A retrospective review of trends and clinical characteristics of methamphetamine-related acute psychiatric admissions in a South African context

Objective: Epidemiological studies indicate that methamphetamine (MA) abuse poses a major challenge to health in the Western Cape. The objectives of this study were to retrospectively assess the trends, clinical characteristics and treatment demand of MArelated admissions to a psychiatric ward in this region. Method: The clinical records of patients admitted to an acute psychiatric admission ward at Tygerberg Hospital from 1 January 2002 to 30 June 2002 and 1 January 2006 to 30 June 2006, were retrospectively reviewed. Admission numbers including those of adolescent and adult substance users were compared for both study periods. Study samples comparing demographic profile, admission status, length of stay, psychopathology, treatment requirements and referral pattern to other disciplines between MA users and non-users were collected for the 2006 period. Results: There was a significant (

Complex dynamics of defective interfering baculoviruses during serial passage in insect cells

Defective interfering (DI) viruses are thought to cause oscillations in virus levels, known as the 'Von Magnus effect'. Interference by DI viruses has been proposed to underlie these dynamics, although experimental tests of this idea have not been forthcoming. For the baculoviruses, insect viruses commonly used for the expression of heterologous proteins in insect cells, the molecular mechanisms underlying DI generation have been investigated. However, the dynamics of baculovirus populations harboring DIs have not been studied in detail. In order to address this issue, we used quantitative real-time PCR to determine the levels of helper and DI viruses during 50 serial passages of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) in Sf21 cells. Unexpectedly, the helper and DI viruses changed levels largely in phase, and oscillations were highly irregular, suggesting the presence of chaos. We therefore developed a simple mathematical model of baculovirus-DI dynamics. This theoretical model reproduced patterns qualitatively similar to the experimental data. Although we cannot exclude that experimental variation (noise) plays an important role in generating the observed patterns, the presence of chaos in the model dynamics was confirmed with the computation of the maximal Lyapunov exponent, and a Ruelle-Takens-Newhouse route to chaos was identified at decreasing production of DI viruses, using mutation as a control parameter. Our results contribute to a better understanding of the dynamics of DI baculoviruses, and suggest that changes in virus levels over passages may exhibit chaos.The authors thank Javier Carrera, Just Vlak and Lia Hemerik for helpful discussion. MPZ was supported by a Rubicon Grant from the Netherlands Organization for Scientific Research (NWO, www.nwo.nl) and a 'Juan de la Cierva' postdoctoral contract (JCI-2011-10379) from the Spanish 'Secretaria de Estado de Investigacion, Desarrollo e Innovacion'. JS was supported by the Botin Foundation. SFE was supported by grant BFU2012-30805, also from the Spanish 'Secretaria de Estado de Investigacion, Desarrollo e Innovacion'.Zwart, MP.; Pijlman, G.; Sardanyes Cayuela, J.; Duarte, J.; Januario, C.; Elena Fito, SF. (2013). Complex dynamics of defective interfering baculoviruses during serial passage in insect cells. Journal of Biological Physics. 