bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Novel Strains of Torulaspora delbrueckii Isolated from the Honey Bee Microbiome and Their Use in Honey Fermentation
Authors: Barry Joseph , Metz Mindy , Hughey Justin , Quirk Adam , Bochman Matthew
Published: March 2018

Yeasts are ubiquitous microbes found in virtually all environments. Many yeast species can ferment sugar into ethanol and CO2, and humans have taken advantage of these characteristics to produce fermented beverages for thousands of years. As a naturally abundant source of fermentable sugar, honey has had a central role in such fermentations since Neolithic times. However, as beverage fermentation has become industrialized, the processes have been streamlined, including the narrow and almost exclusive usage of yeasts in the genus Saccharomyces for fermentation. We set out to identify wild honey- or honey-bee-related yeasts that can be used in honey fermentation. Here, we isolated two strains of Torulaspora delbrueckii from the gut of a locally collected honey bee. Both strains were able to ferment honey sugar into mead but failed to metabolize more than a modest amount of wort sugar in trial beer fermentations. Further, the meads fermented by the T. delbrueckii strains displayed better sensory characteristics than mead fermented by a champagne yeast. The combination of T. delbrueckii and champagne yeast strains was also able to rapidly ferment honey at an industrial scale. Thus, wild yeasts represent a largely untapped reservoir for the introduction of desirable sensory characteristics in fermented beverages such as mead.
Non-Pleiotropic Coupling of Daily and Seasonal Temporal Isolation in the European Corn Borer
Authors: Levy Rebecca , Kozak Genevieve , Dopman Erik
Published: March 2018

Speciation often involves the coupling of multiple isolating barriers to produce reproductive isolation, but how coupling is generated among different premating barriers is unknown. We measure the degree of coupling between the daily mating time and seasonal mating time between strains of European corn borer (Ostrinia nubilalis) and evaluate the hypothesis that the coupling of different forms of allochrony is due to a shared genetic architecture, involving genes with pleiotropic effects on both timing phenotypes. We measure differences in gene expression at peak mating times and compare these genes to previously identified candidates that are associated with changes in seasonal mating time between the corn borer strains. We find that the E strain, which mates earlier in the season, also mates 2.7 h earlier in the night than the Z strain. Earlier daily mating is correlated with the differences in expression of the circadian clock genes cycle, slimb, and vrille. However, different circadian clock genes associate with daily and seasonal timing, suggesting that the coupling of timing traits is maintained by natural selection rather than pleiotropy. Juvenile hormone gene expression was associated with both types of timing, suggesting that circadian genes activate common downstream modules that may impose constraint on future evolution of these traits.
The Impact of Acoustic Imaging Geometry on the Fidelity of Seabed Bathymetric Models
Authors: Hughes Clarke John
Published: March 2018

Attributes derived from digital bathymetric models (DBM) are a powerful means of analyzing seabed characteristics. Those models however are inherently constrained by the method of seabed sampling. Most bathymetric models are derived by collating a number of discrete corridors of multibeam sonar data. Within each corridor the data are collected over a wide range of distances, azimuths and elevation angles and thus the quality varies significantly. That variability therefore becomes imprinted into the DBM. Subsequent users of the DBM, unfamiliar with the original acquisition geometry, may potentially misinterpret such variability as attributes of the seabed. This paper examines the impact on accuracy and resolution of the resultant derived model as a function of the imaging geometry. This can be broken down into the range, angle, azimuth, density and overlap attributes. These attributes in turn are impacted by the sonar configuration including beam widths, beam spacing, bottom detection algorithms, stabilization strategies, platform speed and stability. Superimposed over the imaging geometry are residual effects due to imperfect integration of ancillary sensors. As the platform (normally a surface vessel), is moving with characteristic motions resulting from the ocean wave spectrum, periodic residuals in the seafloor can become imprinted that may again be misinterpreted as geomorphological information.
Three-Dimensional Growth of Flexural Slip Fault-Bend and Fault-Propagation Folds and Their Geomorphic Expression
Authors: Bernal Asdrúbal , Hardy Stuart , Gawthorpe Robert
Published: March 2018

