bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Thermal Differences and Variation of Cl–F–OH Ratios on Cu-Ni-PGE Mineralization in the Contact Aureole of the South Kawishiwi Intrusion, Duluth Complex
Authors: Benkó Zsolt , Mogessie Aberra , Molnár Ferenc , Hauck Steven A. , Severson Mark J. , Ettinger Karl
Published: December 2018

In the contact metamorphic aureole of the Duluth Complex, Cu-Ni-PGE mineralization occurs locally up to 100 m from the intrusion-footwall contact (Spruce Road area), whereas elsewhere (Dunka Pit deposit) the footwall granite and metapelite (Serpentine deposit) are barren. This study aimed to understand the effect of temperature and halogen fugacity variations on the presence or absence of mineralization in these footwall units. The mafic mineral assemblages, two-pyroxene, titanium-in-quartz, and biotite-apatite thermometers indicate that temperatures could be as high as 920 °C in the mineralized areas of the footwall, whereas the maximum temperature was lower by about 100 °C in the unmineralized part of the intrusion. Variation of the halogen concentrations and fugacities was monitored with the analysis of halogen concentrations in biotite and apatite. Fluorine and chlorine concentrations in biotite increase as a function of the distance from contact in the mineralized drill core and decrease in the unmineralized zones. Chlorine concentrations in apatite increase parallel with the distance from contact in the mineralized zones, whereas fluorine concentrations show only minor variation. Concentrations of these elements may have had subtle effect on the partial melting in the footwall units and indirectly facilitated the infiltration of the sulfide liquid into the footwall.
The Prenatal Microbiome: A New Player for Human Health
Authors: D’Argenio Valeria
Published: December 2018

The last few years have featured an increasing interest in the study of the human microbiome and its correlations with health status. Indeed, technological advances have allowed the study of microbial communities to reach a previously unthinkable sensitivity, showing the presence of microbes also in environments usually considered as sterile. In this scenario, microbial communities have been described in the amniotic fluid, the umbilical blood cord, and the placenta, denying a dogma of reproductive medicine that considers the uterus like a sterile womb. This prenatal microbiome may play a role not only in fetal development but also in the predisposition to diseases that may develop later in life, and also in adulthood. Thus, the aim of this review is to report the current knowledge regarding the prenatal microbiome composition, its association with pathological processes, and the future perspectives regarding its manipulation for healthy status promotion and maintenance.
Differing Contributions of Classical Risk Factors to Type 2 Diabetes in Multi-Ethnic Malaysian Populations
Authors: Abdullah Noraidatulakma , Abdul Murad Nor Azian , Attia John , Oldmeadow Christopher , Kamaruddin Mohd Arman , Abd Jalal Nazihah , Ismail Norliza , Jamal Rahman , Scott Rodney J. , Holliday Elizabeth G.
Published: December 2018

The prevalence of type 2 diabetes is escalating rapidly in Asian countries, with the rapid increase likely attributable to a combination of genetic and lifestyle factors. Recent research suggests that common genetic risk variants contribute minimally to the rapidly rising prevalence. Rather, recent changes in dietary patterns and physical activity may be more important. This nested case-control study assessed the association and predictive utility of type 2 diabetes lifestyle risk factors in participants from Malaysia, an understudied Asian population with comparatively high disease prevalence. The study sample comprised 4077 participants from The Malaysian Cohort project and included sub-samples from the three major ancestral groups: Malay (n = 1323), Chinese (n = 1344) and Indian (n = 1410). Association of lifestyle factors with type 2 diabetes was assessed within and across ancestral groups using logistic regression. Predictive utility was quantified and compared between groups using the Area Under the Receiver-Operating Characteristic Curve (AUC). In predictive models including age, gender, waist-to-hip ratio, physical activity, location, family history of diabetes and average sleep duration, the AUC ranged from 0.76 to 0.85 across groups and was significantly higher in Chinese than Malays or Indians, likely reflecting anthropometric differences. This study suggests that obesity, advancing age, a family history of diabetes and living in a rural area are important drivers of the escalating prevalence of type 2 diabetes in Malaysia.
Maternal Education, Fertility, and Child Survival in Comoros
Authors: Oyekale Abayomi Samuel , Maselwa Thonaeng Charity
Published: December 2018

Reduction in child mortality is a demographic progress of significant socioeconomic development relevance in Africa. This paper analyzed the effect of maternal education and fertility on child survival in the Islands of Comoros. The 2012 Demographic and Health Survey (DHS) data were used. A two-stage probit regression method was used for data analysis. The results showed that about 75% of the children’s mothers had given birth to between one and five children, while more than half did not have any form of formal education. The results of the two-stage probit regression showed that while child survival reduced significantly (p < 0.05) with the age of the heads of households, residence in the Ngazidja region, being born as twins, mother’s number of business trips, and number of marital unions, it increased with maternal education, fertility, male household headship, and the child being breastfed immediately after birth. It was concluded that efforts to enhance maternal education would reduce child mortality. It is also critical to promote child breastfeeding among women, while regional characteristics promoting differences in child mortality in Comoros Islands should be properly addressed with keen focus on the Ngazidja region.
Shadow Puppets and Neglected Diseases (2): A Qualitative Evaluation of a Health Promotion Performance in Rural Indonesia
Authors: Williams Courtney , Stewart Donald E. , Bendrups Dan , Laksono Budi , Susilo Joko , Amaral Salvador , Kurscheid Johanna , Gray Darren J.
Published: December 2018

