bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysing Atmospheric Processes and Climatic Drivers of Tree Defoliation to Determine Forest Vulnerability to Climate Warming
Authors: Sánchez-Salguero Raúl , Camarero J. , Grau José , De la Cruz Ana , Gil Paula , Minaya Mayte , Fernández-Cancio Ángel
Published: December 2016

Crown defoliation is extensively monitored across European forests within the International Co-operative Programme (ICP) as a proxy of forest health. Climate warming and drought are assumed to be the major drivers of tree growth and crown defoliation, particularly in seasonally dry areas such as the Mediterranean Basin. Here we analyse how climate, drought, and atmospheric processes are related to defoliation time series of five oak and five pine species that are dominant across Spanish ICP monitoring forest plots. We found that warmer and drier conditions during April were linked to enhanced defoliation. Warm April conditions were also related to high values of the Atlantic Multi-decadal Oscillation (AMO), thereby indicating large-scale links between atmospheric processes, temperature, and defoliation patterns. The temperature-defoliation association was species-specific since some tree species from wet sites showed a weak association (e.g., Quercus robur L.) whereas others from dry sites (e.g., Quercus ilex L.) presented the strongest associations. The latter tree species could be considered vulnerable to heat stress in terms of leaf shedding. We also explored if defoliation was related to radial growth and found negative associations in relatively dry areas. Warmer and drier conditions linked to increasing AMO values are connected to the post-1990s rise of defoliation in Spanish ICP forest plots. Combined incorporation of defoliation and growth into mortality models can provide insights into assessments of forest vulnerability.
Does the ‘One Map Initiative’ Represent a New Path for Forest Mapping in Indonesia? Assessing the Contribution of the REDD+ Initiative in Effecting Forest Governance Reform
Authors: Mulyani Mari , Jepson Paul
Published: December 2016

This study investigates one notable result that the REDD+ (‘Reducing Emissions from Deforestation and forest Degradation, and enhancing forest carbon stocks and conservation’) initiative effected within Indonesia’s forest institutions. It argues that during its interplay with existing National forest institutions REDD+ produced a significant benefit; namely, the ‘one map initiative’ (OMI) being the government’s response to the call for greater transparency and enabling of REDD+ implementation. It asks: “Does the ‘One Map Initiative’ signify a switch to a new path of map-making, or is it just another innovation within an existing path dependence of forest governance?” Through eighty semi-structured interviews with ‘REDD+ policy actors’ and the deployment of ‘path dependence’ theory, this study seeks to determine the extent to which the REDD+ initiative created a ‘critical juncture’ (i.e., momentum for institutions to move to a new path). This study maps the institutional path dependence within forest-mapping as a means for the state to gain control of forest resources. In its development process the OMI has shown its ability to break the old path-dependence of map-making (e.g., lack of transparency, low level of public participation, and poor coordination amongst ministries). Moreover, this paper identified several historical events (i.e., ‘critical junctures’) that preceded the REDD+ initiative as contributing factors to the relative success of REDD+ in effecting forest governance reform.
Differentiation of Alternate Harvesting Practices Using Annual Time Series of Landsat Data
Authors: Jarron Lukas , Hermosilla Txomin , Coops Nicholas , Wulder Michael , White Joanne , Hobart Geordie , Leckie Donald
Published: December 2016

Sustainable forest management practices allow for a range of harvest prescriptions, including clearcut, clearcut with residual, and partial or selective cutting, which are largely distinguished by the amount of canopy cover removed. The different prescriptions are aimed to emulate natural disturbance, encourage regeneration (seed trees), or offer other ecosystem services, such as the maintenance of local biodiversity or habitat features. Using remotely sensed data, stand-replacing disturbance associated with clearcutting is commonly accurately detected. Novel time series-based change detection products offer an opportunity to determine the capacity to detect and label a wider range of harvest practices. In this research, we demonstrate the capacity of time series imagery, spectral metrics, and related attributed change products, to distinguish between different harvesting practices over a study area in central British Columbia, Canada. Producer’s accuracy of harvest attribution was 79%, with 93% of harvest blocks >5 ha accurately identified. In relation to the amount of canopy cover removed, clearcut harvesting was the most accurately classified (84%), followed by clearcut with residual (79%), and partial cut (64%). Applying detailed spectral metrics derived from Landsat data revealed clearcut and partial cuts to be spectrally distinct. The annual nature of the Landsat time series also offers spatial harvest information within typical, often decadal, forest inventory update cycles. The statistically significant (p < 0.05) relationship between harvest practices and Landsat spectral information indicates a capacity to add increased attribution richness to remote sensing depictions of forest harvest.
A New Statistical Approach to the Optical Spectral Variability in Blazars
Authors: Acosta-Pulido Jose , Castro Segura Noel , Carnerero Maria , Raiteri Claudia
Published: December 2016

