bluuebunny/crossref_metadata_2025 huggingface dataset:
Under-Five Mortality and Associated Factors: Evidence from the Nepal Demographic and Health Survey (2001–2016)
Authors: Ghimire Pramesh Raj , Agho Kingsley E. , Ezeh Osita Kingsley , Renzaho Andre M. N. , Dibley Michael , Raynes-Greenow Camille
Published: April 2019

Child mortality in Nepal has reduced, but the rate is still above the Sustainable Development Goal target of 20 deaths per 1000 live births. This study aimed to identify common factors associated with under-five mortality in Nepal. Survival information of 16,802 most recent singleton live births from the Nepal Demographic and Health Survey for the period (2001–2016) were utilized. Survey-based Cox proportional hazard models were used to examine factors associated with under-five mortality. Multivariable analyses revealed the most common factors associated with mortality across all age subgroups included: mothers who reported previous death of a child [adjusted hazard ratio (aHR) 17.33, 95% confidence interval (CI) 11.44, 26.26 for neonatal; aHR 13.05, 95% CI 7.19, 23.67 for post-neonatal; aHR 15.90, 95% CI 11.38, 22.22 for infant; aHR 16.98, 95% CI 6.19, 46.58 for child; and aHR 15.97, 95% CI 11.64, 21.92 for under-five mortality]; nonuse of tetanus toxoids (TT) vaccinations during pregnancy (aHR 2.28, 95% CI 1.68, 3.09 for neonatal; aHR 1.86, 95% CI 1.24, 2.79 for post-neonatal; aHR 2.44, 95% CI 1.89, 3.15 for infant; aHR 2.93, 95% CI 1.51, 5.69 for child; and aHR 2.39, 95% CI 1.89, 3.01 for under-five mortality); and nonuse of contraceptives among mothers (aHR 1.69, 95% CI 1.21, 2.37 for neonatal; aHR 2.69, 95% CI 1.67, 4.32 for post-neonatal; aHR 2.01, 95% CI 1.53, 2.64 for infant; aHR 2.47, 95% CI 1.30, 4.71 for child; and aHR 2.03, 95% CI 1.57, 2.62 for under-five mortality). Family planning intervention as well as promotion of universal coverage of at least two doses of TT vaccine are essential to help achieve child survival Sustainable Development Goal (SDG) targets of <20 under-five deaths and <12 neonatal deaths per 1000 births by the year 2030.
Prevalence and Psychosocial Predictors of Homophobic Victimization among Adolescents
Authors: Rodríguez-Hidalgo Antonio J. , Hurtado-Mellado Almudena
Published: April 2019

Bullying and discrimination seriously damage the development and health of adolescents with non-heteronormative sexual orientation. Adolescents from sexual minorities are more likely to be the object of bullying. This research aims to know more about the prevalence, frequency, and some associated factors and predictors of homophobic victimization in adolescents, depending on their sexual orientation. A total of 820 Secondary Schools students took part in this study (average age = 14.87; SD = 1.72; 48.3% were boys and 51.7% were girls) by filling in a self-report questionnaire. The results showed that adolescents suffer homophobic victimization, regardless of their sexual orientation; however, homosexuals and bisexuals suffered it more frequently than heterosexuals. Homophobic victimization could be associated—in heterosexuals and people with doubts about their sexual orientation, positively with bullying victimization, bullying aggression and cyberbullying aggression. Homophobic victimization could be predicted—in heterosexuals, positively due to self-depreciation, and negatively due to communication and relationship skills; and in homosexuals and bisexuals, positively, because of affective empathy. The results are discussed and new lines of study and intervention are proposed.
Medically Unexplained Symptoms (MUS): Faults and Implications
Authors: Tack Michiel
Published: April 2019

The classification of medically unexplained symptoms (MUS) could have negative consequences for patients with functional somatic syndromes (FSS). By grouping related but distinct syndromes into one label, the MUS classification fails to inform clinicians about their patients’ health condition. In research settings, the MUS classification makes patient samples more heterogeneous, obstructing research into the underlying pathology of FSS. Long-term studies have shown that MUS are often appraised as medically explained symptoms at follow-up and vice versa, raising doubts about the reliability of this distinction.
Assessment of Ecosystem Service Quality and Its Correlation with Landscape Patterns in Haidian District, Beijing
Authors: Wang Boya , Liu Zhicheng , Mei Yuting , Li Wenjie
Published: April 2019