The three-dimensional growth of fault-related folds is known to be an important process during the development of compressive mountain belts. However, comparatively little is known concerning the manner in which fold growth is expressed in topographic relief and local drainage networks. Here we report results from a coupled kinematic and surface process model of fault-related folding. We consider flexural slip fault-bend and fault-propagation folds that grow in both the transport and strike directions, linked to a surface process model that includes bedrock channel development and hillslope diffusion. We investigate various modes of fold growth under identical surface process conditions and critically analyse their geomorphic expression. Fold growth results in the development of steep forelimbs and gentler, wider backlimbs resulting in asymmetric drainage basin development (smaller basins on forelimbs, larger basins on backlimbs). However, topographies developed above fault-propagation folds are more symmetric than those developed above fault-bend folds as a result of their different forelimb kinematics. In addition, the surface expression of fault-bend and fault-propagation folds depends both on the slip distribution along the fault and on the style of fold growth. When along-strike plunge is a result of slip events with gently decreasing slip towards the fault tips (with or without lateral propagation), large plunge-panel drainage networks are developed at the expense of backpanel (transport-opposing) and forepanel (transport-facing) drainage basins. In contrast, if the fold grows as a result of slip events with similar displacements along strike, plunge-panel drainage networks are poorly developed (or are transient features of early fold growth) and restricted to lateral fold terminations, particularly when the number of propagation events is small. The absence of large-scale plunge-panel drainage networks in natural examples suggests that the latter mode of fold growth may be more common. The advective component of deformation (implicit in kink-band migration models of fault-bend and fault-propagation folding) exerts a strong control on drainage basin development. In particular, as drainage lengthens with fold growth, more linear, parallel drainage networks are developed as compared to the dendritic patterns developed above simple uplifting structures. Over the 1 Ma of their development the folds modelled here only attain partial topographic equilibrium, as new material is continually being advected through active axial surfaces on both fold limbs and faults are propagating in both the transport and strike directions. We also find that the position of drainage divides at the Earth’s surface has a complex relationship to the underlying fold axial surface locations.
Spatiotemporal Characteristics and Health Risk Assessment of Heavy Metals in PM2.5 in Zhejiang Province
Authors: Wang Xiaofeng , He Shengliang , Chen Shuchang , Zhang Yongli , Wang Aihong , Luo Jinbin , Ye Xialiang , Mo Zhe , Wu Lizhi , Xu Peiwei , Cai Gaofeng , Chen Zhijian , Lou Xiaoming
Published: March 2018

The spatiotemporal characteristics and human health risks of 12 heavy metals (Al, As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sb, Se, and Tl) in fine particulate matter (PM2.5) in Zhejiang Province were investigated. The annual average PM2.5 concentration was 58.83 µg/m3 in 2015 in Zhejiang. Element contents in PM2.5 varied greatly with the season and locations. Al, Pb, and Mn were the most abundant elements among the studied metal(loid)s in PM2.5. The non-carcinogenic risks of the 12 elements through inhalation and dermal contact exposure were lower than the safe level for children and adults. However, there were potential non-carcinogenic risks of Tl, As, and Sb for children and Tl for adults through ingestion exposure. The carcinogenic risks from As, Be, Cd, Cr, Pb, and Ni through inhalation exposure were less than the acceptable level (1 × 10−4) for children and adults. Pb may carry a potential carcinogenic risk for both children and adults through ingestion. More attention should be paid to alleviate non-carcinogenic and carcinogenic health risks posed by particle-bound toxic elements through ingestion exposure.
Importance of Footwear for Preventing Xerosis and Hyperkeratosis in Older People with Psychiatric Disorders Living in an Institution
Authors: Pérez-Pico Ana , Marcos-Tejedor Félix , Iglesias-Sánchez María , Acevedo Raquel
Published: March 2018

Few studies have focused on the relation between the use and characteristics of footwear and the presence of foot lesions in people with psychiatric disorders. This work analyzes the influence of different footwear habits on the presence of deformities and ungueal and dermal pathologies of the foot of institutionalized people with psychiatric disorders compared to people without these disorders. A transversal and observational study was conducted on 107 participants, divided into two groups who have used different types of shoes throughout their lives. The control group comprised 63 autonomous people who mainly use leather footwear and a study group of 44 institutionalized people with intellectual disabilities and psychiatric disorders who mainly use textile footwear. There were significant differences between populations. The group with psychiatric disorders presented more xerosis and hyperkeratosis. Footwear with inappropriate characteristics is a possible causal agent of skin alterations. Wearing footwear with quality textile uppers, e.g., fabric or felt, could influence the appearance of these alterations. Leather footwear is recommended for institutionalized people to reduce symptoms of xerosis and improve their quality of life.
Influence of Algae Age and Population on the Response to TiO2 Nanoparticles
Authors: Metzler David , Erdem Ayca , Huang Chin
Published: March 2018

This work shows the influence of algae age (at the time of the exposure) and the initial algae population on the response of green algae Raphidocelis subcapitata to titanium dioxide nanoparticles (TiO2 NPs). The different algae age was obtained by changes in flow rate of continually stirred tank reactors prior to NP exposure. Increased algae age led to a decreased growth, variations in chlorophyll content, and an increased lipid peroxidation. Increased initial algae population (0.3−4.2 × 106 cells/mL) at a constant NP concentration (100 mg/L) caused a decline in the growth of algae. With increased initial algae population, the lipid peroxidation and chlorophyll both initially decreased and then increased. Lipid peroxidation had 4× the amount of the control at high and low initial population but, at mid-ranged initial population, had approximately half the control value. Chlorophyll a results also showed a similar trend. These results indicate that the physiological state of the algae is important for the toxicological effect of TiO2 NPs. The condition of algae and exposure regime must be considered in detail when assessing the toxicological response of NPs to algae.
Sedentary Behaviour and Hair Cortisol Amongst Women Living in Socioeconomically Disadvantaged Neighbourhoods: A Cross-Sectional Study
Authors: Teychenne Megan , Olstad Dana Lee , Turner Anne I. , Costigan Sarah A. , Ball Kylie
Published: March 2018

