue culture polystyrene surfaces using UV photolithography to control the cell size, and the influence of cell size on the cellular uptake of gold NPs was investigated. Cells with a large size had a high total cellular uptake, but showed a low average uptake per unit area of cells. Cells with a small size showed opposite behaviors. The results were related to both cell/NP contacting area and membrane tension. A large cell size was beneficial for a high total cellular uptake due to the large contact area with the NPs. On the other hand, the large cell size resulted in high membrane tension that required high wrapping energy for engulfing of NPs and thus reduced the uptake. The two oppositely working effects decided the cellular uptake of NPs. The results would shed light on the influence of the cellular microenvironment on cellular uptake behavior. PMID:27095054

  20. 77 FR 15665 - Cellular Service, Including Changes in Licensing of Unserved Area; Interim Restrictions and...

    Science.gov (United States)

    2012-03-16

    ... the first time included mandatory coverage of geography (rather than population). In our proposed... of all areas or population centers in a geographic-based license. 33. We also seek comment on whether... bidding. Disputes over existing CGSA boundaries and the distribution of the remaining Unserved Area...

  1. 76 FR 75470 - Drivers of CMVs: Restricting the Use of Cellular Phones

    Science.gov (United States)

    2011-12-02

    .... \\13\\ For further discussion, see the Research section of the NPRM (75 FR 80020). FMCSA specifically... telephone qualifies as texting (49 CFR 390.5) and, therefore, is already prohibited while driving (75 FR... Federal Register published on January 17, 2008 (73 FR 3316), or you may visit...

  2. 76 FR 23923 - Hazardous Materials: Restricting the Use of Cellular Phones by Drivers of Commercial Motor...

    Science.gov (United States)

    2011-04-29

    ... on the Nation's highways by reducing the prevalence of distracted driving-related crashes, fatalities... Transportation (US DOT) is leading the effort to end the dangerous practice of distracted driving on our nation's... distracted driving. Additionally, several states have forbidden the operation of many types of...

  3. 75 FR 59579 - Restrictions on Railroad Operating Employees' Use of Cellular Telephones and Other Electronic...

    Science.gov (United States)

    2010-09-27

    ... defined for the study as driver behavior that diverts the driver's attention away from the driving task... multiple means of measuring the effects of driver distraction including observational studies of driver behavior, crash-based studies, and experimental studies of driving performance. Each type of study has...

  4. 75 FR 80014 - Drivers of CMVs: Restricting the Use of Cellular Phones

    Science.gov (United States)

    2010-12-21

    ... many of the risks associated with real world driving; Naturalistic driving studies use cameras and instrumentation in participants' vehicles to provide a clear picture of driver distraction under real-world... Management System published in the Federal Register on January 17, 2008 (73 FR 3316). II. Abbreviations...

  5. 75 FR 27672 - Restrictions on Railroad Operating Employees' Use of Cellular Telephones and Other Electronic...

    Science.gov (United States)

    2010-05-18

    ... control systems and digital timepieces from the definition. The first exception makes clear that this.... 73 FR 58702, Oct. 7, 2008). This FRA action was in part a response to the accidents discussed above... Transportation Modes The use of cell phones and other electronic devices has become ubiquitous in...

  6. Conformal restriction: the chordal case

    OpenAIRE

    Lawler, Gregory; Schramm, Oded; Werner, Wendelin

    2002-01-01

    We characterize and describe all random subsets $K$ of a given simply connected planar domain (the upper half-plane $\\H$, say) which satisfy the ``conformal restriction'' property, i.e., $K$ connects two fixed boundary points (0 and $\\infty$, say) and the law of $K$ conditioned to remain in a simply connected open subset $D$ of $\\H$ is identical to that of $\\Phi(K)$, where $\\Phi$ is a conformal map from $\\H$ onto $D$ with $\\Phi(0)=0$ and $\\Phi(\\infty)=\\infty$. The construction of this family ...

  7. Electromagnetic Fields Restrictions and Approximation

    CERN Document Server

    Katsenelenbaum, Boris Z

    2003-01-01

    The fields scattered by metallic bodies or radiated by some types of antennas are created by the surfaces currents and therefore they are subject to some restrictions. The book is the first one where the properties of these fields are investigated in details. The properties have the important significance for the antenna synthesis, body shape reconstruction and other diffraction problems. The material of the book lies in the meetingpoint of the antenna theory, highfrequency electrodynamics and inverse scattering problems. The author is an internationally renowned investigator in the field of e

  8. Rurality study of restricted areas

    Directory of Open Access Journals (Sweden)

    Sergio Rivaroli

    2011-02-01

    Full Text Available Two main perspectives of investigation emerge from the study of a territory’s rurality: a geographical approach and a sociological approach. The research examines the sub-regional study case of ‘Nuovo circondario imolese’. The analysis shows that the combination of traditional institutional criteria with detailed informations about the territory, generates more accurate results which determine a better comprehension of the characteristics of restricted areas’ rurality. Over the period 1991-2001, the study highlights an increase in rural areas. This result could be interpreted as an effect of urban sprawl’s intensification, that increases the competition between non-farm residences and agricultural activities.

  9. Origami interleaved tube cellular materials

    International Nuclear Information System (INIS)

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

  10. Restrictions on trade in distribution services

    OpenAIRE

    Kaleeswaran Kalirajan

    2001-01-01

    Identifies and quantifies restrictions affecting domestic and international trade in distribution services - mainly wholesaling and retailing - in 38 economies, including Australia. The paper also explores the price and cost implications of restrictions in food distribution services.

  11. Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers.

    Science.gov (United States)

    Mariño, Guillermo; Pietrocola, Federico; Madeo, Frank; Kroemer, Guido

    2014-01-01

    Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We surmise that there are 3 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the inhibition of acetyltransferases, which are enzymes that transfer acetyl groups from AcCoA to other molecules, mostly leucine residues in cellular proteins, or (iii) the stimulation of deacetylases, which catalyze the removal of acetyl groups from leucine residues. There are several examples of rather nontoxic natural compounds that act as AcCoA depleting agents (e.g., hydroxycitrate), acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine) or deacetylase activators (e.g., nicotinamide, resveratrol), and that are highly efficient inducers of autophagy in vitro and in vivo, in rodents. Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage. Hence, we classify them as "caloric restriction mimetics" (CRM). Here, we speculate that CRM may mediate their broad health-improving effects by triggering the same molecular pathways that usually are elicited by long-term caloric restriction or short-term starvation and that imply the induction of autophagy as an obligatory event conferring organismal, organ- or cytoprotection. PMID:25484097

  12. Cellular mechanisms during vascular development

    OpenAIRE

    Blum, Yannick

    2012-01-01

    The vascular system is an essential organ in vertebrate animals and provides the organism with enough oxygen and nutrients. It is composed of an interconnected network of blood vessels, which form using a number of different morphogenetic mechanisms. Angiogenesis describes the formation of new blood vessels from preexisting vessels. A number of molecular pathways have been shown to be essential during angiogenesis. However, cellular architecture of blood vessels as well as cellular mechanisms...

  13. Predictive Modelling of Cellular Load

    OpenAIRE

    Carolan, Emmett; McLoone, Seamus; Farrell, Ronan

    2015-01-01

    This work examines the temporal dynamics of cellular load in four Irish regions. Large scale underutilisation of network resources is identified both at the regional level and at the level of individual cells. Cellular load is modeled and prediction intervals are generated. These prediction intervals are used to put an upper bound on usage in a particular cell at a particular time. Opportunities for improvements in network utilization by incorporating these upper bounds on usage are identifie...

  14. Cellular automaton for chimera states

    OpenAIRE

    García-Morales, Vladimir

    2016-01-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the...

  15. Bronchial Responsiveness in Patients with Restrictive Spirometry

    OpenAIRE

    Keddissi, Jean I.; Elya, Marwan K.; Farooq, Saif U.; Youness, Houssein A.; Kellie R. Jones; Ahmed Awab; Kinasewitz, Gary T.

    2013-01-01

    Background. Improvement in PFT after bronchodilators is characteristic of obstructive airway diseases such as COPD. However, improvement in patients with restrictive pattern is occasionally seen. We aim to determine the clinical significance of a bronchodilator responsive restrictive defect. Methods. Patients with restrictive spirometry and a bronchodilator study were identified at the University of Oklahoma and Oklahoma City VAMC between September 2003 and December 2009. Restriction was defi...

  16. Restrictive Cardiomyopathy: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Bilal Bin Abdullah*, Mehboob.M.Kalburgi, Sahana Shetty and Satyasrinivas

    2011-04-01

    Full Text Available We report a 28 years old male presenting with heart failure. A thorough clinical evaluation directed us towards restrictive heart disease. Doppler echocardiographic study was used as a main modality of diagnosis and cardiac catheterization confirmed the diagnosis of idiopathic restrictive cardiomyopathy. We express the contribution of clinical findings and appropriate diagnostic measures in approaching a case of Restrictive cardiomyopathy (RCM.

  17. 试析贫困大学生就业难的深层社会因素%A Deep Social Factor Analysis on the Restriction of Poor College Students Employment Difficulty

    Institute of Scientific and Technical Information of China (English)

    彭仲生; 罗筑华

    2012-01-01

    当前大学生就业难已经成了大学生、学生家长、高等学校及社会共同的感受和普遍关注的问题,而作为大学生中的弱势群体——贫困大学生的就业则更是得到了有关各方的高度重视.为进一步探明当前贫困大学生就业难的潜因,为今后解决贫困大学生就业问题打好前期基础,文章对贫困大学生就业困难的深层社会因素进行了初步分析,并提出了一些可操作性的对策和措施.%Employment difficulty of college students has become consensus and concern of college students, parents, colleges and society in recent years, and for poor college students, the vulnerable group of the university, their employment problem has attracted more intensive attention from the society. In order to explore the potent factors of employment difficulty of poor college students and to make a good preparation for the solution to this problem, this article attempts to make an analysis of the reasons and countermeasure of poor college students' employment difficulty from the perspective of society.

