bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Parasitic Dinoflagellate Amoebophrya sp. Infecting Akashiwo sanguinea in Coastal Waters of China
Authors: Chen Tiantian , Liu Yun , Song Shuqun , Li Caiwen
Published: November 2017

The endoparasitic dinoflagellate Amoebophrya infects a number of free‐living marine dinoflagellates, including harmful algal bloom species. The parasitoid eventually kills its host and has been proposed to be a significant loss factor for dinoflagellate blooms in restricted coastal waters. For several decades, the difficulties of culturing host‐parasitoid systems have been a great obstacle for further research on the biology of Amoebophrya. Here, we established an Akashiwo sanguinea‐Amoebophrya sp. coculture from Chinese coastal waters and studied the parasitoid's generation time, dinospore survival and infectivity, as well as its host specificity. The lifespan of Amoebophrya sp. ex. A. sanguinea was approximately 58 h. The infective dinospores can survive up to 78 h in ambient waters but gradually lose their infectivity. The parasitoid was unable to infect other dinoflagellate species, its infection rate reached as high as 91% when the ratio of dinospores to host cells was 20:1. The high infectivity of dinospores suggests that the Amoebophrya strain was capable of removing a considerable fraction of host biomass within a short period, but that it is probably unable to maintain high infection levels under nonbloom conditions of its host, due to limited survival and time constraints in encountering host cells.
Frequency of Leaving the House and Mortality from Age 70 to 95
Authors: Jacobs Jeremy M. , Hammerman‐Rozenberg Aliza , Stessman Jochanan
Published: November 2017

Objectives

To determine the association between frequency of leaving the house and mortality.

Design

Prospective follow‐up of an age‐homogenous, representative, community‐dwelling birth cohort (born 1920–21) from the Jerusalem Longitudinal Study (1990–2015).

Setting

Home.

Participants

Individuals aged 70 (n = 593), 78 (n = 973), 85 (n = 1164), and 90 (n = 645), examined in 1990, 1998, 2005, and 2010, respectively.

Measurements

Frequency of leaving the house, defined as daily (6–7/week), often (2–5/week), and rarely (≤1/week); geriatric assessment; all‐cause mortality (2010–15). Kaplan‐Meier survival charts and proportional hazards models adjusted for social (sex, marital status, financial status, loneliness), functional (sex, self‐rated health, fatigue, depression, physical activity, activity of daily living difficulty), and medical (sex, chronic pain, visual impairment, hearing impairment, diabetes mellitus, hypertension, ischemic heart disease, chronic kidney disease) covariates.

Results

At ages 70, 78, 85, and 90, frequency of going out daily was 87.0%, 80.6%, 65.6%, and 48.4%; often was 6.4%, 9.5%, 17.4%, and 11.3%; and rarely was 6.6%, 10.0%, 17.0%, and 40.3% respectively. Decreasing frequency of going out was associated with negative social, functional, and medical characteristics. Survival rates were lowest among those leaving rarely and highest among those going out daily throughout follow‐up. Similarly, compared with rarely leaving the house, unadjusted mortality hazard ratios (HRs) were lowest among subjects leaving daily and remained significant after adjustment for social, functional and medical covariates. Among subjects leaving often, unadjusted HRs showed a similar effect of smaller magnitude, with attenuation of significance after adjustment in certain models. Findings were unchanged after excluding subjects dying within 6 months of follow‐up.

Conclusion

In community‐dwelling elderly adults aged 70 to 90, leaving the house daily was associated with lower mortality risk, independent of social, functional, or medical status.
Calmodulin‐like skin protein protects against spatial learning impairment in a mouse model of Alzheimer disease
Authors: Kusakari Shinya , Nawa Mikiro , Sudo Katsuko , Matsuoka Masaaki
Published: November 2017

Humanin and calmodulin‐like skin protein (CLSP) inhibits Alzheimer disease (AD)‐related neuronal cell death via the heterotrimeric humanin receptor in vitro. It has been suggested that CLSP is a central agonist of the heterotrimeric humanin receptor in vivo. To investigate the role of CLSP in the AD pathogenesis in vivo, we generated mouse CLSP‐1 transgenic mice, crossed them with the APPswe/PSEN1dE9 mice, a model mouse of AD, and examined the effect of CLSP over‐expression on the pathological phenotype of the AD mouse model. We found that over‐expression of the mouse CLSP‐1 gene attenuated spatial learning impairment, the loss of a presynaptic marker synaptophysin, and the inactivation of STAT3 in the APPswe/PSEN1dE9 mice. On the other hand, CLSP over‐expression did not affect levels of Aβ, soluble Aβ oligomers, or gliosis. These results suggest that the CLSP‐mediated attenuation of memory impairment and synaptic loss occurs in an Aβ‐independent manner. The results of this study may serve as a hint to the better understanding of the AD pathogenesis and the development of AD therapy.

image
The Queer Art of Biblical Reading: Matthew 25:31–46 (Caritas Christiana) ThroughCaritas Romana
Authors: Menéndez‐Antuña Luis
Published: November 2017