Performing arts used as a method of spreading health information dates back to the origins of storytelling. However, interventions in developing, non-Western countries typically utilize Western entertainment forms. This qualitative investigation assesses responses to an intervention designed around traditional Javanese shadow puppetry (wayang kulit). Semi-structured interviews provided in-depth responses from a sample (N = 12) of villagers. Responses analyzed both cross-case and within-case, focused on perceptions of the music and storyline, responses to the intervention, and the perceived appropriateness of wayang kulit for disseminating a health message. Wayang kulit was considered to be interesting and easy to remember, but concerns remained regarding the reliability of information provided through the drama. The fusion of traditional and modern music and story elements were perceived positively. Some participants were inspired to improve their hygiene practices, although the lack of motivation, or belief that they were unable to change was noted. The performance was generally received positively in terms of the nature of the intervention, the fusion of traditional and Western music and story elements, as well as the use of wayang kulit to spread health information. The study provides guidance for modifications to the production, prior to scaling up.
Building Sustainable Supply Chains for Organizations Based on QFD: A Case Study
Authors: Wu Zhifeng , Zhai Senjing , Hong Jiangtao , Zhang Yibin , Shi Keren
Published: December 2018

Environmental protection has been increasingly emphasized by stakeholders, including social organizations, the government, and the public. As a result, building a sustainable supply chain has now become a part of social corporate responsibility as well as a challenge for firms, including small and medium-sized enterprises (SMEs). Taking a chemical enterprise (called enterprise C, in this paper) as an example, this paper uses quality function deployment (QFD) techniques and sets up a house of quality (HOQ) to investigate how a SME can achieve sustainable supply chain management. Specifically, in this paper we build a performance measurement system focusing on economic performance, environmental performance, and social performance. These three types of performance measure, in turn, include fifty-nine secondary indicators. Furthermore, an analytic hierarchy process (AHP) has been adopted to calculate the weight of each indicator. Benchmarking has also been used, to determine how much the enterprise should improve on each indicator. Based on the HOQ model, we conclude that avoiding waste, recycling resources, and sustainable exploitation are most important internal abilities of enterprise C.
Association between Atmospheric Particulate Pollutants and Mortality for Cardio-Cerebrovascular Diseases in Chinese Korean Population: A Case-Crossover Study
Authors: Zhang Chao , Quan Zhenyu , Wu Qincheng , Jin Zhezhen , Lee Joseph H. , Li Chunhua , Zheng Yuxin , Cui Lianhua
Published: December 2018

Background: Air pollution in large Chinese cities has led to recent studies that highlighted the relationship between particulate matters (PM) and elevated risk of cardio-cerebrovascular mortality. However, it is unclear as to whether: (1) The same adverse relations exist in cities with relatively low levels of air pollution; and (2) the relationship between the two are similar across ethnic groups. Methods: We collected data of PM2.5 (PM with an aerodynamic diameter ≤ 2.5 µm) and PM10 (aerodynamic diameter ≤ 10 µm) in the Yanbian Korean Autonomous Prefecture between 1 January 2015 and 31 December 2016. Using a time-stratified case-crossover design, we investigated whether levels of particulate pollutants influence the risk of cardio-cerebrovascular disease mortality among ethnic Korean vs. ethnic Han residents residing in the Yanbian Korean Autonomous Prefecture. Results: Under the single air pollutant model, the odds ratios (ORs) of cardio-cerebrovascular disease were 1.025 (1.024–1.026) for each 10 μg/m3 increase in PM2.5 at lag0 day, 1.012 (1.011–1.013) for each 10 μg/m3 increase in PM10 at lag1 day. In the multi-pollutant model adjusted by PM10, SO2, and NO2, the ORs of cardio-cerebrovascular disease were 1.150 (1.145–1.155) for ethnic Koreans and 1.154 (1.149–1.158) for ethnic Hans for each 10 μg/m3 increase in PM2.5. In the multi-pollutant model adjusted by PM2.5, SO2, and NO2, the ORs of cardio-cerebrovascular disease were 1.050 (1.047–1.053) for ethnic Koreans and 1.041 (1.039–1.043) for ethnic Hans for each 10 μg/m3 increase in PM10. Conclusion: This study showed that PM2.5 and PM10 were associated with increased risks of acute death events in residential cardio-cerebrovascular disease in Yanbian, China.
Wealth Inequality as a Predictor of Subjective Health, Happiness and Life Satisfaction among Nepalese Women
Authors: He Zhifei , Cheng Zhaohui , Bishwajit Ghose , Zou Dongsheng
Published: December 2018