  18. Observability in electric power networks: a method of ways of factorization in state estimation with equality restrictions; Observabilidade em redes de energia: um metodo de caminhos de fatoracao em estimacao de estado com restricoes de igualdade

    Energy Technology Data Exchange (ETDEWEB)

    Vicentino, Flavio Antonio

    1997-07-01

    A theory of network observability that mixes graph concepts and factorization of the gain matrix G has been recently developed. It uses data already available in Power System Operating Centers. That theory is easy to understand and implement and does not require subroutines other than the ones used in static state estimation. However, this new theory has been implemented only for the case of state estimation in Normal Equation Formulation (N E). However, the N E Method presents some inherent numerical difficulties. Such numerical difficulties are usually related to the disparity in the measurements weights (high values for zero-injections measurements and low values for pseudo-measurements) and the presence of short lines in the network, as well. In order to solve such numerical difficulties, new methods have come up, such as: Normal Equation Method with Equality Constraints (N E/C), where Lagrange's Multiplier Method can be applied to minimize a function while satisfying a set of constraints; Hachtel's Method, which is formulated the same way as N E/C Method, although an equation of residual vector is introduced in solution process; Hybrid Method, which is a general formulation behaving as the N E/C Method at one extreme, and as Hachtel's Method at the other. Thus, the aim of this work is to treat the adaptation of the network observability Method by using path graphs, with the state estimation in the form of a minimization problem with equality constraints. As the Hybrid Method is a generalization form of the state estimator with constraints, this formulation is used to develop the proposed theory. Extreme case (as the pure Hachtel's Method) are also considered. (author)

  19. Cellular vs. organ approaches to dose estimates

    International Nuclear Information System (INIS)

    The cellular distribution of tissue-incorporated radionuclides has generally been neglected in the dosimetry of internal emitters. Traditional dosimetry assumes homogeneous distribution of radionuclides in organs of interest, while presuming that the ranges of particulate radiations are large relative to typical cell diameters. The macroscopic distribution of dose thus calculated has generally served as a sufficient approximation for the energy deposited within radiosensitive sites. However, with the increasing utilization of intracellular agents, such as thallium-201, it has become necessary to examine the microscopic distribution of energy at the cellular level. This is particularly important in the instance of radionuclides that decay by electron capture or by internal conversion with the release of Auger and Coster-Kronig electrons. In many instances, these electrons are released as a dense shower of low-energy particles with ranges of subcellular dimensions. The high electron density in the immediate vicinity of the decaying atom produces a focal deposition of energy that far exceeds the average dose taken over several cell diameters. These studies point out the increasing need to take into account the microscopic distribution of dose on the cellular level as radionuclides distributed in cells become more commonplace, especially if the decay involves electron capture or internal conversion. As radiotracers are developed for the measurement of intracellular functions these factors should be given greater consideration. 16 references, 5 figures, 5 tables

  20. p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer

    DEFF Research Database (Denmark)

    Tschaharganeh, Darjus F; Xue, Wen; Calvisi, Diego F;

    2014-01-01

    The p53 tumor suppressor coordinates a series of antiproliferative responses that restrict the expansion of malignant cells, and as a consequence, p53 is lost or mutated in the majority of human cancers. Here, we show that p53 restricts expression of the stem and progenitor-cell-associated protei...... by p53 restricts cellular plasticity and tumorigenesis in liver cancer.......The p53 tumor suppressor coordinates a series of antiproliferative responses that restrict the expansion of malignant cells, and as a consequence, p53 is lost or mutated in the majority of human cancers. Here, we show that p53 restricts expression of the stem and progenitor-cell-associated protein...

  1. Hierarchical Cellular Structures in High-Capacity Cellular Communication Systems

    CERN Document Server

    Jain, R K; Agrawal, N K

    2011-01-01

    In the prevailing cellular environment, it is important to provide the resources for the fluctuating traffic demand exactly in the place and at the time where and when they are needed. In this paper, we explored the ability of hierarchical cellular structures with inter layer reuse to increase the capacity of mobile communication network by applying total frequency hopping (T-FH) and adaptive frequency allocation (AFA) as a strategy to reuse the macro and micro cell resources without frequency planning in indoor pico cells [11]. The practical aspects for designing macro- micro cellular overlays in the existing big urban areas are also explained [4]. Femto cells are inducted in macro / micro / pico cells hierarchical structure to achieve the required QoS cost effectively.

  2. 21世纪初波兰的东方政策及其制约因素%Poland’s Eastern Policy and Its Restricting Factors in the Early 21st Century

    Institute of Scientific and Technical Information of China (English)

    赵艳霞; 唐更田

    2013-01-01

      21世纪初,随着波兰“入约加盟”,东方问题开始凸显,积极活跃的东方政策遂成为波兰的优先外交政策。地缘政治与现实利益、历史积淀与文化传统以及精英集团的政策理念与公众情绪等各种复杂的国内外因素,决定21世纪波兰的东方政策仍以对俄政策为核心,防范俄罗斯对波兰的威胁是其主要战略意图,并以此为基础在一定程度上决定着波兰对乌克兰、白俄罗斯和南高加索等东欧中亚国家的政策。而欧盟、美国则成为波兰推行东方政策的主要借助力量,实现欧盟东方政策的“波兰化”是波兰实现东方政策的最理想方式。%In the early 21st century, with Poland’s accession to NATO, Eastern problem became prominent. An active eastern policy became a prior foreign policy. In the 21st century, Poland’s eastern policy still kept Russia as the center, which was decided by complex factors at home and abroad like geopolitics, practical interests, historical accumulation, cultural tradition, elite crew’s policy principle and public mood. Preventing Russian threaten was the main strategic idea, which also decided Poland’s policies toward Ukraine, Belarus and the Southern Caucasus, and other Central Asian Eastern Europe countries. EU and U.S.A. became Poland’s main relay powers to push“eastern policy”. Therefore, the“Polonization”of EU’s“eastern policy”was the best way to realize its own“eastern policy”.

  3. Factors Restricting the Healthy Development of Non-governmental Institutions of Higher Learning from the Perspective of Public Spirit%从公共精神看民办高校健康发展的制约因素

    Institute of Scientific and Technical Information of China (English)

    薛金玲; 宋秋蓉

    2012-01-01

      公共精神是西方现代公民文化的核心观念,指在承认个人独立自主性的前提下,公民所拥有的着眼于社会整体的公共精神。目前我国部分民办高校办学者缺乏诚信自律意识、法制规则意识、公共责任意识等公共精神,并在一定程度上存在着背离公共精神的家族化意识。办学者缺乏相关的公共精神,是制约民办高校健康发展的重要因素。我国君主专制制度和儒家文化的负面效应是办学者缺乏公共精神的主要原因。昔日私立南开大学校长张伯苓所拥有的公共精神,值得当今民办高校的办学者学习。%  Public spirit, as the core concept of modern citizen culture in western world , refers to the consciousness of society as a whole held by citizens with the acknowledgement of full personal independence and autonomy .Some of the current administrators in non-governmental institutions of higher learning in China lack the public spirit of the awareness of integrity and self -discipline, regulation and legislation, as well as the sense of public responsibility .To some extends, they depart from public spirit and be-lieve in family consciousness.This is one of the main factors that prevent non-governmental institutions of higher learning from their healthy developments .The negative effect from China's autocratic monarchy and Confucian culture is one of the main reasons for administrators'lack of public spirit.The lifelong affection of public spirit of Zhang Boling , a former president of Nankai Uni-versity, is well worth learning by his peers today .

  4. Adjuvant effect of granulocyte-macrophage colony-stimulating factor coding gene on cellular immunity of Japanese encephalitis virus DNA vaccine%粒细胞-巨噬细胞集落刺激因子编码基因对乙型脑炎DNA疫苗细胞免疫增强效应的影响

    Institute of Scientific and Technical Information of China (English)

    翟永贞; 李喜梅; 周言; 张丹; 邓宝成; 冯国和

    2009-01-01

    Objective To study the adjuvant effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) coding gene on cellular immunity induced by Japanese encephalitis (JE) virus DNA vaccine. Methods GM-CSF coding gene was amplified by nested-reverse transcriptase-polymerase chain reaction (RT-PCR) technique from BALB/c murine spleen cells. Recombinant plasmids pJME/GM-CSF and pGM-CSF were constructed by JE virus (JEV) prM-E protein with GM-CSF coding gene or GM-CSF coding gene only, respectively. The plasmids were transfected into China hamster ovary (CHO) cells by Lipofectamine 2000. The coding protein expressions and distributions were detected by immunofluorescence. The BALB/c mice were vaccinated with indicated immunogens with or without GM-CSF gene. The changes of T lymphocyte subsets in the spleen and levels of intracellular cytokines, such as interferon (IFN)-γ and interleukin (IL)-4 of splenic cells from mice immunized with different immunogens were evaluated by flow cytometry. The cytotoxicity T lymphocyte (CTL) activity was assessed by lactate dehydrogenase (LDH). The data were compared by one-factor analysis of variance and least significant difference. Results The constructed recombinant pGM-CSF and pJME/GM-CSF were confirmed by restrict enzyme digestion and DNA sequencing. The expressions of the above proteins were mainly in the cytoplasm and minor on cell membrane. The percentage of CD4+ T lymphocytes in pJME/GM-CSF vaccinated group was (33.90±0.79)%, which was significantly higher than that of in other groups (t values were 9. 818, 6. 804, 6.594, 10.061, 9.380, and 17.675, all P<0.05). The percentages of CD4+T lymphocytes in pJME +pGM-CSF (0) and pJME+pGM-CSF (-3) vaccinated groups were (29.83±0.61)% and (29.70±0.51)%, respectively, which were both higher than that in pJME+pGM-CSF (+3) vaccinated group of (27.69+0.50)% (t=3.466, t=3.255, both P<0.05). The percentages of CD8+ T cells in pJME/GM-CSF and pJME+pGM-CSF vaccinated groups were both

  5. Restriction genes for retroviruses influence the risk of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Bjørn A Nexø

    Full Text Available We recently described that the autoimmune, central nervous system disease, multiple sclerosis (MS, is genetically associated with the human endogenous retroviral locus, HERV-Fc1, in Scandinavians. A number of dominant human genes encoding factors that restrict retrovirus replication have been known for a long time. Today human restriction genes for retroviruses include amongst others TRIMs, APOBEC3s, BST2 and TREXs. We have therefore looked for a role of these retroviral restriction genes in MS using genetic epidemiology. We here report that markers in two TRIMs, TRIM5 and TRIM22 and a marker in BST2, associated statistically with the risk of getting MS, while markers in or near APOBEC3s and TREXs showed little or no effect. This indicates that the two TRIMs and BST2 influence the risk of disease and thus supports the hypothesis of a viral involvement.