The place of eros in Christian theology has always been a contested one, not least because it is positioned as being at odds with agape, the kind of love that embodies gospel ethics. Matthew 25:31–46 calls us to “feed the hungry,” “quench the thirsty,” “shelter the homeless,” “clothe the naked,” and “visit the imprisoned” as emblematic examples of agapic love. This essay shows how a queer act, specifically that of a woman breastfeeding a starving man as depicted in the tradition ofCaritas Romana, can fulfill the ethical demands in Matthew's pericope. It demonstrates how the action first narrated by Valerius Maximus and then represented by Paul Peter Rubens beautifully fulfills the Matthean agapic demands, and concludes that queer practices have the potential to fulfill the gospel demands, situating the erotic at the core of the agapic.
Discussing Racial Justice in Light of 2016: Black Lives Matter, a Trump Presidency, and the Continued Struggle for Justice
Authors: Teresa Dávila María
Published: November 2017

The broad fields of ethical reflection on racialization, racial justice, black liberation theology, and queer theology of color must come to terms with the year 2016, which can be framed on one side with the Black Lives Matter movement, and on the other side with a presidential election cycle in which racism and racial justice played particularly salient roles. Against this backdrop, this book discussion looks at recent literature on racial justice asking three questions. How does historical consciousness shape contemporary ethical thought on racial justice? In what ways do the intersectionalities of gender and sexuality, immigration and transnationality, class, and contemporary culture present particular challenges and new possibilities? And how do the ethical frameworks of religious traditions contribute to the development of public theology for racial justice? The conclusion considers how religious ethics concerned with racial justice does harm or contributes to religiously grounded responses to racial injustice. Reflection on these questions points to the need for ongoing engagement with the black experience—broadly construed and within the context of multiple intersections—in the United States and globally in ethical analysis. However, this in turn makes particular and critical demands on how it is that we are to both teach and read religious ethics and political theology at our institutions, as well as in the churches.
Comparing preferred attribute elicitation to trained panelists' evaluations using a novel food product
Authors: McSweeney Matthew B. , Sisopha Anita , T'ien Caroline , Rector Megan , Duizer Lisa M.
Published: November 2017

The present study compares a new rapid sensory method, preferred attribute elicitation (PAE), to a trained panelists' evaluations, using cookies containing green tea extract (GTE) as a model. The cookies contained added amounts of 0, 2, 4, 7, and 9% GTE based on the weight of flour. Ten trained panelists evaluated the cookies. The panelists were trained for 10 one‐hour sessions followed by three replicates of testing. Additionally, 43 panelists in two different sessions (n = 25 and 18), evaluated the five samples following the PAE method. RV coefficients were used to provide a numerical value for the degree of similarity between the descriptive data obtained from the PAE sessions and the descriptive analysis panel. The RV coefficient for the two PAE sessions was .843, indicating a very high similarity between the sessions. However, the RV coefficient comparing the two PAE sessions to the descriptive analysis data were .554 and .179, respectively. These results indicate that the PAE method was not comparable to the trained panelists' evaluations. Future work needs to identify when PAE is the most suitable method to use and to modify the existing methodology to make it a more efficient method.

Practical applications

Preferred attribute elicitation (PAE) is a rapid sensory analysis method that uses untrained panelists to evaluate attributes of a product and determine what attributes drive consumer liking. This study investigates how the technique (using untrained panelist) compares to a trained panel when testing baked products differing in flavor intensity. There was not a relationship between the PAE sessions and trained panel for the flavors of this particular product. More work must be done to determine why the evaluations of the flavor was not consistent if PAE is to be used in future sensory trials.
Contextual Factors Associated with Implementing Active Support in Community Group Homes in the United States: A Qualitative Investigation
Authors: Qian Xueqin , Tichá Renáta , Stancliffe Roger
Published: November 2017

Although numerous studies in the U.K. and Australia have shown that Active Support (AS) is an effective intervention in increasing staff assistance and engagement for people with intellectual and developmental disabilities (IDD) who live in small community residential settings, studies in Taiwan and the U.S. did not replicate these results. The mixed findings may be due to the unique challenges faced by small community group homes serving people with disabilities from different countries. The purpose of this qualitative study was to describe the views of participants in a AS implementation study about contextual factors that affected their efforts at implementing AS in a U.S. context. Interviews were conducted with Direct Support Professionals (DSPs) and AS trainers. A focus group was conducted with directors from organizations that implemented AS in the U.S. This study revealed several reported challenges to AS implementation, including the lack of leadership support, lack of buy‐in, and high staff turnover rate. Despite these difficulties, study participants identified positive impacts of AS on both DSPs and people with disabilities. Implications of these findings are discussed.
The thrill of bullying. Bullying, humour and the making of community
Authors: Søndergaard Dorte Marie
Published: November 2017

Humour can be utilised to mark out the boundaries of social groups, to produce and restore dignity, but also to produce contempt, marginalise and exclude. Humour and ridicule can be used to influence hierarchies and positioning among children in the classroom and it can have strong effects in school groups saturated with bullying practices. Ridicule appears to be widespread, very much feared, and not easily amenable to adult interventions. With this article, I look into the many and frequently subtle ways humour intertwines itself in relational practices among children, with a particular focus on children in groups plagued by bullying and social tension. I focus on the entanglement of humour in the complex manoeuvrings that characterise children's worlds, and the subtle mechanisms involved in the self‐regulation of their communities in and outside schools. The analyses and analytical understanding that I develop are grounded in qualitative data such as interviews with children and extensive observation in schools and in after school care.
Pharmacokinetic profiles of the two major active metabolites of metamizole (dipyrone) in cats following three different routes of administration
Authors: Lebkowska‐Wieruszewska B. , Kim T. W. , Chea B. , Owen H. , Poapolathep A. , Giorgi M.
Published: November 2017

