bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal Tracking of Histo-Blood Group Antigen Expression and Norovirus Binding in Oyster Gastrointestinal Cells
Authors: TIAN PENG , ENGELBREKTSON ANNA L. , MANDRELL ROBERT E.
Published: December 2016

Noroviruses (NORs) are the most common cause of viral gastroenteritis outbreaks. Outbreaks are often associated with the consumption of contaminated oysters and generally occur between the months of November and March, when oysters produce the highest levels of glycogen. Oyster glycogen has been proposed as playing a role in NOR accumulation. Recent research indicates that histo-blood group antigens (HBGAs) function as viral receptors on human gastrointestinal cells. In this study, oyster glycogen was tested to determine whether it contains HBGA-like molecules and whether it plays a role in NOR binding. The correlation between the amount of HBGA expression and NOR binding also was measured. We also tested whether seasonal changes affected HBGA expression and binding of recombinant NORs. The results indicate that recombinant NOR binding is highly correlated with HBGA expression in Virginica (Crassostrea virginica), Pacific (Crassostrea gigas), and Kumamato (Crassostrea sikamea) oysters, but the association does not have a seasonal pattern. No obvious trend in either HBGA expression or recombinant NOR binding by month was noted. A significant increase in recombinant NOR binding was observed in Virginica and Pacific oysters in a season not generally associated with NOR gastroenteritis outbreaks. A significant increase in HBGA expression also was observed for Pacific and Virginica oysters in the same season. Paradoxically, HBGA expression and NOR binding both were higher in oysters produced in the non–NOR gastroenteritis season (April through October) than in those produced in the NOR gastroenteritis season (November through March), suggesting that seasonal NOR gastroenteritis outbreaks are not associated with high levels of HBGA expression or NOR binding.
Antimicrobial Activity of Extracts of Edible Wild and Cultivated Mushrooms against Foodborne Bacterial Strains
Authors: VENTURINI M. E. , RIVERA C. S. , GONZALEZ C. , BLANCO D.
Published: December 2016

The antimicrobial activity of aqueous, methanol, hexane, and ethyl acetate extracts from edible wild and cultivated mushrooms against nine foodborne pathogenic bacterial strains (Escherichia coli O157:H7, Salmonella Enteritidis, Shigella sonnei, Vibrio parahaemolyticus, Yersinia enterocolitica, Bacillus cereus, Clostridium perfringens, Listeria monocytogenes, and Staphylococcus aureus) was screened with a disk diffusion assay. Twenty-nine of the 48 species tested had antimicrobial activity. Methanol, ethyl acetate, and aqueous extracts accounted for 92.8% of the positive assays, whereas the hexane extracts accounted for only 7.2%. Gram-positive bacteria were more sensitive than gram-negative bacteria to fungal extracts, and C. perfringens was the most sensitive microorganism. Aqueous extracts from Clitocybe geotropa and Lentinula edodes had the highest antimicrobial activity against all the bacterial strains tested.
Parameters for Determining Inoculated Pack/Challenge Study Protocols†,‡
Authors:   ADOPTED 20 MARCH 2009, WASHINGTON, D.C. NATIONAL ADVISORY COMMITTEE ON MICROBIOLOGICAL CRITERIA FOR FOODS
Published: December 2016

The National Advisory Committee on Microbiological Criteria for Foods developed guidelines for conducting challenge studies on pathogen inhibition and inactivation studies in a variety of foods. The document is intended for use by the food industry, including food processors, food service operators, and food retailers; federal, state, and local food safety regulators; public health officials; food testing laboratories; and process authorities. The document is focused on and limited to bacterial inactivation and growth inhibition and does not make specific recommendations with respect to public health. The Committee concluded that challenge studies should be designed considering the most current advances in methodologies, current thinking on pathogens of concern, and an understanding of the product preparation, variability, and storage conditions. Studies should be completed and evaluated under the guidance of an expert microbiologist in a qualified laboratory and should include appropriate statistical design and data analyses. This document provides guidelines for choice of microorganisms for studies, inoculum preparation, inoculum level, methods of inoculation, incubation temperatures and times, sampling considerations, and interpreting test results. Examples of appropriately designed growth inhibition and inactivation studies are provided.
Reduction of Patulin in Apple Cider by UV Radiation
Authors: DONG QINGFANG , MANNS DAVID C. , FENG GUOPING , YUE TIANLI , CHUREY JOHN J. , WOROBO RANDY W.
Published: December 2016

The presence of the mycotoxin patulin in processed apple juice and cider presents a continual challenge to the food industry as both consumer health and product quality issues. Although several methods for control and/or elimination of patulin have been proposed, no unifying method has been commercially successful for reducing patulin burdens while maintaining product quality. In the present study, exposure to germicidal UV radiation was evaluated as a possible commercially viable alternative for the reduction and possible elimination of the patulin mycotoxin in fresh apple cider. UV exposure of 14.2 to 99.4 mJ/cm2 resulted in a significant and nearly linear decrease in patulin levels while producing no quantifiable changes in the chemical composition (i.e., pH, Brix, and total acids) or organoleptic properties of the cider. For the range of UV doses tested, patulin levels decreased by 9.4 to 43.4%; the greatest reduction was achieved after less than 15 s of UV exposure. The method of UV radiation (the CiderSure 3500 system) is an easily implemented, high-throughput, and cost-effective method that offers simultaneous UV pasteurization of cider and juice products and reduction and/or elimination of patulin without unwanted alterations in the final product.
Combined Chitosan-Thyme Treatments with Modified Atmosphere Packaging on a Ready-to-Cook Poultry Product
Authors: GIATRAKOU V. , NTZIMANI A. , SAVVAIDIS I. N.
Published: December 2016

