Major Fallacies Surrounding Stone Artifacts and Assemblages

While lithic objects can potentially inform us about past adaptations and behaviors, it is important to develop a comprehensive understanding of all of the various processes that influence what we recover from the archaeological record. We argue here that many assumptions used by archaeologists to derive behavioral inferences through the definition, conceptualization, and interpretation of both individual stone artifact forms and groups of artifacts identified as assemblages do not fit squarely with what we have learned from both ethnographic sources and analyses of archaeological materials. We discuss this in terms of two fallacies. The first is the fallacy of the “desired end product” in stone artifact manufacture, which also includes our ability to recognize such end products. The second fallacy has to do with the notions that lithic assemblages represent simple accumulations of contemporary behaviors and the degree to which the composition of the depositional units we study reliably match the kinds of activities that took place. Although it is beyond the scope of this paper to offer a comprehensive set of new methodologies and theoretical perspectives to solve these problems, our goal here is to stress the importance of rethinking some of our most basic assumptions regarding the nature of lithic objects and how they become part of the archaeological record. Such a revision is needed if we want to be able to develop research questions that can be addressed with the data we have available to us

The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR

Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl−-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by activating adenylate cyclase and we show that Ca2+-stimulated type I adenylate cyclase is expressed in the developing human lung. Together, these observations suggest that physiological fetal hypercalcemia, acting on the CaSR, promotes human fetal lung development via cAMP-dependent opening of CFTR. Disturbances in this process would be expected to permanently impact lung structure and might predispose to certain postnatal respiratory disease

Breast cancer in lesbians and bisexual women: Systematic review of incidence, prevalence and risk studies

This article is made available through the Brunel Open Access Publishing Fund. © 2013 Meads and Moore; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The UK Parliamentary Enquiry and USA Institute of Medicine state that lesbians may be at a higher risk of breast cancer but there is insufficient information. Lesbians and bisexual (LB) women have behavioural risk-factors at higher rates compared to heterosexuals such as increased alcohol intake and higher stress levels. Conversely, breast cancer rates are higher in more affluent women yet income levels in LB women are relatively low. This systematic review investigated all evidence on whether there is, or likely to be, higher rates of breast cancer in LB women. Methods: Cochrane library (CDSR, CENTRAL, HTA, DARE, NHSEED), MEDLINE, EMBASE, PsychINFO, CAB abstracts, Web of Science (SCI, SSCI), SIGLE and Social Care Online databases were searched to October 2013. Unpublished research and specific lesbian, gay and bisexual websites were checked, as were citation lists of relevant papers. Included were studies in LB populations reporting breast cancer incidence or prevalence rates, risk model results or risk-factor estimates. Inclusions, data-extraction and quality assessment were by two reviewers with disagreements resolved by discussion. Results: Searches found 198 references. No incidence rates were found. Nine studies gave prevalence estimates - two showed higher, four showed no differences, one showed mixed results depending on definitions, one had no comparison group and one gave no sample size. All studies were small with poor methodological and/or reporting quality. One incidence modelling study suggested a higher rate. Four risk modelling studies were found, one Rosner-Colditz and three Gail models. Three suggested higher and one lower rate in LB compared to heterosexual women. Six risk-factor estimates suggested higher risk and one no difference between LB and heterosexual women. Conclusions: The only realistic way to establish rates in LB women would be to collect sexual orientation within routine statistics, including cancer registry data, or from large cohort studies