This study was performed to determine pharmacokinetic profiles of the two active metabolites of the analgesic drug metamizole (dipyrone, MET), 4‐methylaminoantipyrine (MAA), and 4‐aminoantipyrine (AA), after intravenous (i.v., intramuscular (i.m.), and oral (p.o.) administration in cats. Six healthy mixed‐breed cats were administered MET (25 mg/kg) by i.v., i.m., or p.o. routes in a crossover design. Adverse clinical signs, namely salivation and vomiting, were detected in all groups (i.v. 67%, i.m. 34%, and p.o. 15%). The mean maximal plasma concentration of MAA for i.v., i.m., and p.o. administrations was 148.63 ± 106.64, 18.74 ± 4.97, and 20.59 ± 15.29 μg/ml, respectively, with about 7 hr of half‐life in all routes. Among the administration routes, the area under the plasma concentration curve (AUC) value was the lowest after i.m. administration and the AUCEV/i.v. ratio was higher in p.o. than the i.m. administration without statistical significance. The plasma concentration of AA was detectable up to 24 hr, and the mean plasma concentrations were smaller than MAA. The present results suggest that MET is converted into the active metabolites in cats as in humans. Further pharmacodynamics and safety studies should be performed before any clinical use.
Insecticide susceptibility status in Mexican populations of Stegomyia aegypti (= Aedes aegypti): a nationwide assessment
Authors: KURI‐MORALES P. A. , CORREA‐MORALES F. , GONZÁLEZ‐ACOSTA C. , MORENO‐GARCIA M. , SANTOS‐LUNA R. , ROMÁN‐PÉREZ S. , SALAZAR‐PENAGOS F. , LOMBERA‐GONZÁLEZ M. , SÁNCHEZ‐TEJEDA G. , GONZÁLEZ‐ROLDÁN J. F.
Published: November 2017

In Mexico, mosquito vector‐borne diseases are of public health concern as a result of their impact on human morbidity and mortality. The use of insecticides against adult mosquitoes is one of the most common ways of controlling mosquito population densities. However, the use of these compounds has resulted in the development of insecticide resistance. The aim of this study was to estimate susceptibility to six pyrethroids, two carbamates and two organophosphates in Mexican populations of Stegomyia aegypti (Linnaeus, 1762) (= Aedes aegypti) (Diptera: Culicidae) mosquitoes. Bottle insecticide susceptibility tests, with 1 h exposure, were performed on adult mosquitoes from 75 localities across 28 states. At 30 min of exposure, the proportion of fallen mosquitoes was recorded. After 60 min of exposure, mosquitoes were recovered in non‐treated containers and mortality was determined at 24 h after the set‐up of the experiment. In general, the carbamate insecticides represented the most effective group in terms of the proportion of mosquitoes fallen at 30 min (72–100%) and 24‐h mortality (97–100%). High and widespread resistance to pyrethroids Types I and II and, to a lesser extent, to organophosphates was observed. Insecticide susceptibility among and within states was highly variable.
Host preference and network properties in biotrophic plant–fungal associations
Authors: Põlme Sergei , Bahram Mohammad , Jacquemyn Hans , Kennedy Peter , Kohout Petr , Moora Mari , Oja Jane , Öpik Maarja , Pecoraro Lorenzo , Tedersoo Leho
Published: November 2017

Analytical methods can offer insights into the structure of biological networks, but mechanisms that determine the structure of these networks remain unclear. We conducted a synthesis based on 111 previously published datasets to assess a range of ecological and evolutionary mechanisms that may influence the plant‐associated fungal interaction networks.

We calculated the relative host effect on fungal community composition and compared nestedness and modularity among different mycorrhizal types and endophytic fungal guilds. We also assessed how plant–fungal network structure was related to host phylogeny, environmental and sampling properties.

Orchid mycorrhizal fungal communities responded most strongly to host identity, but the effect of host was similar among all other fungal guilds. Community nestedness, which did not differ among fungal guilds, declined significantly with increasing mean annual precipitation on a global scale. Orchid and ericoid mycorrhizal fungal communities were more modular than ectomycorrhizal and root endophytic communities, with arbuscular mycorrhizal fungi in an intermediate position.

Network properties among a broad suite of plant‐associated fungi were largely comparable and generally unrelated to phylogenetic distance among hosts. Instead, network metrics were predominantly affected by sampling and matrix properties, indicating the importance of study design in properly inferring ecological patterns.
Impact of Ultraviolet Radiation on Expression of Transforming Growth Factor β, Smad2, Metalloproteinases‐1, ‐3, ‐8, ‐9, Cathepsin K and Progerin
Authors: Ciążyńska Magdalena , Bednarski Igor A. , Wódz Karolina , Narbutt Joanna , Sobjanek Michał , Woźniacka Anna , Lesiak Aleksandra
Published: November 2017