In the present study, natural antimicrobials chitosan and thyme, and their combination, were evaluated for their effect on the shelf life of a ready-to-cook (RTC) chicken-pepper kebab (skewer) stored under modified atmosphere packaging (MAP) conditions at 4 ± 0.5°C for 14 days. The following treatments were examined: control samples stored under aerobic packaging (A), samples stored under MAP (M), samples treated with 1.5% chitosan (vol/wt) and stored under MAP (M-CH), samples treated with 0.2% thyme essential oil (vol/wt) (M-T), and samples treated with 1.5% chitosan (vol/wt) and 0.2% thyme essential oil (vol/wt) and stored under MAP (M-CH-T). Treatment M-CH-T significantly affected aerobic plate counts and counts of lactic acid bacteria, Pseudomonas spp., Brochothrix thermosphacta, Enterobacteriaceae, and yeasts and molds during the entire storage period. Similarly, lipid oxidation of the RTC product was retarded (M-CH-T treatment) during storage, whereas redness was maintained in M-T, M-CH, and M-CH-T samples. Based primarily on sensory data (taste attribute), M-CH and M-T treatments extended RTC product shelf life by 6 days, whereas M-CH-T treatment resulted in a product with a shelf life of 14 days that maintained acceptable sensory characteristics (shelf life of the control was 6 days).
Survival of Salmonella and Staphylococcus aureus in Mexican Red Salsa in a Food Service Setting
Authors: FRANCO WENDY , HSU WEI-YEA , SIMONNE AMARAT H.
Published: December 2016

Mexican red salsa is one of the most common side dishes in Mexican cuisine. According to data on foodborne illnesses collected by the Centers for Disease Control and Prevention, salsa was associated with 70 foodborne illness outbreaks between 1990 and 2006. Salsa ingredients such as tomatoes, cilantro, and onions often have been implicated in foodborne illness outbreaks. Mexican-style restaurants commonly prepare a large batch of red salsa, store it at refrigeration temperatures, and then serve it at room temperature. Salmonella is one of the top etiologies in foodborne illness outbreaks associated with salsa, and our preliminary studies revealed the consistent presence of Staphylococcus aureus in restaurant salsa. In the present study, we evaluated the survival of Salmonella Enteritidis and S. aureus inoculated into restaurant-made salsa samples stored at ambient (20°C) and refrigeration (4°C) temperatures. These test temperature conditions represent best-case and worst-case scenarios in restaurant operations. Salmonella survived in all samples stored at room temperature, but S. aureus populations significantly decreased after 24 h of storage at room temperature. No enterotoxin was detected in samples inoculated with S. aureus at 6.0 log CFU/g. Both microorganisms survived longer in refrigerated samples than in samples stored at room temperature. Overall, both Salmonella and S. aureus survived a sufficient length of time in salsa to pose a food safety risk.
Potential of Pediococcus pentosaceus (L006) Isolated from Maize Leaf To Suppress Fumonisin-Producing Fungal Growth
Authors: DALIE D. K. D. , DESCHAMPS A. M. , ATANASOVA-PENICHON V. , RICHARD-FORGET F.
Published: December 2016

The present study was aimed at characterizing the ability of lactic acid bacteria isolated from maize to repress the growth of fumonisin-producing fungi. A total of 67 isolates were screened for their antifungal activity against Fusarium proliferatum and Fusarium verticillioides by using the overlay method. The most efficient antifungal isolate was identified as Pediococcus pentosaceus (L006), on the basis of physiological and biochemical characterization and 16S rRNA gene sequencing. Production of the antifungal metabolite by this isolate commenced at the end of the growth exponential phase (8 h) and reached a maximum level after a long period of incubation (120 h). The antifungal metabolites produced were shown to be heat stable, resistant to proteolytic enzyme treatments, and pH dependent. The exact chemical nature of these substances remains to be clarified.
Ethnocracy and Post-Ethnocracy in Fiji
Authors: Ramesh Sanjay
Published: December 2016