Women living in socioeconomically disadvantaged neighbourhoods are at heightened risk of experiencing psychological stress. Therefore, identifying potential risk factors for stress is important to support positive mental health. A growing body of research has linked sedentary behaviour with mental ill-health (e.g., depression and anxiety); however, little research has specifically investigated potential linkages between sedentary behaviour and stress. Therefore, the aim of this study was to investigate the association between common types of sedentary behaviour and objectively-measured stress (as measured by hair cortisol levels) amongst women living in socioeconomically disadvantaged neighbourhoods. During 2012–2013, 72 women (aged 18–46 years) living in socioeconomically disadvantaged neighbourhoods self-reported sedentary behaviour (TV viewing, computer use, overall sitting time) and provided hair samples. Hair cortisol levels were measured using enzyme-linked immunosorbent assay. Linear regression models examined cross-sectional associations between sedentary behaviour and hair cortisol levels. There was no association between any type of sedentary behaviour (TV viewing, computer use, or overall sitting time) and hair cortisol levels in either crude or adjusted models. Sedentary behaviour may not be linked to hair cortisol level (stress) in women living in socioeconomically disadvantaged neighbourhoods. Further studies utilising objective measures of both sedentary behaviour and stress are required to confirm these findings.
Roma Housing and Eating in 1775 and 2013: A Comparison
Authors: Kozubik Michal , Van Dijk Jitse , Odraskova Barbora
Published: March 2018

We compared housing and the eating habits of Roma. Contemporary findings (2013) were compared with those from the first monothematic work on Roma (1775), which depicts their housing and eating habits, especially regarding the differences between social classes. Data were obtained from a journal (1775) and from semi-structured interviews (2013) with more than 70 Roma women and men who live in segregated and excluded settlements at the edges of villages or scattered among the majority. Data were collected in two villages and one district town in the Tatra region, where the data from the 1775 measurements originated. We used classical sociological theory to interpret the obtained data. The main findings showed differences between specific social classes then and now regarding housing, as well as the eating habits related to both conditions among the Roma in the Tatra region. The houses of rich Roma families did not differ from the houses of the majority population. The huts of the poorest inhabitants of settlements did not meet any hygiene standards. Typical Roma foods such as gója or marikľa were the traditional foods of Slovak peasants living in poverty in the country. We concluded that the housing and eating habits of the citizens of poor settlements located in the eastern parts of Slovakia are still similar to those of two centuries ago. The existing social exclusion may be explained partly from this finding.
Understanding Outdoor Gyms in Public Open Spaces: A Systematic Review and Integrative Synthesis of Qualitative and Quantitative Evidence
Authors: Lee Janet , Lo Temmy , Ho Rainbow
Published: March 2018

(1) Background: An outdoor gym (OG) is environmental infrastructure built in a public open space to promote structured physical activity. The provision of OGs is increasingly seen as an important strategy to realize public health agendas promoting habitual physical activity. A systematic review was conducted to synthesize characteristics of OG and OG users’ experiences and perceptions in different cultural contexts; (2) Methods: Online searches of multidisciplinary databases were conducted in health, sport and recreation, and urban planning disciplines. Characteristics of OGs were synthesized by integrating evidence from quantitative, qualitative, and mix-methods studies. The experiences and perceptions of OG users from both qualitative data and survey responses were synthesized through framework analysis; (3) Results: Nine studies met the inclusion criteria (three quantitative studies, four mixed-methods studies, and two pure qualitative studies). None were excluded on the basis of quality. OGs mainly serve adult and older adult population groups. Their size, design, and instructional support vary across studies. The inclusion of functional types of equipment did not have a unified standard. Regarding experiences and perceptions of OGs, five major themes emerged: “health”, “social connectedness”, “affordable”, “support”, and “design and promotion”; (4) Conclusions: The OG characteristics synthesis guides the direction in further studies regarding exploration of design parameters. The qualitative and quantitative synthesis revealed that health was a central theme of users’ experiences. OGs are also spaces where community-dwellers can find social connectedness while participating in structured physical activity at no cost. Findings from this review create knowledge support for OG as environmental infrastructure for further research and facilitate the understanding of users’ experiences and perceptions of OGs in different cultural contexts.
Radiofrequency Electromagnetic Radiation and Memory Performance: Sources of Uncertainty in Epidemiological Cohort Studies
Authors: Brzozek Christopher , Benke Kurt , Zeleke Berihun , Abramson Michael , Benke Geza
Published: March 2018

Uncertainty in experimental studies of exposure to radiation from mobile phones has in the past only been framed within the context of statistical variability. It is now becoming more apparent to researchers that epistemic or reducible uncertainties can also affect the total error in results. These uncertainties are derived from a wide range of sources including human error, such as data transcription, model structure, measurement and linguistic errors in communication. The issue of epistemic uncertainty is reviewed and interpreted in the context of the MoRPhEUS, ExPOSURE and HERMES cohort studies which investigate the effect of radiofrequency electromagnetic radiation from mobile phones on memory performance. Research into this field has found inconsistent results due to limitations from a range of epistemic sources. Potential analytic approaches are suggested based on quantification of epistemic error using Monte Carlo simulation. It is recommended that future studies investigating the relationship between radiofrequency electromagnetic radiation and memory performance pay more attention to treatment of epistemic uncertainties as well as further research into improving exposure assessment. Use of directed acyclic graphs is also encouraged to display the assumed covariate relationship.
What Persons with Chronic Health Conditions Need to Maintain or Return to Work—Results of an Online-Survey in Seven European Countries
Authors: Foitzek Nicole , Ávila Carolina , Ivandic Ivana , Bitenc Črtomir , Cabello Maria , Gruber Sonja , Leonardi Matilde , Muñoz-Murillo Amalia , Scaratti Chiara , Tobiasz-Adamczyk Beata , Vlachou Anastasia , Esteban Eva , Sabariego Carla , Coenen Michaela
Published: March 2018