Ultraviolet radiation (UVR) is one of the most important environmental factors involved in photoaging. Exposure to UVR leads to dysregulation of expression of cell cycle‐related proteins which play key role in skin photodegradation that pretends to develop carcinogenesis. This study examines the role of various UVB doses on the expression of transforming growth factor beta (TGF‐β), Smad2, cathepsin K, progerin and matrix metalloproteinases (MMPs)‐1,‐3,‐8,‐9. A group consisting of 63 healthy individuals underwent one of the following treatments: (1) whole body exposed to UVB irradiation on each of 10 consecutive days with 0.7 MED, or (2) whole‐body irradiation as described followed by a single erythemal UVB dose on a small body area, or (3) irradiated only with a single erythemal UVB dose on small body area, or (4) were not irradiated at all (control group). When we compared all irradiated groups to the control group, there was significantly higher expression of TGF‐β, MMP‐1,‐3,‐9 and cathepsin K proteins evaluated by Western blot method. The results suggest the role of UVB in impairment of proteins expression that is involved in cell cycle's regulation. Changes in the protein expression involved by acute and chronic UVR confirm its essential role in skin photodestruction. Moreover, obtained result indicates the tendency to occurrence of photoadaptation phenomenon.
More Reasons Why Jurisprudence Is Not Legal Philosophy
Authors: Robertson Michael
Published: November 2017

It is generally assumed, without argument, that legal theory, legal philosophy, philosophy of law, and jurisprudence all mean the same thing. This paper rejects that assumption, and in particular the assumption that jurisprudence is the same thing as legal philosophy. This assumption has recently been challenged by Roger Cotterrell in his article “Why Jurisprudence Is Not Legal Philosophy,” and I seek to build on his arguments by adding insights found in the work of Stanley Fish.
Asymptotic Approximations for Radial Spheroidal Wavefunctions with Complex Size Parameter
Authors: Martin P. A.
Published: November 2017

Radial spheroidal wavefunctions are functions of four variables, usually denoted by m, n, x, and γ, the last of which is known as the size parameter. This parameter becomes complex when the problem of scattering of a sound pulse by a spheroid is treated using a Laplace transform with respect to time together with the method of separation of variables. Several asymptotic approximations, involving modified Bessel functions, are developed and analyzed.
The TCP4 transcription factor regulates trichome cell differentiation by directly activating GLABROUS INFLORESCENCE STEMS in Arabidopsis thaliana
Authors: Vadde Batthula Vijaya Lakshmi , Challa Krishna Reddy , Nath Utpal
Published: November 2017

Trichomes are the first cell type to be differentiated during the morphogenesis of leaf epidermis and serve as an ideal model to study cellular differentiation. Many genes involved in the patterning and differentiation of trichome cells have been studied over the past decades, and the majority of these genes encode transcription factors that specifically regulate epidermal cell development. However, the upstream regulators of these genes that link early leaf morphogenesis with cell type differentiation are less studied. The TCP proteins are the plant‐specific transcription factors involved in regulating diverse aspects of plant development including lateral organ morphogenesis by modulating cell proliferation and differentiation. Here, we show that the miR319‐regulated class II TCP proteins, notably TCP4, suppress trichome branching in Arabidopsis leaves and inflorescence stem by direct transcriptional activation of GLABROUS INFLORESCENCE STEMS (GIS), a known negative regulator of trichome branching. The trichome branch number is increased in plants with reduced TCP activity and decreased in the gain‐of‐function lines of TCP4. Biochemical analyses show that TCP4 binds to the upstream regulatory region of GIS and activates its expression. Detailed genetic analyses show that GIS and TCP4 work in same pathway and GIS function is required for TCP4‐mediated regulation of trichome differentiation. Taken together, these results identify a role for the class II TCP genes in trichome differentiation, thus providing a connection between organ morphogenesis and cellular differentiation.
Overcoming the Barriers to Successful Completion of GED Programs among Prison and Jail Inmates
Authors: Batchelder John Stuart , O’Neill Austin , Rodriguez Ashley Diane , Tibbs Rebecca
Published: November 2017

This study examines the barriers faced by inmates participating in General Educational Development (GED) courses in prisons and jails, with the goal of proposing strategies for the removal of these barriers. By examining the literature surrounding prison and jail GED programs, the factors are categorized as those unique to each inmate (inmate factors), those experienced within the prison environment (environmental factors), and barriers that arise as a result of social conditions (outside factors). By examining various similar examples in the literature, solutions are discussed that have helped prison inmates overcome similar barriers.
To Explore the Research and Development Competence and School-to-Work Transition for Hospitality Students
Authors: Ko Wen-Hwa , Chen Chieh-Ying
Published: November 2017

This research focuses on the research and development competence and school-to-work transition on occupation selection for hospitality students with the use of social cognitive career theory. The positive attitude construct is the most identifiable for the research and development competences. For the school-to-work constructs, the most identifiable is the construct of learning and exploration, while the most identifiable among the self-efficacy constructs is the personal work attitude construct. The students' research and development competence and school-to-work transition to occupation selection are revealed. While the expectation result of professional competence is not significant; the others show significantly positive impact.
Predicting effects of hearing-instrument signal processing on consonant perception
Authors: Zaar Johannes , Schmitt Nicola , Derleth Ralph-Peter , DiNino Mishaela , Arenberg Julie G. , Dau Torsten
Published: November 2017