Landscape architecture with urban green space as the main research object is an evidence-based science. It is an important issue to optimize green space systems from the point of view of ecosystem services. In this paper, high-resolution (1.5 m resolution) remote sensing images are combined with data-processing software, such as ENVI, ArcGIS, and Fragstats, to evaluate ecosystem service quality and compute the landscape pattern in the Haidian District (Beijing, China), so that the relationship between the ecosystem service quality and landscape pattern can be quantitatively studied and a strategy can be provided for green space optimization in cities. The following conclusions are drawn: (1) for the evaluated quality of 14 ecosystem services in Haidian District (refer to Section Analysis of the Association of the Percentage of Patches (PLAND) Index of Forest Land and Quality of Ecosystem Service in Haidian District). Forest land is the main provider of the ecosystem service in Haidian District, while construction land only provides cultural services; (2) on the whole, the spatial distribution of the ecosystem services in Haidian District gradually decreases from the west to the east, which basically matches with the spatial distribution of the forest land. The regulating service and supporting service are matched with the distribution of the urban green space. The cultural service is closely associated with history resource points; and (3) the analysis results of the association between landscape pattern and ecosystem service quality show that the percentage of patches (PLAND) index for forest land has a significant logarithmic relationship with the regulating service and supporting service. The critical value of the PLAND index is 30. Besides the Xishan area with the most coverage of forest land, the landscape shape index (LSI) of the brushwood has a logarithmic relationship with the ecosystem service quality. The critical value of the LSI value is 50. Finally, this paper proposes an area optimization strategy of green space in Haidian District from the view of the ecosystem system service. The Xishan area is classified into the ecosystem red line to control city expansion. The regulating and supporting services can be enhanced in the north flat area by improving the patch shape index. The ecosystem service capabilities can be improved by adding the forest land in the existing green space for the southeast urban areas.
Setting-Specific and Symptom-Specific Association between Secondhand Smoke Exposure and Depressive Symptoms
Authors: Ye Xiaohua , Huang Jingya , Xia Liang , Xu Xiaojun , Gong Xiao , Xu Yanjun
Published: April 2019

Few studies have focused on the potential relationship between secondhand smoke (SHS) exposure and depressive symptoms. This study aimed to explore the potential association between SHS exposure and depressive symptoms and differentiate this association in setting-specific exposure and symptom-specific outcomes. A cross-sectional study was conducted in Guangdong province of China from September to December 2010 using a multistage sampling method to randomly sample adults aged 18 years and older. SHS exposure was defined as inhalation by non-smokers of the smoke exhaled from smokers for at least 1 day a week in the past 30 days. Depressive symptoms were measured using the nine-item Patient Health Questionnaire. The zero-inflate negative binomial regression models were used to explore the associations between SHS exposure and depressive symptoms. A total of 2771 non-smokers were included in this study, with mean age of 49.6 ± 14.0 years and 70.3% of females. The prevalence of depressive symptoms was significantly higher in participants with SHS exposure than in those without exposure (incidence rate ratio (IRR) = 1.32, 95% confidence interval (CI) 1.16–1.51), and there were similar positive associations for SHS exposure in medical facilities (IRR = 1.37, 95% CI 1.17–1.61) and in schools (IRR = 1.46, 95% CI 1.20–1.77). Notably, there was a monotonically increasing dose-response relationship between frequency of SHS exposure and depressive symptoms. When differentiating this relationship by the dimensions of depressive symptoms, there were similar dose-response relationships for cognitive-affective and somatic symptoms. When differentiating this relationship by sex, only females showed a significant dose-response relationship. Our findings suggest dose-response relationships between SHS exposure and depressive symptoms in sex-specific and symptom-specific manners. Future longitudinal studies are needed to establish the biological mechanisms of the impact of SHS exposure.
New Innovations in Wound Healing and Repair
Authors: Cowin Allison J.
Published: April 2019

Wounds are a largely unrecognized, spiraling epidemic that affect millions of people world-wide [...]
The Effect of Molecular Weight on the Antibacterial Activity of N,N,N-Trimethyl Chitosan (TMC)
Authors: Sahariah Priyanka , Cibor Dorota , Zielińska Dorota , Hjálmarsdóttir Martha Á. , Stawski Dawid , Másson Már
Published: April 2019

N,N,N-trimethyl chitosan (TMC) with 93% degree of trimethylation was synthesized. TMC and the chitosan starting material were subjected to acidic hydrolysis to produce 49 different samples with a reduced average molecular weight (Mw) ranging from 2 to 144 kDa. This was done to allow the investigation of the relationship between antibacterial activity and Mw over a wide Mw range. NMR investigation showed that hydrolysis did not affect the degree of trimethylation (DSTRI) or the structure of the polymer backbone. The activity of TMC against Staphylococcus aureus (S. aureus) increased sharply with Mw until a certain Mw value (critical Mw for high activity, CMW) was reached. After the CMW, the activity was not affected by a further increase in the Mw. A similar pattern of activity was observed for chitosan. The CMW was determined to be 20 kDa for TMC and 50 kDa for chitosan.
A Privacy-Preserving Protocol for Utility-Based Routing in DTNs
Authors: Jiang Qingfeng , Deng Kun , Zhang Lei , Liu Chun
Published: April 2019

In the utility-based routing protocol of delay-tolerant networks (DTNs), nodes calculate routing utility value by encounter time, frequency, and so on, and then forward messages according to the utility. The privacy information of encounter time and frequency will be leaked when nodes communicate with real IDs. Node ID anonymity can protect the privacy information, but it also prevents nodes from collecting encounter information to calculate the real utility value. To solve the above problem, this paper proposes a privacy-preserving protocol for utility-based routing (PPUR) in DTNs. When node encounter occurs in PPUR, they anonymously generate and collect the encounter record information by pseudo-IDs. Then, nodes forward the information to a trusted authority (TA), which calculates the routing utility value and returns it to the nodes, so that nodes can protect the privacy information and obtain the real utility value at the same time. PPUR also protects the confidentiality and integrity of messages through hashing and digital signature. The experimental results show that PPUR can not only protect nodes’ privacy information, but also effectively forward messages with real utility value.
Zig-Zag Based Single-Pass Connected Components Analysis
Authors: Bailey Donald G. , Klaiber Michael J.
Published: April 2019

