bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioleaching of copper from old flotation tailings samples (Copper Mine Bor, Serbia)
Authors: Stankovic Srdjan , Moric Ivana , Pavic Aleksandar , Vojnovic Sandra , Vasiljevic Branka , Cvetkovic Vladica
Published: September 2014

Bioleaching of samples taken from depths of 10, 15, and 20 meters from old
flotation tailings of the Copper Mine Bor was conducted in shaken flasks
using extremely acidic water of Lake Robuleas lixiviant. Yield of copper
after five weeks of the bioleaching experiment was 68.34?1.21% for 15 m
sample, 72.57?0.57% for 20 m sample and 97.78?5.50% for 10 m sample. The
obtained results were compared to the results of acid leaching of the same
samples and it was concluded that bioleaching was generally more efficient
for the treatment of samples taken from depths of 10 m and 20 m. The content
of pyrite in the 20 m sample, which contained the highest amount of this
mineral, was reduced after bioleaching. Benefits of this approach are:
recovery of substantial amounts of copper, reducing the environmental impact
of flotation tailings and the application of abundant and free water from the
Robule acidic lake as lixiviant. Results of the experiment showed that
bioleaching can be more efficient than acid leaching for copper extraction
from flotation tailings with higher sulfide contents.
Ezra Pound's Lost Book: Orientamenti
Authors: Nicholls Peter
Published: September 2014

Little has been written about Ezra Pound's extensive contributions to the Rome-based paper Meridiano di Roma between 1938 and 1943, though they provide important insight into the poet's thinking and state of mind during the last years of the Italian regime. I discussed these pieces in a preliminary way back in 1984 (in my Ezra Pound: Politics, Economics and Writing) but there has been surprisingly little interest in them since (even Robert Casillo's authoritative The Genealogy of Demons: Anti-Semitism, Fascism, and the Myths of Ezra Pound [1988] largely ignores them). The present essay explores the context and content of these pieces, looking especially at the selection Pound published under the title Orientamenti, a volume quickly destroyed when the Allies occupied Italy. Key issues are Pound's equivocal relation to the Italian regime, the obsessive, ideological cast of his thinking at this time, and his peculiarly restricted sense of what was happening at this climatic moment in modern history.
Colour verbs in Modern Greek: A cognitive approach
Authors: Charitonidis Chariton
Published: September 2014

This paper gives an outlook on how the coordination between phonology and semantics in verb derivation may look, and which constraints the distinction between possible/established, possible/novel, and not possible/forced verbs can be mapped onto. The object of investigation are the colour -ízo verbs in Modern Greek. The analysis is mainly based on the studies by Berlin & Kay (1969) , Kay & McDaniel (1978) , and Kay & Maffi (1999) on basic colour terms. The colour verbs in Modern Greek are compared with the English colour verbs. It is shown that systematic gaps linked to the causative/inchoative paradigm of -ízo verbs are due to the semantics of the base rather than deficiencies in the base's morphophonological character. The lower the evolutional stage that a base can be fitted to, the more likely an -ízo derivative will be produced.
Temperature and Relative Humidity Inside Trailers During Finishing Pig Loading and Transport in Cold and Mild Weather
Authors: McGlone John , Johnson Anna , Sapkota Avi , Kephart Rebecca
Published: September 2014

The effect of bedding levels and trailer compartment on internal trailer temperature and relative humidity (RH) during loading and transport of finishing pigs was evaluated in cold and mild weather. Three levels of bedding were used in each experiment: 0.6 m3, 1.2 m3, and 2.4 m3. In mild weather, internal temperatures were lower when 1.2 m3 or 2.4 m3 of bedding were used during loading and transport compared to 0.6 m3 (P < 0.05). Internal trailer temperature increased in a quadratic fashion in the top front compartment when 1.2 m3 was used (P < 0.05), and in a linear fashion in the top rear compartment when 2.4 m3 were used in cold weather (P < 0.05). In mild weather, temperature increased linearly in the top front compartment with heavy bedding levels. Relative humidity increased in a linear fashion in the top front compartment with 0.6 m3, bottom front with 1.2 m3, and top front with 1.2 m3 in cold weather (P < 0.05). In general, temperature and RH increased as bedding levels increased in both cold and mild temperatures. Excess bedding can absorb more moisture, resulting in transport loss and decreased animal welfare.
Tourists’ Perceptions of the Free-Roaming Dog Population in Samoa
Authors: Beckman Magnus , Hill Kate , Farnworth Mark , Bolwell Charlotte , Bridges Janis , Acke Els
Published: September 2014