This study investigated the influence of hearing-aid (HA) and cochlear-implant (CI) processing on consonant perception in normal-hearing (NH) listeners. Measured data were compared to predictions obtained with a speech perception model [Zaar and Dau (2017). J. Acoust. Soc. Am. 141, 1051–1064] that combines an auditory processing front end with a correlation-based template-matching back end. In terms of HA processing, effects of strong nonlinear frequency compression and impulse-noise suppression were measured in 10 NH listeners using consonant-vowel stimuli. Regarding CI processing, the consonant perception data from DiNino et al. [(2016). J. Acoust. Soc. Am. 140, 4404–4418] were considered, which were obtained with noise-vocoded vowel-consonant-vowel stimuli in 12 NH listeners. The inputs to the model were the same stimuli as were used in the corresponding experiments. The model predictions obtained for the two data sets showed a large agreement with the perceptual data both in terms of consonant recognition and confusions, demonstrating the model's sensitivity to supra-threshold effects of hearing-instrument signal processing on consonant perception. The results could be useful for the evaluation of hearing-instrument processing strategies, particularly when combined with simulations of individual hearing impairment.
Ultrafast direct electron transfer at organic semiconductor and metal interfaces
Authors: Xiang Bo , Li Yingmin , Pham C. Huy , Paesani Francesco , Xiong Wei
Published: November 2017

Conformation-specific direct interfacial electron transfer is observed by the first ultrafast electric field–induced VSFG.
Structural rearrangements governing Johari-Goldstein relaxations in metallic glasses
Authors: Yu Hai-Bin , Richert Ranko , Samwer Konrad
Published: November 2017

Atomistic simulations reveal that secondary relaxations in metallic glasses originate from string-like atomic motions.
Reactive oxygen species leave a damage trail that reveals water channels in Photosystem II
Authors: Weisz Daniel A. , Gross Michael L. , Pakrasi Himadri B.
Published: November 2017

This study illuminates the locations of water channels within Photosystem II, a large membrane protein complex.
Extreme enrichment in atmospheric
15
N
15
N
Authors: Yeung Laurence Y. , Li Shuning , Kohl Issaku E. , Haslun Joshua A. , Ostrom Nathaniel E. , Hu Huanting , Fischer Tobias P. , Schauble Edwin A. , Young Edward D.
Published: November 2017

Upper-atmospheric chemistry and biological N
2
cycling engage in a planetary-scale tug-of-war seen in
15
N
15
N of air.
Suppression of FIP200 and autophagy by tumor-derived lactate promotes naïve T cell apoptosis and affects tumor immunity
Authors: Xia Houjun , Wang Wei , Crespo Joel , Kryczek Ilona , Li Wei , Wei Shuang , Bian Zhaoqun , Maj Tomasz , He Mingxiao , Liu Rebecca J. , He Youwen , Rattan Ramandeep , Munkarah Adnan , Guan Jun-Lin , Zou Weiping
Published: November 2017

Tumor-derived lactate induced naïve T cell apoptosis via suppressing FIP200 expression and autophagy formation, resulting in mitochondria activation and imbalance of Bcl-2 family members in T cells.
TCR engagement negatively affects CD8 but not CD4 CAR T cell expansion and leukemic clearance
Authors: Yang Yinmeng , Kohler M. Eric , Chien Christopher D. , Sauter Christopher T. , Jacoby Elad , Yan Chunhua , Hu Ying , Wanhainen Kelsey , Qin Haiying , Fry Terry J.
Published: November 2017

TCR engagement induces CD8 CAR T cell exhaustion and poor in vivo functionality in mice.
Apoptotic debris goes in the Bim
Authors: Miner Jonathan
Published: November 2017

Lack of Bim expression in myeloid cells induces lupus nephritis in mice.
The vicious epigenetic cycle of neuronal activation
Authors: Novarino Gaia
Published: November 2017

Seizure-induced increase in ΔFosB expression reduces calbindin-28k and might explain cognitive impairments in seizure disorders.
Candida auris: an Emerging Fungal Pathogen
Authors: Spivak Emily S. , Hanson Kimberly E.
Published: November 2017

Candida auris
has emerged globally as a multidrug-resistant health care-associated fungal pathogen. Recent reports highlight ongoing challenges due to organism misidentification, high rates of antifungal drug resistance, and significant patient mortality. The predilection for transmission within and between health care facilities possibly promoted by virulence factors that facilitate skin colonization and environmental persistence is unique among
Candida
species. This minireview details the global emergence of
C. auris
and discusses issues relevant to clinical microbiology laboratories, hospital infection control, and antimicrobial stewardship efforts.
Insight into the Roles of E3 Ubiquitin Ligase c-Cbl, ESCRT Machinery, and Host Cell Signaling in Kaposi's Sarcoma-Associated Herpesvirus Entry and Trafficking
Authors: Kumar Binod , Roy Arunava , Veettil Mohanan Valiya , Chandran Bala
Published: November 2017