  6. The ability of multimerized cyclophilin A to restrict retrovirus infection.

    Science.gov (United States)

    Javanbakht, Hassan; Diaz-Griffero, Felipe; Yuan, Wen; Yeung, Darwin F; Li, Xing; Song, Byeongwoon; Sodroski, Joseph

    2007-10-10

    In owl monkeys, the typical retroviral restriction factor of primates, TRIM5alpha, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection. PMID:17574642

  7. The ability of multimerized cyclophilin A to restrict retrovirus infection

    International Nuclear Information System (INIS)

    In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection

  8. Asymptotics for restricted integer compositions

    CERN Document Server

    Malandro, Martin E

    2011-01-01

    We study the compositions of an integer n where the part sizes of the compositions are restricted to lie in a finite set. We obtain asymptotic formulas for the number of such compositions, the total and average number of parts among all such compositions, and the total and average number of times a particular part size appears among all such compositions. Several of our asymptotics have the additional property that their absolute errors---not just their percentage errors---go to 0 as n goes to infinity. Along the way we also obtain recurrences and generating functions for calculating several of these quantities. Our asymptotic formulas come from the meromorphic analysis of our generating functions. Our results also apply to questions about certain kinds of tilings and rhythm patterns.

  9. INTERPOLATION WITH RESTRICTED ARC LENGTH

    Institute of Scientific and Technical Information of China (English)

    Petar Petrov

    2003-01-01

    For given data (ti,yi), I= 0,1,…,n,0 = t0 <t1 <…<tn = 1we study constrained interpolation problem of Favard type inf{‖f"‖∞|f∈W2∞[0,1],f(ti)=yi,i=0,…,n,l(f;[0,1])≤l0}, wherel(f";[0,1])=∫1 0 / 1+f'2(x)dx is the arc length off in [0,1]. We prove the existence of a solution f* of the above problem, that is a quadratic spline with a second derivative f"* , which coincides with one of the constants - ‖f"*‖∞,0,‖f"*‖∞ between every two consecutive knots. Thus, we extend a result ofKarlin concerning Favard problem, to the case of restricted length interpolation.

  10. Gentile statistics and restricted partitions

    Indian Academy of Sciences (India)

    C S Srivatsan; M V N Murthy; R K Bhaduri

    2006-03-01

    In a recent paper (Tran et al, Ann. Phys. 311, 204 (2004)), some asymptotic number theoretical results on the partitioning of an integer were derived exploiting its connection to the quantum density of states of a many-particle system. We generalise these results to obtain an asymptotic formula for the restricted or coloured partitions $p_{k}^{s} (n)$, which is the number of partitions of an integer into the summand of th powers of integers such that each power of a given integer may occur utmost times. While the method is not rigorous, it reproduces the well-known asymptotic results for = 1 apart from yielding more general results for arbitrary values of .

  11. Continuum representations of cellular solids

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  12. Prognosis of Different Cellular Generations

    Directory of Open Access Journals (Sweden)

    Preetish Ranjan

    2013-04-01

    Full Text Available Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequency reuse at a smaller distance. Maximizing the number of times each channel can be reused in a given geographical area is the key to an efficient cellular system design. During the past three decades, the world has seen significant changes in telecommunications industry. There have been some remarkable aspects to the rapid growth in wireless communications, as seen by the large expansion in mobile systems. This paper focuses on “Past, Present & Future of Cellular Telephony” and some light has been thrown upon the technologies of the cellular systems, namely 1G, 2G, 2.5G, 3G and future generations like 4G and 5G systems as well.

  13. Aging, cellular senescence, and cancer.

    Science.gov (United States)

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  14. Novel Materials for Cellular Nanosensors

    DEFF Research Database (Denmark)

    Sasso, Luigi

    The monitoring of cellular behavior is useful for the advancement of biomedical diagnostics, drug development and the understanding of a cell as the main unit of the human body. Micro- and nanotechnology allow for the creation of functional devices that enhance the study of cellular dynamics by...... modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces...... and that offer advantages of functionalization, and conducting polymers were used as electrochemical sensor surface modifications for increasing the sensitivity towards relevant analytes, with focus on the detection of dopamine released from cells via exocytosis. Vertical peptide nanowires were...

  15. Cellular-based preemption system

    Science.gov (United States)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  16. Blood Flow Restricted Exercise and Vascular Function

    Directory of Open Access Journals (Sweden)

    Masahiro Horiuchi

    2012-01-01

    Full Text Available It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  17. Adaptive stochastic cellular automata: Applications

    Science.gov (United States)

    Qian, S.; Lee, Y. C.; Jones, R. D.; Barnes, C. W.; Flake, G. W.; O'Rourke, M. K.; Lee, K.; Chen, H. H.; Sun, G. Z.; Zhang, Y. Q.; Chen, D.; Giles, C. L.

    1990-09-01

    The stochastic learning cellular automata model has been applied to the problem of controlling unstable systems. Two example unstable systems studied are controlled by an adaptive stochastic cellular automata algorithm with an adaptive critic. The reinforcement learning algorithm and the architecture of the stochastic CA controller are presented. Learning to balance a single pole is discussed in detail. Balancing an inverted double pendulum highlights the power of the stochastic CA approach. The stochastic CA model is compared to conventional adaptive control and artificial neural network approaches.

  18. Cellular senescence in aging primates.

    Science.gov (United States)

    Herbig, Utz; Ferreira, Mark; Condel, Laura; Carey, Dee; Sedivy, John M

    2006-03-01

    The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status. PMID:16456035

  19. Cellular automaton for chimera states

    Science.gov (United States)

    García-Morales, Vladimir

    2016-04-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the system spontaneously splitting into stable domains separated by static boundaries, some synchronously oscillating and the others incoherent. When the coupling range is local, nontrivial coherent structures with different periodicities are formed.

  20. Prognosis of Different Cellular Generations

    OpenAIRE

    Preetish Ranjan; Prabhat Kumar

    2013-01-01

    Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequen...

  1. Analyzing the Restrictive Factors of Student Practice Intention Cultivation and Countermeasure in the University History Teaching%大学历史教学中学生实践动机培养的制约因素及对策分析

    Institute of Scientific and Technical Information of China (English)

    王小丽; 肖守库; 勾正刚; 许广灵

    2012-01-01

    实践动机是实践能力的构成要素之一。大学历史教学中存在着诸多制约学生实践动机培养的因素,历史教学应从培养实践兴趣,形成实践内驱力;构建研究性课堂,激发实践成就动机;加强实践教学环节,创设实践压力场景;营造实践氛国,优化实践动机培养外部环境来构建学生实践动机培养的对策,为学生实践能力发展创造条件。%Practice intention is one of component factors of practice ability. There are many factors to restrict cultivation of practice intention in the course of history teaching. Therefore, history teaching cultivates practice intention of student from cultivating practice interest and coming into practice interior power;building up study class and arousing practice achievement intention;beefing up practice teaching segment and setting up practice pressure scene;making practice atmosphere and perfecting external environment of practice intention cultivation. These countermeasures will create advantageous conditions for student cultivating practice intention cultivation and developing practice ability.

  2. From cellular doses to average lung dose

    International Nuclear Information System (INIS)

    Sensitive basal and secretory cells receive a wide range of doses in human bronchial and bronchiolar airways. Variations of cellular doses arise from the location of target cells in the bronchial epithelium of a given airway and the asymmetry and variability of airway dimensions of the lung among airways in a given airway generation and among bronchial and bronchiolar airway generations. To derive a single value for the average lung dose which can be related to epidemiologically observed lung cancer risk, appropriate weighting scenarios have to be applied. Potential biological weighting parameters are the relative frequency of target cells, the number of progenitor cells, the contribution of dose enhancement at airway bifurcations, the promotional effect of cigarette smoking and, finally, the application of appropriate regional apportionment factors. Depending on the choice of weighting parameters, detriment-weighted average lung doses can vary by a factor of up to 4 for given radon progeny exposure conditions. (authors)

  3. Extrauterine growth restriction: Universal problem among premature infants

    Directory of Open Access Journals (Sweden)

    Brunnella Alcantara Chagas de FREITAS

    2016-02-01

    Full Text Available ABSTRACT Objective: To analyze the growth rate of premature infants in the first weeks of life and factors associated with extrauterine growth restriction. Methods: This is a cross-sectional study of 254 premature infants in a neonatal intensive care unit conducted from January 1, 2008 to December 31, 2010. Infants who died or had malformations incompatible with life were excluded. Median weight curves according to gestational age were constructed for the first four weeks of life. The Fenton growth chart calculations provided the weight Z-scores. Extrauterine growth restriction was defined as corrected weight-for-age Z-score ≤-2. Perinatal, morbidity, and health care variables were analyzed. The Poisson regression model yielded the prevalenceratios . Associations between extrauterine growth restriction and the perinatal, morbidity, and care variables were investigated. Poisson regression controlled possible confounding factors. Results: The frequency of extrauterine growth restriction was 24.0%. Most (85.0% small-for-gestational-age infants developed extrauterine growth restriction; 55.3% of extrauterine growth restriction cases involved small-for-gestational-age infants. Premature infants with gestational age >32 weeks did not recover the median birth weight until the third week of life and had a higher frequency of small-for-gestational-age. The Z-scores of non-small-for-gestational-age infants decreased more after birth than those of small-for-gestational-age infants. extrauterine growth restriction was associated with small-for-gestational-age (PR=6.14; 95%CI=3.33-11.33;p <0.001 and time without enteral diet (PR=1.08; 95%CI=1.04-1.13; p =0.010. Conclusion: Extrauterine growth restriction occurs in premature infants of all gestational age. The participation of small-for-gestational-age and nutritional practices in its genesis is noteworthy. We suggest prospective studies of all premature infants. The implementation of best care practices

  4. Competition between Jagged-Notch and Endothelin1 Signaling Selectively Restricts Cartilage Formation in the Zebrafish Upper Face

    Science.gov (United States)

    Barske, Lindsey; Askary, Amjad; Zuniga, Elizabeth; Balczerski, Bartosz; Bump, Paul; Nichols, James T.; Crump, J. Gage