A study was undertaken to establish how visiting tourists to Samoa perceived free-roaming dogs (Canis familiaris) and their management, additionally some factors that influence their perceptions were assessed. Questionnaires were administered to 281 tourists across Samoa over 5 weeks. Free-roaming dogs were seen by 98.2% (n = 269/274) of respondents, with 64.9% (n = 137/211) reporting that their presence had a negative effect on overall holiday experience. Respondents staying in the Apia (capital city) area were more likely to consider dogs a problem (p < 0.0001), and there was a significant association between whether the respondent owned a dog and if they thought dogs were a nuisance in Samoa (p < 0.003). Forty-four percent (20/89) of non-dog owners agreed that dogs were a nuisance compared to 22% (80/182) of dog owners. The majority felt that dogs required better control and management in Samoa (81%, n = 222) and that there were too many “stray” dogs (67.9%, n = 188). More respondents were negatively affected by the dogs’ presence (64.9%, 137/211), and felt that the dogs made their holiday worse, than respondents that felt the dogs’ presence improved their holiday experience (35.1%, 74/211). Most respondents stated that the dogs had a low impact (one to three; 68%, 187/275) on their stay in Samoa, whilst 24% (65/275) and 8% (23/275) stated they had a medium or high impact, respectively, on their stay. Respondents showed strong support for humane population management. Free-roaming dogs present a complex problem for Samoa and for its tourism industry in particular. The findings of this study further support the need for more discussion and action about the provision of veterinary services and population management for dogs in Samoa. It also provides information complementing an earlier study of the attitudes of local Samoans.
Proteasome- and Ethanol-Dependent Regulation of HCV-Infection Pathogenesis
Authors: Osna Natalia , Ganesan Murali , Donohue Terrence
Published: September 2014

This paper reviews the role of the catabolism of HCV and signaling proteins in HCV protection and the involvement of ethanol in HCV-proteasome interactions. HCV specifically infects hepatocytes, and intracellularly expressed HCV proteins generate oxidative stress, which is further exacerbated by heavy drinking. The proteasome is the principal proteolytic system in cells, and its activity is sensitive to the level of cellular oxidative stress. Not only host proteins, but some HCV proteins are degraded by the proteasome, which, in turn, controls HCV propagation and is crucial for the elimination of the virus. Ubiquitylation of HCV proteins usually leads to the prevention of HCV propagation, while accumulation of undegraded viral proteins in the nuclear compartment exacerbates infection pathogenesis. Proteasome activity also regulates both innate and adaptive immunity in HCV-infected cells. In addition, the proteasome/immunoproteasome is activated by interferons, which also induce “early” and “late” interferon-sensitive genes (ISGs) with anti-viral properties. Cleaving viral proteins to peptides in professional immune antigen presenting cells and infected (“target”) hepatocytes that express the MHC class I-antigenic peptide complex, the proteasome regulates the clearance of infected hepatocytes by the immune system. Alcohol exposure prevents peptide cleavage by generating metabolites that impair proteasome activity, thereby providing escape mechanisms that interfere with efficient viral clearance to promote the persistence of HCV-infection.
Repositioning of Tyrosine Kinase Inhibitors as Antagonists of ATP-Binding Cassette Transporters in Anticancer Drug Resistance
Authors: Wang Yi-Jun , Zhang Yun-Kai , Kathawala Rishil , Chen Zhe-Sheng
Published: September 2014

The phenomenon of multidrug resistance (MDR) has attenuated the efficacy of anticancer drugs and the possibility of successful cancer chemotherapy. ATP-binding cassette (ABC) transporters play an essential role in mediating MDR in cancer cells by increasing efflux of drugs from cancer cells, hence reducing the intracellular accumulation of chemotherapeutic drugs. Interestingly, small-molecule tyrosine kinase inhibitors (TKIs), such as AST1306, lapatinib, linsitinib, masitinib, motesanib, nilotinib, telatinib and WHI-P154, have been found to have the capability to overcome anticancer drug resistance by inhibiting ABC transporters in recent years. This review will focus on some of the latest and clinical developments with ABC transporters, TKIs and anticancer drug resistance.
The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy
Authors: Patel Mira , Kim Jennifer , Ruzevick Jacob , Li Gordon , Lim Michael
Published: September 2014

The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.
Monoclonal Antibodies Specific for STAT3β Reveal Its Contribution to Constitutive STAT3 Phosphorylation in Breast Cancer
Authors: Bharadwaj Uddalak , Kasembeli Moses , Eckols T. , Kolosov Mikhail , Lang Paul , Christensen Kurt , Edwards Dean , Tweardy David
Published: September 2014

Since its discovery in mice and humans 19 years ago, the contribution of alternatively spliced Stat3, Stat3β, to the overall functions of Stat3 has been controversial. Tyrosine-phosphorylated (p) Stat3β homodimers are more stable, bind DNA more avidly, are less susceptible to dephosphorylation, and exhibit distinct intracellular dynamics, most notably markedly prolonged nuclear retention, compared to pStat3α homodimers. Overexpression of one or the other isoform in cell lines demonstrated that Stat3β acted as a dominant-negative of Stat3α in transformation assays; however, studies with mouse strains deficient in one or the other isoform indicated distinct contributions of Stat3 isoforms to inflammation. Current immunological reagents cannot differentiate Stat3β proteins derived from alternative splicing vs. proteolytic cleavage of Stat3α. We developed monoclonal antibodies that recognize the 7 C-terminal amino acids unique to Stat3β (CT7) and do not cross-react with Stat3α. Immunoblotting studies revealed that levels of Stat3β protein, but not Stat3α, in breast cancer cell lines positively correlated with overall pStat3 levels, suggesting that Stat3β may contribute to constitutive Stat3 activation in this tumor system. The ability to unambiguously discriminate splice alternative Stat3β from proteolytic Stat3β and Stat3α will provide new insights into the contribution of Stat3β vs. Stat3α to oncogenesis, as well as other biological and pathological processes.
Spectro-Fluor™ Technology for Reliable Detection of Proteins and Biomarkers of Disease: A Pioneered Research Study
Authors: Menaa Farid , Menaa Bouzid , Sharts Olga
Published: September 2014