Kaposi's sarcoma-associated herpesvirus (KSHV)
in vitro
infection of dermal endothelial cells begins with its binding to host cell surface receptor molecules such as heparan sulfate (HS), integrins (α3β1, αVβ3, and αVβ5), xCT, and EphA2 receptor tyrosine kinase (EphA2R). These initial events initiate dynamic host protein-protein interactions involving a multimolecular complex of receptors, signal molecules (focal adhesion kinase [FAK], Src, phosphatidylinositol 3-kinase [PI3-K], and RhoA-GTPase), adaptors (c-Cbl, CIB1, Crk, p130Cas, and GEF-C3G), actin, and myosin II light chain that lead to virus entry via macropinocytosis. Here we discuss how KSHV hijacks c-Cbl, an E3 ubiquitin ligase, to monoubiquitinate the receptors and actin, which acts like a marker for trafficking (similar to zip codes), resulting in the recruitment of the members of the host endosomal sorting complexes required for transport (ESCRT) Hrs, Tsg101, EAP45, and the CHMP5 and -6 proteins (zip code readers) recognizing the ubiquitinated protein and adaptor machinery to traffic through the different endosomal compartments in the cytoplasm to initiate the macropinocytic process and infection.
Persistence of an Oncogenic Papillomavirus Genome Requires
cis
Elements from the Viral Transcriptional Enhancer
Authors: Van Doorslaer Koenraad , Chen Dan , Chapman Sandra , Khan Jameela , McBride Alison A.
Published: November 2017

Human papillomavirus (HPV) genomes are replicated and maintained as extrachromosomal plasmids during persistent infection. The viral E2 proteins are thought to promote stable maintenance replication by tethering the viral DNA to host chromatin. However, this has been very difficult to prove genetically, as the E2 protein is involved in transcriptional regulation and initiation of replication, as well as its assumed role in genome maintenance. This makes mutational analysis of viral
trans
factors and
cis
elements in the background of the viral genome problematic and difficult to interpret. To circumvent this problem, we have developed a complementation assay in which the complete wild-type HPV18 genome is transfected into primary human keratinocytes along with subgenomic or mutated replicons that contain the minimal replication origin. The wild-type genome provides the E1 and E2 proteins in
trans
, allowing us to determine additional
cis
elements that are required for long-term replication and partitioning of the replicon. We found that, in addition to the core replication origin (and the three E2 binding sites located therein), additional sequences from the transcriptional enhancer portion of the URR (upstream regulatory region) are required in
cis
for long-term genome replication.

IMPORTANCE
Human papillomaviruses infect cutaneous and mucosal epithelial cells of the host, and this results in very-long-lived, persistent infection. The viral genomes are small, circular, double-stranded DNA molecules that replicate extrachromosomally in concert with cellular DNA. This replication strategy requires that the virus has a robust mechanism to partition and retain the viral genomes in dividing cells. This has been difficult to study, because viral transcription, replication, and partitioning are regulated by the same viral proteins and involve overlapping elements in the viral genome. We developed a complementation assay that allows us to separate these functions and define the elements required for long-term replication and stable maintenance replication of the HPV genome. This has important implications, as disruption of viral maintenance replication can eliminate viral genomes from infected cells, thus curing persistent HPV infection.
Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers
Authors: Nguyen Sophie , Baker Kristi , Padman Benjamin S. , Patwa Ruzeen , Dunstan Rhys A. , Weston Thomas A. , Schlosser Kyle , Bailey Barbara , Lithgow Trevor , Lazarou Michael , Luque Antoni , Rohwer Forest , Blumberg Richard S. , Barr Jeremy J.
Published: November 2017

Bacterial viruses are among the most numerous biological entities within the human body. These viruses are found within regions of the body that have conventionally been considered sterile, including the blood, lymph, and organs. However, the primary mechanism that bacterial viruses use to bypass epithelial cell layers and access the body remains unknown. Here, we used
in vitro
studies to demonstrate the rapid and directional transcytosis of diverse bacteriophages across confluent cell layers originating from the gut, lung, liver, kidney, and brain. Bacteriophage transcytosis across cell layers had a significant preferential directionality for apical-to-basolateral transport, with approximately 0.1% of total bacteriophages applied being transcytosed over a 2-h period. Bacteriophages were capable of crossing the epithelial cell layer within 10 min with transport not significantly affected by the presence of bacterial endotoxins. Microscopy and cellular assays revealed that bacteriophages accessed both the vesicular and cytosolic compartments of the eukaryotic cell, with phage transcytosis suggested to traffic through the Golgi apparatus via the endomembrane system. Extrapolating from these results, we estimated that 31 billion bacteriophage particles are transcytosed across the epithelial cell layers of the gut into the average human body each day. The transcytosis of bacteriophages is a natural and ubiquitous process that provides a mechanistic explanation for the occurrence of phages within the body.

IMPORTANCE
Bacteriophages (phages) are viruses that infect bacteria. They cannot infect eukaryotic cells but can penetrate epithelial cell layers and spread throughout sterile regions of our bodies, including the blood, lymph, organs, and even the brain. Yet how phages cross these eukaryotic cell layers and gain access to the body remains unknown. In this work, epithelial cells were observed to take up and transport phages across the cell, releasing active phages on the opposite cell surface. Based on these results, we posit that the human body is continually absorbing phages from the gut and transporting them throughout the cell structure and subsequently the body. These results reveal that phages interact directly with the cells and organs of our bodies, likely contributing to human health and immunity.
Use of prostaglandins in duct-dependent congenital heart conditions
Authors: Singh Yogen , Mikrou Paraskevi
Published: November 2017