    2016-01-01

    The intricate shaping of the facial skeleton is essential for function of the vertebrate jaw and middle ear. While much has been learned about the signaling pathways and transcription factors that control facial patterning, the downstream cellular mechanisms dictating skeletal shapes have remained unclear. Here we present genetic evidence in zebrafish that three major signaling pathways − Jagged-Notch, Endothelin1 (Edn1), and Bmp − regulate the pattern of facial cartilage and bone formation by controlling the timing of cartilage differentiation along the dorsoventral axis of the pharyngeal arches. A genomic analysis of purified facial skeletal precursors in mutant and overexpression embryos revealed a core set of differentiation genes that were commonly repressed by Jagged-Notch and induced by Edn1. Further analysis of the pre-cartilage condensation gene barx1, as well as in vivo imaging of cartilage differentiation, revealed that cartilage forms first in regions of high Edn1 and low Jagged-Notch activity. Consistent with a role of Jagged-Notch signaling in restricting cartilage differentiation, loss of Notch pathway components resulted in expanded barx1 expression in the dorsal arches, with mutation of barx1 rescuing some aspects of dorsal skeletal patterning in jag1b mutants. We also identified prrx1a and prrx1b as negative Edn1 and positive Bmp targets that function in parallel to Jagged-Notch signaling to restrict the formation of dorsal barx1+ pre-cartilage condensations. Simultaneous loss of jag1b and prrx1a/b better rescued lower facial defects of edn1 mutants than loss of either pathway alone, showing that combined overactivation of Jagged-Notch and Bmp/Prrx1 pathways contribute to the absence of cartilage differentiation in the edn1 mutant lower face. These findings support a model in which Notch-mediated restriction of cartilage differentiation, particularly in the second pharyngeal arch, helps to establish a distinct skeletal pattern in the upper

  5. Repaglinide at a cellular level

    DEFF Research Database (Denmark)

    Krogsgaard Thomsen, M; Bokvist, K; Høy, M;

    2002-01-01

    To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in ra...

  6. Cellular signalling properties in microcircuits

    DEFF Research Database (Denmark)

    Toledo-Rodriguez, Maria; El Manira, Abdeljabbar; Wallén, Peter; Svirskis, Gytis; Hounsgaard, Jørn

    2005-01-01

    Molecules and cells are the signalling elements in microcircuits. Recent studies have uncovered bewildering diversity in postsynaptic signalling properties in all areas of the vertebrate nervous system. Major effort is now being invested in establishing the specialized signalling properties at th...... cellular and molecular levels in microcircuits in specific brain regions. This review is part of the TINS Microcircuits Special Feature....

  7. Quantum Cloning by Cellular Automata

    OpenAIRE

    D'Ariano, G. M.; Macchiavello, C.; M. Rossi

    2012-01-01

    We introduce a quantum cellular automaton that achieves approximate phase-covariant cloning of qubits. The automaton is optimized for 1-to-2N economical cloning. The use of the automaton for cloning allows us to exploit different foliations for improving the performance with given resources.

  8. Analysis of cellular manufacturing systems

    NARCIS (Netherlands)

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van Jan-Kees

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handli

  9. Tumor Restrictions to Oncolytic Virus

    Directory of Open Access Journals (Sweden)

    Markus Vähä-Koskela

    2014-04-01

    Full Text Available Oncolytic virotherapy has advanced since the days of its conception but therapeutic efficacy in the clinics does not seem to reach the same level as in animal models. One reason is premature oncolytic virus clearance in humans, which is a reasonable assumption considering the immune-stimulating nature of the oncolytic agents. However, several studies are beginning to reveal layers of restriction to oncolytic virotherapy that are present before an adaptive neutralizing immune response. Some of these barriers are present constitutively halting infection before it even begins, whereas others are raised by minute cues triggered by virus infection. Indeed, we and others have noticed that delivering viruses to tumors may not be the biggest obstacle to successful therapy, but instead the physical make-up of the tumor and its capacity to mount antiviral defenses seem to be the most important efficacy determinants. In this review, we summarize the constitutive and innate barriers to oncolytic virotherapy and discuss strategies to overcome them.

  10. Cardiac MRI in restrictive cardiomyopathy

    International Nuclear Information System (INIS)

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  11. Cardiac MRI in restrictive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Singh Gulati, G., E-mail: gulatigurpreet@rediffmail.com [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Seth, S. [Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Sharma, S. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India)

    2012-02-15

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  12. Nonparametric estimation and inference under shape restrictions

    OpenAIRE

    Horowitz, Joel; LEE, Sokbae

    2015-01-01

    Economic theory often provides shape restrictions on functions of interest in applications, such as monotonicity, convexity, non-increasing (non-decreasing) returns to scale, or the Slutsky inequality of consumer theory; but economic theory does not provide finite-dimensional parametric models. This motivates nonparametric estimation under shape restrictions. Nonparametric estimates are often very noisy. Shape restrictions stabilize nonparametric estimates without imposing arbitrary restricti...

  13. Measuring Regulatory Restrictions in Logistics Services

    OpenAIRE

    Hollweg, Claire; Marn-Heong WONG

    2009-01-01

    This study measures the extent of restrictions on trade in logistics services in the ASEAN+6 economies by constructing a logistics regulatory restrictiveness index for each economy that quantifies the extent of government regulations faced by logistics service providers. This is the first study of its kind to construct a regulatory index of the entire logistics sector, which includes the main modes of international transport and customs restrictions. The indices show that large differences ex...

  14. Measuring the Restrictiveness of International Trade Policy.

    OpenAIRE

    Anderson, James E.; Neary, J. Peter

    1994-01-01

    This article provides an introduction to the trade restrictiveness index (TRI), which equals the uniform tariff that is welfare equivalent to a given pattern of trade protection. Unlike standard measures of trade restrictiveness, the TRI has a solid theoretical basis, can incorporate both tariffs and quantitative restrictions, and can be adapted to construct the trade policy equivalent of domestic distortions, the article compares a number of applications and describes procedures for operatio...

  15. Effects of T592 phosphomimetic mutations on tetramer stability and dNTPase activity of SAMHD1 can not explain the retroviral restriction defect.

    Science.gov (United States)

    Bhattacharya, Akash; Wang, Zhonghua; White, Tommy; Buffone, Cindy; Nguyen, Laura A; Shepard, Caitlin N; Kim, Baek; Demeler, Borries; Diaz-Griffero, Felipe; Ivanov, Dmitri N

    2016-01-01

    SAMHD1, a dNTP triphosphohydrolase, contributes to interferon signaling and restriction of retroviral replication. SAMHD1-mediated retroviral restriction is thought to result from the depletion of cellular dNTP pools, but it remains controversial whether the dNTPase activity of SAMHD1 is sufficient for restriction. The restriction ability of SAMHD1 is regulated in cells by phosphorylation on T592. Phosphomimetic mutations of T592 are not restriction competent, but appear intact in their ability to deplete cellular dNTPs. Here we use analytical ultracentrifugation, fluorescence polarization and NMR-based enzymatic assays to investigate the impact of phosphomimetic mutations on SAMHD1 tetramerization and dNTPase activity in vitro. We find that phosphomimetic mutations affect kinetics of tetramer assembly and disassembly, but their effects on tetramerization equilibrium and dNTPase activity are insignificant. In contrast, the Y146S/Y154S dimerization-defective mutant displays a severe dNTPase defect in vitro, but is indistinguishable from WT in its ability to deplete cellular dNTP pools and to restrict HIV replication. Our data suggest that the effect of T592 phosphorylation on SAMHD1 tetramerization is not likely to explain the retroviral restriction defect, and we hypothesize that enzymatic activity of SAMHD1 is subject to additional cellular regulatory mechanisms that have not yet been recapitulated in vitro. PMID:27511536

  16. 1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

    Directory of Open Access Journals (Sweden)

    Lars-Oliver Klotz

    2014-09-01

    Full Text Available Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others to cellular and inter-cellular signaling processes are discussed: (i naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings.

  17. Different modulation by dietary restriction of adipokine expression in white adipose tissue sites in the rat

    Directory of Open Access Journals (Sweden)

    Esteve Montserrat

    2009-07-01

    Full Text Available Abstract Background White adipose tissue (WAT is a disperse organ acting as energy storage depot and endocrine/paracrine controlling factor in the management of energy availability and inflammation. WAT sites response under energy-related stress is not uniform. In the present study we have analyzed how different WAT sites respond to limited food restriction as a way to better understand the role of WAT in the pathogenesis of the metabolic syndrome. Methods Overweight male rats had their food intake reduced a 40% compared with free-feeding controls. On day ten, the rats were killed; circulating glucose, insulin, leptin, adiponectin, triacylglycerols and other parameters were measured. The main WAT sites were dissected: mesenteric, retroperitoneal, epididymal and subcutaneous inguinal, which were weighed and frozen. Later all subcutaneous WAT was also dissected and weighed. Samples were used for DNA (cellularity analysis and mRNA extraction and semiquantitarive RT-PCR analysis of specific cytokine gene expressions. Results There was a good correlation between serum leptin and cumulative WAT leptin gene mRNA, but not for adiponectin. Food restriction reduced WAT size, but not its DNA content (except for epididymal WAT. Most cytokines were correlated to WAT site weight, but not to DNA. There was WAT site specialization in the differential expression (and probably secretion of adipokines: subcutaneous WAT showed the highest concentration for leptin, CD68 and MCP-1, mesenteric WAT for TNFα (and both tissues for the interleukins 1β and 6; resistin was highly expressed in subcutaneous and retroperitoneal WAT. Conclusion Food restriction induced different patterns for mesenteric and the other WAT sites, which may be directly related to both the response to intestine-derived energy availability, and an inflammatory-related response. However, retroperitoneal WAT, and to a lower extent, subcutaneous and epididymal, reacted decreasing the expression of

  18. Incorporating theoretical restrictions into forecasting by projection methods

    OpenAIRE

    Raffaella Giacomini

    2012-01-01

    We propose a method for modifying a given density forecast in a way that incorporates the information contained in theory-based moment conditions. An example is "improving" the forecasts from atheoretical econometric models, such as factor models or Bayesian VARs, by ensuring that they satisfy theoretical restrictions given for example by Euler equations or Taylor rules. The method yields a new density (and thus point-) forecast which has a simple and convenient analytical expression and whic...

  19. Incorporating theoretical restrictions into forecasting by projection methods

    OpenAIRE

    Giacomini, Raffaella; Ragusa, Giuseppe

    2011-01-01

    We propose a method for modifying a given density forecast in a way that incorporates the information contained in theory-based moment conditions. An example is "improving" the forecasts from atheoretical econometric models, such as factor models or Bayesian VARs, by ensuring that they satisfy theoretical restrictions given for example by Euler equations or Taylor rules. The method yields a new density (and thus point-) forecast which has a simple and convenient analytical expression and whic...