2012 Wild Blueberry Project Reports

The 2012 edition of the Wild Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Do wild blueberries alleviate risk factors related to the Metabolic Syndrome? 2. Development of effective intervention measures to maintain and improve food safety for wild blueberries 3. Control tactics for blueberry pest insects, 2012 4. Development and implementation of a wild blueberry thrips IPM program, 2012 5. IPM 6. Biology of blueberry and pest insects, 2012 7. Biology of beneficial insects and blueberry pollination, 2012 8. Pesticide residues on lowbush blueberry, 2012 9. Maine wild blueberry –mummy berry research and extension 10. Efficacy of Apogee growth regulator for stimulating rhizome growth into bare spots in wild blueberry fields 11. Velpar by Matrix pre and post-emergence applications - demonstration plots 12. Wild blueberry Extension Education Program in 2012 INPUT SYSTEMS STUDY: 13. Systems approach to improving the sustainability of wild blueberry production, Year Three of a four-year study – experimental design 14. Food safety- Prevalence study of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella spp. on lowbush blueberries (Vaccinium angustifolium) 15. Abundance of insect pest species and natural enemies in lowbush blueberry fields maintained under different management practices 16. Input Systems Study: Systems approach to improving the sustainability of wild blueberry production, Year 3 of a four-year study, disease management results 17. Plant productivity, Year Three of a four-year study 18. Systems approach to improving the sustainability of wild blueberry production, Year Three of a four-year study, weed management results 19. Effects of organic and conventional management systems on the phosphorus solubility of lowbush blueberry barren soils 20. Systems approach to improving sustainability of wild blueberry production – soil health and chemistry measures 21. Evaluation of fungicides for control of mummy berry disease (ancillary study) 22. Systems approach to improving the sustainability of wild blueberry production – Ancillary land-leveling study, Year Two of a four-year study (ancillary study) 23. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2012 results from the 2011 trial (ancillary study) 24. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2012 trial (ancillary study) 25. Evaluation of herbicides for control of fineleaf sheep fescue for grass control in wild blueberries (ancillary study) 26. Pre-emergence application timing and rate of Alion and Sandea in combination with Velpar or Sinbar on weed control and injury to wild blueberry (ancillary study) 27. Compost and mulch effects on soil health and nutrient dynamics in wild blueberry (ancillary study

Falls and mobility in Parkinson's disease: protocol for a randomised controlled clinical trial

Background Although physical therapy and falls prevention education are argued to reduce falls and disability in people with idiopathic Parkinson\u27s disease, this has not yet been confirmed with a large scale randomised controlled clinical trial. The study will investigate the effects on falls, mobility and quality of life of (i) movement strategy training combined with falls prevention education, (ii) progressive resistance strength training combined with falls prevention education, (iii) a generic life-skills social program (control group). Methods/Design People with idiopathic Parkinson\u27s disease who live at home will be recruited and randomly allocated to one of three groups. Each person shall receive therapy in an out-patient setting in groups of 3-4. Each group shall be scheduled to meet once per week for 2 hours for 8 consecutive weeks. All participants will also have a structured 2 hour home practice program for each week during the 8 week intervention phase. Assessments will occur before therapy, after the 8 week therapy program, and at 3 and 12 months after the intervention. A falls calendar will be kept by each participant for 12 months after outpatient therapy. Consistent with the recommendations of the Prevention of Falls Network Europe group, three falls variables will be used as the primary outcome measures: the number of fallers, the number of multiple fallers and the falls rate. In addition to quantifying falls, we shall measure mobility, activity limitations and quality of life as secondary outcomes. Discussion This study has the potential to determine whether outpatient movement strategy training combined with falls prevention education or progressive resistance strength training combined with falls prevention education are effective for reducing falls and improving mobility and life quality in people with Parkinson\u27s disease who live at home

Amplification and demultiplexing in insulin-regulated Akt protein kinase pathway in adipocytes.

Akt plays a major role in insulin regulation of metabolism in muscle, fat, and liver. Here, we show that in 3T3-L1 adipocytes, Akt operates optimally over a limited dynamic range. This indicates that Akt is a highly sensitive amplification step in the pathway. With robust insulin stimulation, substantial changes in Akt phosphorylation using either pharmacologic or genetic manipulations had relatively little effect on Akt activity. By integrating these data we observed that half-maximal Akt activity was achieved at a threshold level of Akt phosphorylation corresponding to 5-22% of its full dynamic range. This behavior was also associated with lack of concordance or demultiplexing in the behavior of downstream components. Most notably, FoxO1 phosphorylation was more sensitive to insulin and did not exhibit a change in its rate of phosphorylation between 1 and 100 nm insulin compared with other substrates (AS160, TSC2, GSK3). Similar differences were observed between various insulin-regulated pathways such as GLUT4 translocation and protein synthesis. These data indicate that Akt itself is a major amplification switch in the insulin signaling pathway and that features of the pathway enable the insulin signal to be split or demultiplexed into discrete outputs. This has important implications for the role of this pathway in disease