Fiji’s history is interspersed with ethnic conflict, military coups, new constitutions and democratic elections. Ethnic tensions started to increase in the 1960s and reached its peak with violent indigenous Fijian ethnic assertion in the form of military coups in 1987. Following the coup, the constitution adopted at independence was abrogated and a constitution that provided indigenous political hegemony was promulgated in 1990. However, by 1993, there were serious and irreparable divisions within the indigenous Fijian community, forcing coup leader Sitiveni Rabuka to spearhead a constitution review. The result of the review was the multiracial 1997 Constitution which failed to resolve deep seated ethnic tensions, resulting in another nationalist coup in 2000 and a mutiny at the military barracks in December of that year. Following the failed mutiny, the Commander of the Republic of the Fiji Military Forces, Voreqe Bainimarama, publicly criticised nationalist policies of the government of Prime Minister Laisenia Qarase, culminating in another military coup in 2006. The new military government started plans to de-ethnise the Fijian state and promulgated a constitution that promoted ethnic equality.Post independence Fiji is characterised by these conflicts over ethnocracy. The ethnic hegemony of indigenous Fijian chiefs is set against inter-ethnic counter hegemony. While democratic politics encourages inter-ethic alliance-building, the ethnic hegemony of the chiefs has been asserted by force. Latterly, the fragmentation of the ethnic hegemony has reconfigured inter-ethnic alliances, and the military has emerged as a vehicle for de-ethnicisation. The article analyses this cyclical pattern of ethnic hegemony and multiethnic counter hegemony as a struggle over (and against) Fijian ethnocracy.
Factors Differentiating Research Involvement among Faculty Members: A Perspective from Cambodia
Authors: Eam Phyrom
Published: December 2016

Despite very low research involvement and productivity of its faculty, research activities are not totally absent at Cambodian higher education institutions. This study seeks to diagnose influential factors that differentiate between Cambodian faculty who get involved in research activities and those who do not, with special emphases placed on involvement in research activities that are decently context-specific. Self-reported survey questionnaires were administered to faculty at ten selected Cambodian universities; the total sample (with usable returned questionnaire sets) amounted to 444 faculty members. Drawing on logistic regression analysis, the study detected that faculty obtaining their terminal degrees abroad, being full-timers, spending more time on research, and having high research self-efficacy were more likely to engage in research activities. As for institutional characteristics, large faculty size and available research funding sources were also correlated with research involvement. This study situates the findings in the research context of Cambodian higher education and discusses the practical meanings that the statistically significant variables imply.
Book review: Gregorutti, G., & Delgado, J. E. (Eds.). (2015). Private universities in Latin America: Research and innovation in the knowledge economy. New York: Palgrave Macmillan.
Authors: Salto Dante J
Published: December 2016

Established on a Napoleonic, professional training mission, universities in Latin America have not centered their activities in conducting research. This statement applies to traditional public universities, though Latin America’s leading universities boast some research tradition. Contemporary worldwide trends such as the increased economic value of knowledge, the demand of private firms to develop research and innovation, the multiplication of accountability stages, and the rise of new modes of academic activity have led public and private universities in Latin America to increase their research footprint. In most cases, public universities have driven this push. Private universities, rather than developing comprehensive research portfolios, tend to cover niches of research that are usually funded by international agencies or other non-governmental organizations. Thus, Private universities in Latin America: Research and innovation in the knowledge economy is mainly about outliers, what we might call the research underdogs of higher education (HE), and how they have grown due to or despite public policy.
Fact/Value Holism, Feminist Philosophy, and Nazi Cancer Research
Authors: Clough Sharyn
Published: December 2016

Fact/value holism has become commonplace in philosophy of science, especially in feminist literature. However, that facts are bearers of empirical content, while values are not, remains a firmly-held distinction. I support a more thorough-going holism: both facts and values can function as empirical claims, related in a seamless, semantic web. I address a counterexample from Kourany (2010) where facts and values seem importantly discontinuous, namely, the simultaneous support by the Nazis of scientifically sound cancer research and morally unsound political policies. I conclude that even by the criteria available at the time, Nazi cancer research was empirically weak, and the weaknesses in their research are continuous with their moral failures in just the ways predicted by the holism I support.
Love and Resistance: Moral Solidarity in the Face of Perceptual Failure
Authors: Emerick Barrett
Published: December 2016

In this paper I explore how we ought to respond to the problematic inner lives of those that we love. I argue for an understanding of love that is radical and challenging—a powerful form of resistance within the confines of everyday relationships. I argue that love, far from the platitudinous and saccharine view, does not call for our acceptance of others’ failings. Instead, loving another means believing in their potential to grow and holding them to account when they fail. I argue that loving others means meeting them where they are and working to understand the role that oppressive ideologies, coupled with cognitive biases, play in generating and entrenching their problematic mental states. I then argue that we ought not disengage with our loved ones or write them off as lost causes, nor should we accept that we will simply “agree to disagree.” Instead, we should stand in moral solidarity with our loved ones and press them to become better while simultaneously understanding that such moral growth is usually a slow and painful process—often, the project of a lifetime.
The Epistemological and the Moral/Political in Epistemic Responsibility: Beginnings and Reworkings in Lorraine Code’s Work
Authors: Koggel Christine M.
Published: December 2016

This is the first paper in the invited collection. Koggel starts with Code’s first book to record the key objections she raises against traditional and mainstream epistemological accounts. They are the sort of objections that will thread their way through all her work and be important to the development of feminist epistemology. I will then introduce, summarize, and discuss the work Code does on virtue ethics in Epistemic Responsibility and speculate on why she abandons this path in the rest of her work. Code uses virtue ethics and, specifically, virtues of the intellect, to frame an account of moral responsibility that I find interesting, promising, and still relevant to the contemporary revival of virtue ethics and to feminist epistemology more generally.
Knowledge and Awareness about Colorectal Cancer and Its Screening Guidelines among Doctors in Al Ahsa, Eastern Province, Kingdom of Saudi Arabia
Authors: Surendra Bathula , Hashir Muhammad Mujtaba , Al Harbi Fahad Salman , Al Nuwaysir Mohammed Jassim , Al Khaldi Khalid Majed , Alqahtani Abdulrahman Majid
Published: December 2016