Chronic health conditions represent the major share of the disease burden in Europe and have a significant impact on work. This study aims to: (1) identify factors that have a negative or positive impact on the work lives of persons with chronic health conditions; (2) explore the needs of these persons to maintain a job or return to work and (3) compare these results with respect to these persons’ occupational status. An online survey was performed in seven European countries. Open-ended survey questions were analyzed using qualitative methods. In total, 487 participants with six chronic health conditions participated. The majority of participants named work-related aspects (such as career development, stress at the workplace, work structure and schedule as well as workload), support of others and attitudes of others as being the factors positively and negatively impact their work lives the most. Our study shed light on the importance of changing the attitudes of supervisors and co-workers to counteract stigmatization of persons with chronic health conditions in the workplace. In conclusion, this study provides a basis for developing new strategies of integration and reintegration at work for persons with chronic health conditions in European countries.
Physical Activity Environment and Japanese Adults’ Body Mass Index
Authors: Koohsari Mohammad , Kaczynski Andrew , Hanibuchi Tomoya , Shibata Ai , Ishii Kaori , Yasunaga Akitomo , Nakaya Tomoki , Oka Koichiro
Published: March 2018

Evidence about the impacts of the physical activity environment on adults’ weight in the context of Asian countries is scarce. Likewise, no study exists in Asia examining whether Walk Score®—a free online walkability tool—is related to obesity. This study aimed to examine associations between multiple physical activity environment measures and Walk Score® ratings with Japanese adults’ body mass index (BMI). Data from 1073 adults in the Healthy Built Environment in Japan study were used. In 2011, participants reported their height and weight. Environmental attributes, including population density, intersection density, density of physical activity facilities, access to public transportation, and availability of sidewalks, were calculated using Geographic Information Systems. Walk Scores® ratings were obtained from the website. Multiple linear regression analysis was conducted to examine the association between each environmental attribute and BMI. Adjusting for covariates, all physical activity environmental attributes were negatively associated with BMI. Similarly, an increase of one standard deviation of Walk Score® was associated with a 0.29 (95% confidence interval (CI) of −0.49–−0.09) decrease in BMI. An activity-friendly built environment was associated with lower adults’ BMI in Japan. Investing in healthy community design may positively impact weight status in non-Western contexts.
Legionella spp. Risk Assessment in Recreational and Garden Areas of Hotels
Authors: Papadakis Antonios , Chochlakis Dimosthenis , Sandalakis Vassilios , Keramarou Maria , Tselentis Yannis , Psaroulaki Anna
Published: March 2018

Several Travel-associated Legionnaires’ disease (TALD) cases occur annually in Europe. Except from the most obvious sites (cooling towers and hot water systems), infections can also be associated with recreational, water feature, and garden areas of hotels. This argument is of great interest to better comprehend the colonization and to calculate the risk to human health of these sites. From July 2000–November 2017, the public health authorities of the Island of Crete (Greece) inspected 119 hotels associated with TALD, as reported through the European Legionnaires’ Disease Surveillance Network. Five hundred and eighteen samples were collected from decorative fountain ponds, showers near pools and spas, swimming pools, spa pools, garden sprinklers, drip irrigation systems (reclaimed water) and soil. Of those, 67 (12.93%), originating from 43 (35.83%) hotels, tested positive for Legionella (Legionella pneumophila serogroups 1, 2, 3, 6, 7, 8, 13, 14, 15 and non-pneumophila species (L. anisa, L. erythra, L. taurinensis, L. birminghamensis, L. rubrilucens). A Relative Risk (R.R.) > 1 (p < 0.0001) was calculated for chlorine concentrations of less than 0.2 mg/L (R.R.: 54.78), star classification (<4) (R.R.: 4.75) and absence of Water Safety Plan implementation (R.R.: 3.96). High risk (≥104 CFU/L) was estimated for pool showers (16.42%), garden sprinklers (7.46%) and pool water (5.97%).
An Efficient Shortest Path Routing Algorithm for Directed Indoor Environments
Authors: Alamri Sultan
Published: March 2018