Socioeconomic status has shown to be associated with subjective health, well-being, satisfaction with overall life and estimation of happiness. The body of research concerning the question of whether higher economic status leads to better health and well-being are mostly from developed countries. The present study was therefore conducted among women in Nepal with an aim to investigate whether household wealth status is associated with satisfaction about (1) self-reported health, (2) happiness, and (3) life overall. Methods: Subjects were 5226 Nepalese women aged between 15 and 24 years. Cross-sectional data were extracted from round 5 of the Nepal Multiple Indicator Cluster Survey (NMICS), conducted in 2014, and analyzed using chi-square tests of association, bivariate and multivariable regression methods. Results: Wealth status was significantly associated with satisfaction about health, estimation of happiness and satisfaction. Compared with women in the poorest households, the odds of positive estimation about overall happiness were respectively 30% higher for poorer (p < 0.0001; 95% CI = 1.653–3.190), 80% higher for middle (p = 0.001; 95% CI = 1.294–2.522), 64% higher for richer (p = 0.006; 95% CI = 1.155–2.326), and 40% higher for richest households. The odds of reporting satisfaction about life were respectively 97% higher for poorer (p < 0.0001; 95% CI = 1.680–2.317), 41% higher for middle (p < 0.0001; 95% CI = 1.165–1.715), 62% higher for richer (p < 0.0001; 95% CI = 1.313–2.003), and 31% higher for richest households (p = 0.043; 95% CI = 1.008–1.700). Conclusion: Our results conclude that women in households with lower wealth status report poorer subjective health, quality of life and happiness. However, the findings need to be interpreted in light of the existing sociocultural conditions mediating the role of household wealth status on women’s lives.
The Epigenetic Regulation of HCC Metastasis
Authors: Han Tae-Su , Ban Hyun Seung , Hur Keun , Cho Hyun-Soo
Published: December 2018

Epigenetic alterations, such as histone modification, DNA methylation, and miRNA-mediated processes, are critically associated with various mechanisms of proliferation and metastasis in several types of cancer. To overcome the side effects and limited effectiveness of drugs for cancer treatment, there is a continuous need for the identification of more effective drug targets and the execution of mechanism of action (MOA) studies. Recently, epigenetic modifiers have been recognized as important therapeutic targets for hepatocellular carcinoma (HCC) based on their reported abilities to suppress HCC metastasis and proliferation in both in vivo and in vitro studies. Therefore, here, we introduce epigenetic modifiers and alterations related to HCC metastasis and proliferation, and their molecular mechanisms in HCC metastasis. The existing data suggest that the study of epigenetic modifiers is important for the development of specific inhibitors and diagnostic targets for HCC treatment.
Biocompatibility and Biological Efficiency of Inorganic Calcium Filled Bacterial Cellulose Based Hydrogel Scaffolds for Bone Bioengineering
Authors: Basu Probal , Saha Nabanita , Alexandrova Radostina , Andonova-Lilova Boyka , Georgieva Milena , Miloshev George , Saha Petr
Published: December 2018

The principal focus of this work is the in-depth analysis of the biological efficiency of inorganic calcium-filled bacterial cellulose (BC) based hydrogel scaffolds for their future use in bone tissue engineering/bioengineering. Inorganic calcium was filled in the form of calcium phosphate (β-tri calcium phosphate (β-TCP) and hydroxyapatite (HA)) and calcium carbonate (CaCO3). The additional calcium, CaCO3 was incorporated following in vitro bio-mineralization. Cell viability study was performed with the extracts of BC based hydrogel scaffolds: BC-PVP, BC-CMC; BC-PVP-β-TCP/HA, BC-CMC-β-TCP/HA and BC-PVP-β-TCP/HA-CaCO3, BC-CMC-β-TCP/HA-CaCO3; respectively. The biocompatibility study was performed with two different cell lines, i.e., human fibroblasts, Lep-3 and mouse bone explant cells. Each hydrogel scaffold has facilitated notable growth and proliferation in presence of these two cell types. Nevertheless, the percentage of DNA strand breaks was higher when cells were treated with BC-CMC based scaffolds i.e., BC-CMC-β-TCP/HA and BC-CMC-β-TCP/HA-CaCO3. On the other hand, the apoptosis of human fibroblasts, Lep-3 was insignificant in BC-PVP-β-TCP/HA. The scanning electron microscopy confirmed the efficient adhesion and growth of Lep-3 cells throughout the surface of BC-PVP and BC-PVP-β-TCP/HA. Hence, among all inorganic calcium filled hydrogel scaffolds, ‘BC-PVP-β-TCP/HA’ was recommended as an efficient tissue engineering scaffold which could facilitate the musculoskeletal (i.e., bone tissue) engineering/bioengineering.
A Native Human Monoclonal Antibody Targeting HCMV gB (AD-2 Site I)
Authors: McVoy Michael M. , Tenorio Edgar , Kauvar Lawrence M.
Published: December 2018

Hyperimmune globulin (HIG) has shown efficacy against human cytomegalovirus (HCMV) for both transplant and congenital transmission indications. Replicating that activity with a monoclonal antibody (mAb) offers the potential for improved consistency in manufacturing, lower infusion volume, and improved pharmacokinetics, as well as reduced risk of off-target reactivity leading to toxicity. HCMV pathology is linked to its broad cell tropism. The glycoprotein B (gB) envelope protein is important for infections in all cell types. Within gB, the antigenic determinant (AD)-2 Site I is qualitatively more highly-conserved than any other region of the virus. TRL345, a high affinity (Kd = 50 pM) native human mAb to this site, has shown efficacy in neutralizing the infection of fibroblasts, endothelial and epithelial cells, as well as specialized placental cells including trophoblast progenitor cells. It has also been shown to block the infection of placental fragments grown ex vivo, and to reduce syncytial spread in fibroblasts in vitro. Manufacturing and toxicology preparation for filing an IND (investigational new drug) application with the US Food and Drug Administration (FDA) are expected to be completed in mid-2019.
Therapeutic Vulnerabilities in FLT3-Mutant AML Unmasked by Palbociclib
Authors: Uras Iris Z. , Maurer Barbara , Nebenfuehr Sofie , Zojer Markus , Valent Peter , Sexl Veronika
Published: December 2018