Quantitative and qualitative characterization of fluorinated molecules represents an important task. Fluorine-based medicinal chemistry is a fast-growing research area due to the positive impact of fluorine in drug discovery, and clinical and molecular imaging (e.g., magnetic resonance imaging, positron emission tomography). Common detection methods include fluorinated-based labelling using radioactive isotopes or fluorescent dyes. Nevertheless, these molecular imaging methods can be harmful for health due to the potential instability of fluorochromes and cytoxicity of radioisotopes. Therefore, these methods often require expensive precautionary measures. In this context, we have developed, validated and patented carbon-fluorine spectroscopy (CFS™), recently renamed Spectro-Fluor™ technology, which among a non-competitive family of in-house made devices called PLIRFA™ (Pulsed Laser Isochronic Raman and Fluorescence Apparatus™), allows reliable detection of Carbon-Fluorine (C-F) bonds. C-F bonds are known to be stable and safe labels once incorporated to any type of molecules, cells, compounds or (nano-) materials. In this pioneered research study, we used Spectro-Fluor™ to assess biomarkers. As a proof-of-principle experiment, we have established a three-step protocol intended to rapid protein detection, which simply consisted of: (i) incorporating a sufficient concentration of an aromatic amino-acid (fluorinated versus non-fluorinated) into cultured cells; (ii) simultaneously isolating the fluorinated protein of interest and the non-fluorinated form of the protein (control) by immune-precipitation; (iii) comparatively analyzing the respective spectrum obtained for the two protein forms by Spectro-Fluor™. Thereby, we were able to differentiate, from colon cancer cells HCT-116, the fluorinated and non-fluorinated forms of p21, a key transcriptional factor and downstream target of p53, the so-called “guardian of the genome”. Taken together, our data again demonstrates the beneficial alternative use of Spectro-Fluor™, which once combined with an innovative methodology permits one to quickly, reliably, safely and cost-effectively detect physiological or pathological proteins in cells.
REDD+ Policy Approaches in the Congo Basin: A Comparative Analysis of Cameroon and the Democratic Republic of Congo (DRC)
Authors: Fobissie Kalame , Alemagi Dieudonne , Minang Peter
Published: September 2014

The Congo Basin forests are a prime location for implementing REDD+. National REDD+ policy processes are ongoing and many REDD+ pilot initiatives are being demonstrated. However, the level of national engagement, progress and distribution of REDD+ activities varies considerably in the different Congo Basin countries. This study therefore uses a set of criteria to assess national and international policy initiatives and approaches for advancing REDD+ implementation in Cameroon and the Democratic Republic Congo (DRC), two countries where more than two thirds of the Congo Basin forests are concentrated. Our findings show that (i) both countries have shown the highest political presence at the international climate negotiations but DRC has invested more in the size of its delegation and side events; (ii) REDD+ donors, initiatives, and funding are disproportionately skewed towards DRC making it technically more advanced; (iii) the high political interest and institutional reforms in DRC favors private sector investments in REDD+ programs; and (iv) the REDD+ policy process is internally-driven in Cameroon with a strong national ownership, while it is externally-driven in DRC with weak national ownership. To advance REDD+, the government of DRC should embark on capacity building programs that ensure the transfer of REDD+ technical know-how from international to national actors while Cameroon needs to speed-up governance reforms and be more flexible in order to attract influential international REDD+ actors. This paper further provides specific recommendations.
Chromium in Drinking Water: Association with Biomarkers of Exposure and Effect
Authors: Sazakli Eleni , Villanueva Cristina , Kogevinas Manolis , Maltezis Kyriakos , Mouzaki Athanasia , Leotsinidis Michalis
Published: September 2014

An epidemiological cross-sectional study was conducted in Greece to investigate health outcomes associated with long-term exposure to chromium via drinking water. The study population consisted of 304 participants. Socio-demographics, lifestyle, drinking water intake, dietary habits, occupational and medical history data were recorded through a personal interview. Physical examination and a motor test were carried out on the individuals. Total chromium concentrations were measured in blood and hair of the study subjects. Hematological, biochemical and inflammatory parameters were determined in blood. Chromium in drinking water ranged from <0.5 to 90 μg·L−1 in all samples but one (220 μg·L−1), with a median concentration of 21.2 μg·L−1. Chromium levels in blood (median 0.32 μg·L−1, range <0.18–0.92 μg·L−1) and hair (median 0.22 μg·g−1, range 0.03–1.26 μg·g−1) were found within “normal range” according to the literature. Personal lifetime chromium exposure dose via drinking water, calculated from the results of the water analyses and the questionnaire data, showed associations with blood and hair chromium levels and certain hematological and biochemical parameters. Groups of subjects whose hematological or biochemical parameters were outside the normal range were not correlated with chromium exposure dose, except for groups of subjects with high triglycerides or low sodium. Motor impairment score was not associated with exposure to chromium.
Concurrent Fetal Exposure to Multiple Environmental Chemicals along the U.S.—Mexico Border: An Exploratory Study in Brownsville, Texas
Authors: Sexton Ken , Salinas Jennifer
Published: September 2014