INTRODUCTION: Cancer is a major public health problem. Worldwide, colorectal cancer (CRC) is a leading cause of deaths due to cancer in both men and women. Among, Saudi men, CRC is the most common malignancy while it is the third most common among Saudi women. Over, two decades the incidence and deaths due to CRC have been steadily increasing in Saudi Arabia. Regular and timely screening has the potential in reducing the incidence and deaths due to colorectal cancer. The present study is conducted to evaluate the knowledge and awareness about colorectal cancer and its screening among the doctors.OBJECTIVES: To measure the frequency of knowledge and awareness about colorectal cancer and its screening guidelines among doctors in Al-Ahssa.METHODS: A questionnaire based survey of the doctors (Specialists & residents), working in different hospitals and primary health centers under the Ministry of Health in Al Ahssa region, Eastern province, KSA.  Knowledge and awareness about colorectal cancer and its screening among the doctors is evaluated.RESULTS: Over 80% of the doctors knew, screening reduces deaths due to CRC. Only 60% were aware about the risk factors and less than 50% knew the clinical features of CRC. About 60% doctors agreed Colonoscopy is gold standard screening test. While, less than 60% knew the ideal age to initiate screening and the actual interval of screening tests in the standard risk and high-risk population. Fewer than 25% doctors were aware about the American cancer society recommended screening guidelines. Majority of the doctors expressed keen interest to know and receive information about CRC and its screening guidelines. CONCLUSIONS: Regular and timely screening reduces deaths due to CRC. There is a need for improving knowledge and awareness of doctors about CRC and its screening. Awareness among the doctors improves uptake of screening by the general and high-risk population.
The Effect of Service Quality Dimensions on Customers’ Loyalty through Customer Satisfaction in Jordanian Islamic Bank
Authors: Muala Ayed Al
Published: December 2016

The goal of this paper is to investigate the effect of banking Service Quality Dimensions on customers’ satisfaction, and customers’ loyalty. The dimensions include tangibility, reliability, empathy, responsiveness, and assurance. The researcher used a questionnaire survey to elicit data from the participants of the study. The sample included 250 questionnaires. They were distributed over a number of Islamic Bank customers in Jordan, particularly in the capital city “Amman”. The results of the study showed that there is a positive effect of Tangibility, Reliability, Empathy, Responsiveness, Assurance, on customer satisfaction toward customers’ loyalty. This has confirmed the Hypothesis of the study (H1, H2, H3, H4, and H6) in terms of being significantly and positively related to customers’ satisfaction and loyalty. On the other hand, one hypothesis is insignificant impact which is H5.
Nyama Choma Culture: Implications of Increased Red Meat and Alcohol Consumption in East Africa
Authors: Gorski Irena , Chung Wan-Chen , Herr Kelli , Mehta Khanjan
Published: December 2016

Nyama Choma Culture (NCC) reflects a way of life in East Africa based on the increased consumption of red meat and alcohol which seemingly projects a higher social status. The rising emergence of these cultural practices has positive as well as negative implications on individuals, their families, and larger socio-economic systems. This article draws from a variety of sources to provide an objective description of the implications of NCC on the people adopting it as well as society at large. These concerns are categorized into four primary areas: public health, the food industry, climate change, and community microeconomics. As the dynamics and impacts of NCC are already being felt in developing countries, this cultural phenomenon calls for careful monitoring and consideration in the design of policies and practices to champion the economic, social, and environmental sustainability of community nutrition systems and regional food value chains.
Pollen viability of Salix myrtilloides L. – an endangered species in Poland
Authors: Pogorzelec Magdalena , Serafin Artur , Banach-Albińska Barbara , Szczurowska Agnieszka , Parzymies Marzena , Bronowicka-Mielniczuk Urszula
Published: December 2016

Salix myrtilloides L. (swamp willow) is the most endangered species among the boreal Salix species in Poland. The number and size of its population have been decreasing constantly since the 1990s. The main aim of the study was to determine the viability of collected S. myrtilloides pollen and optimal conditions for its in vitro germination. The pollen of S. myrtilloides was collected from 25 male individuals from a population growing in the mid-forest peat bog Dekowina (Sobibór Landscape Park) in May 2014. Two methods were applied to estimate the viability of fresh and stored pollen: staining pollen with 2% acetocarmine solution and in vitro germinability. Various temperature (11°C, 23°C) and light conditions as well as different concentrations of glucose (1%, 2.5%, 5%, or 7.5%) were tested for the optimization of in vitro germination. We documented relatively high S. myrtilloides pollen viability. Pollen tube growth was found to be largely affected by both glucose content in the medium and thermal conditions during germination. Fresh pollen germinated most effectively on the medium with 2.5% glucose (stored pollen – in 5% glucose), at 23°C and in the presence of light. We conclude that pollen viability of S. myrtilloides does not seem to be a limiting factor for reproductive success. Moreover, the pollen is not sterile even after storage for 12 months. The S. myrtilloides individuals from the Dekowina peat bog produce viable pollen grains that are able to germinate and therefore it can be used to pollinate other populations present in the Polesie Lubelskie region for gene pool enrichment.
Reliability and availability assessment of diesel locomotive using Fault Tree Analysis
Authors: Szkoda Maciej , Kaczor Grzegorz
Published: December 2016