39(2):327-342. doi:10.1007/s10867-013-9317-9S327342392Von Magnus, P.: Incomplete forms of influenza virus. Adv. Virus. Res. 2, 59–79 (1954)Huang, A.S.: Defective interfering viruses. Annu. Rev. Microbiol. 27, 101–117 (1973)Kool, M., Voncken, J.W., Vanlier, F.L.J., Tramper, J., Vlak, J.M.: Detection and analysis of Autographa californica nuclear polyhedrosis-virus mutants with defective interfering properties. Virology 183, 739–746 (1991)Wickham, T.J., Davis, T., Granados, R.R., Hammer, D.A., Shuler, M.L., Wood, H.A.: Baculovirus defective interfering particles are responsible for variations in recombinant protein-production as a function of multiplicity of infection. Biotechnol. Lett. 13, 483–488 (1991)Pijlman, G.P., van den Born, E., Martens, D.E., Vlak, J.M.: Autographa californica baculoviruses with large genomic deletions are rapidly generated in infected insect cells. Virology 283, 132–138 (2001)Giri, L., Feiss, M.G., Bonning, B.C., Murhammer, D.W.: Production of baculovirus defective interfering particles during serial passage is delayed by removing transposon target sites in fp25k. J. Gen. Virol. 93, 389–399 (2012)King, L.A., Possee, R.D.: The Baculovirus Expression System. University Press, Cambridge (1992)Lee, H.Y., Krell, P.J.: Reiterated DNA fragments in defective genomes of Autographa californica nuclear polyhedrosis virus are competent for AcMNPV-dependent DNA replication. Virology 202, 418–429 (1994)Pijlman, G.P., Dortmans, J., Vermeesch, A.M.G., Yang, K., Martens, D.E., Goldbach, R.W., Vlak, J.M.: Pivotal role of the non-hr origin of DNA replication in the genesis of defective interfering baculoviruses. J. Virol. 76, 5605–5611 (2002)Pijlman, G.P., van Schijndel, J.E., Vlak, J.M.: Spontaneous excision of BAC vector sequences from bacmid-derived baculovirus expression vectors upon passage in insect cells. J. Gen. Virol. 84, 2669–2678 (2003)Pijlman, G.P., Vermeesch, A.M.G., Vlak, J.M.: Cell line-specific accumulation of the baculovirus non-hr origin of DNA replication in infected insect cells. J. Invertebr. Pathol. 84, 214–219 (2003)Roux, L., Simon, A.E., Holland, J.J.: Effects of defective interfering viruses on virus-replication and pathogenesis in vitro and in vivo. Adv. Virus. Res. 40, 181–211 (1991)Grabau, E.A., Holland, J.J.: Analysis of viral and defective-interfering nucleocapsids in acute and persistent infection by Rhadoviruses. J. Gen. Virol. 60, 87–97 (1982)Kawai, A., Matsumoto, S., Tanabe, K.: Characterization of Rabies viruses recovered from persistently infected BHK cells. Virology 67, 520–533 (1975)Roux, L., Holland, J.J.: Viral genome synthesis in BHK-21 cells persistently infected with Sendai virus. Virology 100, 53–64 (1980)Palma, E.L., Huang, A.: Cyclic production of vesicular stomatitis virus cause by defective interfering particles. J. Infect. Dis. 129, 402–410 (1974).Stauffer Thompson, K.A., Yin, J.: Population dynamics of an RNA virus and its defective interfering particles in passage cultures. Virol. J. 7, 257–266 (2010)Szathmáry, E.: Cooperation and defection – playing the field in virus dynamics. J. Theor. Biol. 165, 341–356 (1993)Bangham, C.R.M., Kirkwood, T.B.L.: Defective interfering particles – effects in modulating virus growth and persistence. Virology 179, 821–826 (1990)Kirkwood, T.B.L., Bangham, C.R.M.: Cycles, chaos, and evolution in virus cultures – a model of defective interfering particles. Proc. Natl. Acad. Sci. USA 91, 8685–8689 (1994)De Gooijer, C.D., Koken, R.H.M., van Lier, F.L.J., Kool, M., Vlak, J.M., Tramper, J.: A structured dynamic model for the baculovirus infection process in insect-cell reactor configurations. Biotech. Bioeng. 