Single-pass connected components analysis (CCA) algorithms suffer from a time overhead to resolve labels at the end of each image row. This work demonstrates how this overhead can be eliminated by replacing the conventional raster scan by a zig-zag scan. This enables chains of labels to be correctly resolved while processing the next image row. The effect is faster processing in the worst case with no end of row overheads. CCA hardware architectures using the novel algorithm proposed in this paper are, therefore, able to process images at higher throughput than other state-of-the-art methods while reducing the hardware requirements. The latency introduced by the conversion from raster scan to zig-zag scan is compensated for by a new method of detecting object completion, which enables the feature vector for completed connected components to be output at the earliest possible opportunity.
New R-Based Methodology to Optimize the Identification of Root Endophytes against Heterobasidion parviporum
Authors: Rigerte Linda , Blumenstein Kathrin , Terhonen Eeva
Published: April 2019

Many root fungal endophytes inhabiting forest trees have potential impact on the health and disease progression of certain tree species. Hence, the screening of root endophytes for their biocontrol abilities is relevant for their potential to protect their hosts against invaders. The aim of this research is to screen for the potential inhibitory effects of selected conifer root endophytes during interaction, in vitro, with the root rot pathogen, Heterobasidion parviporum. Here, we introduce a guideline that facilitates the use of root fungal endophytes as biocontrol agents. We isolated fungal root endophytes from eight different conifers. These root fungal endophytes were evaluated for their antagonism against the root rot pathogen, H. parviporum, by means of paired-culture antagonism assays. We determined the antagonism of the isolated root fungal endophytes to elucidate potential biocontrol applications. For the analysis, a software package in R was developed. Endophyte candidates with antagonistic potential were identified.
Regulation of Osteoclast Differentiation and Skeletal Maintenance by Histone Deacetylases
Authors: Faulkner Bora , Astleford Kristina , Mansky Kim C.
Published: April 2019

Bone is a dynamic tissue that must respond to developmental, repair, and remodeling cues in a rapid manner with changes in gene expression. Carefully-coordinated cycles of bone resorption and formation are essential for healthy skeletal growth and maintenance. Osteoclasts are large, multinucleated cells that are responsible for breaking down bone by secreting acids to dissolve the bone mineral and proteolytic enzymes that degrade the bone extracellular matrix. Increased osteoclast activity has a severe impact on skeletal health, and therefore, osteoclasts represent an important therapeutic target in skeletal diseases, such as osteoporosis. Progression from multipotent progenitors into specialized, terminally-differentiated cells involves carefully-regulated patterns of gene expression to control lineage specification and emergence of the cellular phenotype. This process requires coordinated action of transcription factors with co-activators and co-repressors to bring about proper activation and inhibition of gene expression. Histone deacetylases (HDACs) are an important group of transcriptional co-repressors best known for reducing gene expression via removal of acetyl modifications from histones at HDAC target genes. This review will cover the progress that has been made recently to understand the role of HDACs and their targets in regulating osteoclast differentiation and activity and, thus, serve as potential therapeutic target.
Bio-mining of Lanthanides from Red Mud by Green Microalgae
Authors: Čížková Mária , Mezricky Dana , Rucki Marian , Tóth Tivadar M. , Náhlík Vít , Lanta Vojtěch , Bišová Kateřina , Zachleder Vilém , Vítová Milada
Published: April 2019

Red mud is a by-product of alumina production containing lanthanides. Growth of green microalgae on red mud and the intracellular accumulation of lanthanides was tested. The best growing species was Desmodesmus quadricauda (2.71 cell number doublings/day), which accumulated lanthanides to the highest level (27.3 mg/kg/day), if compared with Chlamydomonas reinhardtii and Parachlorella kessleri (2.50, 2.37 cell number doublings and 24.5, 12.5 mg/kg per day, respectively). With increasing concentrations of red mud, the growth rate decreased (2.71, 2.62, 2.43 cell number doublings/day) due to increased shadowing of cells by undissolved red mud particles. The accumulated lanthanide content, however, increased in the most efficient alga Desmodesmus quadricauda within 2 days from zero in red-mud free culture to 12.4, 39.0, 54.5 mg/kg of dry mass at red mud concentrations of 0.03, 0.05 and 0.1%, respectively. Red mud alleviated the metal starvation caused by cultivation in incomplete nutrient medium without added microelements. Moreover, the proportion of lanthanides in algae grown in red mud were about 250, 138, 117% higher than in culture grown in complete nutrient medium at red mud concentrations of 0.03, 0.05, 0.1%. Thus, green algae are prospective vehicles for bio-mining or bio-leaching of lanthanides from red mud.
Inorganic Polysulfides and Related Reactive Sulfur–Selenium Species from the Perspective of Chemistry
Authors: Kharma Ammar , Grman Marian , Misak Anton , Domínguez-Álvarez Enrique , Nasim Muhammad Jawad , Ondrias Karol , Chovanec Miroslav , Jacob Claus
Published: April 2019