There is mounting concern that cumulative exposure to diverse chemicals in the environment may contribute to observed adverse health outcomes in the Lower Rio Grande Valley of Texas. To investigate this situation, biomarker concentrations of organochlorine (OC) pesticides/metabolites, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) were measured in maternal and umbilical cord blood from pregnant Hispanic women in Brownsville, TX. Results show that both mothers and fetuses were exposed concurrently to a variety of relatively low-level, hazardous environmental chemicals. Approximately 10% of the blood specimens had comparatively high concentrations of specific OC pesticides, PCBs and PAHs. Because many pregnant women in Brownsville live in socioeconomically-disadvantaged and environmentally-challenging circumstances, there is appropriate concern that exposure to these exogenous substances, either individually or in combination, may contribute to endemic health problems in this population, including cardiovascular disease, obesity, and diabetes. The challenge is to identify individuals at highest comparative risk and then implement effective programs to either prevent or reduce cumulative exposures that pose significant health-related threats.
Gender-Associated Genomic Differences in Colorectal Cancer: Clinical Insight from Feminization of Male Cancer Cells
Authors: Ali Rola , Marafie Makia , Bitar Milad , Al-Dousari Fahad , Ismael Samar , Haider Hussain , Al-Ali Waleed , Jacob Sindhu , Al-Mulla Fahd
Published: September 2014

Gender-related differences in colorectal cancer (CRC) are not fully understood. Recent studies have shown that CRC arising in females are significantly associated with CpG island methylator phenotype (CIMP-high). Using array comparative genomic hybridization, we analyzed a cohort of 116 CRCs (57 males, 59 females) for chromosomal copy number aberrations (CNA) and found that CRC in females had significantly higher numbers of gains involving chromosome arms 1q21.2–q21.3, 4q13.2, 6p21.1 and 16p11.2 and copy number losses of chromosome arm 11q25 compared to males. Interestingly, a subset of male CRCs (46%) exhibited a "feminization" phenomenon in the form of gains of X chromosomes (or an arm of X) and/or losses of the Y chromosome. Feminization of cancer cells was significantly associated with microsatellite-stable CRCs (p-value 0.003) and wild-type BRAF gene status (p-value 0.009). No significant association with other clinicopathological parameters was identified including disease-free survival. In summary, our data show that some CNAs in CRC may be gender specific and that male cancers characterized by feminization may constitute a specific subset of CRCs that warrants further investigation.
Intermittently Administered Parathyroid Hormone [1–34] Promotes Tendon-Bone Healing in a Rat Model
Authors: Bi Fanggang , Shi Zhongli , Jiang Shuai , Guo Peng , Yan Shigui
Published: September 2014

The objective of this study was to investigate whether intermittent administration of parathyroid hormone [1–34] (PTH[1–34]) promotes tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in vivo. A rat model of ACL reconstruction with autograft was established at the left hind leg. Every day, injections of 60 μg PTH[1–34]/kg subcutaneously were given to the PTH group rats (n = 10) for four weeks, and the controls (n = 10) received saline. The tendon-bone healing process was evaluated by micro-CT, biomechanical test, histological and immunohistochemical analyses. The effects of PTH[1–34] on serum chemistry, bone microarchitecture and expression of the PTH receptor (PTH1R) and osteocalcin were determined. Administration of PTH[1–34] significantly increased serum levels of calcium, alkaline phosphatase (AP), osteocalcin and tartrate-resistant acid phosphatase (TRAP). The expression of PTH1R on both osteocytes and chondrocyte-like cells at the tendon-bone interface was increased in the PTH group. PTH[1–34] also enhanced the thickness and microarchitecture of trabecular bone according to the micro-CT analysis. The results imply that systematically intermittent administration of PTH[1–34] promotes tendon-bone healing at an early stage via up-regulated PTH1R. This method may enable a new strategy for the promotion of tendon-bone healing after ACL reconstruction.
The Biological Function and Clinical Utilization of CD147 in Human Diseases: A Review of the Current Scientific Literature
Authors: Xiong Lijuan , Edwards Carl , Zhou Lijun
Published: September 2014

CD147 or EMMPRIN is a member of the immunoglobulin superfamily in humans. It is widely expressed in human tumors and plays a central role in the progression of many cancers by stimulating the secretion of matrix metalloproteinases (MMPs) and cytokines. CD147 regulates cell proliferation, apoptosis, and tumor cell migration, metastasis and differentiation, especially under hypoxic conditions. CD147 is also important to many organ systems. This review will provide a detailed overview of the discovery, characterization, molecular structure, diverse biological functions and regulatory mechanisms of CD147 in human physiological and pathological processes. In particular, recent studies have demonstrated the potential application of CD147 not only as a phenotypic marker of activated regulatory T cells but also as a potential diagnostic marker for early-stage disease. Moreover, CD147 is recognized as an effective therapeutic target for hepatocellular carcinoma (HCC) and other cancers, and exciting clinical progress has been made in HCC treatment using CD147-directed monoclonal antibodies.
Association of CDKN2BAS Polymorphism rs4977574 with Coronary Heart Disease: A Case-Control Study and a Meta-Analysis
Authors: Huang Yi , Ye Huadan , Hong Qingxiao , Xu Xuting , Jiang Danjie , Xu Limin , Dai Dongjun , Sun Jie , Gao Xiang , Duan Shiwei
Published: September 2014