  20. The Restriction .on Educational Quality in Rural Schools

    Institute of Scientific and Technical Information of China (English)

    艾丽娜

    2012-01-01

    In order to understand the educational quality in rural schools, I went deep into Huangjia Middle School( situated in Northern China) to make the research. In this article, I focus on the restrictions on educational qualitys, which is one of the main themes about rural education. The factors influencing quality in rural schools are analyzed in this article .It is concluded that educational quality depends on the relationship of teaching and learning and its supporting context.

  1. Does Intellectual Property Restrict Output? An Analysis of Pharmaceutical Markets*

    OpenAIRE

    Darius Lakdawalla; Tomas Philipson

    2012-01-01

    Standard analysis of intellectual property focuses on the balance between incentives for research and the welfare costs of restraining output through monopoly pricing. We present evidence from the pharmaceutical industry that output often fails to rise after patent expirations. Patents restrict output by allowing monopoly pricing but may also boost output and welfare by improving incentives for marketing, a form of nonprice competition. We analyze how nonprice factors such as marketing mitiga...

  2. Molecular and cellular mechanisms of cadmium carcinogenesis

    International Nuclear Information System (INIS)

    Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

  3. Dietary restriction, cell proliferation and carcinogenesis: a preliminary study

    International Nuclear Information System (INIS)

    Four groups of female Swiss Webster mice were given either laboratory chow or a purified (semi-synthetic) diet (AIN-76A) either ad libitum or at 75% of the ad libitum rate for about 30 days. Three tissues, the crypt cells of the jejunum, the dermis and the basal epithelial cells of the esophagus were investigated using [3H]thymidine labelling and by counting mitoses; four other tissues, the alveolar cells of the mammary gland, the crypt cells of the duodenum and colo-rectum, and the transitional cells of the urinary bladder were examined using [3H]thymidine labelling only. In each case dietary restriction led to a reduction of cellular proliferation assessed by these indices. The potential of the approach for the study of the effects of dietary modification on the introduction of cancer is discussed. (author). 22 refs

  4. Estimation of average causal effect using the restricted mean residual lifetime as effect measure

    DEFF Research Database (Denmark)

    Mansourvar, Zahra; Martinussen, Torben

    2016-01-01

    Although mean residual lifetime is often of interest in biomedical studies, restricted mean residual lifetime must be considered in order to accommodate censoring. Differences in the restricted mean residual lifetime can be used as an appropriate quantity for comparing different treatment groups ...... is also applied to an observational data set of patients after an acute myocardial infarction event....... with respect to their survival times. In observational studies where the factor of interest is not randomized, covariate adjustment is needed to take into account imbalances in confounding factors. In this article, we develop an estimator for the average causal treatment difference using the restricted...

  5. A sentinel protein assay for simultaneously quantifying cellular processes

    Czech Academy of Sciences Publication Activity Database

    Soste, M.; Hrabáková, Rita; Wanka, S.; Melnik, A.; Boersema, P.; Maiolica, A.; Wernas, T.; Tognetti, M.; von Mering, Ch.; Picotti, P.

    2014-01-01

    Roč. 11, č. 10 (2014), s. 1045-1048. ISSN 1548-7091 R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : targeted proteomics * selected reaction monitoring * cellular signaling Subject RIV: CE - Biochemistry Impact factor: 32.072, year: 2014

  6. Regulation of ARE-mRNA Stability by Cellular Signaling

    DEFF Research Database (Denmark)

    Damgaard, Christian Kroun; Lykke-Andersen, Jens

    response to different cellular cues they can become either stabilized, allowing expression of a given gene, or further destabilized to silence their expression. These tightly regulated mRNAs include many that encode growth factors, proto-oncogenes, cytokines, and cell cycle regulators. Failure to properly...

  7. Caveolar vesicles generate DNA damage and perpetuate cellular aging

    Institute of Scientific and Technical Information of China (English)

    Keith Wheaton

    2011-01-01

    @@ The replicative limit of human fibroblasts has long provided a model to assess the molecular mechanisms underlying cellular aging [1].In culture, fibroblasts which reach the end of their proliferative lifespan acquire profound molecular changes that limit their response to growth factors, and cause permanent exit from the cell cycle [2].

  8. Cellular events and biomarkers of wound healing

    Directory of Open Access Journals (Sweden)

    Shah Jumaat Mohd. Yussof

    2012-01-01

    Full Text Available Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs and the tissue inhibitors of these metalloproteinases (TIMPs. MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds.

  9. Cellular solidification of transparent monotectics

    Science.gov (United States)

    Kaulker, W. F.

    1986-01-01

    Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

  10. Cellular ceramics in combustion environments

    Energy Technology Data Exchange (ETDEWEB)

    Fuessel, Alexander; Boettge, Daniela; Adler, Joerg; Marschallek, Felix; Michaelis, Alexander [Fraunhofer Institute for Ceramic Technologies and Systems IKTS, Dresden (Germany)

    2011-11-15

    Cellular materials have become increasingly interesting for applications in combustion environments. Improvements like high power efficiency and low emissions are the main targets of technological development in combustion processes. However, despite scientific and technical success in developing new or improved burner concepts over recent years, a lot of problems remain to be solved in the field of materials science: due to the high power density of the burners the materials are subjected to high loads in terms of thermal shock, temperature and corrosion, especially in so-called porous burner technology. This article shows some examples of research and development strategies and results in developing improved cellular ceramics. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. Designing Underwater Cellular Networks Parameters

    Directory of Open Access Journals (Sweden)

    Pejman Khadivi

    2008-09-01

    Full Text Available Oceanographic data collection, pollution monitoring, offshore exploration, disaster prevention, assisted navigation and tactical surveillance are some of the applications of underwater networks. Underwater networks should send the gathered information to other users or an offshore station via a base station in the sea. Since the available bandwidth in underwater is severely limited, frequency reuse and cellular networks concepts are very important. In this paper, after driving the ratio of signal to interference for underwater acoustic channels, the constraints for the cell radius are determined. One of the important results of this work is that, for special parameters like bandwidth, it may be impossible to provide the required signal to interference ratio and bandwidth for the network users. Furthermore, in this paper, number of supportable users, per-user bandwidth, and the user capacity for a cellular underwater network are determined.

  12. An Event Restriction Interval Theory of Tense

    Science.gov (United States)

    Beamer, Brandon Robert

    2012-01-01

    This dissertation presents a novel theory of tense and tense-like constructions. It is named after a key theoretical component of the theory, the event restriction interval. In Event Restriction Interval (ERI) Theory, sentences are semantically evaluated relative to an index which contains two key intervals, the evaluation interval and the event…

  13. 44 CFR 402.2 - Restricted commodities.

    Science.gov (United States)

    2010-10-01

    ... Positive List (15 CFR part 399) (as amended from time to time) of the Comprehensive Export Schedule of the... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Restricted commodities. 402.2... SHIPMENTS ON AMERICAN FLAG SHIPS AND AIRCRAFT (T-1, INT. 1) § 402.2 Restricted commodities. The...

  14. Restricting mutualistic partners to enforce trade reliance

    Science.gov (United States)

    Wyatt, Gregory A. K.; Kiers, E. Toby; Gardner, Andy; West, Stuart A.

    2016-01-01

    Mutualisms are cooperative interactions between members of different species, often involving the trade of resources. Here, we suggest that otherwise-cooperative mutualists might be able to gain a benefit from actively restricting their partners' ability to obtain resources directly, hampering the ability of the restricted partner to survive and/or reproduce without the help of the restricting mutualist. We show that (i) restriction can be favoured when it makes the resources of the restricting individual more valuable to their partner, and thus allows them to receive more favourable terms of trade; (ii) restriction maintains cooperation in conditions where cooperative behaviour would otherwise collapse; and (iii) restriction can lead to either an increase or decrease in a restricted individual's fitness. We discuss the applicability of this scenario to mutualisms such as those between plants and mycorrhizal fungi. These results identify a novel conflict in mutualisms as well as several public goods dilemmas, but also demonstrate how conflict can help maintain cooperation. PMID:26813888

  15. 42 CFR 73.13 - Restricted experiments.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Restricted experiments. 73.13 Section 73.13 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING... restricted experiment with a HHS select agent or toxin unless approved by and conducted in accordance...

  16. 30 CFR 56.11008 - Restricted clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 56.11008 Section 56.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Travelways § 56.11008 Restricted clearance. Where...

  17. 50 CFR 648.203 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... Herring Fishery § 648.203 Gear restrictions. (a) Midwater trawl gear may only be used by a vessel issued a... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restrictions. 648.203 Section 648.203 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC...

  18. 50 CFR 648.144 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... Fishery § 648.144 Gear restrictions. (a) Trawl gear restrictions—(1) General. (i) Otter trawlers whose... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restrictions. 648.144 Section 648.144 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC...

  19. 50 CFR 660.506 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... restrictions. The only fishing gear authorized for use in the reduction fishery for northern anchovy off... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Gear restrictions. 660.506 Section 660.506 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC...

  20. 50 CFR 648.163 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... Bluefish Fishery § 648.163 Gear restrictions. If the Council determines through its annual review or... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Gear restrictions. 648.163 Section 648.163 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC...

  1. 50 CFR 665.664 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Gear restrictions. 665.664 Section 665.664 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... § 665.664 Gear restrictions. Only selective gear may be used to harvest coral from any precious...

  2. 50 CFR 665.464 - Gear restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Gear restrictions. 665.464 Section 665.464 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... Gear restrictions. Only selective gear may be used to harvest coral from any precious coral permit area....

  3. 40 CFR 1033.740 - Credit restrictions.

    Science.gov (United States)

    2010-07-01

    ... restrictions. Use of emission credits generated under this part 1033 or 40 CFR part 92 is restricted depending on the standards against which they were generated. (a) Credits from 40 CFR part 92. NOX and PM credits generated under 40 CFR part 92 may be used under this part in the same manner as NOX and...