The article presents an application of a method based on fault tree analysis and the Monte Carlo simulation in the assessment of reliability and availability of the rail means of transport. The primary target of the presented method is a cause and effect assessment of the occurrence of undesirable events, the determination of selected reliability indices and identification of the weakest components of rail vehicle that affect the downtime and technical availability most strongly. To illustrate the application of the presented method, the results of a project involving a 6Dg diesel locomotive, carried out in cooperation with the biggest Polish rail carrier, are shown. The assessment of availability and reliability was based on real operation data of a selected sample of seventy-five locomotives. Based on the collected data from the operation of the 6Dg locomotives, the times-to-failure and the times-to repair models were determined. A fault tree model of the locomotive was developed to assess the influence of the faults of the components on the reliability of the vehicle. A discrete simulation process allows to obtain a chosen characteristics and values of the selected measures, which – according to the authors – may be applied to assess the reliability and availability of the rail vehicles. Specialist software including Weibull++, BlockSim and MiniTab aided calculations were performed. The software includes and advanced solutions in the range of the reliability and availability simulations. The test results indicate that the proposed solution has a wide applicability potential.
Vehicle selection model with respect to Economic Order Quantity
Authors: Wasiak Mariusz
Published: December 2016

The matter of vehicle selection, optimizing the order quantity or optimizing logistics costs is extensively discussed in both Polish and foreign literature. In numerous publications, the necessity of decision making in transport or in other related areas with respect to total logistics costs is addressed. Nevertheless, problems arising from the effect of vehicle selection on Economic Order Quantity (EOQ), while fully taking into account transport costs, fails to be mentioned. This paper presents a decision-making model for transport selection taking into consideration total logistics costs and a newly obtained formula for the economic order quantity which separates transport costs into fixed costs, variable costs dependent on the driving distance and operation time, as well as other variable costs. Analyses pertaining to the impact of cargo value and volumetric weight on vehicle selection and on Economic Order Quantity are also conducted.
El derecho a participar en la vida cultural y sus consecuencias para el aprendizaje: una historia de vida
Authors: Segarra Arnau Tomás
Published: December 2016

El trabajo que se presenta es una síntesis de una investigación sobre la participación en la vida cultural, que tiene como objetivos incidir en aquello que motiva su desarrollo y conocer los aprendizajes que se derivan del mismo. La investigación se ha llevado a cabo partiendo del enfoque biográfico-narrativo, mediante algunas de las herramientas que le son propias: el biograma, la entrevista biográ ca y el uso de fuentes documentales. El principal resultado de la investigación es la historia de vida de Jaime, una persona que vive en una pequeña población de la provincia de Castellón, muy implicada en los procesos de participación en la vida cultural de su municipio, tanto desde el mundo asociativo como desde el institucional. Las conclusiones destacan que los aprendizajes relacionados con la participación en la vida cultural se mani estan en las cuestiones de la identidad cultural y de la convivencia, en el concepto de ciudadanía activa y en la institucionalización de la cultura.
Science from women’s lives. Better Science? How gendered studies improve science and lives
Authors: Magallón Portolés Carmen
Published: December 2016

Recent gender analyses have been opening new paths for innovation and excellence. They are the basis for the Gendered Innovations project, led by the science historian Londa Schiebinger, in joint collaboration with the European Union. However, this work did not come out of nowhere; it is supported by decades of gender and science studies consisting of different research lines that critically reviewed the history of science and recovered the story of women’s contributions to different scientific fields. This paper reviews the origin and genealogy of the project, highlights its positive effects, and highlights examples of its achievements.
BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development
Authors: Shin Jaeyoung , Watanabe Shuichi , Hoelper Soraya , Krüger Marcus , Kostin Sawa , Pöling Jochen , Kubin Thomas , Braun Thomas
Published: December 2016

Migration of skeletal muscle precursor cells is a key step during limb muscle development and depends on the activity of PAX3 and MET. Here, we demonstrate that BRAF serves a crucial function in formation of limb skeletal muscles during mouse embryogenesis downstream of MET and acts as a potent inducer of myoblast cell migration. We found that a fraction of BRAF accumulates in the nucleus after activation and endosomal transport to a perinuclear position. Mass spectrometry based screening for potential interaction partners revealed that BRAF interacts and phosphorylates PAX3. Mutation of BRAF dependent phosphorylation sites in PAX3 impaired the ability of PAX3 to promote migration of C2C12 myoblasts indicating that BRAF directly activates PAX3. Since PAX3 stimulates transcription of the Met gene we propose that MET signaling via BRAF fuels a positive feedback loop, which maintains high levels of PAX3 and MET activity required for limb muscle precursor cell migration.
Two subunits of human ORC are dispensable for DNA replication and proliferation
Authors: Shibata Etsuko , Kiran Manjari , Shibata Yoshiyuki , Singh Samarendra , Kiran Shashi , Dutta Anindya
Published: December 2016