Routing systems for outdoor space have become the focus of many research works. Such routing systems are based on spatial road networks where moving objects (such as cars) are affected by the directed roads and the movement of traffic, which may include traffic jams. Indoor routing, on the other hand, must take into account the features of indoor space such as walls and rooms. In this paper, we take indoor routing in a new direction whereby we consider the features that a building has in common with outdoor spaces. Inside some buildings, there may be directed floors where moving objects must move in a certain direction through directed corridors in order to reach a certain location. For example, on train platforms or in museums, movement in the corridors may be directed. In these directed floor spaces, a routing system enabling a visitor to take the shortest path to a certain location is essential. Therefore, this work proposes a new approach for buildings with directed indoor spaces, where each room can be affected by the density of the moving objects. The proposed system obtains the shortest path between objects or rooms taking into consideration the directed indoor space and the capacity of the objects to move within each room/cell.
Survivin-Based Treatment Strategies for Squamous Cell Carcinoma
Authors: Santarelli Andrea , Mascitti Marco , Lo Russo Lucio , Sartini Davide , Troiano Giuseppe , Emanuelli Monica , Lo Muzio Lorenzo
Published: March 2018

Survivin, an anti-apoptotic molecule abundantly expressed in most human neoplasms, has been reported to contribute to cancer initiation and drug resistance in a wide variety of human tumors. Efficient downregulation of survivin can sensitize tumor cells to various therapeutic interventions, generating considerable efforts in its validation as a new target in cancer therapy. This review thoroughly analyzes up-to-date information on the potential of survivin as a therapeutic target for new anticancer treatments. The literature dealing with the therapeutic targeting of survivin will be reviewed, discussing specifically squamous cell carcinomas (SCCs), and with emphasis on the last clinical trials. This review gives insight into the recent developments undertaken in validating various treatment strategies that target survivin in SCCs and analyze the translational possibility, identifying those strategies that seem to be the closest to being incorporated into clinical practice. The most recent developments, such as dominant-negative survivin mutants, RNA interference, anti-sense oligonucleotides, small-molecule inhibitors, and peptide-based immunotherapy, seem to be helpful for effectively downregulating survivin expression and reducing tumor growth potential, increasing the apoptotic rate, and sensitizing tumor cells to chemo- and radiotherapy. However, selective and efficient targeting of survivin in clinical trials still poses a major challenge.
Evaluation of Two Liver Treatment Strategies in a Mouse Model of Niemann–Pick-Disease Type C1
Authors: Ebner Lynn , Gläser Anne , Bräuer Anja , Witt Martin , Wree Andreas , Rolfs Arndt , Frank Marcus , Vollmar Brigitte , Kuhla Angela
Published: March 2018

Niemann–Pick-disease type C1 (NPC1) is an autosomal-recessive cholesterol-storage disorder. Besides other symptoms, NPC1 patients develop liver dysfunction and hepatosplenomegaly. The mechanisms of hepatomegaly and alterations of lipid metabolism-related genes in NPC1 disease are still poorly understood. Here, we used an NPC1 mouse model to study an additive hepatoprotective effect of a combination of 2-hydroxypropyl-β-cyclodextrin (HPβCD), miglustat and allopregnanolone (combination therapy) with the previously established monotherapy using HPβCD. We examined transgene effects as well as treatment effects on liver morphology and hepatic lipid metabolism, focusing on hepatic cholesterol transporter genes. Livers of Npc1−/− mice showed hepatic cholesterol sequestration with consecutive liver injury, an increase of lipogenetic gene expression, e.g., HMG-CoA, a decrease of lipolytic gene expression, e.g., pparα and acox1, and a decrease of lipid transporter gene expression, e.g., acat1, abca1 and fatp2. Both, combination therapy and monotherapy, led to a reduction of hepatic lipids and an amelioration of NPC1 liver disease symptoms. Monotherapy effects were related to pparα- and acox1-associated lipolysis/β-oxidation and to fatp2-induced fatty acid transport, whereas the combination therapy additionally increased the cholesterol transport via abca1 and apoE. However, HPβCD monotherapy additionally increased cholesterol synthesis as indicated by a marked increase of the HMG-CoA and srebp-2 mRNA expression, probably as a result of increased hepatocellular proliferation.
Mammalian Plakins, Giant Cytolinkers: Versatile Biological Functions and Roles in Cancer
Authors: Hu Lifang , Huang Zizhan , Wu Zixiang , Ali Arshad , Qian Airong
Published: March 2018

Cancer is a highly lethal disease that is characterized by aberrant cell proliferation, migration, and adhesion, which are closely related to the dynamic changes of cytoskeletons and cytoskeletal-adhesion. These will further result in cell invasion and metastasis. Plakins are a family of giant cytolinkers that connect cytoskeletal elements with each other and to junctional complexes. With various isoforms composed of different domain structures, mammalian plakins are broadly expressed in numerous tissues. They play critical roles in many cellular processes, including cell proliferation, migration, adhesion, and signaling transduction. As these cellular processes are key steps in cancer development, mammalian plakins have in recent years attracted more and more attention for their potential roles in cancer. Current evidence shows the importance of mammalian plakins in various human cancers and demonstrates mammalian plakins as potential biomarkers for cancer. Here, we introduce the basic characteristics of mammalian plakins, review the recent advances in understanding their biological functions, and highlight their roles in human cancers, based on studies performed by us and others. This will provide researchers with a comprehensive understanding of mammalian plakins, new insights into the development of cancer, and novel targets for cancer diagnosis and therapy.
Functional Characterization of Novel Atrial Fibrillation-Linked GJA5 (Cx40) Mutants
Authors: Noureldin Mahmoud , Chen Honghong , Bai Donglin
Published: March 2018