We present a spectral variability study of a sample of about 25 bright blazars, based on optical spectroscopy. Observations cover the period from the end of 2008 to mid 2015, with an approximately monthly cadence. Emission lines have been identified and measured in the spectra, which permits us to classify the sources into BL Lac-type or FSRQs, according to the commonly used EW limit. We have obtained synthetic photometry and produced colour-magnitude diagrams which show different trends associated with the object classes: generally, BL Lacs tend to become bluer when brighter and FSRQs become redder when brighter, although several objects exhibit both trends, depending on brightness. We have also applied a pattern recognition algorithm to obtain the minimum number of physical components which can explain the variability of the optical spectrum. We have used NMF (Non-Negative Matrix Factorization) instead of PCA (Principal Component Analysis) to avoid un-realistic negative components. For most targets we found that 2 or 3 meta-components are enough to explain the observed spectral variability.
Potential Inhibitory Influence of miRNA 210 on Regulatory T Cells during Epicutaneous Chemical Sensitization
Authors: Long Carrie , Lukomska Ewa , Marshall Nikki , Nayak Ajay , Anderson Stacey
Published: December 2016

Toluene diisocyanate (TDI) is a potent low molecular weight chemical sensitizer and a leading cause of chemical-induced occupational asthma. The regulatory potential of microRNAs (miRNAs) has been recognized in a variety of disease states, including allergic disease; however, the roles of miRNAs in chemical sensitization are largely unknown. In a previous work, increased expression of multiple miRNAs during TDI sensitization was observed and several putative mRNA targets identified for these miRNAs were directly related to regulatory T-cell (Treg) differentiation and function including Foxp3 and Runx3. In this work, we show that miR-210 expression is increased in the mouse draining lymph node (dLN) and Treg subsets following dermal TDI sensitization. Alterations in dLN mRNA and protein expression of Treg related genes/putative miR-210 targets (foxp3, runx3, ctla4, and cd25) were observed at multiple time points following TDI exposure and in ex vivo systems. A Treg suppression assay, including a miR-210 mimic, was utilized to investigate the suppressive ability of Tregs. Cells derived from TDI sensitized mice treated with miR-210 mimic had less expression of miR-210 compared to the acetone control suggesting other factors, such as additional miRNAs, might be involved in the regulation of the functional capabilities of these cells. These novel findings indicate that miR-210 may have an inhibitory role in Treg function during TDI sensitization. Because the functional roles of miRNAs have not been previously elucidated in a model of chemical sensitization, these data contribute to the understanding of the potential immunologic mechanisms of chemical induced allergic disease.
Ameliorative Effect of Curcumin-Encapsulated Hyaluronic Acid–PLA Nanoparticles on Thioacetamide-Induced Murine Hepatic Fibrosis
Authors: Chen Yu-Nong , Hsu Shih-Lan , Liao Ming-Yuan , Liu Yi-Ting , Lai Chien-Hung , Chen Ji-Feng , Nguyen Mai-Huong , Su Yung-Hsiang , Chen Shang-Ting , Wu Li-Chen
Published: December 2016

In this study, we developed curcumin-encapsulated hyaluronic acid–polylactide nanoparticles (CEHPNPs) to be used for liver fibrosis amelioration. CD44, the hyaluronic acid (HA) receptor, is upregulated on the surface of cancer cells and on activated hepatic stellate cells (aHSCs) rather than normal cells. CEHPNPs could bind to CD44 and be internalized effectively through endocytosis to release curcumin, a poor water-soluble liver protective agent. Thus, CEHPNPs were potentially not only improving drug efficiency, but also targeting aHSCs. HA and polylactide (PLA) were crosslinked by adipic acid dihydrazide (ADH). The synthesis of HA–PLA was monitored by Fourier-transform infrared (FTIR) and Nuclear Magnetic Resonance (NMR). The average particle size was approximately 60–70 nm as determined by dynamic light scattering (DLS) and scanning electron microscope (SEM). Zeta potential was around −30 mV, which suggested a good stability of the particles. This drug delivery system induced significant aHSC cell death without affecting quiescent HSCs, hepatic epithelial, and parenchymal cells. This system reduced drug dosage without sacrificing therapeutic efficacy. The cytotoxicity IC50 (inhibitory concentration at 50%) value of CEHPNPs was approximately 1/30 to that of the free drug treated group in vitro. Additionally, the therapeutic effects of CEHPNPs were as effective as the group treated with the same curcumin dose intensity in vivo. CEHPNPs significantly reduced serum aspartate transaminase/alanine transaminase (ALT/AST) significantly, and attenuated tissue collagen production and cell proliferation as revealed by liver biopsy. Conclusively, the advantages of superior biosafety and satisfactory therapeutic effect mean that CEHPNPs hold great potential for treating hepatic fibrosis.
Assessment of a Culturally-Tailored Sexual Health Education Program for African American Youth
Authors: Zellner Lawrence Tiffany , Henry Akintobi Tabia , Miller Assia , Archie-Booker Elaine , Johnson Tarita , Evans Donoria
Published: December 2016