Polysulfides (H2Sx) represent a class of reactive sulfur species (RSS) which includes molecules such as H2S2, H2S3, H2S4, and H2S5, and whose presence and impact in biological systems, when compared to other sulfur compounds, has only recently attracted the wider attention of researchers. Studies in this field have revealed a facet-rich chemistry and biological activity associated with such chemically simple, still unusual inorganic molecules. Despite their chemical simplicity, these inorganic species, as reductants and oxidants, metal binders, surfactant-like “cork screws” for membranes, components of perthiol signalling and reservoirs for inorganic hydrogen sulfide (H2S), are at the centre of complicated formation and transformation pathways which affect numerous cellular processes. Starting from their chemistry, the hidden presence and various roles of polysulfides in biology may become more apparent, despite their lack of clear analytical fingerprints and often murky biochemical footprints. Indeed, the biological chemistry of H2Sx follows many unexplored paths and today, the relationship between H2S and its oxidized H2Sx species needs to be clarified as a matter of “unmistaken identity”. Simultaneously, emerging species, such as HSSeSH and SenS8−n, also need to be considered in earnest.
Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review
Authors: Grochowski Cezary , Blicharska Eliza , Baj Jacek , Mierzwińska Aleksandra , Brzozowska Karolina , Forma Alicja , Maciejewski Ryszard
Published: April 2019

The aim of this paper was to review recent literature (from 2000 onwards) and summarize the newest findings on fluctuations in the concentration of some essential macro- and microelements in those patients with a history of chronic alcohol abuse. The focus was mainly on four elements which the authors found of particular interest: Iron, magnesium, copper, and manganese. After independently reviewing over 50 articles, the results were consistent with regard to iron and magnesium. On the other hand, data were limited, and in some cases contradictory, as far as copper and manganese were concerned. Iron overload and magnesium deficiency are two common results of an excessive and prolonged consumption of alcohol. An increase in the levels of iron can be seen both in the serum and within the cells, hepatocytes in particular. This is due to a number of factors: Increased ferritin levels, lower hepcidin levels, as well as some fluctuations in the concentration of the TfR receptor for transferrin, among others. Hypomagnesemia is universally observed among those suffering from alcoholism. Again, the causes for this are numerous and include malnutrition, drug abuse, respiratory alkalosis, and gastrointestinal problems, apart from the direct influence of excessive alcohol intake. Unfortunately, studies regarding the levels of both copper and manganese in the case of (alcoholic) liver disease are scarce and often contradictory. Still, the authors have attempted to summarize and give a thorough insight into the literature available, bearing in mind the difficulties involved in the studies. Frequent comorbidities and mutual relationships between the elements in question are just some of the complications in the study of this topic.
Structural and Functional Characterization of the Human Thymidylate Synthase (hTS) Interface Variant R175C, New Perspectives for the Development of hTS Inhibitors
Authors: Pozzi Cecilia , Ferrari Stefania , Luciani Rosaria , Costi Maria Paola , Mangani Stefano
Published: April 2019

Human thymidylate synthase (hTS) is pivotal for cell survival and proliferation, indeed it provides the only synthetic source of dTMP, required for DNA biosynthesis. hTS represents a validated target for anticancer chemotherapy. However, active site-targeting drugs towards hTS have limitations connected to the onset of resistance. Thus, new strategies have to be applied to effectively target hTS without inducing resistance in cancer cells. Here, we report the generation and the functional and structural characterization of a new hTS interface variant in which Arg175 is replaced by a cysteine. Arg175 is located at the interface of the hTS obligate homodimer and protrudes inside the active site of the partner subunit, in which it provides a fundamental contribution for substrate binding. Indeed, the R175C variant results catalytically inactive. The introduction of a cysteine at the dimer interface is functional for development of new hTS inhibitors through innovative strategies, such as the tethering approach. Structural analysis, performed through X-ray crystallography, has revealed that a cofactor derivative is entrapped inside the catalytic cavity of the hTS R175C variant. The peculiar binding mode of the cofactor analogue suggests new clues exploitable for the design of new hTS inhibitors.
Profiling and Structural Characterization of High Neu5Gc or Sulfate-Containing O-glycans from Hyla Rabbit Intestinal Mucin
Authors: Fu Qianyun , Li Guoyun , Wang Chen , Wang Ya , Li Qinying , Hao Jiejie , Yu Guangli
Published: April 2019

Intestinal mucins constitute the major component of the mucus covering the epithelium of the gastrointestinal tract, thereby forming a barrier against microbial colonization. Rabbits are bred in large numbers worldwide, with little known about intestinal O-glycosylation despite this insight being crucial to the understanding of host-pathogen interactions. In the present study, a major mucin-type glycopeptide (RIF6) of hyla rabbit intestine was isolated and the O-glycans were extensively characterized based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with bioinformatics approaches. Thirty-three O-glycans were identified, and most of them were sulfated or sialylated glycans. It was worth noting that Neu5Gc-containing structures within sialylated O-glycans accounted for 91%, which were extremely different from that of other species including humans, mice, chickens, etc. Sulfated glycans accounted for 58%, unique disufated and sulfated-sialylated glycans were also detected in rabbit intestinal mucin. These structural characterization reflected species diversity and may provide deeper insights into explaining the adaptability of hyla rabbit to the environment.
Effects of Carbazole Derivatives on Neurite Outgrowth and Hydrogen Peroxide-Induced Cytotoxicity in Neuro2a Cells
Authors: Furukawa Yoshiko , Sawamoto Atsushi , Yamaoka Mizuki , Nakaya Makiko , Hieda Yuhzo , Choshi Tominari , Hatae Noriyuki , Okuyama Satoshi , Nakajima Mitsunari , Hibino Satoshi
Published: April 2019