Congenital heart disease (CHD) remains a leading cause of infant mortality, which is even higher in infants with undiagnosed duct-dependent CHDs. Up to 39%–50% of infants with critical CHD are being discharged undiagnosed from the hospital. Infants with duct-dependent critical CHD remain well during the fetal period and may deteriorate when the ductus arteriosus (commonly called ‘duct’) closes after birth. It is critical to open or maintain ductus arteriosus patent in infants with duct-dependent CHDs. Prostaglandin E1 (alprostadil marketed as ‘Prostin VR ’) and prostaglandin E2 (dinoprostone) are used to maintain a patent ductus arteriosus and the dose of medication depends on the clinical presentation. Delay in starting prostaglandin infusion can have deleterious effects on infants and can even lead to death. These infants often present as an emergency, and professionals caring for these infants need to have a good understanding of these conditions and medications used for ductal patency.
The association between gastro-oesophageal reflux disease and subsequent rheumatoid arthritis occurrence: a nested case–control study from Taiwan
Authors: Lin Herng-Ching , Xirasagar Sudha , Lee Cha-Ze , Huang Chung-Chien , Chen Chao-Hung
Published: November 2017

Objective

Gastro-oesophageal reflux disease (GORD) is a common comorbidity among patients with rheumatoid arthritis (RA). While GORD has been attributed to the antirheumatic medications, no studies of human cohorts have investigated a link between GORD and RA. This study investigates whether GORD is associated with a subsequent RA diagnosis over a 5-year follow-up using a population-based dataset.

Setting

Taiwan

Participants

We used data from the Taiwan Longitudinal Health Insurance Database. The study group consisted of 13 645 patients with an ambulatory claim showing a GORD diagnosis. We used propensity score matching to select 13 645 comparison patients (one per study patient with GORD).

Intervention

We tracked each patient’s claims over a 5-year period to identify those who subsequently received a diagnosis of RA. Cox proportional hazard (PH) regression modelling was used for analysis.

Results

Over 5-year follow-up, RA incidence rate per 1000 person-years was 2.81 among patients with GORD and 0.84 among the comparison group. Cox PH modelling showed that GORD was independently associated with a 2.84-fold increased risk of RA (95% CI 2.09 to 3.85) over 5-year follow-up, after adjusting for the number of ambulatory care visits within the year following the index date (to mitigate surveillance bias).

Conclusions

We observed that GORD might associate with subsequent RA occurrence. Because current treatment guidelines for RA emphasise early diagnosis and prompt treatment, the observed association between GORD and RA may help acquaint clinicians to patients with GORD with higher RA risk and facilitate early diagnosis and treatment.
Prevalence of health services usage and associated factors in the Amazon region of Brazil: a population-based cross-sectional study
Authors: Araujo Maria Elizete A , Silva Marcus T , Galvao Tais F , Pereira Mauricio G
Published: November 2017

Objectives

To estimate the prevalence of healthcare use and associated factors in the Manaus metropolitan region and to describe the reasons for lack of access.

Design

Cross-sectional population-based study.

Setting

A survey conducted between May and August of 2015 in eight cities from Manaus metropolitan region, Amazonas, Brazil.

Participants

4001 adults ≥18 years of age.

Primary outcomes measures

Physician visits, dentist visits and hospitalisations in the last 12 months were the primary outcomes. Associated factors were investigated through the calculation of prevalence ratio (PR) obtained by hierarchical Poisson regression modelling.

Results

4001 adults were included in the study, 53% of whom were women. The self-reported prevalence of medical visits was 77% (95% CI 75% to 77%); dentist visits, 36% (95% CI 34% to 37%) and hospital admission, 7% (95% CI 6% to 7%). Physician visits were higher in women PR=1.18 (95% CI 1.14 to 1.23), the elderly PR=1.18 (95% CI 1.10 to 1.26) and people with health insurance PR=1.14 (95% CI 1.10 to 1.19). Dentist visits declined with older age PR=0.38 (95% CI 0.30 to 0.49), lower education level PR=0.62 (95% CI 0.51 to 0.74) and lower economic class PR=0.65 (95% CI 0.57 to 0.75). Hospitalisations were found to be twice as frequent for women than for men and three times as frequent among those who reported very poor health status. Among the individuals who did not receive medical attention in the previous 2 weeks, 58% reported lack of facilities or appointment unavailable and 14% reported lack of doctors.

Conclusion

While more than half visited the doctor in the last year, a lower proportion of people with socioeconomic inequities visited the dentist. Organisational and service policies are needed to increase equity in health services in the region.
Exploring the effects of transfers and readmissions on trends in population counts of hospital admissions for coronary heart disease: a Western Australian data linkage study
Authors: Lopez Derrick , Nedkoff Lee , Knuiman Matthew , Hobbs Michael S T , Briffa Thomas G , Preen David B , Hung Joseph , Beilby John , Mathur Sushma , Reynolds Anna , Sanfilippo Frank M
Published: November 2017

Objectives

To develop a method for categorising coronary heart disease (CHD) subtype in linked data accounting for different CHD diagnoses across records, and to compare hospital admission numbers and ratios of unlinked versus linked data for each CHD subtype over time, and across age groups and sex.

Design

Cohort study.

Data source

Person-linked hospital administrative data covering all admissions for CHD in Western Australia from 1988 to 2013.