The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1. The ORC1 or ORC2-depleted cells replicate with decreased chromatin loading of MCM2-7 and become critically dependent on another ATPase, CDC6, for survival and DNA replication. Thus, either the ORC ring lacking a subunit, even its ATPase subunit, can load enough MCM2-7 in partnership with CDC6 to initiate DNA replication, or cells have an ORC-independent, CDC6-dependent mechanism to load MCM2-7 on origins of replication
Malaria parasite CelTOS targets the inner leaflet of cell membranes for pore-dependent disruption
Authors: Jimah John R , Salinas Nichole D , Sala-Rabanal Monica , Jones Nathaniel G , Sibley L David , Nichols Colin G , Schlesinger Paul H , Tolia Niraj H
Published: December 2016

Apicomplexan parasites contain a conserved protein CelTOS that, in malaria parasites, is essential for traversal of cells within the mammalian host and arthropod vector. However, the molecular role of CelTOS is unknown because it lacks sequence similarity to proteins of known function. Here, we determined the crystal structure of CelTOS and discovered CelTOS resembles proteins that bind to and disrupt membranes. In contrast to known membrane disruptors, CelTOS has a distinct architecture, specifically binds phosphatidic acid commonly present within the inner leaflet of plasma membranes, and potently disrupts liposomes composed of phosphatidic acid by forming pores. Microinjection of CelTOS into cells resulted in observable membrane damage. Therefore, CelTOS is unique as it achieves nearly universal inner leaflet cellular activity to enable the exit of parasites from cells during traversal. By providing novel molecular insight into cell traversal by apicomplexan parasites, our work facilitates the design of therapeutics against global pathogens.
Rörlig kunskap och flyttbara färdigheter – skolad arbetskraft vid fästningsbygget Sveaborg på 1750-talet
Authors: Gustafsson Sofia Maria
Published: December 2016

Mobile knowledge and transferable skills: The construction of Sveaborg Fortress by a skilled workforce in the 1750s.In the international debate about whether military investment can lead to economic growth, one of the key arguments has been the transfer of knowledge from the military to civil society. The construction of the sea fortress of Sveaborg (Suomenlinna) just off the coast of Helsinki in mid-eighteenth-century Finland provides a good example of this transfer. This huge military investment took place in peacetime and centred mainly on trade related to construction and shipbuilding, the very commerce that was also highly desirable for civil society. The army had to find its own construction solutions, most notably brickwork that used new techniques, and these innovations were later adopted by civilian entrepreneurs. The army also brought in skilled craftsmen to Helsinki, who, due to their limited number, also helped train soldiers in different skills. After working on Sveaborg, some of these craftsmen moved over to civilian employers or settled down in Helsinki as burghers. Similarly, demobilized soldiers returned home, taking their acquired skills with them. Between the army and civil society, therefore, there was a constant interaction and mutual exchange of knowledge and technology.
Splay fault branching from the Hikurangi subduction shear zone: Implications for slow slip and fluid flow
Authors: Plaza‐Faverola A. , Henrys S. , Pecher I. , Wallace L. , Klaeschen D.
Published: December 2016

Prestack depth migration data across the Hikurangi margin, East Coast of the North Island, New Zealand, are used to derive subducting slab geometry, upper crustal structure, and seismic velocities resolved to ∼14 km depth. We investigate the potential relationship between the crustal architecture, fluid migration, and short‐term geodetically determined slow slip events. The subduction interface is a shallow dipping thrust at <7 km depth near the trench and steps down to 14 km depth along an ∼18 km long ramp, beneath Porangahau Ridge. This apparent step in the décollement is associated with splay fault branching and coincides with a zone of maximum slip (90 mm) inferred on the subduction interface during slow slip events in June and July 2011. A low‐velocity zone beneath the plate interface, updip of the plate interface ramp, is interpreted as fluid‐rich overpressured sediments capped with a low permeability condensed layer of chalk and interbedded mudstones. Fluid‐rich sediments have been imbricated by splay faults in a region that coincides with the step down in the décollement from the top of subducting sediments to the oceanic crust and contribute to spatial variation in frictional properties of the plate interface that may promote slow slip behavior in the region. Further, transient fluid migration along splay faults at Porangahau Ridge may signify stress changes during slow slip.
Moderne Strategien zur Synthese funktioneller Fluorophore
Authors: de Moliner Fabio , Kielland Nicola , Lavilla Rodolfo , Vendrell Marc
Published: December 2016

