“Templatic backcopying” in Guarijio abbreviated reduplication

Although a wide array of phonological properties seem to backcopy in reduplication, it is an open question whether reduplicative templates can backcopy as well. It has been argued that natural languages do not have reduplicative constructions where the base truncates to match the truncated reduplicant (McCarthy & Prince, 1994; McCarthy & Prince, 1999; Spaelti, 1997; inter alia). In Guarijio Abbreviated Reduplication (Miller, 1996), however, both copies of the reduplicative construction truncate, instantiating the pattern that has been claimed not to exist. This paper argues that the Guarijio case fills this typological gap. Although the data can be given a templatic backcopying analysis, this paper defends a Morphological Doubling Theory (MDT) analysis using cophonologies (Inkelas & Zoll, 2005). In MDT, Guarijio Abbreviated Reduplication results from the parallel imposition of a truncating cophonology in each copy of the reduplicative construction. Guarijio Abbreviated Reduplication is predicted to exist by MDT together with other documented cases of parallel phonological modification in reduplication. I am grateful to many people for helpful comments and suggestions, including Isabel Barreras Aguilar, Laura Downing, Nicholas Fleisher, Andrew Garrett, Jason Haugen, Larry Hyman, Yuni Kim, Teresa McFarland, David Mortensen, Mary Paster, Eric Raimy, and Timothy Thornes as well as the audience of the LSA 2005 Annual Meeting in Oakland. I would like to extend a special thanks to Alan Yu for his detailed comments and suggestions to latter versions of this paper. I am particularly indebted to Sharon Inkelas, for her generous advice, feedback, and numerous discussions throughout the development of this paper. I am also grateful to two anonymous reviewers for their comments and criticisms, and especially to Ingo Plag for his patience and detailed suggestions as editor. All remaining errors and omissions are mine. This study was made possible by fellowships by CONACYT (Consejo Nacional de Ciencia y Tecnología, México), the University of California Institute for Mexico and the United States (UCMEXUS) and Fulbright.     

GMP Production of Liposomes—A New Industrial Approach

A new scalable liposome production system is presented, which is based on the ethanol injection technique. The system permits liposome manufacture regardless of production scale, as scale is determined only by free disposable vessel volumes. Once the parameters are defined, an easy scale up can be performed by just changing the process vessels. These vessels are fully sterilizeable and all raw materials are transferred into the sanitized and sterilized system via 0.2 μm filters to guarantee an aseptic production.

Liposome size can be controlled by the local lipid concentration at the injection point depending on process parameters like injection pressure, lipid concentration and injection rate. These defined process parameters are furthermore responsible for highly reproducible results with respect to vesicle diameters and encapsulation rates Compared to other technologies like the film method which is normally followed by size reduction through high pressure homogenization, ultrasonication or extrusion, no mechanical forces are needed to generate homogeneous and narrow distributed liposomes.

Another important advantage of this method is the suitability for the entrapment of many different drug substances such as large hydrophilic proteins by passive encapsulation, small amphiphilic drugs by a one step remote loading technique or membrane association of antigens for vaccination approaches     

Separate Intramolecular Targets for Protein Kinase A Control N-Methyl-d-aspartate Receptor Gating and Ca2+ Permeability

Protein kinase A (PKA) enhances synaptic plasticity in the central nervous system by increasing NMDA receptor current amplitude and Ca²⁺ flux in an isoform-dependent yet poorly understood manner. PKA phosphorylates multiple residues on GluN1, GluN2A, and GluN2B subunits in vivo, but the functional significance of this multiplicity is unknown. We examined gating and permeation properties of recombinant NMDA receptor isoforms and of receptors with altered C-terminal domain (CTDs) prior to and after pharmacological inhibition of PKA. We found that PKA inhibition decreased GluN1/GluN2B but not GluN1/GluN2A gating; this effect was due to slower rates for receptor activation and resensitization and was mediated exclusively by the GluN2B CTD. In contrast, PKA inhibition reduced NMDA receptor-relative Ca²⁺ permeability (P_Ca/P_Na) regardless of the GluN2 isoform and required the GluN1 CTD; this effect was due primarily to decreased unitary Ca²⁺ conductance, because neither Na⁺ conductance nor Ca²⁺-dependent block was altered substantially. Finally, we show that both the gating and permeation effects can be reproduced by changing the phosphorylation state of a single residue: GluN2B Ser-1166 and GluN1 Ser-897, respectively. We conclude that PKA effects on NMDA receptor gating and Ca²⁺ permeability rely on distinct phosphorylation sites located on the CTD of GluN2B and GluN1 subunits. This separate control of NMDA receptor properties by PKA may account for the specific effects of PKA on plasticity during synaptic development and may lead to drugs targeted to alter NMDA receptor gating or Ca²⁺ permeability.     