Many studies have demonstrated that oxidative stress plays an important role in several ailments including neurodegenerative diseases and cerebral ischemic injury. Previously we synthesized some carbazole compounds that have anti-oxidant ability in vitro. In this present study, we found that one of these 22 carbazole compounds, compound 13 (3-ethoxy-1-hydroxy-8- methoxy-2-methylcarbazole-5-carbaldehyde), had the ability to protect neuro2a cells from hydrogen peroxide-induced cell death. It is well known that neurite loss is one of the cardinal features of neuronal injury. Our present study revealed that compound 13 had the ability to induce neurite outgrowth through the PI3K/Akt signaling pathway in neuro2a cells. These findings suggest that compound 13 might exert a neurotrophic effect and thus be a useful therapy for the treatment of brain injury.
Investigation of the Biological Activities and Characterization of Bioactive Constituents of Ophiorrhiza rugosa var. prostrata (D.Don) & Mondal Leaves through In Vivo, In Vitro, and In Silico Approaches
Authors: Adnan Md. , Nazim Uddin Chy Md. , Mostafa Kamal A.T.M. , Azad Md Obyedul Kalam , Paul Arkajyoti , Uddin Shaikh Bokhtear , Barlow James W. , Faruque Mohammad Omar , Park Cheol Ho , Cho Dong Ha
Published: April 2019

Ophiorrhiza rugosa var. prostrata is one of the most frequently used ethnomedicinal plants by the indigenous communities of Bangladesh. This study was designed to investigate the antidiarrheal, anti-inflammatory, anthelmintic and antibacterial activities of the ethanol extract of O. rugosa leaves (EEOR). The leaves were extracted with ethanol and subjected to in vivo antidiarrheal screening using the castor oil-induced diarrhea, enteropooling, and gastrointestinal transit models. Anti-inflammatory efficacy was evaluated using the histamine-induced paw edema test. In parallel, in vitro anthelmintic and antibacterial activities were evaluated using the aquatic worm and disc diffusion assays respectively. In all three diarrheal models, EEOR (100, 200 and 400 mg/kg) showed obvious inhibition of diarrheal stool frequency, reduction of the volume and weight of the intestinal contents, and significant inhibition of intestinal motility. Also, EEOR manifested dose-dependent anti-inflammatory activity. Anthelmintic action was deemed significant (P < 0.001) with respect to the onset of paralysis and helminth death. EEOR also resulted in strong zones of inhibition when tested against both Gram-positive and Gram-negative bacteria. GC-MS analysis identified 30 compounds within EEOR, and of these, 13 compounds documented as bioactive showed good binding affinities to M3 muscarinic acetylcholine, 5-HT3, tubulin and GlcN-6-P synthase protein targets in molecular docking experiments. Additionally, ADME/T and PASS analyses revealed their drug-likeness, likely safety upon consumption and possible pharmacological activities. In conclusion, our findings scientifically support the ethnomedicinal use and value of this plant, which may provide a potential source for future development of medicines.
Chemical Constituents of Vigna luteola and Their Anti-inflammatory Bioactivity
Authors: Lam Sio-Hong , Li Yue-Chiun , Kuo Ping-Chung , Hwang Tsong-Long , Yang Mei-Lin , Wang Chien-Chiao , Tzen Jason T. C.
Published: April 2019

Seventy-three compounds were identified from the methanol extract of V. luteola, and among these, three new (1–3) were characterized by spectroscopic and mass spectrometric analyses. The isolated constituents were assessed for anti-inflammatory potential evaluation, and several purified principles exhibited significant superoxide anion and elastase inhibitory effects.
Evaluation and Optimization of the Anti-Melanogenic Activity of 1-(2-Cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone Derivatives
Authors: Kim Byung-Hak , Hong Soo-Nam , Ye Sang-Kyu , Park Jung-Youl
Published: April 2019

The chemical modification and optimization of biologically active compounds are essential steps in the identification of promising lead compounds for drug development. We previously reported the anti-melanogenic activity of 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone (chalcone 21). In this study, we synthesized 21 derivatives of chalcone 21 and evaluated their anti-melanogenic activity in α-MSH-induced B16F10 cells. (E)-N-(4-(3-(2-(Cyclohexylmethoxy)phenyl)-3-oxoprop-1-en-1-yl)phenyl)acetamide (chalcone 21-21) exhibited the strongest inhibition of cellular melanin production, with an IC50 value of 0.54 μM. It was more potent than chalcone 21 and the known anti-melanogenic agents kojic acid and arbutin, whose IC50 values were 4.9, 38.5, and 148.4 μM, respectively. Chalcone 21-21 decreased the expression and activity of tyrosinase. It also decreased the expression of TRP1, TRP2 and MITF, the phosphorylation of CREB and ERK1/2, and the transcriptional activity of MITF and CRE. Our results demonstrate that chalcone-21-21 is an effective lead compound with anti-melanogenic activity.
Perilla frutescens Britton: A Comprehensive Study on Flavor/Taste and Chemical Properties During the Roasting Process
Authors: Lee Jookyeong , Kim Da-Som , Cho Jinju , Hong Seong Jun , Pan Jeong Hoon , Kim Jae Kyeom , Shin Eui-Cheol
Published: April 2019