The goal of our study was to explore the significant association between a non-protein coding single nucleotide polymorphism (SNP) rs4977574 of CDKN2BAS gene and coronary heart disease (CHD). A total of 590 CHD cases and 482 non-CHD controls were involved in the present association study. A strong association of rs4977574 with CHD was observed in females (genotype: p = 0.002; allele: p = 0.002, odd ratio (OR) = 1.57, 95% confidential interval (CI) = 1.18–2.08). Moreover, rs4977574 was more likely to be a risk variant of CHD under the recessive model in females (χ2 = 10.29, p = 0.003, OR = 2.14, 95% CI = 1.31–2.77). A breakdown analysis by age had shown that there was an 87% increased risk of CHD for females younger than 65 years (genotype: χ2 = 14.64, degrees of freedom (df) = 2, p = 0.0002; allele: χ2 = 11.31, df = 1, p = 0.0008, OR = 1.87, 95% CI = 1.30–2.70). Similar observation was also found in males younger than 65 years (genotype: χ2 = 8.63, df = 2, p = 0.04; allele: χ2 = 7.55, df = 1, p = 0.006, OR = 1.45, 95% CI = 1.11–1.90). p values were adjusted by age, sex, smoking, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Meta-analysis of 23 studies among 36,452 cases and 39,781 controls showed a strong association between rs4977574 and the risk of CHD (p < 0.0001, OR = 1.27, 95% CI = 1.22–1.31).
DNA and RNA Quadruplex-Binding Proteins
Authors: Brázda Václav , Hároníková Lucia , Liao Jack , Fojta Miroslav
Published: September 2014

Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc.), the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Sequences with the potential to form quadruplexes are widely present in genome of all organisms. They are found often in repetitive sequences such as telomeric ones, and also in promoter regions and 5' non-coding sequences. Recently, many proteins with binding affinity to G-quadruplexes have been identified. One of the initially portrayed G-rich regions, the human telomeric sequence (TTAGGG)n, is recognized by many proteins which can modulate telomerase activity. Sequences with the potential to form G-quadruplexes are often located in promoter regions of various oncogenes. The NHE III1 region of the c-MYC promoter has been shown to interact with nucleolin protein as well as other G-quadruplex-binding proteins. A number of G-rich sequences are also present in promoter region of estrogen receptor alpha. In addition to DNA quadruplexes, RNA quadruplexes, which are critical in translational regulation, have also been predicted and observed. For example, the RNA quadruplex formation in telomere-repeat-containing RNA is involved in interaction with TRF2 (telomere repeat binding factor 2) and plays key role in telomere regulation. All these fundamental examples suggest the importance of quadruplex structures in cell processes and their understanding may provide better insight into aging and disease development.
Abscisic Acid (ABA) Regulation of Arabidopsis SR Protein Gene Expression
Authors: Cruz Tiago , Carvalho Raquel , Richardson Dale , Duque Paula
Published: September 2014

Serine/arginine-rich (SR) proteins are major modulators of alternative splicing, a key generator of proteomic diversity and flexible means of regulating gene expression likely to be crucial in plant environmental responses. Indeed, mounting evidence implicates splicing factors in signal transduction of the abscisic acid (ABA) phytohormone, which plays pivotal roles in the response to various abiotic stresses. Using real-time RT-qPCR, we analyzed total steady-state transcript levels of the 18 SR and two SR-like genes from Arabidopsis thaliana in seedlings treated with ABA and in genetic backgrounds with altered expression of the ABA-biosynthesis ABA2 and the ABA-signaling ABI1 and ABI4 genes. We also searched for ABA-responsive cis elements in the upstream regions of the 20 genes. We found that members of the plant-specific SC35-Like (SCL) Arabidopsis SR protein subfamily are distinctively responsive to exogenous ABA, while the expression of seven SR and SR-related genes is affected by alterations in key components of the ABA pathway. Finally, despite pervasiveness of established ABA-responsive promoter elements in Arabidopsis SR and SR-like genes, their expression is likely governed by additional, yet unidentified cis-acting elements. Overall, this study pinpoints SR34, SR34b, SCL30a, SCL28, SCL33, RS40, SR45 and SR45a as promising candidates for involvement in ABA-mediated stress responses.
Hope for GWAS: Relevant Risk Genes Uncovered from GWAS Statistical Noise
Authors: Correia Catarina , Diekmann Yoan , Vicente Astrid , Pereira-Leal José
Published: September 2014