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Recently, four novel heterozygous Cx40 mutations—K107R, L223M, Q236H, and I257L—were identified in 4 of 310 unrelated AF patients and a followup genetic analysis of the mutant carriers’ families showed that the mutants were present in all the affected members. To study possible alterations associated with these Cx40 mutants, including their cellular localization and gap junction (GJ) function, we expressed GFP-tagged and untagged mutants in connexin-deficient model cells. All four Cx40 mutants showed clustered localization at cell–cell junctions similar to that observed of wildtype Cx40. However, cell pairs expressing Cx40 Q236H, but not the other individual mutants, displayed a significantly lower GJ coupling conductance (Gj) than wildtype Cx40. Similarly, co-expression of Cx40 Q236H with Cx43 resulted in a significantly lower Gj. Transjunctional voltage-dependent gating (Vj gating) properties were also altered in the GJs formed by Q236H. Reduced GJ function and altered Vj gating may play a role in promoting the Q236H carriers to AF.
Protein Expression in Tonsillar and Base of Tongue Cancer and in Relation to Human Papillomavirus (HPV) and Clinical Outcome
Authors: Ramqvist Torbjörn , Näsman Anders , Franzén Bo , Bersani Cinzia , Alexeyenko Andrey , Becker Susanne , Haeggblom Linnea , Kolev Aeneas , Dalianis Tina , Munck-Wikland Eva
Published: March 2018

Human papillomavirus (HPV) is a major etiological factor for tonsillar and the base of tongue cancer (TSCC/BOTSCC). HPV-positive and HPV-negative TSCC/BOTSCC present major differences in mutations, mRNA expression and clinical outcome. Earlier protein studies on TSCC/BOTSCC have mainly analyzed individual proteins. Here, the aim was to compare a larger set of cancer and immune related proteins in HPV-positive and HPV-negative TSCC/BOTSCC in relation to normal tissue, presence of HPV, and clinical outcome. Fresh frozen tissue from 42 HPV-positive and 17 HPV-negative TSCC/BOTSCC, and corresponding normal samples, were analyzed for expression of 167 proteins using two Olink multiplex immunoassays. Major differences in protein expression between TSCC/BOTSCC and normal tissue were identified, especially in chemo- and cytokines. Moreover, 34 proteins, mainly immunoregulatory proteins and chemokines, were differently expressed in HPV-positive vs HPV-negative TSCC/BOTSCC. Several proteins were potentially related to clinical outcome for HPV-positive or HPV-negative tumors. For HPV-positive tumors, these were mostly related to angiogenesis and hypoxia. Correlation with clinical outcome of one of these, VEGFA, was validated by immunohistochemistry. Differences in immune related proteins between HPV-positive and HPV-negative TSCC/BOTSCC reflect the stronger activity of the immune defense in the former. Angiogenesis related proteins might serve as potential targets for therapy in HPV-positive TSCC/BOTSCC.
Inactivation of SREBP-1a Phosphorylation Prevents Fatty Liver Disease in Mice: Identification of Related Signaling Pathways by Gene Expression Profiles in Liver and Proteomes of Peroxisomes
Authors: Knebel Birgit , Hartwig Sonja , Jacob Sylvia , Kettel Ulrike , Schiller Martina , Passlack Waltraud , Koellmer Cornelia , Lehr Stefan , Müller-Wieland Dirk , Kotzka Jorg
Published: March 2018

The key lipid metabolism transcription factor sterol regulatory element-binding protein (SREBP)-1a integrates gene regulatory effects of hormones, cytokines, nutrition and metabolites as lipids, glucose, or cholesterol via phosphorylation by different mitogen activated protein kinase (MAPK) cascades. We have previously reported the impact of SREBP-1a phosphorylation on the phenotype in transgenic mouse models with liver-specific overexpression of the N-terminal transcriptional active domain of SREBP-1a (alb-SREBP-1a) or a MAPK phosphorylation site-deficient variant (alb-SREBP-1a∆P; (S63A, S117A, T426V)), respectively. In this report, we investigated the molecular basis of the systemic observations by holistic analyses of gene expression in liver and of proteome patterns in lipid-degrading organelles involved in the pathogenesis of metabolic syndrome, i.e., peroxisomes, using 2D-DIGE and mass spectrometry. The differences in hepatic gene expression and peroxisomal protein patterns were surprisingly small between the control and alb-SREBP-1a mice, although the latter develop a severe phenotype with visceral obesity and fatty liver. In contrast, phosphorylation site-deficient alb-SREBP-1a∆P mice, which are protected from fatty liver disease, showed marked differences in hepatic gene expression and peroxisomal proteome patterns. Further knowledge-based analyses revealed that disruption of SREBP-1a phosphorylation resulted in massive alteration of cellular processes, including signs for loss of targeting lipid pathways.
Knocking down Insulin Receptor in Pancreatic Beta Cell lines with Lentiviral-Small Hairpin RNA Reduces Glucose-Stimulated Insulin Secretion via Decreasing the Gene Expression of Insulin, GLUT2 and Pdx1
Authors: Wang Jie , Gu Wenyi , Chen Chen
Published: March 2018