While significant progress has been made in the treatment of acute myeloid leukemia (AML), not all patients can be cured. Mutated in about 1/3 of de novo AML, the FLT3 receptor tyrosine kinase is an attractive target for drug development, activating mutations of the FLT3 map to the juxtamembrane domain (internal tandem duplications, ITD) or the tyrosine kinase domain (TKD), most frequently at codon D835. While small molecule tyrosine kinase inhibitors (TKI) effectively target ITD mutant forms, those on the TKD are not responsive. Moreover, FLT3 inhibition fails to induce a persistent response in patients due to mutational resistance. More potent compounds with broader inhibitory effects on multiple FLT3 mutations are highly desirable. We describe a critical role of CDK6 in the survival of FLT3+ AML cells as palbociclib induced apoptosis not only in FLT3–ITD+ cells but also in FLT3–D835Y+ cells. Antineoplastic effects were also seen in primary patient-derived cells and in a xenograft model, where therapy effectively suppressed tumor formation in vivo at clinically relevant concentrations. In cells with FLT3–ITD or -TKD mutations, the CDK6 protein not only affects cell cycle progression but also transcriptionally regulates oncogenic kinases mediating intrinsic drug resistance, including AURORA and AKT—a feature not shared by its homolog CDK4. While AKT and AURORA kinase inhibitors have significant therapeutic potential in AML, single agent activity has not been proven overly effective. We describe synergistic combination effects when applying these drugs together with palbociclib which could be readily translated to patients with AML bearing FLT3–ITD or –TKD mutations. Targeting synergistically acting vulnerabilities, with CDK6 being the common denominator, may represent a promising strategy to improve AML patient responses and to reduce the incidence of selection of resistance-inducing mutations.
Decreased PEDF Expression Promotes Adipogenic Differentiation through the Up-Regulation of CD36
Authors: Huang Kuang-Tzu , Hsu Li-Wen , Chen Kuang-Den , Kung Chao-Pin , Goto Shigeru , Chen Chao-Long
Published: December 2018

Adipogenesis is a tightly regulated cellular process that involves the action of multiple signaling pathways. Characterization of regulators that are associated with adipose development is crucial to understanding the mechanisms underlying obesity and other metabolic disorders. Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein that was first described as a neurotrophic factor. The role of PEDF in lipid metabolism was established when adipose triglyceride lipase (ATGL), a major triglyceride hydrolase, was characterized as its binding partner. In this study, we investigated the downstream effects of PEDF on adipogenic differentiation using rat adipose-derived stem cells (AdSCs) and the mouse pre-adipocyte cell line 3T3-L1. Knocking down PEDF in differentiating cells resulted in elevated levels of ATGL and CD36, as well as other adipogenic markers, with a concomitant increase in adipocyte number. CD36, a scavenger receptor for a variety of ligands, regulated proliferation and lipogenic gene expression during adipogenesis. The CD36 increase due to PEDF down-regulation might be a result of elevated PPARγ. We further demonstrated that PEDF expression was regulated by dexamethasone, a synthetic glucocorticoid that is widely used for adipogenesis at the transcriptional level. Taken together, our findings highlight that PEDF negatively regulates adipogenesis through the regulation of various signaling intermediates, and it may play a crucial role in lipid metabolic disorders.
GhHB12, a HD-ZIP I Transcription Factor, Negatively Regulates the Cotton Resistance to Verticillium dahliae
Authors: He Xin , Wang Tianyi , Zhu Wan , Wang Yujing , Zhu Longfu
Published: December 2018

The homeodomain-leucine zipper (HD-ZIP) is a plant-specific transcription factor family that plays important roles in plant developmental processes in response to multiple stressors. We previously isolated a cotton HD-ZIP class I transcription factor gene, GhHB12, which is regulated by the circadian clock and photoperiodism. Furthermore, it regulates cotton architecture, phase transition, and photoperiod sensitivity. Here we report that GhHB12 was induced by methyl jasmonate (MeJA) and Verticillium dahliae infection. Additionally, stress-responsive elements were found in the GhHB12 promoter. Promoter fusion analysis showed that GhHB12 was predominantly expressed in primary roots and that it was induced by mechanical damage. Overexpression of GhHB12 increased susceptibility of the cotton plant to the fungal pathogens Botrytis cinerea and V. dahliae, which was coupled with suppression of the jasmonic acid (JA)-response genes GhJAZ2 and GhPR3. Our results suggest that GhHB12, a cotton stress-responsive HD-ZIP I transcription factor, negatively regulates cotton resistance to V. dahliae by suppressing JA-response genes.
Caspase-3 Mediated Cell Death in the Normal Development of the Mammalian Cerebellum
Authors: Lossi Laura , Castagna Claudia , Merighi Adalberto
Published: December 2018

Caspase-3, onto which there is a convergence of the intrinsic and extrinsic apoptotic pathways, is the main executioner of apoptosis. We here review the current literature on the intervention of the protease in the execution of naturally occurring neuronal death (NOND) during cerebellar development. We will consider data on the most common altricial species (rat, mouse and rabbit), as well as humans. Among the different types of neurons and glia in cerebellum, there is ample evidence for an intervention of caspase-3 in the regulation of NOND of the post-mitotic cerebellar granule cells (CGCs) and Purkinje neurons, as a consequence of failure to establish proper synaptic contacts with target (secondary cell death). It seems possible that the GABAergic interneurons also undergo a similar type of secondary cell death, but the intervention of caspase-3 in this case still remains to be clarified in full. Remarkably, CGCs also undergo primary cell death at the precursor/pre-migratory stage of differentiation, in this instance without the intervention of caspase-3. Glial cells, as well, undergo a process of regulated cell death, but it seems possible that expression of caspase-3, at least in the Bergmann glia, is related to differentiation rather than death.
Tannic Acid-Induced Surface-Catalyzed Secondary Nucleation during the Amyloid Fibrillation of Hen Egg-White Lysozyme
Authors: Tian Jing , Yu Yang , Wang Yao , Li Haoyi , Yang Lujuan , Du Baoan , Ma Gang
Published: December 2018

