Novel dimeric β-helical model of an ice nucleation protein with bridged active sites

<p>Abstract</p> <p>Background</p> <p>Ice nucleation proteins (INPs) allow water to freeze at high subzero temperatures. Due to their large size (>120 kDa), membrane association, and tendency to aggregate, an experimentally-determined tertiary structure of an INP has yet to be reported. How they function at the molecular level therefore remains unknown.</p> <p>Results</p> <p>Here we have predicted a novel β-helical fold for the INP produced by the bacterium <it>Pseudomonas borealis</it>. The protein uses internal serine and glutamine ladders for stabilization and is predicted to dimerize via the burying of a solvent-exposed tyrosine ladder to make an intimate hydrophobic contact along the dimerization interface. The manner in which <it>Pb</it>INP dimerizes also allows for its multimerization, which could explain the aggregation-dependence of INP activity. Both sides of the <it>Pb</it>INP structure have tandem arrays of amino acids that can organize waters into the ice-like clathrate structures seen on antifreeze proteins.</p> <p>Conclusions</p> <p>Dimerization dramatically increases the 'ice-active' surface area of the protein by doubling its width, increasing its length, and presenting identical ice-forming surfaces on both sides of the protein. We suggest that this allows sufficient anchored clathrate waters to align on the INP surface to nucleate freezing. As <it>Pb</it>INP is highly similar to all known bacterial INPs, we predict its fold and mechanism of action will apply to these other INPs.</p

Exploring Ecodynamics of Coastal Foragers Using Integrated Faunal Records from Čḯxwicən Village (Strait of Juan de Fuca, Washington, U.S.A.)

Extensive 2004 excavation of Čḯxwicən (pronounced ch-WHEET-son), traditional home of the Lower Elwha Klallam Tribe in northwest Washington State, U.S.A., documented human occupation spanning the last 2700 years with fine geo-stratigraphic control and 102 radiocarbon samples. Remains of multiple plankhouses were documented. Occupation spans large-magnitude earthquakes, periods of climate change, and change in nearshore habitat. Our project began in 2012 as a case study to explore the value of human ecodynamics in explaining change and stability in human-animal relationships on the Northwest Coast through analysis of faunal and geo-archaeological records. Field sampling was explicitly designed to allow for integration of all faunal classes (birds, fish, mammals, and invertebrates), thus facilitating our ability to track how different taxa were affected by external factors and cultural processes. With over one million specimens, the faunal assemblage represents one of the largest on the North Pacific Coast. Invertebrate records reveal striking changes in intertidal habitat that are linked to the formation of the sheltered harbor and catastrophic events such as tsunamis. Analysis suggests a high level of consistency in the structure of resource use (evenness and richness) across 2150 years of occupation, despite increase in intensity of human use and a shift to plankhouse occupation. Trends in fish and invertebrate representation do not correspond to changing ocean conditions, while changes in abundance of herring, salmon, burrowing bivalves and urchins are consistent with impacts from tsunamis. Comparison of resource use between two well-sampled houses before and after one tsunami suggests that while both households were resilient, they negotiated the event in different ways

Exploring ecodynamics of coastal foragers using integrated faunal records from Čix\u3csup\u3ew\u3c/sup\u3eicən village (Strait of Juan de Fuca, Washington, U.S.A.)