African American youth are affected disproportionately by sexually transmitted infections (STIs), human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), and teenage pregnancy when compared to other racial groups. This paper evaluates the effectiveness of the To Help Young People Establish (2 HYPE) Abstinence Club, a behavioral intervention designed to promote delayed sexual activity among African American youth ages 12–18 in Atlanta, Georgia. The intervention included 20 h of curriculum and creative arts instruction. Pre- and post-intervention survey data collected from 2008–2010 were analyzed to determine the effectiveness of the intervention. Intervention (n = 651) and comparison (n = 112) groups were compared through analysis of variance and multivariate logistic regression models. There was a statistically significant increase in intervention youth who were thinking about being abstinent (p = 0.0005). Those who had not been engaged in sexual activity were two times more likely to plan abstinence compared to participants that had been previously sexually active previously (odds ratio 2.41; 95% confidence interval 1.62, 3.60). Significant results hold implications for subsequent community-based participatory research and practice that broadens the understanding of the relevance of marriage, as just one among other life success milestones that may hold more importance to African American youth in positioning the value of delayed and responsible sexual activity towards effective STIs, HIV/AIDS, and teen pregnancy risk reduction interventions.
A Survey of Snakebite Knowledge among Field Forces in China
Authors: Chen Chulin , Gui Li , Kan Ting , Li Shuang , Qiu Chen
Published: December 2016

Background: A snakebite is a neglected extrinsic injury associated with high morbidity and global mortality. Members of Chinese field forces are at high risk of snakebites, and their perception and knowledge of snakebites are unknown. The aim of this study is to assess perception and knowledge of snakebites in field forces in southeast China; Methods: A cross-sectional questionnaire-based survey was conducted in July 2016. A total of 216 field force members participated in this study; Results: A total of 10.3% had experienced snakebites and 86.4% rated their demands for knowledge about snakebite as “high”. No significant correlation between the actual and perceived snakebite knowledge status was detected (κ = 0.0237, p = 0.3852). Ineffective and harmful traditional first-aid methods, such as the application of tourniquets, sucking the venom out of the wound, and making local incisions, were used by more than three quarters of the respondents. However, pressure immobilization bandages were applied by only 17.3% of members. The proportion of responses for each question was not significantly different among the respondents when considering separate demographic groups; Conclusions: Snakebite knowledge among Chinese field force members is inadequate and in some cases misleading, when focusing on manifestation, prevention, and first-aid. A pragmatic, intensive educational scheme should be undertaken in at-risk populations.
Changes in Depressive Symptoms among Older Adults with Multiple Chronic Conditions: Role of Positive and Negative Social Support
Authors: Ahn SangNam , Kim Seonghoon , Zhang Hongmei
Published: December 2016

Depression severely affects older adults in the United States. As part of the social environment, significant social support was suggested to ameliorate depression among older adults. We investigate how varying forms of social support moderate depressive symptomatology among older adults with multiple chronic conditions (MCC). Data were analyzed using a sample of 11,400 adults, aged 65 years or older, from the 2006–2012 Health and Retirement Study. The current study investigated the moderating effects of positive or negative social support from spouse, children, other family, and friends on the association between MCC and depression. A linear mixed model with repeated measures was used to estimate the effect of MCC on depression and its interactions with positive and negative social support in explaining depression among older adults. Varying forms of social support played different moderating roles in depressive symptomatology among older adults with MCC. Positive spousal support significantly weakened the deleterious effect of MCC on depression. Conversely, all negative social support from spouse, children, other family, and friends significantly strengthened the deleterious effect of MCC on depression. Minimizing negative social support and maximizing positive spousal support can reduce depression caused by MCC and lead to successful aging among older adults.
Bisphenol A and Ovarian Reserve among Infertile Women with Polycystic Ovarian Syndrome
Authors: Zhou Wei , Fang Fang , Zhu Wenting , Chen Zi-Jiang , Du Yanzhi , Zhang Jun
Published: December 2016

To better understand possible effects of bisphenol A (BPA) exposure on ovarian reserve in women with polycystic ovary syndrome (PCOS), we measured creatinine adjusted urinary BPA (BPA_Cre) concentrations and used regression models to evaluate the association between urinary BPA level and antral follicle count (AFC), antimullerian hormone (AMH), day-3 follicle stimulating hormone levels (FSH) and inhibin B (INHB) in 268 infertile women diagnosed with PCOS. BPA was detected in all women with a median concentration of 2.35 ng/mL (the 25th and 75th percentiles of 1.47 ng/mL and 3.95 ng/mL). A unit increase in BPA_Cre was associated with a significant decrease of 0.34 in AFC (β = −0.34, 95% CI = −0.60, −0.08; p = 0.01). Likewise, BPA was negatively associated with AMH and day-3 FSH levels, but neither of them reached statistical significance. No association was observed between BPA and INHB. Our results suggest that in women with PCOS, BPA may affect ovarian follicles and, therefore, reduce ovarian reserve.
Hotspot Identification for Shanghai Expressways Using the Quantitative Risk Assessment Method
Authors: Chen Can , Li Tienan , Sun Jian , Chen Feng
Published: December 2016