Hundreds of genetic variants have been associated to common diseases through genome-wide association studies (GWAS), yet there are limits to current approaches in detecting true small effect risk variants against a background of false positive findings. Here we addressed the missing heritability problem, aiming to test whether there are indeed risk variants within GWAS statistical noise and to develop a systematic strategy to retrieve these hidden variants. Employing an integrative approach, which combines protein-protein interactions with association data from GWAS for 6 common diseases, we found that associated-genes at less stringent significance levels (p < 0.1) with any of these diseases are functionally connected beyond noise expectation. This functional coherence was used to identify disease-relevant subnetworks, which were shown to be enriched in known genes, outperforming the selection of top GWAS genes. As a proof of principle, we applied this approach to breast cancer, supporting well-known breast cancer genes, while pinpointing novel susceptibility genes for experimental validation. This study reinforces the idea that GWAS are under-analyzed and that missing heritability is rather hidden. It extends the use of protein networks to reveal this missing heritability, thus leveraging the large investment in GWAS that produced so far little tangible gain.
Evaluation of Bio-VOC Sampler for Analysis of Volatile Organic Compounds in Exhaled Breath
Authors: Kwak Jae , Fan Maomian , Harshman Sean , Garrison Catherine , Dershem Victoria , Phillips Jeffrey , Grigsby Claude , Ott Darrin
Published: September 2014

Monitoring volatile organic compounds (VOCs) from exhaled breath has been used to determine exposures of humans to chemicals. Prior to analysis of VOCs, breath samples are often collected with canisters or bags and concentrated. The Bio-VOC breath sampler, a commercial sampling device, has been recently introduced to the market with growing use. The main advantage for this sampler is to collect the last portion of exhaled breath, which is more likely to represent the air deep in the lungs. However, information about the Bio-VOC sampler is somewhat limited. Therefore, we have thoroughly evaluated the sampler here. We determined the volume of the breath air collected in the sampler was approximately 88 mL. When sampling was repeated multiple times, with the succeeding exhalations applied to a single sorbent tube, we observed linear relationships between the normalized peak intensity and the number of repeated collections with the sampler in many of the breath VOCs detected. No moisture effect was observed on the Tenax sorbent tubes used. However, due to the limitation in the collection volume, the use of the Bio-VOC sampler is recommended only for detection of VOCs present at high concentrations unless repeated collections of breath samples on the sampler are conducted.
Development of an Advanced Synthetic Route to Macrosphelides and Its Application to the Discovery of a More Potent Macrosphelide Derivative
Authors: Heo Yu , Lee Hunseok , Shin Young , Paek Seung-Mann
Published: September 2014

The discovery of a more cytotoxic macrosphelide derivative, including its total synthesis and bioassay are described. Application of the Koide protocol to a readily available propagylic alcohol allowed the rapid and practical synthesis of a macrosphelide A skeleton. This strategy enabled the successful improvement of the cytotoxic activity of the macrosphelide derivative.
Discovery of New Imidazole Derivatives Containing the 2,4-Dienone Motif with Broad-Spectrum Antifungal and Antibacterial Activity
Authors: Liu Chunli , Shi Ce , Mao Fei , Xu Yong , Liu Jinyan , Wei Bing , Zhu Jin , Xiang Mingjie , Li Jian
Published: September 2014

A compound containing an imidazole moiety and a 2,4-dienone motif with significant activity toward several fungi was discovered in a screen for new antifungal compounds. Then, a total of 26 derivatives of this compound were designed, synthesized and evaluated through in vitro and in vivo antifungal activity assays. Several compounds exhibited improved antifungal activities compared to the lead compound. Of the derivatives, compounds 31 and 42 exhibited strong, broad-spectrum inhibitory effects toward Candida spp. In particular, the two derivatives exhibited potent antifungal activities toward the fluconazole-resistant isolate C. albicans 64110, with both having MIC values of 8 µg/mL. In addition, they had significant inhibitory effects toward two Gram-positive bacteria, Staphylococcus aureus UA1758 (compound 31: MIC = 8 µg/mL; compound 42: MIC = 4 µg/mL) and Staphylococcus epidermidis UF843 (compound 31: MIC = 8 µg/mL; compound 42: MIC = 8 µg/mL). The results of an animal experiment indicated that both compounds could improve the survival rate of model mice infected with ATCC 90028 (fluconazole-susceptible isolate). More importantly, the two compounds exhibited notable in vivo effects toward the fluconazole-resistant C. albicans isolate, which is promising with regard to the clinical problem posed by fluconazole-resistant Candida species.
Selenium-Enriched Foods Are More Effective at Increasing Glutathione Peroxidase (GPx) Activity Compared with Selenomethionine: A Meta-Analysis
Authors: Bermingham Emma , Hesketh John , Sinclair Bruce , Koolaard John , Roy Nicole
Published: September 2014

Selenium may play a beneficial role in multi-factorial illnesses with genetic and environmental linkages via epigenetic regulation in part via glutathione peroxidase (GPx) activity. A meta-analysis was undertaken to quantify the effects of dietary selenium supplementation on the activity of overall GPx activity in different tissues and animal species and to compare the effectiveness of different forms of dietary selenium. GPx activity response was affected by both the dose and form of selenium (p < 0.001). There were differences between tissues on the effects of selenium supplementation on GPx activity (p < 0.001); however, there was no evidence in the data of differences between animal species (p = 0.95). The interactions between dose and tissue, animal species and form were significant (p < 0.001). Tissues particularly sensitive to changes in selenium supply include red blood cells, kidney and muscle. The meta-analysis identified that for animal species selenium-enriched foods were more effective than selenomethionine at increasing GPx activity.
Green Tea Consumption Affects Cognitive Dysfunction in the Elderly: A Pilot Study
Authors: Ide Kazuki , Yamada Hiroshi , Takuma Norikata , Park Mijong , Wakamiya Noriko , Nakase Junpei , Ukawa Yuuichi , Sagesaka Yuko
Published: September 2014