Type 2 diabetes (T2D) is a metabolic disorder characterized by beta cell dysfunction and insulin resistance in fat, muscle and liver cells. Recent studies have shown that the development of insulin resistance in pancreatic beta cell lines may contribute to beta cell dysfunction in T2D. However, there still is a lack of detailed investigations regarding the mechanisms by which insulin deficiency may contribute in diabetes. In this study, we firstly established a stable insulin receptor knockdown cell line in pancreatic beta cells INS-1 (InsRβKD cells) using anti InsRβ small hairpin RNA (InsRβ-shRNA) encoded by lentiviral vectors. The resultant InsRβKD cells demonstrated a significantly reduced expression of InsRβ as determined by real-time PCR and Western blotting analyses. Upon removing glucose from the medium, these cells exhibited a significant decrease in insulin gene expression and protein secretion in response to 20 mM glucose stimulation. In accordance with this insulin reduction, the glucose uptake efficiency as indicated by a 3[H]-2-deoxy-d-glucose assay also decreased. Furthermore, InsRβKD cells showed a dramatic decrease in glucose transporter 2 (GLUT2, encoded by SLC2A2) and pancreatic duodenal homeobox (Pdx1) mRNA expression compared to the controls. These data collectively suggest that pancreatic beta cell insulin resistance contributes to the development of beta cell dysfunction by impairing pancreatic beta cell glucose sensation through the Pdx1- GLUT2 pathway. InsRβKD cells provide a good model to further investigate the mechanism of β-cell dysfunction in T2D.
Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans
Authors: Renouard Sullivan , Corbin Cyrielle , Drouet Samantha , Medvedec Barbara , Doussot Joël , Colas Cyril , Maunit Benoit , Bhambra Avninder , Gontier Eric , Jullian Nathalie , Mesnard François , Boitel Michèle , Abbasi Bilal , Arroo Randolph , Lainé Eric , Hano Christophe
Published: March 2018

Linum flavum hairy root lines were established from hypocotyl pieces using Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were effective for transformation but induction of hairy root phenotype was more stable with strain ATCC 15834. Whereas similar accumulation patterns were observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations were noted between root lines. The influence of culture medium and various treatments (hormone, elicitation and precursor feeding) were evaluated. The highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl jasmonate, and feeding using ferulic acid increased the accumulation of aryltetralin lignans. These results point to the use of hairy root culture lines of Linum flavum as potential sources for these valuable metabolites as an alternative, or as a complement to Podophyllum collected from wild stands.
Seed Hydropriming and Smoke Water Significantly Improve Low-Temperature Germination of Lupinus angustifolius L.
Authors: Płażek Agnieszka , Dubert Franciszek , Kopeć Przemysław , Dziurka Michał , Kalandyk Agnieszka , Pastuszak Jakub , Wolko Bogdan
Published: March 2018

Seed imbibition under cold temperature is dangerous when dry seeds have relatively low water content. The aim of this study was to investigate germination of 20 lines/cultivars of narrow-leaf lupine at 7 °C (cold) and 13 °C (control) under the influence of smoke water and following seed hydropriming for 3 h at 20 °C. The efficacy of individual treatments was examined with regard to seed protection during low-temperature germination. Based on seed germination, vigour at cold was evaluated four days after sowing by means of hypocotyl length, the studied lines/cultivars were divided into three groups with low, high and very high germination rates. Germination vigour correlated with cell membrane permeability, dehydrogenase activity and abscisic acid (ABA) content and was analysed in the seeds one day after sowing. Gibberellin content did not correlate with germination vigour. The seeds of weakly germinating lines/cultivars had the highest cell permeability and ABA content as well as the lowest amylolytic activity at both studied temperatures. Additionally, the vigour of weakly germinating seeds at 7 °C correlated with dehydrogenase activity. Three-hour hydropriming was the most effective for seed germination under cold due to reduced cell membrane permeability and ABA level. Stimulating effects of smoke water on germination under cold could be explained by enhanced dehydrogenase activity.
MicroRNA-146a Deficiency Protects against Listeria monocytogenes Infection by Modulating the Gut Microbiota
Authors: Du Chong-Tao , Gao Wei , Ma Ke , Yu Shui-Xing , Li Na , Yan Shi-Qing , Zhou Feng-Hua , Liu Zhen-Zhen , Chen Wei , Lei Lian-Cheng , Yang Yong-Jun , Han Wen-Yu
Published: March 2018