40, 537–548 (1992)Van Lier, F.L.J., van der Meijs, W.C.J., Grobben, N.G., Olie, R.A., Vlak, J.M., Tramper, J.: Continuous beta-galactosidase production with a recombinant baculovirus insect-cell system in bioreactors. J. Biotechnol. 22, 291–298 (1992)Van Lier, F.L.J., van den Hombergh, J., de Gooijer, C.D., den Boer, M.M., Vlak, J.M., Tramper, J.: Long-term semi-continuous production of recombinant baculovirus protein in a repeated (fed-)batch two-stage reactor system. Enzyme Microb. Technol. 18, 460–466 (1996)Zwart, M.P., Erro, E., van Oers, M.M., de Visser, J.A.G.M., Vlak, J.M.: Low multiplicity of infection in vivo results in purifying selection against baculovirus deletion mutants. J. Gen. Virol. 89, 1220–1224 (2008)Luckow, V.A., Lee, S.C., Barry, G.F., Olins, P.O.: Efficient generation of infectious recombinant baculoviruses by site-specific transposon-mediated insertion of foreign genes into a baculovirus genome propagated in Escherichia coli. J. Virol. 67, 4566–4579 (1993)Vaughn, J.L., Goodwin, R.H., Tompkins, G.J., McCawley, P.: Establishment of 2 cell lines from insect Spodoptera frugiperda (Lepidoptera, Noctuidae). In Vitro 13, 213–217 (1977)Zwart, M.P., van Oers, M.M., Cory, J.S., van Lent, J.W.M., van der Werf, W., Vlak, J.M.: Development of a quantitative real-time PCR for determination of genotype frequencies for studies in baculovirus population biology. J. Virol. Meth. 148, 146–154 (2008)Zwart, M.P., Hemerik, L., Cory, J.S., de Visser, J.A.G.M., Bianchi, F.J.J.A., van Oers, M.M., Vlak, J.M., Hoekstra, R.F., van der Werf, W.: An experimental test of the independent action hypothesis in virus-insect pathosystems. Proc. R. Soc. B 276, 2233–2242 (2009)Olkin, I., Gleser, L.J., Derman, C.: Probability Models and Applications. Macmillan, New York (1994)Parker, T., Chua, L.: Practical Numerical Algorithms for Chaotic Systems. Springer-Verlag, Berlin (1989)Dieci, L., van Vleck, E.S.: Computation of a few Lyapunov exponents for continuous and discrete dynamical systems. J. Appl. Numer. Math. 17, 275–291 (1995)Matsumoto, T., Chua, L.O., Komuro, M.: The double scroll. IEEE Trans. Circuits Syst. 32, 797–818 (1985)Chua, L.O., Komuro, M., Matsumoto, T.: The double scroll family: rigorous proof of chaos. IEEE Trans. Circuits Syst. 33, 1072–1097 (1986)Ramasubramanian, K., Sriram, M.S.: A comparative study of computation of Lyapunov spectra with different algorithms. Phys. D: Nonlin. Phenom. 139, 72–86 (2000)Lee, H.Y., Krell, P.J.: Generation and analysis of defective genomes of Autographa californica nuclear polyhedrosis virus. J. Virol. 66, 4339–4347 (1992)Kovacs, G.R., Choi, J., Guarino, L.A., Summers MD: Functional dissection of the Autographa californica nuclear polyhedrosis virus immediate early 1 transcriptional regulatory protein. J. Virol. 66, 7429–7437 (1992)Legendre, P., Legendre, L.: Numerical Ecology. Elsevier, Amsterdam (1998)Schuster, H.G.: Deterministic Chaos: An Introduction. Wiley-VCH Verlag GmbH & Co. KGaA, Wienheim (2005)Strogatz, S.H.: Nonlinear Dynamics and Chaos: With Applications to Physics, Biology, Chemistry and Engineering. Westview Press, Cambridge (1994)Dennis, B., Desharnais, R.A., Cushing, J.M., Henson, S.M., Constantino, R.F.: Can noise induce chaos? Oikos 102, 329–339 (2003)Crutchfield, J.P., Huberman, B.A.: Fluctuations and the onset of chaos. Phys. Lett. A 77, 407–410 (1980)Crutchfield, J.P., Farmer, J.D.: Fluctuations and simple chaotic dynamics. Phys. Rep. 92, 45–82 (1982