Hotspot identification (HSID) is the first and key step of the expressway safety management process. This study presents a new HSID method using the quantitative risk assessment (QRA) technique. Crashes that are likely to happen for a specific site are treated as the risk. The aggregation of the crash occurrence probability for all exposure vehicles is estimated based on the empirical Bayesian method. As for the consequences of crashes, crashes may not only cause direct losses (e.g., occupant injuries and property damages) but also result in indirect losses. The indirect losses are expressed by the extra delays calculated using the deterministic queuing diagram method. The direct losses and indirect losses are uniformly monetized to be considered as the consequences of this risk. The potential costs of crashes, as a criterion to rank high-risk sites, can be explicitly expressed as the sum of the crash probability for all passing vehicles and the corresponding consequences of crashes. A case study on the urban expressways of Shanghai is presented. The results show that the new QRA method for HSID enables the identification of a set of high-risk sites that truly reveal the potential crash costs to society.
Antimicrobial Resistant Enteropathogenic Escherichia coli and Salmonella spp. in Houseflies Infesting Fish in Food Markets in Zambia
Authors: Songe Mwansa , Hang’ombe Bernard , Knight-Jones Theodore , Grace Delia
Published: December 2016

Diarrhea is one of the most common diseases and is a leading cause of death in developing countries. This is often caused by contaminated food. Poor food hygiene standards are exacerbated by the presence of flies which can transmit a variety of infectious microorganisms, particularly through animal source foods. This fact becomes especially important in developing countries like Zambia, where fish is a highly valued source of protein. Our interest in this study was to identify if the flies that beset food markets in Zambia carry important pathogenic bacteria on their bodies, and subsequently if these bacteria carry resistance genes to commonly used antibiotics, which would indicate problems in eradicating these pathogens. The present study took into account fish vendors’ and consumers’ perception of flies and interest in interventions to reduce their numbers. We conducted semi-structured interviews with (1) traders (comprised of randomly selected males and females) and (2) consumers (including randomly selected males and females). Thereafter, we collected flies found on fish in markets in Mongu and Lusaka districts of Zambia. For the entire study, a total of 418 fly samples were analyzed in the laboratory and Salmonella spp. and enteropathogenic Escherichia coli were isolated from the flies. Further laboratory screening revealed that overall, 17.2% (72/418) (95% CI; 43.2%–65.5%) of total samples analyzed contained Extended-Spectrum Beta-Lactamase (ESBL)-producing E. coli. These significant findings call for a strengthening of the antibiotic administering policy in Zambia and the development of sustainable interventions to reduce fly numbers in food markets and improve food safety and hygiene.
Environmental Determinants of Bronchial Asthma among Saudi School Children in Southwestern Saudi Arabia
Authors: Alqahtani Jobran , Asaad Ahmed , Awadalla Nabil , Mahfouz Ahmed
Published: December 2016

The aim here was to study the possible environmental and dietary determinants of asthma among school-aged children in Southwestern Saudi Arabia. In a cross-sectional study on a representative sample in Najran in Southwestern Saudi Arabia using an Arabic version of the modified ISAAC Phase III, parent-administered questionnaire data were collected. Skin prick tests (SPTs) were performed. The study included 1700 school children, out of them 468 (27.5%) were diagnosed with, cases of bronchial asthma and 20.8% (353) reported a 12-month nocturnal cough (as a proxy of severe asthma). In multivariable analysis, the study identified the following risk factors for having asthma or severe asthma: having dogs in the house, being male, being exposed to dense truck traffic on the street, using wood as a cooking fuel, conducting vigorous exercise, consuming eggs, consuming vegetables, having an allergic sensitization to dog hair, and being exposed to Cladosporium, pigweed, and Bermuda grass. On the other hand, the following food stuffs were found to be protective: seafood, fruit, and dairy products. Comprehensive school educational programs for both children and their parents should be adopted to prevent the use of wood in cooking and heating, to ensure that house pets are properly cared for, and to encourage proper dietary habits. Physicians should be informed of the patterns of allergens in order to improve asthma diagnosis and management.
Connecting the Dots: Linking Environmental Justice Indicators to Daily Dose Model Estimates
Authors: Huang Hongtai , Barzyk Timothy
Published: December 2016

Many different quantitative techniques have been developed to either assess Environmental Justice (EJ) issues or estimate exposure and dose for risk assessment. However, very few approaches have been applied to link EJ factors to exposure dose estimate and identify potential impacts of EJ factors on dose-related variables. The purpose of this study is to identify quantitative approaches that incorporate conventional risk assessment (RA) dose modeling and cumulative risk assessment (CRA) considerations of disproportionate environmental exposure. We apply the Average Daily Dose (ADD) model, which has been commonly used in RA, to better understand impacts of EJ indicators upon exposure dose estimates and dose-related variables, termed the Environmental-Justice-Average-Daily-Dose (EJ-ADD) approach. On the U.S. nationwide census tract-level, we defined and quantified two EJ indicators (poverty and race/ethnicity) using an EJ scoring method to examine their relation to census tract-level multi-chemical exposure dose estimates. Pollutant doses for each tract were calculated using the ADD model, and EJ scores were assigned to each tract based on poverty- or race-related population percentages. Single- and multiple-chemical ADD values were matched to the tract-level EJ scores to analyze disproportionate dose relationships and contributing EJ factors. We found that when both EJ indicators were examined simultaneously, ADD for all pollutants generally increased with larger EJ scores. To demonstrate the utility of using EJ-ADD on the local scale, we approximated ADD levels of lead via soil/dust ingestion for simulated communities with different EJ-related scenarios. The local-level simulation indicates a substantial difference in exposure-dose levels between wealthy and EJ communities. The application of the EJ-ADD approach can link EJ factors to exposure dose estimate and identify potential EJ impacts on dose-related variables.
Gendered Sources of Distress and Resilience among Afghan Refugees in Northern California: A Cross-Sectional Study
Authors: Stempel Carl , Sami Nilofar , Koga Patrick , Alemi Qais , Smith Valerie , Shirazi Aida
Published: December 2016