This study investigated changes of volatile compounds, sniffing test-assisted sensory properties, taste associated-constituent and free amino acid compositions, taste description by electronic-tongue, and chemical characteristics in Perilla frutescens Britton var. acuta Kudo after roasting at 150 °C for 0–8 min. A total of 142 volatile compounds were identified, among which methyl benzoate and limonene were predominant, regardless of roasting time, and these were also detected as the major compounds in the sniffing test by GC-olfactometry. For constituent amino acids analyzed by the acid hydrolysis method using hydrochloric acid (HCl), the concentration of glutamic acid, aspartic acid, and leucine showed an increase pattern with increased roasting time, which results in umami taste, sour taste, and bitter taste, respectively. For free amino acids, valine and hydroxylysine eliciting bitter and bitter and sweet tastes, respectively, also tend to increase by roasting. The pattern of amino acid concentration by roasting was readily matched to the taste description by electronic-tongue but that of sweetness and sourness by electronic-tongue did not coincide with the amino acid composition. For the chemical properties, total phenolic content, antioxidative capacity, and browning intensity tend to increase with roasting but decreased by 8 min. The results of this study provide fundamental information on perilla in both the food industry and cooking environment for the sake of increasing the utilization of perilla as a food source and ingredient.
New Dammarane-Type Saponins from Gynostemma pentaphyllum
Authors: Chen Po-Yen , Chang Chih-Chao , Huang Hui-Chi , Zhang Li-Jie , Liaw Chia-Ching , Lin Yu-Chi , Nguyen Nham-Linh , Vo Thanh-Hoa , Cheng Yung-Yi , Morris-Natschke Susan L. , Lee Kuo-Hsiung , Kuo Yao-Haur
Published: April 2019

Six new dammarane-type saponins, gypenosides CP1-6 (1–6), along with 19 known compounds 7–25, were isolated and characterized from the aerial parts of Gynostemma pentaphyllum. Among these compounds, eight dammarane-type saponins, 2, 5, 6, 7, 11, 12, 13, and 15, exhibited the greatest antiproliferative effects against two human tumor cell lines (A549 and HepG2).
KMUP-1 Ameliorates Ischemia-Induced Cardiomyocyte Apoptosis through the NO–cGMP–MAPK Signaling Pathways
Authors: Lee Meng-Luen , Sulistyowati Erna , Hsu Jong-Hau , Huang Bo-Yau , Dai Zen-Kong , Wu Bin-Nan , Chao Yu-Ying , Yeh Jwu-Lai
Published: April 2019

To test whether KMUP-1 (7-[2-[4-(2-chlorophenyl) piperazinyl]ethyl]-1,3-dimethylxanthine) prevents myocardial ischemia-induced apoptosis, we examined KMUP-1-treated H9c2 cells culture. Recent attention has focused on the activation of nitric oxide (NO)-guanosine 3’, 5’cyclic monophosphate (cGMP)-protein kinase G (PKG) signaling pathway triggered by mitogen-activated protein kinase (MAPK) family, including extracellular-signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 in the mechanism of cardiac protection during ischemia-induced cell-death. We propose that KMUP-1 inhibits ischemia-induced apoptosis in H9c2 cells culture through these pathways. Cell viability was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and apoptotic evaluation was conducted using DNA ladder assay and Hoechst 33342 staining. The level of intracellular calcium was detected using-Fura2-acetoxymethyl (Fura2-AM) staining, and mitochondrial calcium with Rhod 2-acetoxymethyl (Rhod 2-AM) staining under fluorescence microscopic observation. The expression of endothelium NO synthase (eNOS), inducible NO synthase (iNOS), soluble guanylate cyclase α1 (sGCα1), PKG, Bcl-2/Bax ratio, ERK1/2, p38, and JNK proteins were measured by Western blotting assay. KMUP-1 pretreatment improved cell viability and inhibited ischemia-induced apoptosis of H9c2 cells. Calcium overload both in the intracellular and mitochondrial sites was attenuated by KMUP-1 pretreatment. Moreover, KMUP-1 reduced intracellular reactive oxygen species (ROS), increased plasma NOx (nitrite and nitrate) level, and the expression of eNOS. Otherwise, the iNOS expression was downregulated. KMUP-1 pretreatment upregulated the expression of sGCα1 and PKG protein. The ratio of Bcl-2/Bax expression was increased by the elevated level of Bcl2 and decreased level of Bax. In comparison with the ischemia group, KMUP-1 pretreatment groups reduced the expression of phosphorylated extracellular signal-regulated kinases ERK1/2, p-p38, and p-JNK as well. Therefore, KMUP-1 inhibits myocardial ischemia-induced apoptosis by restoration of cellular calcium influx through the mechanism of NO-cGMP-MAPK pathways.
Direct Spectroscopy for Probing the Critical Role of Partial Covalency in Oxygen Reduction Reaction for Cobalt-Manganese Spinel Oxides
Authors: Long Xinghui , Yu Pengfei , Zhang Nian , Li Chun , Feng Xuefei , Ren Guoxi , Zheng Shun , Fu Jiamin , Cheng Fangyi , Liu Xiaosong
Published: April 2019

Nanocrystalline multivalent metal spinels are considered as attractive non-precious oxygen electrocatalysts. Identifying their active sites and understanding their reaction mechanisms are essential to explore novel transition metal (TM) oxides catalysts and further promote their catalytic efficiency. Here we report a systematic investigation, by means of soft X-ray absorption spectroscopy (sXAS), on cubic and tetragonal CoxMn3-xO4 (x = 1, 1.5, 2) spinel oxides as a family of highly active catalysts for the oxygen reduction reaction (ORR). We demonstrate that the ORR activity for oxide catalysts primarily correlates to the partial covalency of between O 2p orbital with Mn4+ 3d t2g-down/eg-up, Mn3+ 3d eg-up and Co3+ 3d eg-up orbitals in octahedron, which is directly revealed by the O K-edge sXAS. Our findings propose the critical influences of the partial covalency between oxygen 2p band and specific metal 3d band on the competition between intermediates displacement of the ORR, and thus highlight the importance of electronic structure in controlling oxide catalytic activity.
Breastfeeding and Human Lactation
Authors: Geddes Donna , Perrella Sharon
Published: April 2019