Differential Migration and Activation Profile of Monocytes after Trophoblast Interaction

Macrophages at the maternal-placental interface coordinate opposite demands under the control of trophoblast cells such as the response against pathogens on one hand, and apoptotic cell clearance and wound healing with the production of suppressor cytokines. Here, we investigated whether trophoblast cells induce maternal monocyte activation towards an alternative activated macrophage profile and whether bacterial or viral stimuli modulate their migratory properties. We used an in vitro model of the maternal-placental interface represented by co-cultures of CD14+ cells isolated from fertile women with first trimester trophoblast cell line (Swan-71 cells) in the presence or absence of pathogen associated molecular pattern (PAMP) stimuli lipopolysaccharide (LPS), peptidoglycan (PGN) or poly [I:C]). Maternal CD14+ cells showed increased CD16 and CD39 expression, both markers associated to an alternative activation profile, with no changes in CD80 expression after trophoblast cell interaction. These changes were accompanied by increased IL-10 and decreased IL-12 production by CD14+ cells. After stimulation with LPS, PGN or poly [I:C], monocytes co-cultured with trophoblast cells had lower production of TNF-α and IL-1β compared with non co-cultured monocytes. Interestingly, monocyte migration towards trophoblast cells was prevented in the presence of LPS or PGN but not after 24h of stimulation with poly [I:C]. LPS or PGN also decreased CCR5, CXCL-8 and CCL5 expression. Finally, trophoblast cells co-cultured with monocytes in the presence of pathological stimuli failed to increase chemokine expression, indicating a bidirectional effect. In conclusion, trophoblast might ‘instruct’ maternal monocytes to express an alternative activation profile and restrain their early recruitment under pathological threats as one of the first strategies to avoid potential tissue damage at the maternal-placental interface.     

Identifying biochemical phenotypic differences between cryptic species

Molecular genetic methods can distinguish divergent evolutionary lineages in what previously appeared to be single species, but it is not always clear what functional differences exist between such cryptic species. We used a metabolomic approach to profile biochemical phenotype (metabotype) differences between two putative cryptic species of the earthworm Lumbricus rubellus. There were no straightforward metabolite biomarkers of lineage, i.e. no metabolites that were always at higher concentration in one lineage. Multivariate methods, however, identified a small number of metabolites that together helped distinguish the lineages, including uncommon metabolites such as Nε-trimethyllysine, which is not usually found at high concentrations. This approach could be useful for characterizing functional trait differences, especially as it is applicable to essentially any species group, irrespective of its genome sequencing status.     

HIV Infection and Awareness among Men Who Have Sex with Men–20 Cities,United States, 2008 and 2011

Over half of HIV infections in the United States occur among men who have sex with men (MSM). Awareness of infection is a necessary precursor to antiretroviral treatment and risk reduction among HIV-infected persons. We report data on prevalence and awareness of HIV infection among MSM in 2008 and 2011, using data from 20 cities participating in the 2008 and 2011 National HIV Behavioral Surveillance System (NHBS) among MSM. Venue-based, time-space sampling was used to recruit men for interview and HIV testing. We analyzed data for men who reported ≥1 male sex partner in the past 12 months. Participants who tested positive were considered to be aware of their infection if they reported a prior positive HIV test. We used multivariable analysis to examine differences between results from 2011 vs. 2008. HIV prevalence was 19% in 2008 and 18% in 2011 (p = 0.14). In both years, HIV prevalence was highest among older age groups, blacks, and men with lower education and income. In multivariable analysis, HIV prevalence did not change significantly from 2008 to 2011 overall (p = 0.51) or in any age or racial/ethnic category (p>0.15 in each category). Among those testing positive, a greater proportion was aware of their infection in 2011 (66%) than in 2008 (56%) (p<0.001). In both years, HIV awareness was higher for older age groups, whites, and men with higher education and income. In multivariable analysis, HIV awareness increased from 2008 to 2011 overall (p<0.001) and for all age and racial/ethnic categories (p<0.01 in each category). In both years, black MSM had the highest HIV prevalence and the lowest awareness among racial/ethnic groups. These findings suggest that HIV-positive MSM are increasingly aware of their infections.     

Prefrontal deep projection neurons enable cognitive flexibility via persistent feedback monitoring

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