Recent studies have emphasized the influence of resettlement factors on the mental health of refugees resettling in developed countries. However, little research has addressed gender differences in the nature and influence of resettlement stressors and sources of resilience. We address this gap in knowledge by investigating how gender moderates and mediates the influence of several sources of distress and resilience among 259 Afghan refugees residing in Northern California (USA). Gender moderated the effects of four factors on levels of distress. Intimate and extended family ties have little correlation with men’s distress levels, but are strongly associated with lower distress for women. English ability is positively associated with lower distress for women, but not men. In terms of gender ideology, traditionally oriented women and egalitarian men have lower levels of distress. And experiencing greater dissonant acculturation increases distress for men, but not women. The influence of gender interaction terms is substantial and patterns may reflect difficulty adapting to a different gender order. Future studies of similar populations should investigate gender differences in sources of distress and resilience, and efforts to assist new arrivals might inform them of changes in gender roles they may experience, and facilitate opportunities to renegotiate gender roles.
The Neurobiological Impact of Ghrelin Suppression after Oesophagectomy
Authors: Murphy Conor , Le Roux Carel
Published: December 2016

Ghrelin, discovered in 1999, is a 28-amino-acid hormone, best recognized as a stimulator of growth hormone secretion, but with pleiotropic functions in the area of energy homeostasis, such as appetite stimulation and energy expenditure regulation. As the intrinsic ligand of the growth hormone secretagogue receptor (GHS-R), ghrelin appears to have a broad array of effects, but its primary role is still an area of debate. Produced mainly from oxyntic glands in the stomach, but with a multitude of extra-metabolic roles, ghrelin is implicated in complex neurobiological processes. Comprehensive studies within the areas of obesity and metabolic surgery have clarified the mechanism of these operations. As a stimulator of growth hormone (GH), and an apparent inducer of positive energy balance, other areas of interest include its impact on carcinogenesis and tumour proliferation and its role in the cancer cachexia syndrome. This has led several authors to study the hormone in the cancer setting. Ghrelin levels are acutely reduced following an oesophagectomy, a primary treatment modality for oesophageal cancer. We sought to investigate the nature of this postoperative ghrelin suppression, and its neurobiological implications.
Neuroblastoma, a Paradigm for Big Data Science in Pediatric Oncology
Authors: Salazar Brittany , Balczewski Emily , Ung Choong , Zhu Shizhen
Published: December 2016

Pediatric cancers rarely exhibit recurrent mutational events when compared to most adult cancers. This poses a challenge in understanding how cancers initiate, progress, and metastasize in early childhood. Also, due to limited detected driver mutations, it is difficult to benchmark key genes for drug development. In this review, we use neuroblastoma, a pediatric solid tumor of neural crest origin, as a paradigm for exploring “big data” applications in pediatric oncology. Computational strategies derived from big data science–network- and machine learning-based modeling and drug repositioning—hold the promise of shedding new light on the molecular mechanisms driving neuroblastoma pathogenesis and identifying potential therapeutics to combat this devastating disease. These strategies integrate robust data input, from genomic and transcriptomic studies, clinical data, and in vivo and in vitro experimental models specific to neuroblastoma and other types of cancers that closely mimic its biological characteristics. We discuss contexts in which “big data” and computational approaches, especially network-based modeling, may advance neuroblastoma research, describe currently available data and resources, and propose future models of strategic data collection and analyses for neuroblastoma and other related diseases.
Vitamin C Protects Chondrocytes against Monosodium Iodoacetate-Induced Osteoarthritis by Multiple Pathways
Authors: Chiu Pu-Rong , Hu Yu-Chen , Huang Tzu-Ching , Hsieh Bau-Shan , Yeh Jou-Pei , Cheng Hsiao-Ling , Huang Li-Wen , Chang Kee-Lung
Published: December 2016

Osteoarthritis (OA) is the most prevalent joint disease. Dietary intake of vitamin C relates to a reduction in cartilage loss and OA. This study examined the efficacy of vitamin C to prevent OA with the in vitro chondrosarcoma cell line (SW1353) and the in vivo monosodium iodoacetate (MIA)-induced OA rat. Results demonstrated that, in SW1353 cells, treatment with 5 μM MIA inhibited cell growth and increased oxidative stress, apoptosis, and proteoglycan loss. In addition, the expression levels of the pro-inflammatory cytokines IL-6, IL-17A, and TNF-α and matrix metalloproteinases (MMPs) MMP-1, MMP-3, and MMP-13 were increased. All of these MIA-induced changes could be prevented with treatment of 100 μM vitamin C. In an animal model, intra-articular injection of MIA-induced cartilage degradation resembled the pathological changes of OA, and treatment of vitamin C could lessen these changes. Unexpectedly, vitamin C’s effects did not strengthen with the increasing dosage, while the 100 mg/kg dosage was more efficient than the 200 or 300 mg/kg dosages. Vitamin C possessed multiple capacities for prevention of OA progress, including a decrease in apoptosis and in the expression of pro-inflammatory cytokines and MMPs in addition to the well-known antioxidation.
Involvement of Host Non-Coding RNAs in the Pathogenesis of the Influenza Virus
Authors: Ma Yanmei , Ouyang Jing , Wei Jingyun , Maarouf Mohamed , Chen Ji-Long
Published: December 2016