Extensive 2004 excavation of Čḯxwicən (pronounced ch-WHEET-son), traditional home of the Lower Elwha Klallam Tribe in northwest Washington State, U.S.A., documented human occupation spanning the last 2700 years with fine geo-stratigraphic control and 102 radiocarbon samples. Remains of multiple plankhouses were documented. Occupation spans large-magnitude earthquakes, periods of climate change, and change in nearshore habitat. Our project began in 2012 as a case study to explore the value of human ecodynamics in explaining change and stability in human-animal relationships on the Northwest Coast through analysis of faunal and geo-archaeological records. Field sampling was explicitly designed to allow for integration of all faunal classes (birds, fish, mammals, and invertebrates), thus facilitating our ability to track how different taxa were affected by external factors and cultural processes. With over one million specimens, the faunal assemblage represents one of the largest on the North Pacific Coast. Invertebrate records reveal striking changes in intertidal habitat that are linked to the formation of the sheltered harbor and catastrophic events such as tsunamis. Analysis suggests a high level of consistency in the structure of resource use (evenness and richness) across 2150 years of occupation, despite increase in intensity of human use and a shift to plankhouse occupation. Trends in fish and invertebrate representation do not correspond to changing ocean conditions, while changes in abundance of herring, salmon, burrowing bivalves and urchins are consistent with impacts from tsunamis. Comparison of resource use between two well-sampled houses before and after one tsunami suggests that while both households were resilient, they negotiated the event in different ways

The Čḯxwicən Project of Northwest Washington State, U.S.A.: Opportunity Lost, Opportunity Found

Čḯxwicən (pronounced ch-WHEET-son) is a 2700 year-old ancestral village of the Lower Elwha Klallam Tribe (LEKT), located on the northwest coast of Washington State, U.S.A. The Čḯxwicən project has scientific values that broadly contribute to research in human ecodynamics and maritime foragers, given the scale of the project, excavation methods, and enormous quantities of faunal materials recovered. The village holds great significance to the LEKT as their traditional village, which includes a sacred burial ground. The project began under challenging circumstances, when the village was inadvertently encountered during a construction project, incurring huge political, social and financial costs. Commitment by the LEKT and Čḯxwicən scholars and other partners turned an “opportunity lost” into an “opportunity found.” This paper provides background to this remarkable site and project goals that guided the Čḯxwicən research project. The Special Issue papers showcase project results, including reflections by tribal members. Overall, the project shows the potential for archaeology and heritage to support reconciliation between tribes and archaeologists and broader society

Using Bone Fragmentation Records to Investigate Coastal Human Ecodynamics: A Case Study From Čḯxwicən (Washington State, USA)

Coastal shell middens are known for their generally excellent preservation and abundant identifiable faunal remains, including delicate fish and bird bones that are often rare or poorly preserved at non-shell midden sites. Thus, when we began our human ecodynamics research project focused on the fauna from Čḯxwicən (45CA523, pronounced ch-WHEET-son), a large ancestral village of the Lower Elwha Klallam Tribe, located on the shore of the Strait of Juan de Fuca, Port Angeles, Washington (USA), we anticipated generally high levels of bone identifiability. We quickly realized that the mammal bones were more fragmented and less identifiable than we had expected, though this was not the case with the bird and fish bone or invertebrate remains. To better understand why this fragmentation occurred at Čḯxwicən, we evaluate numerous hypotheses, including both post-depositional and behavioral explanations. We conclude that multiple factors intersected (to varying degrees) to produce the extreme bone fragmentation and low identifiability of mammal bones at the site, including bone fuel use, marrow extraction, grease rendering, tool production, and post-depositional breakdown. Using a human ecodynamics framework, we further consider how both social factors and external environmental forces may mediate human choices, such as the economic decision to use bone for fuel or render bone grease. We place our findings from Čḯxwicən in a regional context and discuss the potential of the approach for other coastal archaeological sites worldwide

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice.

In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state-of-the-science regarding mTOR inhibitor-associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2-78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR-associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high-dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop

Association of Over-The-Counter Pharmaceutical Sales with Influenza-Like-Illnesses to Patient Volume in an Urgent Care Setting