  4. Stochastic Nature in Cellular Processes

    Institute of Scientific and Technical Information of China (English)

    刘波; 刘圣君; 王祺; 晏世伟; 耿轶钊; SAKATA Fumihiko; GAO Xing-Fa

    2011-01-01

    The importance of stochasticity in cellular processes is increasingly recognized in both theoretical and experimental studies. General features of stochasticity in gene regulation and expression are briefly reviewed in this article, which include the main experimental phenomena, classification, quantization and regulation of noises. The correlation and transmission of noise in cascade networks are analyzed further and the stochastic simulation methods that can capture effects of intrinsic and extrinsic noise are described.

  5. Xtoys cellular automata on xwindows

    CERN Document Server

    Creutz, M

    1995-01-01

    Xtoys is a collection of xwindow programs for demonstrating simulations of various statistical models. Included are xising, for the two dimensional Ising model, xpotts, for the q-state Potts model, xautomalab, for a fairly general class of totalistic cellular automata, xsand, for the Bak-Tang-Wiesenfield model of self organized criticality, and xfires, a simple forest fire simulation. The programs should compile on any machine supporting xwindows.

  6. Cellular reactions to patterned biointerfaces

    OpenAIRE

    Schulte, Vera Antonie

    2012-01-01

    The subject of this thesis is to study cellular reactions to topographically, mechanically and biochemically tunable polymeric biomaterials. Different aspects of in vitro cell-biomaterial interactions were systematically studied with the murine fibroblast cell line NIH L929 and primary human dermal fibroblasts (HDFs). Besides a general cytocompatibility assessment of the applied materials and the quantification of cell adhesion per se, cell morphological changes (e.g. cell spreading) and intr...

  7. Signal processing in cellular clocks

    OpenAIRE

    Forger, Daniel B.

    2011-01-01

    Many biochemical events within a cell need to be timed properly to occur at specific times of day, after other events have happened within the cell or in response to environmental signals. The cellular biochemical feedback loops that time these events have already received much recent attention in the experimental and modeling communities. Here, we show how ideas from signal processing can be applied to understand the function of these clocks. Consider two signals from the network s(t) and r(...

  8. Analysis of cellular manufacturing systems

    OpenAIRE

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van, J.C.

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handling set-up times as well as transfer and process batch size information of multiple products that flow through the system. It is assumed that two sets of discrete material handling devices are used fo...

  9. Cellular Dynamics of RNA Modification

    OpenAIRE

    Yi, Chengqi; Pan, Tao

    2011-01-01

    Decades of research have identified over 100 types of ribonucleosides that are post-transcriptionally modified. Many modified nucleosides are conserved in bacteria, archeae and eukaryotes, while some modified nucleosides are unique to each branch of life. However, the cellular and functional dynamics of RNA modifications remains largely unexplored, mostly due to the lack of functional hypotheses and experimental methods for quantification and large scale analysis. Just as many well characteri...

  10. Cellular Dynamics of RNA Modification

    Science.gov (United States)

    Yi, Chengqi; Pan, Tao

    2011-01-01

    Conspectus Decades of research have identified over 100 types of ribonucleosides that are post-transcriptionally modified. Many modified nucleosides are conserved in bacteria, archeae and eukaryotes, while some modified nucleosides are unique to each branch of life. However, the cellular and functional dynamics of RNA modifications remains largely unexplored, mostly due to the lack of functional hypotheses and experimental methods for quantification and large scale analysis. Just as many well characterized protein and DNA modifications, many RNA modifications are not essential for life. Instead, increasingly more evidence indicates that RNA modifications can play regulatory roles in cells, especially in response to stress conditions. In this Account, we review some known examples of RNA modifications that are dynamically controlled in cells and introduce some contemporary technologies and methods that enhance the studies of cellular dynamics of RNA modifications. Examples of RNA modifications discussed in this Account include (Figure 1): (1) 4-thio uridine (s4U) which can act as a cellular sensor of near UV-light; (2) queuosine (Q) which is a potential biomarker for malignancy; (3) N6-methyl adenine (m6A) which is the prevalent modification in eukaryotic mRNAs; and (4) pseudouridine (ψ) which are inducible by nutrient deprivation. Two recent technical advances that stimulated the studies of cellular dynamics of modified ribonucleosides are also described. First, a genome-wide method combines primer extension and microarray to study N1-methyl adenine (m1A) hypomodification in human tRNA. Second, a quantitative mass spectrometric method investigates dynamic changes of a wide range of tRNA modifications under stress conditions in yeast. In addition, we discuss potential mechanisms that control dynamic regulation of RNA modifications, and hypotheses for discovering potential RNA de-modification enzymes. We conclude the Account by highlighting the need to develop new

  11. CELLULAR FETAL MICROCHIMERISM IN PREECLAMPSIA

    OpenAIRE

    Gammill, Hilary S; Aydelotte, Tessa M.; Guthrie, Katherine A.; Nkwopara, Evangelyn C.; Nelson, J. Lee

    2013-01-01

    Previous studies have shown elevated concentrations of free fetal deoxyribonucleic acid and erythroblasts in maternal circulation in preeclampsia compared with normal pregnancy. Pluripotent and immunocompetent fetal cells also transfer to the maternal circulation during pregnancy, but whether concentrations of fetal mononuclear cells also differed in preeclampsia was unknown. We sought to quantify cellular fetal microchimerism in maternal circulation in women with preeclampsia and healthy con...

  12. The Origins of Cellular Life

    OpenAIRE

    Schrum, Jason P.; Zhu, Ting F.; SZOSTAK, JACK W.

    2010-01-01

    Understanding the origin of cellular life on Earth requires the discovery of plausible pathways for the transition from complex prebiotic chemistry to simple biology, defined as the emergence of chemical assemblies capable of Darwinian evolution. We have proposed that a simple primitive cell, or protocell, would consist of two key components: a protocell membrane that defines a spatially localized compartment, and an informational polymer that allows for the replication and inheritance of fun...

  13. Progress of cellular dedifferentiation research

    Institute of Scientific and Technical Information of China (English)

    LIU Hu-xian; HU Da-hai; JIA Chi-yu; FU Xiao-bing

    2006-01-01

    Differentiation, the stepwise specialization of cells, and transdifferentiation, the apparent switching of one cell type into another, capture much of the stem cell spotlight. But dedifferentiation, the developmental reversal of a cell before it reinvents itself, is an important process too. In multicellular organisms, cellular dedifferentiation is the major process underlying totipotency, regeneration and formation of new stem cell lineages. In humans,dedifferentiation is often associated with carcinogenesis.The study of cellular dedifferentiation in animals,particularly early events related to cell fate-switch and determination, is limited by the lack of a suitable,convenient experimental system. The classic example of dedifferentiation is limb and tail regeneration in urodele amphibians, such as salamanders. Recently, several investigators have shown that certain mammalian cell types can be induced to dedifferentiate to progenitor cells when stimulated with the appropriate signals or materials. These discoveries open the possibility that researchers might enhance the endogenous regenerative capacity of mammals by inducing cellular dedifferentiation in vivo.

  14. Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise

    OpenAIRE

    Valdez, G; Tapia, J; Kang, H; Clemenson, G.D.; Gage, F.H.; Lichtman, Jeff; Sanes, Joshua R.

    2010-01-01

    The cellular basis of age-related behavioral decline remains obscure but alterations in synapses are likely candidates. Accordingly, the beneficial effects on neural function of caloric restriction and exercise, which are among the most effective anti-aging treatments known, might also be mediated by synapses. As a starting point in testing these ideas, we studied the skeletal neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison of NMJs in young adult and aged mice...

  15. A novel family of fluorescent hypoxia sensors reveal strong heterogeneity in tumor hypoxia at the cellular level.

    Science.gov (United States)

    Erapaneedi, Raghu; Belousov, Vsevolod V; Schäfers, Michael; Kiefer, Friedemann

    2016-01-01

    Hypoxia is an intensively investigated condition with profound effects on cell metabolism, migration, and angiogenesis during development and disease. Physiologically, hypoxia is linked to tissue homeostasis and maintenance of pluripotency. Hypoxia also contributes to pathologies including cardiovascular diseases and cancer. Despite its importance, microscopic visualization of hypoxia is largely restricted to the detection of reductively activated probes by immunostaining. Here, we describe a novel family of genetically encoded fluorescent sensors that detect the activation of HIF transcription factors reported by the oxygen-independent fluorescent protein UnaG. It comprises sensors with different switching and memory behavior and combination sensors that allow the distinction of hypoxic and reoxygenated cells. We tested these sensors on orthotopically transplanted glioma cell lines. Using a cranial window, we could visualize hypoxia intravitally at cellular resolution. In tissue samples, sensor activity was detected in regions, which were largely devoid of blood vessels, correlated with HIF-1α stabilization, and were highly heterogeneous at a cellular level. Frequently, we detected recently reoxygenated cells outside hypoxic areas in the proximity of blood vessels, suggestive of hypoxia-promoted cell migration. PMID:26598532

  16. Early cellular signaling responses to axonal injury

    Directory of Open Access Journals (Sweden)

    Wang Ai

    2009-03-01

    Full Text Available Abstract Background We have used optic nerve injury as a model to study early signaling events in neuronal tissue following axonal injury. Optic nerve injury results in the selective death of retinal ganglion cells (RGCs. The time course of cell death takes place over a period of days with the earliest detection of RGC death at about 48 hr post injury. We hypothesized that in the period immediately following axonal injury, there are changes in the soma that signal surrounding glia and neurons and that start programmed cell death. In the current study, we investigated early changes in cellular signaling and gene expression that occur within the first 6 hrs post optic nerve injury. Results We found evidence of cell to cell signaling within 30 min of axonal injury. We detected differences in phosphoproteins and gene expression within the 6 hrs time period. Activation of TNFα and glutamate receptors, two pathways that can initiate cell death, begins in RGCs within 6 hrs following axonal injury. Differential gene expression at 6 hrs post injury included genes involved in cytokine, neurotrophic factor signaling (Socs3 and apoptosis (Bax. Conclusion We interpret our studies to indicate that both neurons and glia in the retina have been signaled within 30 min after optic nerve injury. The signals are probably initiated by the RGC soma. In addition, signals activating cellular death pathways occur within 6 hrs of injury, which likely lead to RGC degeneration.