Amyloid fibrillation by hen egg white lysozyme under the influence of tannic acid was investigated by atomic force microscopy and fluorescence spectroscopy. Tannic acid was found to be able to induce the formation of amyloid fibrils with an interesting mixed morphology. Such morphology features with the existence of areas of thickening alternating with areas of normal height. This novel modulation effect of tannic acid on amyloid fibrillation was interpreted by the established surface-catalyzed secondary nucleation theory. We further performed a fluorescence quenching study to investigate the intermolecular interaction between tannic acid and lysozyme. The results support that lysozyme and tannic acid interact with each other mainly through hydrophobic interactions. We also discussed why hydrogen-bonding interaction is not a dominant factor in the interaction between tannic acid and lysozyme though tannic acid contains a significant amount of hydroxyl groups. Our work provides new insight into the effect of tannic acid, a well-known amyloid inhibitor, on amyloid fibrillation.
New Insight into Sperm Capacitation: A Novel Mechanism of 17β-Estradiol Signalling
Authors: Bosakova Tereza , Tockstein Antonin , Sebkova Natasa , Simonik Ondrej , Adamusova Hana , Albrechtova Jana , Albrecht Tomas , Bosakova Zuzana , Dvorakova-Hortova Katerina
Published: December 2018

17β-estradiol (estradiol) is a natural estrogen regulating reproduction including sperm and egg development, sperm maturation—called capacitation—and sperm–egg communication. High doses can increase germ cell apoptosis and decrease sperm count. Our aim was to answer the biological relevance of estradiol in sperm capacitation and its effect on motility and acrosome reaction to quantify its interaction with estrogen receptors and propose a model of estradiol action during capacitation using kinetic analysis. Estradiol increased protein tyrosine phosphorylation, elevated rate of spontaneous acrosome reaction, and altered motility parameters measured Hamilton-Thorne Computer Assisted Semen Analyzer (CASA) in capacitating sperm. To monitor time and concentration dependent binding dynamics of extracellular estradiol, high-performance liquid chromatography with tandem mass spectrometry was used to measure sperm response and data was subjected to kinetic analysis. The kinetic model of estradiol action during sperm maturation shows that estradiol adsorption onto a plasma membrane surface is controlled by Langmuir isotherm. After, when estradiol passes into the cytoplasm, it forms an unstable adduct with cytoplasmic receptors, which display a signalling autocatalytic pattern. This autocatalytic reaction suggests crosstalk between receptor and non-receptor pathways utilized by sperm prior to fertilization.
Calretinin Functions in Malignant Mesothelioma Cells Cannot Be Replaced by the Closely Related Ca2+-Binding Proteins Calbindin-D28k and Parvalbumin
Authors: Wörthmüller Janine , Oberson Anne , Salicio Valérie , Blum Walter , Schwaller Beat
Published: December 2018

Calretinin (CR; CALB2) belonging to the family of EF-hand Ca2+-binding proteins (CaBP) is widely used as a positive marker for the identification of human malignant mesothelioma (MM) and functionally was suggested to play a critical role during carcinogenesis of this highly aggressive asbestos-associated neoplasm. Increasing evidence suggests that CR not only acts as a prototypical Ca2+ buffer protein, i.e., limiting the amplitude of Ca2+ signals but also as a Ca2+ sensor. No studies have yet investigated whether other closely related CaBPs might serve as substitutes for CR’s functions(s) in MM cells. Genetically modified MM cell lines with medium (MSTO-211H and ZL5) or low (SPC111) endogenous CR expression levels were generated that overexpress either CR’s closest homologue calbindin-D28k (CB) or parvalbumin (PV), the latter considered as a “pure” Ca2+ buffer protein. After lentiviral shCALB2-mediated CR downregulation, in both MSTO-211H and ZL5 cells expressing CB or PV, the CR deficiency-mediated increase in cell death was not prevented by CB or PV. With respect to proliferation and cell morphology of SPC111 cells, CB was able to substitute for CR, but not for CR’s other functions to promote cell migration or invasion. In conclusion, CR has a likely unique role in MM that cannot be substituted by “similar” CaBPs.
Intestinal Anti-Inflammatory Activity of the Aqueous Extract from Ipomoea asarifolia in DNBS-Induced Colitis in Rats
Authors: Da Silva Valéria , De Araújo Aurigena , Araújo Daline , Lima Maíra , Vasconcelos Roseane , De Araújo Júnior Raimundo , Langasnner Silvana , Pedrosa Matheus , De Medeiros Caroline , Guerra Gerlane
Published: December 2018