Breastfeeding is the very means by which humans have thrived and developed as a species [...]
TRP Channels and Migraine: Recent Developments and New Therapeutic Opportunities
Authors: Benemei Silvia , Dussor Greg
Published: April 2019

Migraine is the second-most disabling disease worldwide, and the second most common neurological disorder. Attacks can last many hours or days, and consist of multiple symptoms including headache, nausea, vomiting, hypersensitivity to stimuli such as light and sound, and in some cases, an aura is present. Mechanisms contributing to migraine are still poorly understood. However, transient receptor potential (TRP) channels have been repeatedly linked to the disorder, including TRPV1, TRPV4, TRPM8, and TRPA1, based on their activation by pathological stimuli related to attacks, or their modulation by drugs/natural products known to be efficacious for migraine. This review will provide a brief overview of migraine, including current therapeutics and the link to calcitonin gene-related peptide (CGRP), a neuropeptide strongly implicated in migraine pathophysiology. Discussion will then focus on recent developments in preclinical and clinical studies that implicate TRP channels in migraine pathophysiology or in the efficacy of therapeutics. Given the use of onabotulinum toxin A (BoNTA) to treat chronic migraine, and its poorly understood mechanism, this review will also cover possible contributions of TRP channels to BoNTA efficacy. Discussion will conclude with remaining questions that require future work to more fully evaluate TRP channels as novel therapeutic targets for migraine.
High-Performance Chlorine-Doped Cu2O Catalysts for the Ethynylation of Formaldehyde
Authors: Gao Jie , Yang Guofeng , Li Haitao , Dong Mei , Wang Zhipeng , Li Zhikai
Published: April 2019

The in situ formed Cu+ species serve as active sites in the ethynylation of formaldehyde. The key problem that needs to be solved in this process is how to avoid excessive reduction of Cu2+ to inactive metallic Cu, which tends to decrease the catalytic activity. In this work, Cl−-modified Cu2O catalysts with different Cl content were prepared by co-precipitation. The characterization results demonstrated that Cl− remained in the lattice structure of Cu2O, inducing the expansion of the Cu2O lattice and the enhancement of the Cu–O bond strength. Consequently, the reduction of Cu+ to Cu0 was effectively prevented in reductive media. Moreover, the activity and stability of Cu2O were significantly improved. The Cl− modification increased the yield of 1,4-butynediol (BD) from 73% to 94% at a reaction temperature of 90 °C. More importantly, the BD yield of Cl− modified Cu2O was still as high as 86% during the ten-cycle experiment, whereas the BD yield of Cu2O in the absence of Cl− decreased sharply to 17% at the same reaction conditions. This work provides a simple strategy to stabilize Cu+ in reductive media.
Sumud Freedom Camp: Levinas’ Face-to-Face in Praxis
Authors: Podolsky Robin
Published: April 2019

In Levinas’s thought, the subject emerges and is founded in relationship with the other, in the face-to-face. In response to other’s summons, the call to respond with discourse, not violence to the vulnerable face of another person, the subject is constituted, and all human society, hence all justice, becomes possible. This relationship, in which the other is always higher than oneself, is complicated by questions of justice and politics. The subject is obliged to respond unreservedly to her neighbor, but what happens when neighbors disagree and the necessity to adjudicate claims arises? This paper describes, based on the author’s direct experience and study, the nonviolent practice of relationship-building initiated at Sumud Freedom camp by diaspora Jews, Palestinians and Israelis who came together in the south Hebron desert hills to form a nonviolent community in which to encounter one another. Initiatives such as Sumud Camp do not represent retreats from the political. They do prioritize the interhuman face-to-face, relationship-building, and they seek to evolve political program based on personal investments in other people’s well-being. Thus, they represent an instance of Levinasian praxis from which a grass new roots politics might emerge.
A Deep-Language Mathematical Analysis of Gospels, Acts and Revelation
Authors: Matricciani Emilio , Caro Liberato De
Published: April 2019

The paper aims at casting some light on the interrelations among the Gospels, Acts and Revelation. We do not consider words ranking and their frequency of occurrence, as largely done in the literature, but we analyze, statistically, some mathematical aspects of the texts, which the authors were not conscious of. We use mathematical methods developed for specifically studying deep-language parameters of literary texts, such as the number of words per sentence, the number of characters per word, the number of words per interpunctions, the number of interpunctions per sentence, all very likely peculiar to the writer’s style, after having recalled the punctuation in classical languages. First, we consider the full texts of the canonical Gospels, Acts and Revelation, then the partial texts attributable to the Triple Tradition (Matthew, Mark and Luke), to the Double Tradition (Matthew and Luke), Own Tradition (Matthew and Luke) and Q source. The mathematical/statistical tool used confirms and reinforces some general results concerning the Gospels, Acts, Revelation and Q source, but also evidences some interesting differences concerning the number of words per sentence and words per interpunctions, likely casting some light on the capacity of the short-term memory of the readers/listeners of these texts. All these New Testament writings fit very well in the larger Greek literature of the time. The existence of a proto gospel seems more probable than other possible hypotheses.
Archaeology and Religion in Late Bronze Age Canaan
Authors: Greener Aaron
Published: April 2019