  17. LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis.

    Science.gov (United States)

    Mouta Carreira, C; Nasser, S M; di Tomaso, E; Padera, T P; Boucher, Y; Tomarev, S I; Jain, R K

    2001-11-15

    Lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 is thought to be restricted to lymph vessels and has been used as such to show that tumor lymphangiogenesis occurs on overexpression of lymphangiogenic factors in mouse tumor models. However, these studies have not yet been corroborated in human tumors. Here we show, first, that LYVE-1 is not exclusive to the lymph vessels. Indeed, LYVE-1 is also present in normal hepatic blood sinusoidal endothelial cells in mice and humans. Surprisingly, LYVE-1 is absent from the angiogenic blood vessels of human liver tumors and only weakly present in the microcirculation of regenerative hepatic nodules in cirrhosis, though both vessels are largely derived from the liver sinusoids. Second, we propose a novel approach to identify lymphatics in human and murine liver. By combining LYVE-1 and Prox 1 (a transcription factor) immunohistochemistry, we demonstrate that lymphatics are abundant in cirrhosis. In contrast, in human hepatocellular carcinoma and liver metastases, they are restricted to the tumor margin and surrounding liver. The absence of intratumor lymphatics in hepatocellular carcinomas and liver metastases may impair molecular and cellular transport in these tumors. Finally, the presence of LYVE-1 in liver sinusoidal endothelia suggests that LYVE-1 has functions beyond the lymph vascular system. PMID:11719431

  18. Dynamic properties of cellular neural networks

    Directory of Open Access Journals (Sweden)

    Angela Slavova

    1993-01-01

    Full Text Available Dynamic behavior of a new class of information-processing systems called Cellular Neural Networks is investigated. In this paper we introduce a small parameter in the state equation of a cellular neural network and we seek for periodic phenomena. New approach is used for proving stability of a cellular neural network by constructing Lyapunov's majorizing equations. This algorithm is helpful for finding a map from initial continuous state space of a cellular neural network into discrete output. A comparison between cellular neural networks and cellular automata is made.

  19. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  20. Near BPS skyrmions and restricted harmonic maps

    Science.gov (United States)

    Speight, J. M.

    2015-06-01

    Motivated by a class of near BPS Skyrme models introduced by Adam, Sánchez-Guillén and Wereszczyński, the following variant of the harmonic map problem is introduced: a map φ :(M, g) →(N, h) between Riemannian manifolds is restricted harmonic if it locally extremizes E2 on its SDiff(M) orbit, where SDiff(M) denotes the group of volume preserving diffeomorphisms of (M, g), and E2 denotes the Dirichlet energy. It is conjectured that near BPS skyrmions tend to restricted harmonic maps in the BPS limit. It is shown that φ is restricted harmonic if and only if φ∗ h has exact divergence, and a linear stability theory of restricted harmonic maps is developed, from which it follows that all weakly conformal maps are stable restricted harmonic. Examples of restricted harmonic maps in every degree class R3 → SU(2) and R2 →S2 are constructed. It is shown that the axially symmetric BPS skyrmions on which all previous analytic studies of near BPS Skyrme models have been based, are not restricted harmonic, casting doubt on the phenomenological predictions of such studies. The problem of minimizing E2 for φ :Rk → N over all linear volume preserving diffeomorphisms is solved explicitly, and a deformed axially symmetric family of Skyrme fields constructed which are candidates for approximate near BPS skyrmions at low baryon number. The notion of restricted harmonicity is generalized to restricted F-criticality where F is any functional on maps (M, g) →(N, h) which is, in a precise sense, geometrically natural. The case where F is a linear combination of E2 and E4, the usual Skyrme term, is studied in detail, and it is shown that inverse stereographic projection R3 →S3 ≡ SU(2) is stable restricted F-critical for every such F.

  1. 胰岛素样生长因子Ⅰ受体基因突变与宫内生长受限的研究进展%Development of mutation of insulin-like growth factor Ⅰreceptor and intrauterine growth restriction

    Institute of Scientific and Technical Information of China (English)

    唐梅; 杨凡

    2016-01-01

    目前有关胰岛素生长因子(IGF)家族与胎儿宫内生长受限(IUGR)的研究逐渐增多。在胰岛素样生长因子Ⅰ受体(IGF-ⅠR)基因突变所致 IUGR 患儿中,除了常见的体格生长发育落后,还常合并头小畸形,以及运动、语言发育落后等不同程度的精神发育迟滞。关于 IUGR 发生机制有较多研究,但其确切机制目前尚未明确。目前有关IGF-ⅠR 不同位点的杂合突变导致 IUGR 的研究较多,本文就IGF-ⅠR 不同位点基因突变导致的 IUGR 临床表现及其可能机制进行综述。%In recently years,the amount of researches about relationship between insulin-like growth factor(IGF)family and intrauterine growth restriction(IUGR)was increasing.IUGR which caused by insulin-like growth factor-Ⅰ receptor (IGF-Ⅰ R )mutation usually can lead to mental retardation,such as microcephaly abnormal development in motor and language besides physical growth backwardness.The mechanism of IUGR is still not clear.Now many researches focus on different point heterozygous mutation of IGF-ⅠR which leads to IUGR,and this review will make a summary of the different point mutations.

  2. Cellular functions of p53 and p53 gene family members p63 and p73

    OpenAIRE

    Nadir Koçak; İbrahim Halil Yıldırım; Seval Cing Yıldırım

    2011-01-01

    p53 is a transcription factor that regulates multiple cellular processes that are also important in cellular fates such as cell cycle arrest or programmed cell death. Induction of growth arrest or cell death by p53 prevents the replication of damaged DNA and proliferation of genetically abnormal cells. Therefore, inactivation of p53 by mutation or deletion is also important in ensuring the cellular homeostasis. However, studies showed that p53 deficient mice and cells such as Saos-2 cells are...

  3. Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Wilfried Posch

    2015-06-01

    Full Text Available DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection.

  4. 星形细胞瘤MRI扩散加权成像、肿瘤细胞密度与缺氧诱导因子-1α表达水平的相关性%Correlation Between Diffusion Weighted Imaging, Tumor Cellularity and Expression Level of Hypoxia-inducible Factor-1αin Cerebral Astrocytoma

    Institute of Scientific and Technical Information of China (English)

    崔永鹏; 舒畅; 朱雁兵; 王欢; 郁文芝

    2013-01-01

    Purpose To evaluate the correlation among diffusion weighted imaging (DWI), tumor Cellularity and hypoxia-inducible factor-1α (HIF-1α) for the high and low grade astrocytoma. Materials and Methods DWI was applied with 33 patients with astrocytoma confirmed by pathology, and ADC value was measured. Tumor Cellularity was measured using Scion Image 4.0.3.2. The expression of HIF-1α was tested using immunohistochemisty. Results Mean ADC value was higher in the low grade astrocytoma than that in the high grade astrocytoma (t=7.300, P<0.001). The tumor Cellularity was higher in the high grade astrocytoma than that in the low grade astrocytoma (t=-3.845, P<0.01). HIF-1αexpression could be demonstrated in the low grade [(20.08±10.01)%] and high grade [(47.91±19.03)%] astrocytoma. The negative correlation was demonstrated between ADC value and HIF-1αand tumor Cellularity (r=-0.756,-0.617;P<0.001). The positive correlation was demonstrated between HIF-1αand tumor Cellularity (r=0.622, P<0.001). Conclusion ADC value can be used to discriminate the low and high grade astrocytoma, and the role of HIF-1αshould be further to study with enlarged sample.%目的探讨高级别和低级别星形细胞瘤MRI DWI、肿瘤细胞密度与缺氧诱导因子-1α(HIF-1α)表达水平的相关性。资料与方法对术后病理确诊的33例星形细胞瘤患者术前行MRI DWI检查,并计算肿瘤实质部分的ADC值;用Scion Image 4.0.3.2软件计算肿瘤细胞密度;采用免疫组化检测HIF-1α的表达情况。结果低级别星形细胞瘤的平均ADC值高于高级别星形细胞瘤,差异有统计学意义(t=7.300, P<0.001)。高级别星形细胞瘤平均细胞密度值明显大于低级别星形细胞瘤,差异有统计学意义(t=-3.845, P<0.01)。低级别和高级别星形细胞瘤中均有HIF-1α表达,其表达强度分别为(20.08±10.01)%、(47.91±19.03)%。肿瘤ADC值与HIF-1α标记指数、肿瘤细胞密

  5. Wireless traffic steering for green cellular networks

    CERN Document Server

    Zhang, Shan; Zhou, Sheng; Niu, Zhisheng; Shen, Xuemin (Sherman)

    2016-01-01

    This book introduces wireless traffic steering as a paradigm to realize green communication in multi-tier heterogeneous cellular networks. By matching network resources and dynamic mobile traffic demand, traffic steering helps to reduce on-grid power consumption with on-demand services provided. This book reviews existing solutions from the perspectives of energy consumption reduction and renewable energy harvesting. Specifically, it explains how traffic steering can improve energy efficiency through intelligent traffic-resource matching. Several promising traffic steering approaches for dynamic network planning and renewable energy demand-supply balancing are discussed. This book presents an energy-aware traffic steering method for networks with energy harvesting, which optimizes the traffic allocated to each cell based on the renewable energy status. Renewable energy demand-supply balancing is a key factor in energy dynamics, aimed at enhancing renewable energy sustainability to reduce on-grid energy consum...

  6. Pathologic Cellular Events in Smoking-Related Pancreatitis

    International Nuclear Information System (INIS)

    Pancreatitis, a debilitating inflammatory disorder, results from pancreatic injury. Alcohol abuse is the foremost cause, although cigarette smoking has recently surfaced as a distinct risk factor. The mechanisms by which cigarette smoke and its toxins initiate pathological cellular events leading to pancreatitis, have not been clearly defined. Although cigarette smoke is composed of more than 4000 compounds, it is mainly nicotine and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which have been extensively studied with respect to pancreatic diseases. This review summarizes these research findings and highlights cellular pathways which may be of relevance in initiation and progression of smoking-related pancreatitis

  7. Pathologic Cellular Events in Smoking-Related Pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Thrower, Edwin [Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520 (United States); Veterans Affairs Connecticut Healthcare, West Haven, CT 06516 (United States)

    2015-04-29

    Pancreatitis, a debilitating inflammatory disorder, results from pancreatic injury. Alcohol abuse is the foremost cause, although cigarette smoking has recently surfaced as a distinct risk factor. The mechanisms by which cigarette smoke and its toxins initiate pathological cellular events leading to pancreatitis, have not been clearly defined. Although cigarette smoke is composed of more than 4000 compounds, it is mainly nicotine and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which have been extensively studied with respect to pancreatic diseases. This review summarizes these research findings and highlights cellular pathways which may be of relevance in initiation and progression of smoking-related pancreatitis.