2013 Wild Blueberry Project Reports

The 2013 edition of the Wild Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Development of effective intervention measures to maintain and improve food safety for wild blueberries 2. Do wild blueberries alleviate risk factors related to the Metabolic Syndrome? 3. Wild Blueberry consumption and exercise-induced Oxidative Stress: Inflammatory Response and DNA damage 4. Control tactics for blueberry pest insects, 2013 5. Pesticide residues on wild blueberry, 2013 6. Biology of pest insects and IPM, 2013 7. Biology of blueberry, beneficial insects, and blueberry pollination 8. Biology of spotted wing drosophila, 2013 9. Maine wild blueberry –mummy berry research and extension 10. Evaluation of fungicides for control of mummy berry on lowbush blueberry (2013) 11. Wild blueberry Extension Education Program in 2013 INPUT SYSTEMS STUDY: 12. Systems approach to improving the sustainability of wild blueberry production, Year Four of a four-year study – experimental design 13. Food safety- Prevalence study of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella spp. on lowbush blueberries (Vaccinium angustifolium) 14. Agronomic input effects on sensory quality and chemical composition of wild Maine blueberries 15. Systems approach to improving the sustainability of wild blueberry production, Year four of a four-year study – reports from Frank Drummond 16. Systems approach to improving the sustainability of wild blueberry production, Year 4 of a four-year study, disease management results 17. Systems approach to improving the sustainability of wild blueberry production, Year Four of a four-year study, weed management results 18. Phosphorus and organic matter interactions on short-range ordered minerals in acidic barren soils 19. Systems approach to improving the sustainability of wild blueberry production, preliminary economic comparison for 2012-13 20. Ancillary projects in disease research (ancillary study) 21. Systems approach to improving the sustainability of wild blueberry production – Ancillary land-leveling study, Year Three of a four-year study (ancillary study) 22. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2013 results from the 2012 trial (ancillary study) 23. Evaluation of herbicides for 2012 prune year control of fineleaf sheep fescue in wild blueberries – 2013 crop year results (ancillary study) 24. 2012 pre-emergence application timing and rate of Alion and Sandea in combination with Velpar or Sinbar – 2013 yields (ancillary study) 25. Pre-emergence Sinbar combinations for weed control in a non-crop wild blueberry field – 2012-2014 (ancillary study) 26. Evaluation of three pre-emergence herbicides alone and in combination with Velpar or Sinbar for effects on wild blueberry productivity and weed control (ancillary study) 27. Post-harvest control of red sorrel in a non-crop blueberry field, 2012-2014 (ancillary study) 28. Compost and mulch effects on soil health and nutrient dynamics in wild blueberry (ancillary study) 29. Evaluation of conventional and organic fertilizers on blueberry growth and yield (ancillary study

Endoplasmic reticulum stress and cell death in mTORC1-overactive cells is induced by nelfinavir and enhanced by chloroquine

Inappropriate activation of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is common in cancer and has many cellular consequences including elevated endoplasmic reticulum (ER) stress. Cells employ autophagy as a critical compensatory survival mechanism during ER stress. This study utilised drug-induced ER stress through nelfinavir in order to examine ER stress tolerance in cell lines with hyper-active mTORC1 signalling. Our initial findings in wild type cells showed nelfinavir inhibited mTORC1 signalling and upregulated autophagy, as determined by decreased rpS6 and S6K1 phosphorylation, and SQTSM1 protein expression, respectively. Contrastingly, cells with hyper-active mTORC1 displayed basally elevated levels of ER stress which was greatly exaggerated following nelfinavir treatment, seen through increased CHOP mRNA and XBP1 splicing. To further enhance the effects of nelfinavir, we introduced chloroquine as an autophagy inhibitor. Combination of nelfinavir and chloroquine significantly increased ER stress and caused selective cell death in multiple cell line models with hyper-active mTORC1, whilst control cells with normalised mTORC1 signalling tolerated treatment. By comparing chloroquine to other autophagy inhibitors, we uncovered that selective toxicity invoked by chloroquine was independent of autophagy inhibition yet entrapment of chloroquine to acidified lysosomal/endosomal compartments was necessary for cytotoxicity. Our research demonstrates that combination of nelfinavir and chloroquine has therapeutic potential for treatment of mTORC1-driven tumours

Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.

Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium. Antagonistically, ESX-1 is also essential to block the autophagic flux and deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize to the MCV in an ESX-1-dependent manner, suggesting an important role in the manipulation of autophagy by mycobacteria. Our findings suggest that the infection by M. marinum activates an autophagic response that is simultaneously repressed and exploited by the bacterium to support its survival inside the MCV