The gut microbiota and microRNAs play important roles in the defense against infection. However, the role of miR-146a in L. monocytogenes infection and gut microbiota remains unclear. We tried to determine whether miR-146a controlled L. monocytogenes infection by regulating the gut microbiota. Wild-type and miR-146a-deficient mice or macrophages were used to characterize the impact of miR-146a on animal survival, cell death, bacterial clearance, and gut microbiota following L. monocytogenes challenge. We found that L. monocytogenes infection induced miR-146a expression both in vitro and in vivo. When compared to wild-type mice, miR-146a-deficient mice were more resistant to L. monocytogenes infection. MiR-146a deficiency in macrophages resulted in reduced invasion and intracellular survival of L. monocytogenes. High-throughput sequencing of 16S rRNA revealed that the gut microbiota composition differed between miR-146a-deficient and wild-type mice. Relative to wild-type mice, miR-146a-deficient mice had decreased levels of the Proteobacteria phylum, Prevotellaceae family, and Parasutterella genus, and significantly increased short-chain fatty acid producing bacteria, including the genera Alistipes, Blautia, Coprococcus_1, and Ruminococcus_1. Wild-type mice co-housed with miR-146a-deficient mice had increased resistance to L. monocytogenes, indicating that miR-146a deficiency guides the gut microbiota to alleviate infection. Together, these results suggest that miR-146a deficiency protects against L. monocytogenes infection by regulating the gut microbiota.
Endophytic Mycoflora and Their Bioactive Compounds from Azadirachta Indica: A Comprehensive Review
Authors: Chutulo Eyob Chukalo , Chalannavar Raju Krishna
Published: March 2018

Plants are all inhabited by endophytic fungi in the interior of their tissues. The neem tree Azadirachta is an Indian lilac used for various therapeutic purposes in different forms of preparations. This plant hosts different types of endophytic fungi. In some cases, different tissues of a given plant are inhabited by different endophytic fungi which are discussed in this paper. Recently, there have been new reports on endophytic fungi and their bioactive compounds from Azadirachta indica. The biological function of bioactive compounds was discussed in view of their future industrial prospects. There are a number of different research investigations that examine the endophytes isolated and screened for their potential bioactive secondary metabolites from neem, but there is no comprehensive review on neem endophytes and their secondary metabolites to bring all trends from different researchers together. Therefore, in this review, we have discussed the endophytic fungi from the different tissues of neem, in view of the latest understandings of antimicrobial, antioxidant, and pathogenicity target compounds. Importantly, tracing the previous findings would pave the way to forecast the missing link for future work by researchers.
Photophysical and Photocatalytic Properties of BiSnSbO6 under Visible Light Irradiation
Authors: Luan Jingfei , Huang Panqi
Published: March 2018

BiSnSbO6 with strong photocatalytic activity was first fabricated by a high-temperature, solid-state sintering method. The resulting BiSnSbO6 was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (DRS) and X-ray photoelectron spectroscopy (XPS). The results showed that BiSnSbO6, with a pyrochlore structure and a cubic crystal system by a space group Fd3m, was well crystallized. The lattice parameter or the band gap of BiSnSbO6 was 10.234594 Å or 2.83 eV. Compared with N-doped TiO2, BiSnSbO6 showed higher photocatalytic activity in the degradation of benzotriazole and rhodamine B. The apparent first-order rate constant for BiSnSbO6 in the degradation of benzotriazole and rhodamine B was 0.0182 min−1 and 0.0147 min−1, respectively. On the basis of the scavenger experiment, during the photocatalytic process, the main active species were arranged in order of increasing photodegradation rate: •OH < •O2− < h+. The removal rate of benzotriazole or rhodamine B was approximately estimated to be 100% with BiSnSbO6 as a photocatalyst after 200 min visible-light irradiation. Plentiful CO2 produced by the experiment indicated that benzotriazole or rhodamine B was continuously mineralized during the photocatalytic process. Finally, the possible photodegradation pathways of benzotriazole and rhodamine B were deduced.
Effect of Segregation and Surface Condition on Corrosion of Rheo-HPDC Al–Si Alloys
Authors: Eslami Maryam , Payandeh Mostafa , Deflorian Flavio , Jarfors Anders , Zanella Caterina
Published: March 2018

Corrosion properties of two Al–Si alloys processed by Rheo-high pressure die cast (HPDC) method were examined using polarization and electrochemical impedance spectroscopy (EIS) techniques on as-cast and ground surfaces. The effects of the silicon content, transverse and longitudinal macrosegregation on the corrosion resistance of the alloys were determined. Microstructural studies revealed that samples from different positions contain different fractions of solid and liquid parts of the initial slurry. Electrochemical behavior of as-cast, ground surface, and bulk material was shown to be different due to the presence of a segregated skin layer and surface quality.
Advanced Fabrication of Single-Crystal Diamond Membranes for Quantum Technologies
Authors: Challier Michel , Sonusen Selda , Barfuss Arne , Rohner Dominik , Riedel Daniel , Koelbl Johannes , Ganzhorn Marc , Appel Patrick , Maletinsky Patrick , Neu Elke
Published: March 2018

Many promising applications of single crystal diamond and its color centers as sensor platform and in photonics require free-standing membranes with a thickness ranging from several micrometers to the few 100 nm range. In this work, we present an approach to conveniently fabricate such thin membranes with up to about one millimeter in size. We use commercially available diamond plates (thickness 50 μ m) in an inductively coupled reactive ion etching process which is based on argon, oxygen and SF 6 . We thus avoid using toxic, corrosive feed gases and add an alternative to previously presented recipes involving chlorine-based etching steps. Our membranes are smooth (RMS roughness <1 nm) and show moderate thickness variation (central part: <1 μ m over ≈200 × 200 μ m 2 ). Due to an improved etch mask geometry, our membranes stay reliably attached to the diamond plate in our chlorine-based as well as SF 6 -based processes. Our results thus open the route towards higher reliability in diamond device fabrication and up-scaling.