Non-coding RNAs (ncRNAs) are a new type of regulators that play important roles in various cellular processes, including cell growth, differentiation, survival, and apoptosis. ncRNAs, including small non-coding RNAs (e.g., microRNAs, small interfering RNAs) and long non-coding RNAs (lncRNAs), are pervasively transcribed in human and mammalian cells. Recently, it has been recognized that these ncRNAs are critically implicated in the virus–host interaction as key regulators of transcription or post-transcription during viral infection. Influenza A virus (IAV) is still a major threat to human health. Hundreds of ncRNAs are differentially expressed in response to infection with IAV, such as infection by pandemic H1N1 and highly pathogenic avian strains. There is increasing evidence demonstrating functional involvement of these regulatory microRNAs, vault RNAs (vtRNAs) and lncRNAs in pathogenesis of influenza virus, including a variety of host immune responses. For example, it has been shown that ncRNAs regulate activation of pattern recognition receptor (PRR)-associated signaling and transcription factors (nuclear factor κ-light-chain-enhancer of activated B cells, NF-κB), as well as production of interferons (IFNs) and cytokines, and expression of critical IFN-stimulated genes (ISGs). The vital functions of IAV-regulated ncRNAs either to against defend viral invasion or to promote progeny viron production are summarized in this review. In addition, we also highlight the potentials of ncRNAs as therapeutic targets and diagnostic biomarkers.
Novel Nine-Exon AR Transcripts (Exon 1/Exon 1b/Exons 2–8) in Normal and Cancerous Breast and Prostate Cells
Authors: Hu Dong , McKinnon Ross , Hulin Julie-Ann , Mackenzie Peter , Meech Robyn
Published: December 2016

Nearly 20 different transcripts of the human androgen receptor (AR) are reported with two currently listed as Refseq isoforms in the NCBI database. Isoform 1 encodes wild-type AR (type 1 AR) and isoform 2 encodes the variant AR45 (type 2 AR). Both variants contain eight exons: they share common exons 2–8 but differ in exon 1 with the canonical exon 1 in isoform 1 and the variant exon 1b in isoform 2. Splicing of exon 1 or exon 1b is reported to be mutually exclusive. In this study, we identified a novel exon 1b (1b/TAG) that contains an additional TAG trinucleotide upstream of exon 1b. Moreover, we identified AR transcripts in both normal and cancerous breast and prostate cells that contained either exon 1b or 1b/TAG spliced between the canonical exon 1 and exon 2, generating nine-exon AR transcripts that we have named isoforms 3a and 3b. The proteins encoded by these new AR variants could regulate androgen-responsive reporters in breast and prostate cancer cells under androgen-depleted conditions. Analysis of type 3 AR-GFP fusion proteins showed partial nuclear localization in PC3 cells under androgen-depleted conditions, supporting androgen-independent activation of the AR. Type 3 AR proteins inhibited androgen-induced growth of LNCaP cells. Microarray analysis identified a small set of type 3a AR target genes in LNCaP cells, including genes known to modulate growth and proliferation of prostate cancer (PCGEM1, PEG3, EPHA3, and EFNB2) or other types of human cancers (TOX3, ST8SIA4, and SLITRK3), and genes that are diagnostic/prognostic biomarkers of prostate cancer (GRINA3, and BCHE).
Osteogenic Differentiation in Healthy and Pathological Conditions
Authors: Valenti Maria , Dalle Carbonare Luca , Mottes Monica
Published: December 2016

This review focuses on the osteogenic differentiation of mesenchymal stem cells (MSC), bone formation and turn-over in good and ill skeletal fates. The interacting molecular pathways which control bone remodeling in physiological conditions during a lifelong process are described. Then, alterations of the molecular pathways regulating osteogenesis are addressed. In the aging process, as well as in glucocorticoid-induced osteoporosis, bone loss is caused not only by an unbalanced bone resorption activity, but also by an impairment of MSCs’ commitment towards the osteogenic lineage, in favour of adipogenesis. Mutations affecting the expression of key genes involved in the control of bone development occur in several heritable bone disorders. A few examples are described in order to illustrate the pathological consequences of perturbation in different steps of osteogenic commitment, osteoblast maturation, and matrix mineralization, respectively. The involvement of abnormal MSC differentiation in cancer is then discussed. Finally, a brief overview of clinical applications of MSCs in bone regeneration and repair is presented.
Simultaneous Determination and Pharmacokinetic Study of Six Components in Rat Plasma by HPLC-MS/MS after Oral Administration of Acanthopanax sessiliflorus Fruit Extract
Authors: Du Peng , Lei Mingdao , Liu Yu , Yang Shilin
Published: December 2016