Inflammatory bowel disease is triggered by an uncontrolled immune response associated with genetic, environmental, and intestinal microbiota imbalance. Ipomoea asarifolia (IA), popularly known as “salsa” or “brave salsa”, belongs to the Convolvulaceae family. The aim of this approach was to study the preventive effect of IA aqueous extract in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Rats pretreated with IA extract or sulfasalazine (SSZ) received intracolonic instillation of DNBS in 50% ethanol (v/v). IA extract presented a protective effect against intestinal inflammation, with improvement in the disease activity index and macroscopic damage. IA or SSZ significantly reduced myeloperoxidase activity, and also down-regulation of the gene expression of JNK1, NF-κβ-p65, STAT3, and decreased levels of TNFα, IL-1β, and increased IL-10, associated with a significant improvement of oxidative stress, in addition to a reduction in MDA and an increase of glutathione in colonic tissue. The protective effect of the extract was also confirmed in histological evaluation, showing preservation of the colonic cytoarchitecture. Immunohistochemical analysis revealed down-regulation of NF-κβ-p65, iNOS, IL-17, and up-regulation of SOCs-1 and MUC-2. IA extract presents antioxidant and anti-inflammatory intestinal properties, and proved to be a potential application for preventing damage induced by DNBS.
OsGPAT3 Plays a Critical Role in Anther Wall Programmed Cell Death and Pollen Development in Rice
Authors: Sun Lianping , Xiang Xiaojiao , Yang Zhengfu , Yu Ping , Wen Xiaoxia , Wang Hong , Abbas Adil , Muhammad Khan Riaz , Zhang Yingxin , Cheng Shihua , Cao Liyong
Published: December 2018

In flowering plants, ideal male reproductive development requires the systematic coordination of various processes, in which timely differentiation and degradation of the anther wall, especially the tapetum, is essential for both pollen formation and anther dehiscence. Here, we show that OsGPAT3, a conserved glycerol-3-phosphate acyltransferase gene, plays a critical role in regulating anther wall degradation and pollen exine formation. The gpat3-2 mutant had defective synthesis of Ubisch bodies, delayed programmed cell death (PCD) of the inner three anther layers, and abnormal degradation of micropores/pollen grains, resulting in failure of pollen maturation and complete male sterility. Complementation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) experiments demonstrated that OsGPAT3 is responsible for the male sterility phenotype. Furthermore, the expression level of tapetal PCD-related and nutrient metabolism-related genes changed significantly in the gpat3-2 anthers. Based on these genetic and cytological analyses, OsGPAT3 is proposed to coordinate the differentiation and degradation of the anther wall and pollen grains in addition to regulating lipid biosynthesis. This study provides insights for understanding the function of GPATs in regulating rice male reproductive development, and also lays a theoretical basis for hybrid rice breeding.
A Soft Body Physics Simulator with Computational Offloading to the Cloud
Authors: Danevičius Edvinas , Maskeliūnas Rytis , Damaševičius Robertas , Połap Dawid , Woźniak Marcin
Published: December 2018

We describe the gamification of a soft physics simulator. We developed a game, called Jelly Dude, that allows the player to change and modify the game engine by tinkering with various physics parameters, creating custom game levels and installing scripts. The game engine is capable of simulating soft-body physics and can display the simulation results visually in real-time. In order to ensure high quality graphics in real time, we have implemented intelligent computational offloading to the cloud using Jordan Neural Network (JNN) with a fuzzy logic scheme for short time prediction of network traffic between a client and a cloud server. The experimental results show that computation offloading allowed us to increase the speed of graphics rendering in terms of frames per second, and to improve the precision of soft body modeling in terms of the number of particles used to represent a soft body.
Imidazo-Phenanthroline Ligands as a Convenient Modular Platform for the Preparation of Heteroleptic Cu(I) Photosensitizers
Authors: Schmid Marie-Ann , Rentschler Martin , Frey Wolfgang , Tschierlei Stefanie , Karnahl Michael
Published: December 2018

The capture and storage of solar energy is a promising option to overcome current energy issues. To put such systems into practice, molecular photosensitizers should be based on abundant metals and possess a strong absorption capability for visible light. Therefore, a systematic series of four novel heteroleptic Cu(I) complexes of the type [(P^P)Cu(N^N)]+ (with P^P = xantphos and N^N = different diimine ligands) has been prepared. As an essential feature, these copper photosensitizers contain an imidazole moiety at the backbone of the diimine ligand, which increases the aromatic π-system compared to phenanthroline type ligands. Moreover, 2-(4-bromophenyl)-1-phenyl-1H-imidazo-[4,5-f][1,10]phenanthroline was used as a starting point and modular platform for gradually extended diimine ligands. Suzuki cross-coupling was applied to introduce different kind of substituents in the back of this ligand. Afterwards, a combination of NMR spectroscopy, mass spectrometry, X-ray analysis, cyclic voltammetry, UV/vis and emission spectroscopy was used to investigate the structural, electrochemical and photophysical properties of these compounds. As a result, a reversible reduction, strongly increased extinction coefficients and significantly redshifted absorption maxima (>20 nm) were found compared to traditional Cu(I) photosensitizers without an imidazo moiety. Moreover, these compounds show a bright emission in the solid state.
Validation of the REGARDS Severe Sepsis Risk Score
Authors: Wang Henry E. , Donnelly John P. , Yende Sachin , Levitan Emily B. , Shapiro Nathan I. , Dai Yuling , Zhao Hong , Heiss Gerardo , Odden Michelle , Newman Anne , Safford Monika
Published: December 2018