We studied the association between OTC pharmaceutical sales and volume of patients with influenza-like-illnesses (ILI) at an urgent care center over one year. OTC pharmaceutical sales explain 36% of the variance in the patient volume, and each standard deviation increase is associated with 4.7 more patient visits to the urgent care center (p<0.0001). Cross-correlation function analysis demonstrated that OTC pharmaceutical sales are significantly associated with patient volume during non-flu season (p<0.0001), but only the sales of cough and cold (p<0.0001) and thermometer (p<0.0001) categories were significant during flu season with a lag of two and one days, respectively. Our study is the first study to demonstrate and measure the relationship between OTC pharmaceutical sales and urgent care center patient volume, and presents strong evidence that OTC sales predict urgent care center patient volume year round. © 2013 Liu et al

A systematic review of school-based sexual health interventions to prevent STI/HIV in sub-Saharan Africa

Background The HIV/AIDS epidemic remains of global significance and there is a need to target (a) the adolescent age-groups in which most new infections occur; and (b) sub-Saharan Africa where the greatest burden of the epidemic lies. A focused systematic review of school-based sexual health interventions in sub-Saharan Africa to prevent HIV/AIDS and Sexually Transmitted Infections (STI) in this age group was therefore conducted. Methods Searches were conducted in Medline, Embase, Cinahl and PsychINFO according to agreed a priori criteria for studies published between 1986 and 2006. Further searches were conducted in UNAIDS and WHO (World Health Organization) websites, and 'Google'. Relevant journals were hand-searched and references cited in identified articles were followed up. Data extraction and quality assessment was carried out on studies selected for full text appraisal, and results were analysed and presented in narrative format. Results Some 1,020 possible titles and abstracts were found, 23 full text articles were critically appraised, and 12 articles (10 studies) reviewed, reflecting the paucity of published studies conducted relative to the magnitude of the HIV epidemic in sub-Saharan Africa. Knowledge and attitude-related outcomes were the most associated with statistically significant change. Behavioural intentions were more difficult to change and actual behaviour change was least likely to occur. Behaviour change in favour of abstinence and condom use appeared to be greatly influenced by pre-intervention sexual history. Conclusion There is a great need in sub-Saharan Africa for well-evaluated and effective school-based sexual health interventions

Webinar Training: an acceptable, feasible and effective approach for multi-site medical record abstraction: the BOWII experience

<p>Abstract</p> <p>Background</p> <p>Abstractor training is a key element in creating valid and reliable data collection procedures. The choice between in-person vs. remote or simultaneous vs. sequential abstractor training has considerable consequences for time and resource utilization. We conducted a web-based (webinar) abstractor training session to standardize training across six individual Cancer Research Network (CRN) sites for a study of breast cancer treatment effects in older women (BOWII). The goals of this manuscript are to describe the training session, its participants and participants' evaluation of webinar technology for abstraction training.</p> <p>Findings</p> <p>A webinar was held for all six sites with the primary purpose of simultaneously training staff and ensuring consistent abstraction across sites. The training session involved sequential review of over 600 data elements outlined in the coding manual in conjunction with the display of data entry fields in the study's electronic data collection system. Post-training evaluation was conducted via Survey Monkey^©. Inter-rater reliability measures for abstractors within each site were conducted three months after the commencement of data collection.</p> <p>Ten of the 16 people who participated in the training completed the online survey. Almost all (90%) of the 10 trainees had previous medical record abstraction experience and nearly two-thirds reported over 10 years of experience. Half of the respondents had previously participated in a webinar, among which three had participated in a webinar for training purposes. All rated the knowledge and information delivered through the webinar as useful and reported it adequately prepared them for data collection. Moreover, all participants would recommend this platform for multi-site abstraction training. Consistent with participant-reported training effectiveness, results of data collection inter-rater agreement within sites ranged from 89 to 98%, with a weighted average of 95% agreement across sites.</p> <p>Conclusions</p> <p>Conducting training via web-based technology was an acceptable and effective approach to standardizing medical record review across multiple sites for this group of experienced abstractors. Given the substantial time and cost savings achieved with the webinar, coupled with participants' positive evaluation of the training session, researchers should consider this instructional method as part of training efforts to ensure high quality data collection in multi-site studies.</p