A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of protocatechuic acid (PCA), scopolin, (−)-pinoresinol-4,4′-di-O-β-d-glucopyranoside (PDG), acanthoside D, acanthoside B and hyperin in rat plasma for the first time. The analytes were separated on a C18 column (50 × 2.1 mm, 1.8 µm) and a triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI) source was used for detection. The rat plasma sample was prepared using the protein precipitation procedure. The calibration curves were linear over a concentration range of 1.2–1200.0 ng/mL for PCA, 0.96–960.0 ng/mL for scopolin, 1.12–1120.0 ng/mL for PDG, 1.32–1320.0 ng/mL for acanthoside D, 0.99–990.0 ng/mL for acanthoside B and 1.01–1010.0 ng/mL for hyperin. The intra-day and inter-day precision was less than 11.4% and the relative error (RE) was all within ±15%. The validated method was successfully applied to assess the pharmacokinetics characteristics after the extracts of Acanthopanax sessiliflorus fruits were orally administered to the Sprague-Dawley rat.
TGF-β and Physiological Root Resorption of Deciduous Teeth
Authors: Shimazaki Emi , Karakida Takeo , Yamamoto Ryuji , Kobayashi Saeko , Fukae Makoto , Yamakoshi Yasuo , Asada Yoshinobu
Published: December 2016

The present study was performed to examine how transforming growth factor β (TGF-β) in root-surrounding tissues on deciduous teeth regulates the differentiation induction into odontoclasts during physiological root resorption. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1–R3 or N1–N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1–N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-mediated osteoclast differentiation revealed that proteins from N1–N3 and R1–R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA levels of TGF-β1 in N1 and N2 were significantly increased, and corresponded with levels of osteoprotegerin (OPG). In contrast, the expression level of RANKL was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.
Monitoring the Response of Hyperbilirubinemia in the Mouse Brain by In Vivo Bioluminescence Imaging
Authors: Manni Isabella , Di Rocco Giuliana , Fusco Salvatore , Leone Lucia , Barbati Saviana , Carapella Carmine , Grassi Claudio , Piaggio Giulia , Toietta Gabriele
Published: December 2016

Increased levels of unconjugated bilirubin are neurotoxic, but the mechanism leading to neurological damage has not been completely elucidated. Innovative strategies of investigation are needed to more precisely define this pathological process. By longitudinal in vivo bioluminescence imaging, we noninvasively visualized the brain response to hyperbilirubinemia in the MITO-Luc mouse, in which light emission is restricted to the regions of active cell proliferation. We assessed that acute hyperbilirubinemia promotes bioluminescence in the brain region, indicating an increment in the cell proliferation rate. Immunohistochemical detection in brain sections of cells positive for both luciferase and the microglial marker allograft inflammatory factor 1 suggests proliferation of microglial cells. In addition, we demonstrated that brain induction of bioluminescence was altered by pharmacological displacement of bilirubin from its albumin binding sites and by modulation of the blood–brain barrier permeability, all pivotal factors in the development of bilirubin-induced neurologic dysfunction. We also determined that treatment with minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, or administration of bevacizumab, an anti-vascular endothelial growth factor antibody, blunts bilirubin-induced bioluminescence. Overall the study supports the use of the MITO-Luc mouse as a valuable tool for the rapid response monitoring of drugs aiming at preventing acute bilirubin-induced neurological dysfunction.
Multifunctional Composite Microcapsules for Oral Delivery of Insulin
Authors: Sun Shaoping , Liang Na , Gong Xianfeng , An Weiwei , Kawashima Yoshiaki , Cui Fude , Yan Pengfei
Published: December 2016

In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic ion pairing method. Then the complex was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles by emulsion solvent diffusion method. The PLGA nanoparticles have a mean size of 168 nm and a zeta potential of −29.2 mV. The encapsulation efficiency was increased to 94.2% for the complex. In order to deliver insulin to specific gastrointestinal regions and reduce the burst release of insulin from PLGA nanoparticles, hence enhancing the bioavailability of insulin, enteric targeting multifunctional composite microcapsules were further prepared by encapsulating PLGA nanoparticles into pH-sensitive hydroxypropyl methyl cellulose phthalate (HP55) using organic spray-drying method. A pH-dependent insulin release profile was observed for this drug delivery system in vitro. All these strategies help to enhance the encapsulation efficiency, control the drug release, and protect insulin from degradation. In diabetic fasted rats, administration of the composite microcapsules produced a great enhancement in the relative bioavailability, which illustrated that this formulation was an effective candidate for oral insulin delivery.
Immuno-PET for Clinical Theranostic Approaches
Authors: Bailly Clément , Cléry Pierre-François , Faivre-Chauvet Alain , Bourgeois Mickael , Guérard François , Haddad Ferid , Barbet Jacques , Chérel Michel , Kraeber-Bodéré Françoise , Carlier Thomas , Bodet-Milin Caroline
Published: December 2016