Green tea is known to have various health benefits for humans. However, the effect of green tea consumption on cognitive dysfunction remains to be clinically verified. We conducted a clinical study to investigate the effects of green tea consumption on cognitive dysfunction. Twelve elderly nursing home residents with cognitive dysfunction (Mini-Mental State Examination Japanese version (MMSE-J) score: <28) participated in the study (2 men, 10 women; mean age, 88 years). The participants consumed green tea powder 2 g/day for 3 months. After three months of green tea consumption, the participants’ MMSE-J scores were significantly improved (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03). This result suggests that green tea consumption may be effective in improving cognitive function or reducing the progression of cognitive dysfunction; however, long-term large-scale controlled studies are needed to further clarify the effect.
Effects of Perioperative Supplementation with Omega-3 Fatty Acids on Leukotriene B4 and Leukotriene B5 Production by Stimulated Neutrophils in Patients with Colorectal Cancer: A Randomized, Placebo-Controlled Intervention Trial
Authors: Sorensen Lone , Thorlacius-Ussing Ole , Rasmussen Henrik , Lundbye-Christensen Søren , Calder Philip. , Lindorff-Larsen Karen , Schmidt Erik
Published: September 2014

Omega-3 fatty acids (n-3 FA) may have beneficial clinical and immune-modulating effects in surgical patients. In a randomized, double-blind, prospective, placebo-controlled trial, 148 patients referred for elective colorectal cancer surgery received an n-3 FA-enriched oral nutritional supplement (ONS) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for seven days before surgery. On the day of operation, there was a significant increase in the production of leukotriene B5 (LTB5) (p < 0.01) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p < 0.01), a significant decrease in the production of leukotriene B4 (LTB4) (p < 0.01) and a trend for a decrease in the production of 5-hydroxyeicosatetraenoic acid (5-HETE) (p < 0.1) from stimulated neutrophils in the active group compared with controls. There was no association between LTB4 values and postoperative complications. In conclusion, oral n-3 FA exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications.
2-(Dimethylamino)ethyl Methacrylate/(2-Hydroxyethyl) Methacrylate/α-Tricalcium Phosphate Cryogels for Bone Repair, Preparation and Evaluation of the Biological Response of Human Trabecular Bone-Derived Cells and Mesenchymal Stem Cells
Authors: Volkmer Tiago , Magalhães Joana , Sousa Vania , Santos Luis , Burguera Elena , Blanco Francisco , Román Julio , Rodríguez-Lorenzo Luis
Published: September 2014

The aim of this work is to evaluate the potential of cryogels to be used as scaffolds in tissue engineering. Scaffolds based on the α-tricalcium phosphate reinforced PDMAEMA (Poly(dimethyl aminoethyl methacrylate))/PHEMA (poly(hydroxyethyl methacrylate)) system were prepared and human trabecular bone-derived cells (HTBs) and bone marrow derived-mesenchymal stem cells (BM-MSCs) cultured on them. Several features, such as porosity, pore shape, molecular weight between crosslinks and mesh size, are studied. The most suitable PDMAEMA/PHEMA ratio for cell proliferation has been assessed and the viability, adhesion, proliferation and expression of osteoblastic biochemical markers are evaluated. The PDMAEMA/PHEMA ratio influences the scaffolds porosity. Values between 53% ± 5.7% for a greater content in PHEMA and 75% ± 5.5% for a greater content in PDMAEMA have been obtained. The polymer ratio also modifies the pore shape. A greater content in PDMAEMA leads also to bigger network mesh size. Each of the compositions were non-cytotoxic, the seeded cells remained viable for both BM-MSCs and HTBs. Thus, and based on the structural analysis, specimens with a greater content in PDMAEMA seem to provide a better structural environment for their use as scaffolds for tissue engineering. The α-tricalcium phosphate incorporation into the composition seems to favor the expression of the osteogenic phenotype.
Addressing the Inflammatory Response to Clinically Relevant Polymers by Manipulating the Host Response Using ITIM Domain-Containing Receptors
Authors: Slee Joshua , Christian Abigail , Levy Robert , Stachelek Stanley
Published: September 2014