Set optimization - a rather short introduction

Recent developments in set optimization are surveyed and extended including various set relations as well as fundamental constructions of a convex analysis for set- and vector-valued functions, and duality for set optimization problems. Extensive sections with bibliographical comments summarize the state of the art. Applications to vector optimization and financial risk measures are discussed along with algorithmic approaches to set optimization problems

Functional Implication of Dp71 in Osmoregulation and Vascular Permeability of the Retina

Functional alterations of Müller cells, the principal glia of the retina, are an early hallmark of most retina diseases and contribute to their further progression. The molecular mechanisms of these reactive Müller cell alterations, resulting in disturbed retinal homeostasis, remain largely unknown. Here we show that experimental detachment of mouse retina induces mislocation of the inwardly rectifying potassium channels (Kir4.1) and a downregulation of the water channel protein (AQP4) in Müller cells. These alterations are associated with a strong decrease of Dp71, a cytoskeleton protein responsible for the localization and the clustering of Kir4.1 and AQP4. Partial (in detached retinas) or total depletion of Dp71 in Müller cells (in Dp71-null mice) impairs the capability of volume regulation of Müller cells under osmotic stress. The abnormal swelling of Müller cells In Dp71-null mice involves the action of inflammatory mediators. Moreover, we investigated whether the alterations in Müller cells of Dp71-null mice may interfere with their regulatory effect on the blood-retina barrier. In the absence of Dp71, the retinal vascular permeability was increased as compared to the controls. Our results reveal that Dp71 is crucially implicated in the maintenance of potassium homeostasis, in transmembraneous water transport, and in the Müller cell-mediated regulation of retinal vascular permeability. Furthermore, our data provide novel insights into the mechanisms of retinal homeostasis provided by Müller cells under normal and pathological conditions

Exploring the three PIPs and three TIPs of grapevine for transport of water and atypical substrates through heterologous expression in aqy-null yeast

Aquaporins are membrane channels that facilitate the transport of water and other small molecules across the cellular membranes. We examined the role of six aquaporins of Vitis vinifera (cv. Touriga nacional) in the transport of water and atypical substrates (other than water) in an aqy-null strain of Saccharomyces cerevisiae. Their functional characterization for water transport was performed by stopped-flow fluorescence spectroscopy. The evaluation of permeability coefficients (Pf) and activation energies (Ea) revealed that three aquaporins (VvTnPIP2;1, VvTnTIP1;1 and VvTnTIP2;2) are functional for water transport, while the other three (VvTnPIP1;4, VvTnPIP2;3 and VvTnTIP4;1) are non-functional. TIPs (VvTnTIP1;1 and VvTnTIP2;2) exhibited higher water permeability than VvTnPIP2;1. All functional aquaporins were found to be sensitive to HgCl2, since their water conductivity was reduced (24–38%) by the addition of 0.5 mM HgCl2. Expression of Vitis aquaporins caused different sensitive phenotypes to yeast strains when grown under hyperosmotic stress generated by KCl or sorbitol. Our results also indicate that Vitis aquaporins are putative transporters of other small molecules of physiological importance. Their sequence analyses revealed the presence of signature sequences for transport of ammonia, boron, CO2, H2O2 and urea. The phenotypic growth variations of yeast cells showed that heterologous expression of Vitis aquaporins increased susceptibility to externally applied boron and H2O2, suggesting the contribution of Vitis aquaporins in the transport of these speciesinfo:eu-repo/semantics/publishedVersio

Congenital Hypogonadotropic Hypogonadism Due to GNRH Receptor Mutations in Three Brothers Reveal Sites Affecting Conformation and Coupling

Congenital hypogonadotropic hypogonadism (CHH) is characterized by low gonadotropins and failure to progress normally through puberty. Mutations in the gene encoding the GnRH receptor (GNRHR1) result in CHH when present as compound heterozygous or homozygous inactivating mutations. This study identifies and characterizes the properties of two novel GNRHR1 mutations in a family in which three brothers display normosmic CHH while their sister was unaffected. Molecular analysis in the proband and the affected brothers revealed two novel non-synonymous missense GNRHR1 mutations, present in a compound heterozygous state, whereas their unaffected parents possessed only one inactivating mutation, demonstrating the autosomal recessive transmission in this kindred and excluding X-linked inheritance equivocally suggested by the initial pedigree analysis. The first mutation at c.845 C>G introduces an Arg substitution for the conserved Pro 282 in transmembrane domain (TMD) 6. The Pro282Arg mutant is unable to bind radiolabeled GnRH analogue. As this conserved residue is important in receptor conformation, it is likely that the mutation perturbs the binding pocket and affects trafficking to the cell surface. The second mutation at c.968 A>G introduces a Cys substitution for Tyr 323 in the functionally crucial N/DPxxY motif in TMD 7. The Tyr323Cys mutant has an increased GnRH binding affinity but reduced receptor expression at the plasma membrane and impaired G protein-coupling. Inositol phosphate accumulation assays demonstrated absent and impaired Gαq/11 signal transduction by Pro282Arg and Tyr323Cys mutants, respectively. Pretreatment with the membrane permeant GnRHR antagonist NBI-42902, which rescues cell surface expression of many GNRHR1 mutants, significantly increased the levels of radioligand binding and intracellular signaling of the Tyr323Cys mutant but not Pro282Arg. Immunocytochemistry confirmed that both mutants are present on the cell membrane albeit at low levels. Together these molecular deficiencies of the two novel GNRHR1 mutations lead to the CHH phenotype when present as a compound heterozygote

