2,068 research outputs found

    The SALFORD low-energy house : Learning from our past

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    The SALFORD low-energy house was designed in the late 1970s for Salford City Council in a joint project with the University. A semi-detached experimental pair and a prototype terrace of six mixed dwellings were built and extensively monitored. The results showed substantial energy savings and occupant satisfaction. To mark the University’s focus upon the cross-cutting themes of Energy and Social Justice a new study was launched in 2010 to explore the long-term performance of the SALFORD dwellings

    pH Biosensing by PI4P Regulates Cargo Sorting at the TGN

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    Phosphoinositides, diacylglycerolpyrophosphate, ceramide-1-phosphate, and phosphatidic acid belong to a unique class of membrane signaling lipids that contain phosphomonoesters in their headgroups having pKa values in the physiological range. The phosphomonoester headgroup of phosphatidic acid enables this lipid to act as a pH biosensor as changes in its protonation state with intracellular pH regulate binding to effector proteins. Here, we demonstrate that binding of pleckstrin homology (PH) domains to phosphatidylinositol 4-phosphate (PI4P) in the yeast trans-Golgi network (TGN) is dependent on intracellular pH, indicating PI4P is a pH biosensor. pH biosensing by TGN PI4P in response to nutrient availability governs protein sorting at the TGN, likely by regulating sterol transfer to the TGN by Osh1, a member of the conserved oxysterol-binding protein (OSBP) family of lipid transfer proteins. Thus, pH biosensing by TGN PI4P allows for direct metabolic regulation of protein trafficking and cell growth

    Maternal concentration of polychlorinated biphenyls and dichlorodiphenyl dichlorethylene and birth weight in Michigan fish eaters: a cohort study

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    BACKGROUND: Studies on maternal exposure to polychlorinated biphenyls (PCBs) reported inconsistent findings regarding birth weight: some studies showed no effect, some reported decreased birth weight, and one study found an increase in weights. These studies used different markers of exposure, such as measurement of PCBs in maternal serum or questionnaire data on fish consumption. Additionally maternal exposures, such as dichlorodiphenyl-dichloroethylene (DDE), which are related to PCB exposure and may interfere with the PCB effect, were rarely taken into account. METHODS: Between 1973 and 1991, the Michigan Department of Community Health conducted three surveys to assess PCB and DDE serum concentrations in Michigan anglers. Through telephone interviews with parents, we gathered information on the birth characteristics of their offspring, focusing on deliveries that occurred after 1968. We used the maternal organochlorine (OC) measurement closest to the date of delivery as the exposure. Although one mother may have contributed more than one child, serum concentrations derived from measurements in different surveys could vary for different children from the same mother. The maternal DDE and PCB serum concentrations were categorized as follows: 0 -< 5 microg / L, 5 -< 15 microg / L, 15 -< 25 microg / L, ≥25 microg / L. Using repeated measurement models (Generalized Estimation Equation), we estimated the adjusted mean birth weight controlling for gender, birth order, gestational age, date of delivery as well as maternal age, height, education, and smoking status. RESULTS: We identified 168 offspring who were born after 1968 and had maternal exposure information. We found a reduced birth weight for the offspring of mothers who had a PCB concentration ≥25 microg / L (adjusted birth weight = 2,958 g, p = 0.022). This group, however, was comprised of only seven observations. The association was not reduced when we excluded preterm deliveries. The birth weight of offspring was increased in women with higher DDE concentrations when controlling for PCBs; however, this association was not statistically significant. CONCLUSION: Our results contribute to the body of evidence that high maternal serum PCB concentration may reduce the birth weight in offspring. However, only a small proportion of mothers may actually be exposed to PCB concentrations ≥25 microg / L

    ACSM Expert Consensus Statement on Weight Loss in Weight-Category Sports

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    Weight-category sports are defined by the requirement of a weigh-in before competition to provide performance equity and reduced injury risks by eliminating size discrepancies. Athletes in these sports try to gain a theoretical advantage by competing in weight divisions that are lower than their day-to-day body mass (BM), using a combination of chronic strategies (body-fat losses) and acute manipulations over a period of hours to days before weigh-in ("making weight"). Strategies to support safer practices include minimal competition weight classification based on preseason body composition, reductions in the period between weigh-in and competition, and prohibition of unhealthy weight loss techniques. At an individual level, expert guidance by a sports nutrition professional can help an athlete to establish a pragmatic and long-term approach to BM management, recognizing the nuances of their sport, to achieve favorable outcomes for both health and performance