Die biomedizinische Forschung ist auf die schnelle, akkurate und nicht‐invasive Charakterisierung spezifischer Biomoleküle und Zellen angewiesen. Funktionelle Fluorophore sind für derartige Studien von enormem Nutzen. Da diese komplexen Strukturen oftmals mit konventionellen Mitteln der Synthese nur schwer zugänglich sind, wurden in den letzten Jahren neuartige chemische Prozesse entwickelt. Dieser Kurzaufsatz beschreibt die jüngsten Entwicklungen im Bezug auf Design, Herstellung und Feinregulierung von Fluorophoren mittels Mehrkomponentenreaktionen, C‐H‐Aktivierungsprozessen, Cycloadditionen und Biomolekül‐basierten chemischen Transformationen.
The Transcriptional Coactivator Bob1 Is Associated With Pathologic B Cell Responses in Autoimmune Tissue Inflammation
Authors: Levels Maria J. , Van Tok Melissa N. , Cantaert Tineke , Cañete Juan D. , Kroese Frans G. M. , Germar Kristine , Spits Hergen , Baeten Dominique L. P. , Yeremenko Nataliya G.
Published: December 2016

Objective

The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. We undertook this study to identify molecular switches controlling pathologic B cell responses in rheumatoid arthritis (RA).

Methods

Candidate molecules were identified by gene expression profiling of RA synovitis and validated by quantitative polymerase chain reaction and immunohistochemistry. B cell–specific expression was confirmed by immunofluorescence, immunoblotting, and flow cytometry. The role of Bob1 in pathologic B cell responses was assessed in collagen‐induced arthritis (CIA).

Results

Transcriptional profiling of RA synovitis revealed a prominent B cell signature, with the transcriptional coactivator Bob1 and its putative target BCMA being among the most up‐regulated genes. Further analysis confirmed the microarray data and demonstrated elevated levels of Bob1 in B cells in RA synovium. A functional study showed that Bob1‐deficient mice failed to produce pathogenic anti–type II collagen (anti‐CII) antibodies and were resistant to CIA. Adoptive transfer of cells from Bob1‐deficient and Bob1‐sufficient mice to recombination‐activating gene 1–null mice demonstrated that Bob1 deficiency exclusively in B cells abrogated germinal center (GC) B cell formation, anti‐CII antibody production, and CIA development. Consistent with data from animal studies, immunophenotyping of human B cell subsets revealed increased expression of Bob1, predominantly in centrocytes and centroblasts. Correspondingly, Bob1 expression in RA synovitis was strongly correlated with CD21L, a molecular marker of GCs. In addition, similar Bob1 overexpression and correlation with CD21L expression was evidenced in parotid salivary gland tissue from patients with primary Sjögren's syndrome.

Conclusion

These expression and functional data identify the transcriptional coactivator Bob1 as a candidate molecular switch of pathogenic B cell responses in autoimmune diseases in humans.
Smartphone‐based portable wireless optical system for the detection of target analytes
Authors: Gautam Shreedhar , Batule Bhagwan S , Kim Hyo Yong , Park Ki Soo , Park Hyun Gyu
Published: December 2016

Rapid and accurate on‐site wireless measurement of hazardous molecules or biomarkers is one of the biggest challenges in nanobiotechnology. A novel smartphone‐based Portable and Wireless Optical System (PAWS) for rapid, quantitative, and on‐site analysis of target analytes is described. As a proof‐of‐concept, we employed gold nanoparticles (GNP) and an enzyme, horse radish peroxidase (HRP), to generate colorimetric signals in response to two model target molecules, melamine and hydrogen peroxide, respectively. The colorimetric signal produced by the presence of the target molecules is converted to an electrical signal by the inbuilt electronic circuit of the device. The converted electrical signal is then measured wirelessly via multimeter in the smartphone which processes the data and displays the results, including the concentration of analytes and its significance. This handheld device has great potential as a programmable and miniaturized platform to achieve rapid and on‐site detection of various analytes in a point‐of‐care testing (POCT) manner.
Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study
Authors: Kwon Jihyun , Min Chang‐Ki , Kim Kihyun , Han Jae‐joon , Moon Joon Ho , Kang Hye Jin , Eom Hyeon‐Seok , Kim Min Kyoung , Kim Hyo Jung , Yoon Dok Hyun , Lee Jeong‐Ok , Lee Won Sik , Lee Jae Hoon , Lee Je‐Jung , Choi Yoon‐seok , Kim Sung hyun , Yoon Sung‐soo
Published: December 2016

We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three‐hundred and seventy‐six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second‐line chemotherapy in 142 (37.8%) patients, and third‐line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression‐free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD.
Phylogenetic Studies, Gene Cluster Analysis, and Enzymatic Reaction Support Anthrahydroquinone Reduction as the Physiological Function of Fungal 17β‐Hydroxysteroid Dehydrogenase
Authors: Fürtges Leon , Conradt David , Schätzle Michael A. , Singh Shailesh Kumar , Kraševec Nada , Rižner Tea Lanišnik , Müller Michael , Husain Syed Masood
Published: December 2016