Dozens of temples were excavated in the Canaanite city-states of the Late Bronze Age. These temples were the focal points for the Canaanites’ cultic activities, mainly sacrifices and ceremonial feasting. Numerous poetic and ritual texts from the contemporary city of Ugarit reveal the rich pantheon of Canaanite gods and goddesses which were worshiped by the Canaanites. Archaeological remains of these rites include burnt animal bones and many other cultic items, such as figurines and votive vessels, which were discovered within the temples and sanctuaries. These demonstrate the diverse and receptive character of the Canaanite religion and ritual practices. It seems that the increased Egyptian presence in Canaan towards the end of the period had an influence on the local belief system and rituals in some areas, a fact which is demonstrated by the syncretic architectural plans of several of the temples, as well as by glyptic and votive items. Late Bronze Age religious and cultic practices have attracted much attention from Biblical scholars and researchers of the religion of Ancient Israel who are searching for the similarities and influences between the Late Bronze Age and the following Iron Age.
Commitment to Environmental and Climate Change Sustainability under Competition
Authors: Sim Jeong Eun , Kim Bosung
Published: April 2019

This study investigates how the commitment of firms under competition influences environmental sustainability investment, pricing decisions, and profits of firms. We consider a stylized model where two firms compete in the market and examine three scenarios: (1) both firms commit, (2) only a single firm commits, and (3) neither firm commits. Interestingly, we find that commitment to sustainability investment by all firms results in the lowest sustainability investment in the industry. However, when a commitment is only made by one firm, sustainability investment in the industry can be the highest. Compared with under the no commitment scenario, a committed firm obtains a higher profit regardless of whether the commitment is also made by the competitor, but the competitor may become more profitable than the committed firm when it does not make a commitment. Although commitment by all firms yields the largest profits, it is the least effective from the entire societal perspective, resulting in both the lowest social welfare and the lowest sustainability investment. Instead, commitment by a single firm or no commitment can be the most effective for the entire society. We also discuss the implications of the investment efficiency of sustainability and consumer taste preference.
Including Urban Metabolism Principles in Decision-Making: A Methodology for Planning Waste and Resource Management
Authors: Longato Davide , Lucertini Giulia , Dalla Fontana Michele , Musco Francesco
Published: April 2019

Circular economy and urban metabolism concepts have recently received great attention both in the political and academic arenas, starting a roll-over process of the “take, make, and dispose” dominant economic model that is leading to an ongoing increase of resource consumption and waste generation. However, there is a relative lack of guidelines for introducing such concepts in a decision-making process able to support the design of appropriate policies and strategies and the definition of specific actions to cope with such challenges. This paper attempts to contribute to the recent efforts at incorporating these concepts in policy and decision-making processes by providing a methodology for the development of strategic plans for waste prevention and resource management. The proposed methodology, developed within the Urban_WINS project, combines different quantitative–analytical and qualitative methods and tools, together with a participatory process. The methodology was tested in eight EU cities and allowed to formulate several measures and actions aimed at addressing the challenges posed by the current consumption patterns. Moreover, the participatory approach led to the legitimization of the strategic plans, as well as to raise awareness among stakeholders. Although it might require specific tailor-made adjustments, this methodology is suitable to be replicated in other contexts.
Cosmological Probes of Supersymmetric Field Theory Models at Superhigh Energy Scales
Authors: Ketov Sergei , Khlopov Maxim
Published: April 2019

The lack of positive results in searches for supersymmetric (SUSY) particles at the Large Hadron Collider (LHC) and in direct searches for Weakly Interacting Massive Particles (WIMPs) in the underground experiments may hint to a super-high energy scale of SUSY phenomena beyond the reach of direct experimental probes. At such scales the supergravity models based on Starobinsky inflation can provide the mechanisms for both inflation and superheavy dark matter. However, it makes the indirect methods the only way of testing the SUSY models, so that cosmological probes acquire the special role in this context. Such probes can rely on the nontrivial effects of SUSY physics in the early Universe, which are all model-dependent and thus can provide discrimination of the models and their parameters. The nonstandard cosmological features like Primordial Black Holes (PBHs) or antimatter domains in a baryon-asymmetric universe are discussed as possible probes for high energy scale SUSY physics.
Roles of Shiga Toxins in Immunopathology
Authors: Lee Moo-Seung , Tesh Vernon L.
Published: April 2019

Shigella species and Shiga toxin-producing Escherichia coli (STEC) are agents of bloody diarrhea that may progress to potentially lethal complications such as diarrhea-associated hemolytic uremic syndrome (D+HUS) and neurological disorders. The bacteria share the ability to produce virulence factors called Shiga toxins (Stxs). Research over the past two decades has identified Stxs as multifunctional toxins capable of inducing cell stress responses in addition to their canonical ribotoxic function inhibiting protein synthesis. Notably, Stxs are not only potent inducers of cell death, but also activate innate immune responses that may lead to inflammation, and these effects may increase the severity of organ injury in patients infected with Stx-producing bacteria. In the intestines, kidneys, and central nervous system, excessive or uncontrolled host innate and cellular immune responses triggered by Stxs may result in sensitization of cells to toxin mediated damage, leading to immunopathology and increased morbidity and mortality in animal models (including primates) and human patients. Here, we review studies describing Stx-induced innate immune responses that may be associated with tissue damage, inflammation, and complement activation. We speculate on how these processes may contribute to immunopathological responses to the toxins.