    Role of the mesoamygdaloid dopamine projection in emotional learning

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    Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

    Examining assumptions regarding valid electronic monitoring of medication therapy: development of a validation framework and its application on a European sample of kidney transplant patients

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    BACKGROUND: Electronic monitoring (EM) is used increasingly to measure medication non-adherence. Unbiased EM assessment requires fulfillment of assumptions. The purpose of this study was to determine assumptions needed for internal and external validity of EM measurement. To test internal validity, we examined if (1) EM equipment functioned correctly, (2) if all EM bottle openings corresponded to actual drug intake, and (3) if EM did not influence a patient's normal adherence behavior. To assess external validity, we examined if there were indications that using EM affected the sample representativeness. METHODS: We used data from the Supporting Medication Adherence in Renal Transplantation (SMART) study, which included 250 adult renal transplant patients whose adherence to immunosuppressive drugs was measured during 3 months with the Medication Event Monitoring System (MEMS). Internal validity was determined by assessing the prevalence of nonfunctioning EM systems, the prevalence of patient-reported discrepancies between cap openings and actual intakes (using contemporaneous notes and interview at the end of the study), and by exploring whether adherence was initially uncharacteristically high and decreased over time (an indication of a possible EM intervention effect). Sample representativeness was examined by screening for differences between participants and non-participants or drop outs on non-adherence. RESULTS: Our analysis revealed that some assumptions were not fulfilled: 1) one cap malfunctioned (0.4%), 2) self-reported mismatches between bottle openings and actual drug intake occurred in 62% of the patients (n = 155), and 3) adherence decreased over the first 5 weeks of the monitoring, indicating that EM had a waning intervention effect. CONCLUSION: The validity assumptions presented in this article should be checked in future studies using EM as a measure of medication non-adherence

    Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

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    Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site

    Macroalgal morphogenesis induced by waterborne compounds and bacteria in coastal seawater

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    Axenic gametes of the marine green macroalga Ulva mutabilis Foyn (Ria Formosa, locus typicus) exhibit abnormal development into slow-growing callus-like colonies with aberrant cell walls. Under laboratory conditions, it was previously demonstrated that all defects in growth and thallus development can be completely abolished when axenic gametes are inoculated with a combination of two specific bacterial strains originally identified as Roseo-bacter sp. strain MS2 and Cytophaga sp. strain MS6. These bacteria release diffusible morphogenetic compounds (= morphogens), which act similar to cytokinin and auxin. To investigate the ecological relevance of the waterborne bacterial morphogens, seawater samples were collected in the Ria Formosa lagoon (Algarve, Southern Portugal) at 20 sampling sites and tidal pools to assess their morphogenetic effects on the axenic gametes of U. mutabilis. Specifically the survey revealed that sterile-filtered seawater samples can completely recover growth and morphogenesis of U. mutabilis under axenic conditions. Morphogenetic activities of free-living and epiphytic bacteria isolated from the locally very abundant Ulva species (i.e., U. rigida) were screened using a multiwell-based testing system. The most represented genera isolated from U. rigida were Alteromonas, Pseudoalteromonas and Sulfitobacter followed by Psychrobacter and Polaribacter. Several naturally occurring bacterial species could emulate MS2 activity (= induction of cell divisions) regardless of taxonomic affiliation, whereas the MS6 activity (= induction of cell differentiation and cell wall formation) was species-specific and is probably a feature of difficult-to-culture bacteria. Interestingly, isolated bacteroidetes such as Algoriphagus sp. and Polaribacter sp. could individually trigger complete Ulva morphogenesis and thus provide a novel mode of action for bacterial-induced algal development. This study also highlights that the accumulation of algal growth factors in a shallow water body separated from the open ocean by barrier islands might have strong implications to, for example, the wide usage of natural coastal seawater in algal (land based) aquacultures of Ulva
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