17β‐Hydroxysteroid dehydrogenase (17β‐HSDcl) from the filamentous fungus Curvularia lunata (teleomorph Cochliobolus lunatus) catalyzes NADP(H)‐dependent oxidoreductions of androgens and estrogens. Despite detailed biochemical and structural characterization of 17β‐HSDcl, its physiological function remains unknown. On the basis of amino acid sequence alignment, phylogenetic studies, and the recent identification of the physiological substrates of the homologous MdpC from Aspergillus nidulans and AflM from Aspergillus parasiticus, we propose an anthrahydroquinone as the physiological substrate of 17β‐HSDcl. This is also supported by our analysis of a secondary metabolite biosynthetic gene cluster in C. lunata m118, containing 17β‐HSDcl and ten other genes, including a polyketide synthase probably involved in emodin formation. Chemoenzymatic reduction of emodin by 17β‐HSDcl in the presence of sodium dithionite verified this hypothesis. On the basis of these results, the involvement of a 17β‐HSDcl in the biosynthesis of other anthrahydroquinone‐derived natural products is proposed; hence, 17β‐HSDcl should be more appropriately referred to as a polyhydroxyanthracene reductase (PHAR).
Total Synthesis of Leupyrrins A1 and B1, Highly Potent Antifungal Agents from the Myxobacterium Sorangium cellulosum
Authors: Thiede Sebastian , Wosniok Paul R. , Herkommer Daniel , Debnar Thomas , Tian Maoqun , Wang Tongtong , Schrempp Michael , Menche Dirk
Published: December 2016

Full details on the design, elaboration, and application of efficient strategies for the high‐yielding total syntheses of leupyrrins A1 and B1, unique antifungal agents from the myxobacterium Sorangium cellulosum, are reported. A sequential zirconocene‐mediated diyne‐cyclization, and regioselective opening of the zirconacyclopentadiene intermediate enabled a concise entry into the unique dihydrofuran fragment, whereas another domino reaction was developed for the butyrolactone involving a one‐pot lactol opening, stereoselective aldehyde addition and in situ lactonization. Furthermore, an innovative sp2‐sp3‐cross‐coupling for pyrrole functionalization and an optimized HATU‐mediated amide coupling protocol of two elaborate fragments were established. In addition, an unusual protective group strategy, involving a Teoc‐acetonide protected amine in combination with tert‐butyl and acetate esters, was successfully elaborated. These tactics and strategies are generally useful and may be also applied in the synthesis of other functionalized compounds. It is expected that the material which was obtained by these total syntheses will enable the further exploration of the biological profile of these potent antifungal agents.
Scope and Limitations of Fmoc Chemistry SPPS‐Based Approaches to the Total Synthesis of Insulin Lispro via Ester Insulin
Authors: Dhayalan Balamurugan , Mandal Kalyaneswar , Rege Nischay , Weiss Michael A. , Eitel Simon H. , Meier Thomas , Schoenleber Ralph O. , Kent Stephen B. H.
Published: December 2016

We have systematically explored three approaches based on 9‐fluorenylmethoxycarbonyl (Fmoc) chemistry solid phase peptide synthesis (SPPS) for the total chemical synthesis of the key depsipeptide intermediate for the efficient total chemical synthesis of insulin. The approaches used were: stepwise Fmoc chemistry SPPS; the “hybrid method”, in which maximally protected peptide segments made by Fmoc chemistry SPPS are condensed in solution; and, native chemical ligation using peptide‐thioester segments generated by Fmoc chemistry SPPS. A key building block in all three approaches was a Glu[O‐β‐(Thr)] ester‐linked dipeptide equipped with a set of orthogonal protecting groups compatible with Fmoc chemistry SPPS. The most effective method for the preparation of the 51 residue ester‐linked polypeptide chain of ester insulin was the use of unprotected peptide‐thioester segments, prepared from peptide‐hydrazides synthesized by Fmoc chemistry SPPS, and condensed by native chemical ligation. High‐resolution X‐ray crystallography confirmed the disulfide pairings and three‐dimensional structure of synthetic insulin lispro prepared from ester insulin lispro by this route. Further optimization of these pilot studies could yield an efficient total chemical synthesis of insulin lispro (Humalog) based on peptide synthesis by Fmoc chemistry SPPS.
Hepatocellular carcinoma as an emerging morbidity in the thalassemia syndromes: A comprehensive review
Authors: Moukhadder Hassan M. , Halawi Racha , Cappellini Maria Domenica , Taher Ali T.
Published: December 2016

The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is on the rise. The 2 well recognized HCC risk factors in thalassemia are iron overload and chronic viral infection with hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, which results in genotoxicity, and to immunologic dysregulation, which attenuates cancer immune surveillance. Chronic hepatitis B and C infections lead to necroinflammation, which can prompt progression to HCC, but an independent role of hepatitis B virus in hepatic carcinogenesis among patients with thalassemia has not been demonstrated. Screening patients who have thalassemia using magnetic resonance imaging‐based liver iron concentration measurement and liver ultrasound is recommended for early detection of iron overload and HCC, respectively. Prevention primarily resides in hepatitis B vaccination, donor blood screening, hepatitis treatment, and iron chelation. Although solid data is lacking on the outcomes of HCC treatment in patients with thalassemia, a personalized approach tailored to the individual patient's comorbidities remains necessary for treatment success. Treatment modalities for HCC include surgical resection, chemoembolization, and liver transplantation, among others. Multicenter studies are needed to better explore therapeutic targets that can improve the prognosis of these patients. Cancer 2017;123:751–58. © 2016 American Cancer Society.