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

The Homeodomain Derived Peptide Penetratin Induces Curvature of Fluid Membrane Domains

BACKGROUND:Protein membrane transduction domains that are able to cross the plasma membrane are present in several transcription factors, such as the homeodomain proteins and the viral proteins such as Tat of HIV-1. Their discovery resulted in both new concepts on the cell communication during development, and the conception of cell penetrating peptide vectors for internalisation of active molecules into cells. A promising cell penetrating peptide is Penetratin, which crosses the cell membranes by a receptor and metabolic energy-independent mechanism. Recent works have claimed that Penetratin and similar peptides are internalized by endocytosis, but other endocytosis-independent mechanisms have been proposed. Endosomes or plasma membranes crossing mechanisms are not well understood. Previously, we have shown that basic peptides induce membrane invaginations suggesting a new mechanism for uptake, "physical endocytosis". METHODOLOGY/PRINCIPAL FINDINGS:Herein, we investigate the role of membrane lipid phases on Penetratin induced membrane deformations (liquid ordered such as in "raft" microdomains versus disordered fluid "non-raft" domains) in membrane models. Experimental data show that zwitterionic lipid headgroups take part in the interaction with Penetratin suggesting that the external leaflet lipids of cells plasma membrane are competent for peptide interaction in the absence of net negative charges. NMR and X-ray diffraction data show that the membrane perturbations (tubulation and vesiculation) are associated with an increase in membrane negative curvature. These effects on curvature were observed in the liquid disordered but not in the liquid ordered (raft-like) membrane domains. CONCLUSIONS/SIGNIFICANCE:The better understanding of the internalisation mechanisms of protein transduction domains will help both the understanding of the mechanisms of cell communication and the development of potential therapeutic molecular vectors. Here we showed that the membrane targets for these molecules are preferentially the fluid membrane domains and that the mechanism involves the induction of membrane negative curvature. Consequences on cellular uptake are discussed

TRBP and eIF6 Homologue in Marsupenaeus japonicus Play Crucial Roles in Antiviral Response

Plants and invertebrates can suppress viral infection through RNA silencing, mediated by RNA-induced silencing complex (RISC). Trans-activation response RNA-binding protein (TRBP), consisting of three double-stranded RNA-binding domains, is a component of the RISC. In our previous paper, a TRBP homologue in Fenneropenaeus chinensis (Fc-TRBP) was reported to directly bind to eukaryotic initiation factor 6 (Fc-eIF6). In this study, we further characterized the function of TRBP and the involvement of TRBP and eIF6 in antiviral RNA interference (RNAi) pathway of shrimp. The double-stranded RNA binding domains (dsRBDs) B and C of the TRBP from Marsupenaeus japonicus (Mj-TRBP) were found to mediate the interaction of TRBP and eIF6. Gel-shift assays revealed that the N-terminal of Mj-TRBP dsRBD strongly binds to double-stranded RNA (dsRNA) and that the homodimer of the TRBP mediated by the C-terminal dsRBD increases the affinity to dsRNA. RNAi against either Mj-TRBP or Mj-eIF6 impairs the dsRNA-induced sequence-specific RNAi pathway and facilitates the proliferation of white spot syndrome virus (WSSV). These results further proved the important roles of TRBP and eIF6 in the antiviral response of shrimp