Recent advances in molecular characterization of tumors have allowed identification of new molecular targets on tumor cells or biomarkers. In medical practice, the identification of these biomarkers slowly but surely becomes a prerequisite before any treatment decision, leading to the concept of personalized medicine. Immuno-positron emission tomography (PET) fits perfectly with this approach. Indeed, monoclonal antibodies (mAbs) labelled with radionuclides represent promising probes for theranostic approaches, offering a non-invasive solution to assess in vivo target expression and distribution. Immuno-PET can potentially provide useful information for patient risk stratification, diagnosis, selection of targeted therapies, evaluation of response to therapy, prediction of adverse effects or for titrating doses for radioimmunotherapy. This paper reviews some aspects and recent developments in labelling methods, biological targets, and clinical data of some novel PET radiopharmaceuticals.
A Symmetric Approach Elucidates Multisensory Information Integration
Authors: Tozzi Arturo , Peters James
Published: December 2016

Recent advances in neuronal multisensory integration suggest that the five senses do not exist in isolation of each other. Perception, cognition and action are integrated at very early levels of central processing, in a densely-coupled system equipped with multisensory interactions occurring at all temporal and spatial stages. In such a novel framework, a concept from the far-flung branch of topology, namely the Borsuk-Ulam theorem, comes into play. The theorem states that when two opposite points on a sphere are projected onto a circumference, they give rise to a single point containing their matching description. Here we show that the theorem applies also to multisensory integration: two environmental stimuli from different sensory modalities display similar features when mapped into cortical neurons. Topological tools not only shed new light on questions concerning the functional architecture of mind and the nature of mental states, but also provide an empirically assessable methodology. We argue that the Borsuk-Ulam theorem is a general principle underlying nervous multisensory integration, resulting in a framework that has the potential to be operationalized.
Arsenite as an Electron Donor for Anoxygenic Photosynthesis: Description of Three Strains of Ectothiorhodospira from Mono Lake, California and Big Soda Lake, Nevada
Authors: Hoeft McCann Shelley , Boren Alison , Hernandez-Maldonado Jaime , Stoneburner Brendon , Saltikov Chad , Stolz John , Oremland Ronald
Published: December 2016

Three novel strains of photosynthetic bacteria from the family Ectothiorhodospiraceae were isolated from soda lakes of the Great Basin Desert, USA by employing arsenite (As(III)) as the sole electron donor in the enrichment/isolation process. Strain PHS-1 was previously isolated from a hot spring in Mono Lake, while strain MLW-1 was obtained from Mono Lake sediment, and strain BSL-9 was isolated from Big Soda Lake. Strains PHS-1, MLW-1, and BSL-9 were all capable of As(III)-dependent growth via anoxygenic photosynthesis and contained homologs of arxA, but displayed different phenotypes. Comparisons were made with three related species: Ectothiorhodospira shaposhnikovii DSM 2111, Ectothiorhodospira shaposhnikovii DSM 243T, and Halorhodospira halophila DSM 244. All three type cultures oxidized arsenite to arsenate but did not grow with As(III) as the sole electron donor. DNA–DNA hybridization indicated that strain PHS-1 belongs to the same species as Ect. shaposhnikovii DSM 2111 (81.1% sequence similarity), distinct from Ect. shaposhnikovii DSM 243T (58.1% sequence similarity). These results suggest that the capacity for light-driven As(III) oxidation is a common phenomenon among purple photosynthetic bacteria in soda lakes. However, the use of As(III) as a sole electron donor to sustain growth via anoxygenic photosynthesis is confined to novel isolates that were screened for by this selective cultivation criterion.
(2E,2′E)-3-(4-{[4-(4-Hydroxy-3-methoxyphenyl)but-2-en-1-yl]oxy}phenyl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
Authors: Fareza Muhamad , Mujahidin Didin , Syah Yana
Published: December 2016

A hybrid of eugenol and a chalcone has been synthesized in good yield via cross olefin metathesis. The title compound (3) was characterized by spectroscopic data including NMR, infrared, and ESI-MS.
Comparison of Maraging Steel Micro- and Nanostructure Produced Conventionally and by Laser Additive Manufacturing
Authors: Jägle Eric , Sheng Zhendong , Kürnsteiner Philipp , Ocylok Sörn , Weisheit Andreas , Raabe Dierk
Published: December 2016

Maraging steels are used to produce tools by Additive Manufacturing (AM) methods such as Laser Metal Deposition (LMD) and Selective Laser Melting (SLM). Although it is well established that dense parts can be produced by AM, the influence of the AM process on the microstructure—in particular the content of retained and reversed austenite as well as the nanostructure, especially the precipitate density and chemistry, are not yet explored. Here, we study these features using microhardness measurements, Optical Microscopy, Electron Backscatter Diffraction (EBSD), Energy Dispersive Spectroscopy (EDS), and Atom Probe Tomography (APT) in the as-produced state and during ageing heat treatment. We find that due to microsegregation, retained austenite exists in the as-LMD- and as-SLM-produced states but not in the conventionally-produced material. The hardness in the as-LMD-produced state is higher than in the conventionally and SLM-produced materials, however, not in the uppermost layers. By APT, it is confirmed that this is due to early stages of precipitation induced by the cyclic re-heating upon further deposition—i.e., the intrinsic heat treatment associated with LMD. In the peak-aged state, which is reached after a similar time in all materials, the hardness of SLM- and LMD-produced material is slightly lower than in conventionally-produced material due to the presence of retained austenite and reversed austenite formed during ageing.