Tissue contacting surfaces of medical devices initiate a host inflammatory response, characterized by adsorption of blood proteins and inflammatory cells triggering the release of cytokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS), in an attempt to clear or isolate the foreign object from the body. This normal host response contributes to device-associated pathophysiology and addressing device biocompatibility remains an unmet need. Although widespread attempts have been made to render the device surfaces unreactive, the establishment of a completely bioinert coating has been untenable and demonstrates the need to develop strategies based upon the molecular mechanisms that define the interaction between host cells and synthetic surfaces. In this review, we discuss a family of transmembrane receptors, known as immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors, which show promise as potential targets to address aberrant biocompatibility. These receptors repress the immune response and ensure that the intensity of an immune response is appropriate for the stimuli. Particular emphasis will be placed on the known ITIM-containing receptor, Signal Regulatory Protein Alpha (SIRPα), and its cognate ligand CD47. In addition, this review will discuss the potential of other ITIM-containing proteins as targets for addressing the aberrant biocompatibility of polymeric biomaterials.
Proteomics Advances in the Understanding of Pollen–Pistil Interactions
Authors: Fu Ziyang , Yang Pingfang
Published: September 2014

The first key point to the successful pollination and fertilization in plants is the pollen-pistil interaction, referring to the cellular and molecular levels, which mainly involve the haploid pollen and the diploid pistil. The process is defined as “siphonogamy”, which starts from the capture of pollen by the epidermis of stigma and ends up with the fusion of sperm with egg. So far, the studies of the pollen-pistil interaction have been explicated around the self-compatibility and self-incompatibility (SI) process in different species from the molecular genetics and biochemistry to cellular and signal levels, especially the mechanism of SI system. Among them, numerous proteomics studies based on the advanced technologies from gel-system to gel-free system were conducted, focusing on the interaction, in order to uncover the mechanism of the process. The current review mainly focuses on the recent developments in proteomics of pollen-pistil interaction from two aspects: self-incompatible and compatible pollination. It might provide a comprehensive insight on the proteins that were involved in the regulation of pollen-pistil interaction.
Application of MODIS Land Products to Assessment of Land Degradation of Alpine Rangeland in Northern India with Limited Ground-Based Information
Authors: Tasumi Masahiro , Hirakawa Kiyomi , Hasegawa Nobumi , Nishiwaki Aya , Kimura Rikako
Published: September 2014

Land degradation of alpine rangeland in Dachigam National Park, Northern India, was evaluated in this study using MODerate resolution Imaging Spectroradiometer (MODIS) land products. The park has been used by a variety of livestock holders. With increasing numbers of livestock, the managers and users of the park are apprehensive about degradation of the grazing land. However, owing to weak infrastructure for scientific and statistical data collection and sociopolitical restrictions in the region, a lack of quality ground-based weather, vegetation, and livestock statistical data had prevented scientific assessment. Under these circumstances, the present study aimed to assess the rangeland environment and its degradation using MODIS vegetation, snow, and evapotranspiration products as primary input data for assessment. The result of the analysis indicated that soil water content and the timing of snowmelt play an important role in grass production in the area. Additionally, the possibility of land degradation in heavily-grazed rangeland was indicated via a multiple regression analysis at a decadal timescale, whereas weather conditions, such as rainfall and snow cover, primarily explained year-by-year differences in grass production. Although statistical uncertainties remain in the results derived in this study, the satellite-based data and the analyses will promote understanding of the rangeland environment and suggest the potential for unsustainable land management based on statistical probability. This study provides an important initial evaluation of alpine rangeland, for which ground-based information is limited.
Attitude Heading Reference System Using MEMS Inertial Sensors with Dual-Axis Rotation
Authors: Kang Li , Ye Lingyun , Song Kaichen , Zhou Yang
Published: September 2014

This paper proposes a low cost and small size attitude and heading reference system based on MEMS inertial sensors. A dual-axis rotation structure with a proper rotary scheme according to the design principles is applied in the system to compensate for the attitude and heading drift caused by the large gyroscope biases. An optimization algorithm is applied to compensate for the installation angle error between the body frame and the rotation table’s frame. Simulations and experiments are carried out to evaluate the performance of the AHRS. The results show that the proper rotation could significantly reduce the attitude and heading drifts. Moreover, the new AHRS is not affected by magnetic interference. After the rotation, the attitude and heading are almost just oscillating in a range. The attitude error is about 3° and the heading error is less than 3° which are at least 5 times better than the non-rotation condition.
An Intrusion Detection System for the Protection of Railway Assets Using Fiber Bragg Grating Sensors
Authors: Catalano Angelo , Bruno Francesco , Pisco Marco , Cutolo Antonello , Cusano Andrea
Published: September 2014

We demonstrate the ability of Fiber Bragg Gratings (FBGs) sensors to protect large areas from unauthorized activities in railway scenarios such as stations or tunnels. We report on the technological strategy adopted to protect a specific depot, representative of a common scenario for security applications in the railway environment. One of the concerns in the protection of a railway area centers on the presence of rail-tracks, which cannot be obstructed with physical barriers. We propose an integrated optical fiber system composed of FBG strain sensors that can detect human intrusion for protection of the perimeter combined with FBG accelerometer sensors for protection of rail-track access. Several trials were carried out in indoor and outdoor environments. The results demonstrate that FBG strain sensors bonded under a ribbed rubber mat enable the detection of intruder break-in via the pressure induced on the mat, whereas the FBG accelerometers installed under the rails enable the detection of intruders walking close to the railroad tracks via the acoustic surface waves generated by footsteps. Based on a single enabling technology, this integrated system represents a valuable intrusion detection system for railway security and could be integrated with other sensing functionalities in the railway field using fiber optic technology.