There are no validated systems for characterizing long-term risk of severe sepsis in community-dwelling adults. We tested the ability of the REasons for Geographic and Racial Differences in Stroke-Severe Sepsis Risk Score (REGARDS-SSRS) to predict 10-year severe sepsis risk in separate cohorts of community-dwelling adults. We internally tested the REGARDS-SSRS on the REGARDS-Medicare subcohort. We then externally validated the REGARDS-SSRS using (1) the Cardiovascular Health Study (CHS) and (2) the Atherosclerosis Risk in Communities (ARIC) cohorts. Participants included community-dwelling adults: REGARDS-Medicare, age ≥65 years, n = 9522; CHS, age ≥65 years, n = 5888; ARIC, age 45–64 years, n = 11,584. The primary exposure was 10-year severe sepsis risk, predicted by the REGARDS-SSRS from participant sociodemographics, health behaviors, chronic medical conditions and select biomarkers. The primary outcome was first severe sepsis hospitalizations, defined as the concurrent presence of ICD-9 discharge diagnoses for a serious infection and organ dysfunction. Median SSRS in the cohorts were: REGARDS-Medicare 11 points (IQR 7–16), CHS 10 (IQR 6–15), ARIC 7 (IQR 5–10). Severe sepsis incidence rates were: REGARDS-Medicare 30.7 per 1000 person-years (95% CI: 29.2–32.2); CHS 11.9 (10.9–12.9); ARIC 6.8 (6.3–7.3). SSRS discrimination for first severe sepsis events were: REGARDS-Medicare C-statistic 0.704 (95% CI: 0.691–0.718), CHS 0.696 (0.675–0.716), ARIC 0.697 (0.677–0.716). The REGARDS-SRSS may potentially play a role in identifying community-dwelling adults at high severe sepsis risk.
Special Issue: Treatments for Fungal Infections
Authors: Segal Esther , Elad Daniel
Published: December 2018

Antifungal therapy is complicated compared to antibacterial treatments by the fact that fungi and their hosts are both eukaryotic organisms, resulting in fewer targets for selective activity. [...]
The 9th Santorini Conference: Systems Medicine, Personalised Health and Therapy. “The Odyssey from Hope to Practice”, Santorini, Greece, 30 September–3 October 2018
Authors: Visvikis-Siest Sophie , Gorenjak Vesna , Stathopoulou Maria G. , Petrelis Alexandros M. , Weryha Georges , Masson Christine , Hiegel Brigitte , Kumar Satish , Barouki Robert , Boerwinkle Eric , Dagher Georges , Deloukas Panagiotis , Innocenti Federico , Lamont John , Marschler Michael , Meyer Heiko , Meyer Urs A. , Nofziger Charity , Paulmichl Markus , Vacher Cora , Webster Lynn
Published: December 2018

The 9th traditional biannual conference on Systems Medicine, Personalised Health & Therapy—“The Odyssey from Hope to Practice”, inspired by the Greek mythology, was a call to search for practical solutions in cardio-metabolic diseases and cancer, to resolve and overcome the obstacles in modern medicine by creating more interactions among disciplines, as well as between academic and industrial research, directed towards an effective ‘roadmap’ for personalised health and therapy. The 9th Santorini Conference, under the Presidency of Sofia Siest, the director of the INSERM U1122; IGE-PCV (www.u1122.inserm.fr), University of Lorraine, France, offered a rich and innovative scientific program. It gathered 34 worldwide distinguished speakers, who shared their passion for personalised medicine with 160 attendees in nine specific sessions on the following topics: First day: The Odyssey from hope to practice: Personalised medicine—landmarks and challenges Second day: Diseases to therapeutics—genotype to phenotype an “-OMICS” approach: focus on personalised therapy and precision medicine Third day: Gene-environment interactions and pharmacovigilance: a pharmacogenetics approach for deciphering disease “bench to clinic to reality” Fourth day: Pharmacogenomics to drug discovery: a big data approach and focus on clinical data and clinical practice. In this article we present the topics shared among the participants of the conference and we highlight the key messages.
Synergistic Benefits of Using Expansive and Shrinkage Reducing Admixture on High-Performance Concrete
Authors: Yuan Tian-Feng , Kim Seong-Kyum , Koh Kyung-Teak , Yoon Young-Soo
Published: December 2018

High-performance concrete (HPC) is widely used in construction according to great mechanical properties, but it has a high risk of shrinkage cracking due to autogenous shrinkage stress. Therefore, the aim of this research was to investigate the effect of a combination of expansive admixture (EA) and shrinkage reducing admixture (SA) on the autogenous shrinkage of high-performance concrete without heat treatment. Two different EA to cement weight ratios of 0.0, 5.0%, and two different SA to cement weight ratios of 0.0, and 1.0% were combined and considered. To investigate the differences in the time-zero conditions effect on the autogenous shrinkage behaviors, four different initial points were compared. The test results indicate that the EA and/or SA content was conductive to a little bite increase compressive strength (22.6–37.9%) and tensile strength (<4.8%). According to the synergistic effect of the EA and SA on the HPC, the autogenous shrinkage significantly decreased (<50%), as compared to those specimens with only one type of admixture (EA or SA). Furthermore, all the specimens incurred restrained autogenous shrinkage cracks at an early age, except the specimen using the combined EA and SA. Therefore, it can be concluded that the combination of EA and SA is effective for improving the properties of HPC.
A Review of Bonding Immiscible Mg/Steel Dissimilar Metals
Authors: Song Gang , Li Taotao , Yu Jingwei , Liu Liming
Published: December 2018