  8. Cellular roles of ADAM12 in health and disease

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Albrechtsen, Reidar; Couchman, John R; Wewer, Ulla M

    2008-01-01

    and it is a potential biomarker for breast cancer. It is therefore important to understand ADAM12's functions. Many cellular roles for ADAM12 have been suggested. It is an active metalloprotease, and has been implicated in insulin-like growth factor (IGF) receptor signaling, through cleavage of IGF...... transmitting signals to or from the cell interior. These ADAM12-mediated cellular effects appear to be critical events in both biological and pathological processes. This review presents current knowledge on ADAM12 functions gained from in vitro and in vivo observations, describes ADAM12's role in both normal...... physiology and pathology, particularly in cancer, and discusses important areas for future investigation....

  9. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes.

    Science.gov (United States)

    Komatsu, Tetsuro; Will, Hans; Nagata, Kyosuke; Wodrich, Harald

    2016-04-22

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. PMID:27012198

  10. The thorny path linking cellular senescence to organismalaging

    Energy Technology Data Exchange (ETDEWEB)

    Patil, Christopher K.; Mian, Saira; Campisi, Judith

    2005-08-09

    Half a century is fast approaching since Hayflick and colleagues formally described the limited ability of normal human cells to proliferate in culture (Hayflick and Moorhead, 1961). This finding--that normal somatic cells, in contrast to cancer cells, cannot divide indefinitely--challenged the prevailing idea that cells from mortal multicellular organisms were intrinsically ''immortal'' (Carrell, 1912). It also spawned two hypotheses, essential elements of which persist today. The first held that the restricted proliferation of normal cells, now termed cellular senescence, suppresses cancer (Hayflick, 1965; Sager, 1991; Campisi, 2001). The second hypothesis, as explained in the article by Lorenzini et al., suggested that the limited proliferation of cells in culture recapitulated aspects of organismal aging (Hayflick, 1965; Martin, 1993). How well have these hypotheses weathered the ensuing decades? Before answering this question, we first consider current insights into the causes and consequences of cellular senescence. Like Lorenzini et al., we limit our discussion to mammals. We also focus on fibroblasts, the cell type studied by Lorenzini et al., but consider other types as well. We suggest that replicative capacity in culture is not a straightforward assessment, and that it correlates poorly with both longevity and body mass. We speculate this is due to the malleable and variable nature of replicative capacity, which renders it an indirect metric of qualitative and quantitative differences among cells to undergo senescence, a response that directly alters cellular phenotype and might indirectly alter tissue structure and function.

  11. Cellular Automata-Based Parallel Random Number Generators Using FPGAs

    Directory of Open Access Journals (Sweden)

    David H. K. Hoe

    2012-01-01

    Full Text Available Cellular computing represents a new paradigm for implementing high-speed massively parallel machines. Cellular automata (CA, which consist of an array of locally connected processing elements, are a basic form of a cellular-based architecture. The use of field programmable gate arrays (FPGAs for implementing CA accelerators has shown promising results. This paper investigates the design of CA-based pseudo-random number generators (PRNGs using an FPGA platform. To improve the quality of the random numbers that are generated, the basic CA structure is enhanced in two ways. First, the addition of a superrule to each CA cell is considered. The resulting self-programmable CA (SPCA uses the superrule to determine when to make a dynamic rule change in each CA cell. The superrule takes its inputs from neighboring cells and can be considered itself a second CA working in parallel with the main CA. When implemented on an FPGA, the use of lookup tables in each logic cell removes any restrictions on how the super-rules should be defined. Second, a hybrid configuration is formed by combining a CA with a linear feedback shift register (LFSR. This is advantageous for FPGA designs due to the compactness of the LFSR implementations. A standard software package for statistically evaluating the quality of random number sequences known as Diehard is used to validate the results. Both the SPCA and the hybrid CA/LFSR were found to pass all the Diehard tests.

  12. Proton micromachining of substrate scaffolds for cellular and tissue engineering

    International Nuclear Information System (INIS)

    Three dimensional patterns (grooves and ridges) were micromachined in PMMA using a 600 keV proton beam from the nuclear microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Swiss 3T3 fibroblasts (ATCC CCL92, Rockville, MD) have been seeded onto these patterns, and the following observations have been made: (a) Cells were not found in the grooves (depth 9 μm, width 6.6 μm); (b) Cells were highly aligned and elongated on narrow ridges (4.2 μm wide), with the degree of alignment and elongation reduced for wider ridges. The underlying mechanism responsible of this cellular behaviour is assumed to be induced by the mechanical restrictions imposed by the topographic features on cellular migration, cell adhesion and concomitant changes in the cytoskeletal. The use of topographical stimuli to regulate cell function is an area of high potential, with implications in the engineering of tissue for spare-part surgery. Proton micromachining, which has the unique advantage of being the only technique capable of direct-write 3D micromachining at sub-cellular dimensions has unique advantages in this area of research

  13. Restriction beyond the restriction point: mitogen requirement for G2 passage

    Directory of Open Access Journals (Sweden)

    te Riele Hein

    2006-05-01

    Full Text Available Abstract Cell proliferation is dependent on mitogenic signalling. When absent, normal cells cannot pass the G1 restriction point, resulting in cell cycle arrest. Passage through the G1 restriction point involves inactivation of the retinoblastoma protein family. Consequently, loss of the retinoblastoma protein family leads to loss of the G1 restriction point. Recent work in our lab has revealed that cells possess yet another mechanism that restricts proliferation in the absence of mitogens: arrest in the G2 phase of the cell cycle. Here, we discuss the similarities and differences between these restriction points and the roles of cyclin-dependent kinase inhibitors (CKIs herein.

  14. Urban water restrictions: Attitudes and avoidance

    Science.gov (United States)

    Cooper, Bethany; Burton, Michael; Crase, Lin

    2011-12-01

    In most urban cities across Australia, water restrictions remain the dominant policy mechanism to restrict urban water consumption. The extensive adoption of water restrictions as a means to limit demand, over several years, means that Australian urban water prices have consistently not reflected the opportunity cost of water. Given the generally strong political support for water restrictions and the likelihood that they will persist for some time, there is value in understanding households' attitudes in this context. More specifically, identifying the welfare gains associated with avoiding urban water restrictions entirely would be a nontrivial contribution to our knowledge and offer insights into the benefits of alternative policy responses. This paper describes the results from a contingent valuation study that investigates consumers' willingness to pay to avoid urban water restrictions. Importantly, the research also investigates the influence of cognitive and exogenous dimensions on the utility gain associated with avoiding water restrictions. The results provide insights into the impact of the current policy mechanism on economic welfare.

  15. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice.

    Directory of Open Access Journals (Sweden)

    Marieke van de Ven

    2006-12-01

    Full Text Available How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age, including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W/XPA(-/- that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/- mouse. Specific (but not all types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage.

  16. Molecular and cellular mechanisms of adipogenesis

    Directory of Open Access Journals (Sweden)

    Aleksander Dmitrievich Egorov

    2015-03-01

    Full Text Available The main components of metabolic syndrome include insulin resistance, hypertriglyceridemia and arterial hypertension. Obesity is the cause of metabolic syndrome, mainly as a consequence of the endocrine function of adipose tissue. The volume of adipose tissue depends on the size of individual adipocytes and on their number. The number of adipocytes increases as a result of enhanced adipocyte differentiation. The transcriptional cascade that regulates this differentiation has been well studied. The major adipogenic transcription factor peroxisome proliferator-activated receptor gamma is a ligand-activated nuclear receptor with essential roles in adipogenesis. Its ligands are used to treat metabolic syndrome and type 2 diabetes mellitus. The present article describes the basic molecular and cellular mechanisms of adipogenesis and discusses the impact of insulin, glucocorticoids, cyclic adenosine monophosphate-activating agents, nuclear receptors and transcription factors on the process of adipogenesis. New regulatory regions of the genome that are capable of binding multiple transcription factors are described, and the most promising drug targets for the treatment of metabolic syndrome and obesity, including the homeodomain proteins Pbx1 and Prep1, are discussed.

  17. Game of Life Cellular Automata

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    In the late 1960s, British mathematician John Conway invented a virtual mathematical machine that operates on a two-dimensional array of square cell. Each cell takes two states, live and dead. The cells' states are updated simultaneously and in discrete time. A dead cell comes to life if it has exactly three live neighbours. A live cell remains alive if two or three of its neighbours are alive, otherwise the cell dies. Conway's Game of Life became the most programmed solitary game and the most known cellular automaton. The book brings together results of forty years of study into computational

  18. Cellular automata a parallel model

    CERN Document Server

    Mazoyer, J

    1999-01-01

    Cellular automata can be viewed both as computational models and modelling systems of real processes. This volume emphasises the first aspect. In articles written by leading researchers, sophisticated massive parallel algorithms (firing squad, life, Fischer's primes recognition) are treated. Their computational power and the specific complexity classes they determine are surveyed, while some recent results in relation to chaos from a new dynamic systems point of view are also presented. Audience: This book will be of interest to specialists of theoretical computer science and the parallelism challenge.

  19. Mathematical Physics of Cellular Automata

    CERN Document Server

    Garcia-Morales, Vladimir

    2012-01-01

    A universal map is derived for all deterministic 1D cellular automata (CA) containing no freely adjustable parameters. The map can be extended to an arbitrary number of dimensions and topologies and its invariances allow to classify all CA rules into equivalence classes. Complexity in 1D systems is then shown to emerge from the weak symmetry breaking of the addition modulo an integer number p. The latter symmetry is possessed by certain rules that produce Pascal simplices in their time evolution. These results elucidate Wolfram's classification of CA dynamics.

  20. Estimation in Cellular Radio Systems

    OpenAIRE

    Blom, Jonas; Gunnarsson, Fredrik; Gustafsson, Fredrik

    1999-01-01

    The problem to track time-varying parameters in cellular radio systems is studied, and the focus is on estimation based only on the signals that are readily available. Previous work have demonstrated very good performance, but were relying on analog measurement that are not available. Most of the information is lost due to quantization and sampling at a rate that might be as low as 2 Hz (GSM case). For that matter a maximum likelihood estimator have been designed and exemplified in the case o...