Main outcome

Ratios of (1) unlinked admission counts to contiguous admission (CA) counts (accounting for transfers), and (2) 28-day episode counts (accounting for transfers and readmissions) to CA counts stratified by CHD subtype, sex and age group.

Results

In all CHD subtypes, the ratios changed in a linear or quadratic fashion over time and the coefficients of the trend term differed across CHD subtypes. Furthermore, for many CHD subtypes the ratios also differed by age group and sex. For example, in women aged 35–54 years, the ratio of unlinked to CA counts for non-ST elevation myocardial infarction admissions in 2000 was 1.10, and this increased in a linear fashion to 1.30 in 2013, representing an annual increase of 0.0148.

Conclusion

The use of unlinked counts in epidemiological estimates of CHD hospitalisations overestimates CHD counts. The CA and 28-day episode counts are more aligned with epidemiological studies of CHD. The degree of overestimation of counts using only unlinked counts varies in a complex manner with CHD subtype, time, sex and age group, and it is not possible to apply a simple correction factor to counts obtained from unlinked data.
Association of homocysteine and smoking with cerebral microemboli in patients with mechanical heart valves: a transcranial Doppler study
Authors: Mattia Alicia , Azarpazhooh M Reza , Munoz Claudio , Bogiatzi Chrysi , Quantz Mackenzie A , Spence J David
Published: November 2017

Objectives

Microembolic signals (MES) on transcranial Doppler (TCD) predict stroke and cognitive decline. Plasma levels of total homocysteine (tHcy), a prothrombotic factor, are higher in patients with microemboli in carotid stenosis and in patients with paradoxical embolism. In this study we assessed the association between the level of tHcy and the number of MES in patients with mechanical heart valves (MHVs).

Methods

TCD monitoring was performed to detect MES before and after breathing 100% oxygen and repeated every 2–4 weeks up to six times.

Results

Twenty-five patients with MHVs (mean age: 63.60±10.15 years) participated in this study; 15 were men (66.47±7.25 years) and 10 were women (59.30±12.60 years). In total, there were 126 study visits. In multiple regression, higher tHcy was associated with more MES in both preoxygenation (OR 1.34 (95% CI 1.07 to 1.68, P=0.009)) and postoxygenation (OR 1.40 (95% CI 1.07 to 1.83, P=0.01)) phases. Current smoking and the length of time between the operation and monitoring also correlated with a higher number of MES before and after breathing oxygen, particularly in women.

Conclusions

Higher tHcy and smoking were associated with a higher MES count in both preoxygenation and postoxygenation phases. Because smoking can be stopped and hyperhomocysteinaemia is treatable, these are clinically important findings.
Camel whey protein protects lymphocytes from apoptosis via the PI3K–AKT, NF-κB, ATF-3, and HSP-70 signaling pathways in heat-stressed male mice
Authors: Badr Gamal , Ramadan Nancy K. , Abdel-Tawab Hanem S. , Ahmed Samia F. , Mahmoud Mohamed H.
Published: November 2017

Heat stress (HS) is an environmental factor that depresses the immune systems that mediate dysfunctional immune cells. Camel whey protein (CWP) can scavenge free radicals and enhance immunity. This study investigated the impact of dietary supplementation with CWP on immune dysfunction induced by exposure to HS. Male mice (n = 45) were distributed among 3 groups: control group; HS group; and HS mice that were orally administered CWP (HS + CWP group). The HS group exhibited elevated levels of reactive oxygen species (ROS) and pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor-α) as well as a significant reduction in the IL-2 and IL-4 levels. Exposure to HS resulted in impaired phosphorylation of AKT and IκB-α (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha); increased expression of activating transcription factor 3 (ATF-3) and 70 kDa heat shock proteins (HSP70); and aberrant distribution of CD3+ T cells and CD20+ B cells in the thymus and spleen. Interestingly, HS mice treated with CWP presented significantly restored levels of reactive oxygen species and pro-inflammatory cytokines near the levels observed in the control mice. Furthermore, supplementation of HS mice with CWP enhanced the phosphorylation of AKT and IκB-α; attenuated the expression of ATF-3, HSP70, and HSP90; and improved T and B cell distributions in the thymus and spleen. Our findings reveal a potential immunomodulatory effect of CWP in attenuating immune dysfunction induced by exposure to thermal stress.
Probing light bino and higgsinos at the LHC
Authors: Han Chengcheng
Published: November 2017

Motivated by the naturalness, we study a simplified Minimal Supersymmetric Standard Model (MSSM) scenario where only the bino-like lightest supersymmetric particle (LSP) and higgsino-like next-lightest supersymmetric particle (NLSP) are light. We first scan the parameter space of this scenario, considering the constraints from the Higgs mass, flavor physics, electroweak precision measurements and dark matter experiments. Then in the allowed parameter space, we perform a Monte Carlo simulation for the [Formula: see text] production followed by [Formula: see text] and [Formula: see text]. By examining the presently available trilepton bounds on the wino-like chargino/neutralino, we find that only a narrow region [Formula: see text] and [Formula: see text] on the plane of [Formula: see text] can be excluded. Finally, we explore the potential of trilepton signature in probing such a scenario at 14 TeV Large Hadron Collider (LHC) and find that the region with [Formula: see text] and [Formula: see text] can be covered at [Formula: see text] level with luminosity [Formula: see text].