The challenge of joining immiscible Mg/Steel dissimilar metals lies in the absence of an Fe-Mg intermetallic or Fe-Mg solid solution in an Mg-Fe system, and differences in their physical and chemical properties. Promoting interfacial reaction and regulating the composition of interface layer are beneficial for the formation of an Mg/steel interface layer and to obtain an effective Mg/steel joint. This research work focusses on the bonding of immiscible Mg/steel dissimilar metals: First, an Mg/steel interface layer was designed by controlling the composition of added alloy elements and trace elements in the base metal. Second, the Mg/steel dissimilar metals welding methods were divided into three parts—solid state welding, welding-brazing and fusion welding. The main distinctions between them were difference in interfacial temperature, thickness of interface layer, and type of compound. Third, the orientation relationships (OR) of the Mg/interface layer system and the interface layer/steel system was investigated. In this review, the effect of welding processing parameters, addition of alloy elements, base metal, and different welding methods on the joint’s performance was studied. The mechanical property, microstructure, interface layer and metallurgical reactions of the joint were also examined. The most recent progress in joining immiscible Mg/Steel dissimilar metals and future research prospects are presented at the end of the paper.
Ultrasonic vs Drill Implant Site Preparation: Post-Operative Pain Measurement Through VAS, Swelling and Crestal Bone Remodeling: A Randomized Clinical Study
Authors: Scarano Antonio , Carinci Francesco , Lorusso Felice , Festa Felice , Bevilacqua Lorenzo , Santos de Oliveira Pablo , Maglione Michele
Published: December 2018

Background: Piezosurgery is a surgical procedure that is able to perform osteotomies by a micrometric and selective cut of the bone tissue. The objective of this investigation was to evaluate two different techniques; an ultrasonic device, and a drill approach for implant site preparation. Methods: A total of fifty patients were recruited for the randomized clinical trial to receive dental implants for fixed prosthetic restoration in the posterior mandible and were allotted to two groups. In Group A the implant site was prepared following a drilling technique, while in Group B the implant site was prepared using an ultrasonic device; moreover, the operative duration was recorded. Postoperative pain and swelling were evaluated at 1, 2, 4, and 6 days. The crestal bone resorption was measured at 3 months from implant placement by a three-dimensional tomography evaluation. Results: The findings suggest that osteotomies performed by an ultrasonic device cause less pain and swelling. On the other hand, the piezoelectric preparation was characterized by a significative increase in the operative time. No statistical differences in crestal bone resorption were evident in the two different approaches. Conclusions: According to the outcome of the study, ultrasonic implant bed preparation can be used with success in implantology and could be considered a suitable alternative to traditional drilling techniques for dental fixture placement.
Assessment of the Influence of Acetic Acid Residue on Type I Collagen during Isolation and Characterization
Authors: Bak Seon Young , Lee Sang Woo , Choi Chong Hyuk , Kim Hyun Woo
Published: December 2018

Various methods for isolation of type I collagen using acids, bases, enzymes, and their combinations have been applied. However, a lack of standardization exists among type I collagens isolated by various approaches. Consequently, in this study, we assessed the influence of acetic acid residue on type I collagen isolated by pepsin-acetic acid treatment, the fabrication of collagen-based porous scaffolds, and the seeded cells on collagen scaffolds. Unlike the isolated collagen dialyzed by deionized water (DDW), collagen dialyzed by 0.5 M acetic acid (DAC) exhibited structural and thermal denaturation. Both DDW- and DAC-based porous scaffolds at all collagen concentrations (0.5, 1 and 2% w/v) showed the high degree of porosity (>98%), and their pore morphologies were comparable at the same concentrations. However, the DDW- and DAC-based collagen scaffolds displayed significant differences in their physical properties (weight, thickness, and volume) and swelling behaviors. In particular, the weight losses induced by mechanical stimulation reflected the high degradation of DAC-collagen scaffolds. In cell culture experiments using adipose-derived stem cells (ADSCs), the characteristics of mesenchymal stem cell (MSC) did not change in both DDW- and DAC-collagen scaffolds for 10 days, although cells proliferated less in the DAC-collagen scaffolds. Our results suggest that the elimination of acetic acid residue from isolated collagen is recommended to produce collagen scaffolds that provide a stable environment for cells and cell therapy-related applications.
Comprehensive Evaluation of the Properties of Ultrafine to Nanocrystalline Grade 2 Titanium Wires
Authors: Palán Jan , Procházka Radek , Džugan Jan , Nacházel Jan , Duchek Michal , Németh Gergely , Máthis Kristián , Minárik Peter , Horváth Klaudia
Published: December 2018

This paper describes the mechanical properties and microstructure of commercially pure titanium (Grade 2) processed with Conform severe plastic deformation (SPD) and rotary swaging techniques. This technology enables ultrafine-grained to nanocrystalline wires to be produced in a continuous process. A comprehensive description is given of those properties which should enable straightforward implementation of the material in medical applications. Conform SPD processing has led to a dramatic refinement of the initial microstructure, producing equiaxed grains already in the first pass. The mean grain size in the transverse direction was 320 nm. Further passes did not lead to any additional appreciable grain refinement. The subsequent rotary swaging caused fine grains to become elongated. A single Conform SPD pass and subsequent rotary swaging resulted in an ultimate strength of 1060 MPa and elongation of 12%. The achieved fatigue limit was 396 MPa. This paper describes the production possibilities of ultrafine to nanocrystalline wires made of pure titanium and points out the possibility of serial production, particularly in medical implants.