European mtDNA Variants Are Associated With Differential Responses to Cisplatin, an Anticancer Drug: Implications for Drug Resistance and Side Effects.

Background: Cisplatin, a powerful antitumor agent, causes formation of DNA adducts, and activation of apoptotic pathways. Presently, cisplatin resistance develops in up to 70% of patients but the underlying molecular mechanism(s) are unclear and there are no markers to determine which patients will become resistant. Mitochondria play a significant role not only in energy metabolism but also retrograde signaling (mitochondria to nucleus) that modulates inflammation, complement, and apoptosis pathways. Maternally inherited mitochondrial (mt) DNA can be classified into haplogroups representing different ethnic populations that have diverse susceptibilities to diseases and medications. Methods: Transmitochondrial cybrids, where all cell lines possess identical nuclear genomes but either the H (Southern European) or J (Northern European) mtDNA haplogroups, were treated with cisplatin and analyzed for differential responses related to viability, oxidative stress, and expression levels of genes associated with cancer, cisplatin-induced nephrotoxicity and resistance, apoptosis and signaling pathways. Results: The cisplatin-treated-J cybrids showed greater loss of cell viability along with lower levels of reactive oxygen species and mitochondrial membrane potential compared to cisplatin-treated-H cybrids. After cisplatin treatment, J cybrids showed increased gene expression of BAX, CASP3, and CYP51A, but lower levels of SFRP1 compared to untreated-J cybrids. The cisplatin-treated-H cybrids had elevated expression of CDKN1A/P21, which has a role in cisplatin toxicity, compared to untreated-H cybrids. The cisplatin-treated H had higher transcription levels of ABCC1, DHRS2/HEP27, and EFEMP1 compared to cisplatin-treated-J cybrids. Conclusions: Cybrid cell lines that contain identical nuclei but either H mtDNA mitochondria or J mtDNA mitochondria respond differently to cisplatin treatments suggesting involvement of the retrograde signaling (from mitochondria to nucleus) in the drug-induced cell death. Varying toxicities and transcription levels of the H vs. J cybrids after cisplatin treatment support the hypothesis that mtDNA variants play a role in the expression of genes affecting resistance and side effects of cisplatin

Phenolic metabolism and antioxidant activity during endodormancy of Kiwifruit buds

Bud dormancy is an adaptability process in woody plants that enables them to survive in unfavorable conditions. In the present study, the phenols, antioxidant capacity, and activity of three enzymes were evaluated during endodormancy phases in two Hayward and Tomuri cultivars and two female and male Golden genotypes of kiwifruit buds. The buds were collected from ten-year-old own-rooted vines from the end of October 2015 until the end of January 2016 in the north of Iran. The results revealed that phenols, antioxidant capacity (RSA), phenylalanine ammonia-lyase (PAL), and polyphenol oxidase (PPO) activities of buds significantly increased at the beginning of endodormancy and subsequently decreased at the end of the endodormancy. The POD activity increased in Hayward and Tomuri from the onset of endodormancy and continued for two weeks after the endodormancy release. The total phenol had a positive and significant correlation with RSA and PAL enzyme activity. Furthermore, higher antioxidant capacity and phenols in both male and female Golden genotypes were attributed to the higher PAL enzyme activity in both genotypes. This study proposes that the RSA%, PAL activity, and phenol concentration could be employed as a biomarker to indicate bud dormancy phases in kiwifruit.

The stochastic gravitational-wave background in the absence of horizons

Gravitational-wave astronomy has the potential to explore one of the deepest and most puzzling aspects of Einstein's theory: the existence of black holes. A plethora of ultracompact, horizonless objects have been proposed to arise in models inspired by quantum gravity. These objects may solve Hawking's information-loss paradox and the singularity problem associated with black holes, while mimicking almost all of their classical properties. They are, however, generically unstable on relatively short timescales. Here, we show that this 'ergoregion instability' leads to a strong stochastic background of gravitational waves, at a level detectable by current and future gravitational-wave detectors. The absence of such background in the first observation run of Advanced LIGO already imposes the most stringent limits to date on black-hole alternatives, showing that certain models of 'quantum-dressed' stellar black holes can be at most a small percentage of the total population. The future LISA mission will allow for similar constraints on supermassive black-hole mimickers

Antibacterial mono- and sesquiterpene esters of benzoic acids from Iranian propolis

<p>Abstract</p> <p>Background</p> <p>Propolis (bee glue) has been used as a remedy since ancient times. Propolis from unexplored regions attracts the attention of scientists in the search for new bioactive molecules.</p> <p>Results</p> <p>From Iranian propolis from the Isfahan province, five individual components were isolated: the prenylated coumarin suberosin <b>1</b>, and four terpene esters: tschimgin (bornyl <it>p</it>-hydroxybenzoate) <b>2</b>, tschimganin (bornyl vanillate) <b>3</b>, ferutinin (ferutinol <it>p</it>-hydroxybenzoate) <b>4, </b>and tefernin (ferutinol vanillate) <b>5</b>. All of them were found for the first time in propolis. Compounds <b>2 </b>- <b>5 </b>demonstrated activity against <it>Staphylococcus aureus</it>.</p> <p>Conclusions</p> <p>The results of the present study are consistent with the idea that propolis from unexplored regions is a promising source of biologically active compounds.</p

The association between diet quality and cancer incidence of the head and neck

The association between diet quality and head and neck cancer (HNC) was explored using a population-based case–control study of 1170 HNC cases and 1303 age-, race-, and sex-matched controls from the United States. Diet quality was assessed with three diet quality scores (DQS): (a) Healthy Eating Index 2005 (HEI-2005), (b) Mediterranean Diet Score (MDS), and (c) HNC-specific Mediterranean Diet Score (MDS-HNC), a modified MDS that we developed to be more applicable to HNC. Logistic regression models estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) representing diet quality–incident HNC associations. We examined effect measure modification (EMM) by body mass index (BMI), race, cigarette smoking, and alcohol consumption and associational heterogeneity by HPV-positivity and tumor site. A one standard deviation summary DQS decrement suggested a consistent inverse association (ORs (CIs)) for the HEI-2005, MDS, and MDS-HNC: 1.35 (1.21, 1.50), 1.13 (1.02, 1.25), and 1.17 (1.06, 1.31), respectively. This association did not vary by tumor site or tumor HPV status, though additive EMM by alcohol use and by BMI was observed. Our findings suggest the Mediterranean diet can be used to study HNC in American populations, and that poor diet quality elevates HNC incidence, particularly among alcohol users

Predictors of oropharyngeal cancer survival in Europe

Objectives: HPV16-positive oropharyngeal cancer (OPC) patients experience better outcomes compared to HPV16-negative patients. Currently, strategies for treatment de-escalation are based on HPV status, smoking history and disease stage. However, the appropriate cut-point for smoking and the role of other non-clinical factors in OPC survival remains uncertain. Materials and Methods: We examined factors associated with OPC outcome in 321 patients recruited in a large European multi-center study. Seropositivity for HPV16 E6 was used as a marker of HPV16 positive cancer. Hazard ratios (HR) and confidence intervals (CI) were estimated using Cox proportional models adjusted for potential confounders. Results: Overall 5-year survival following OPC diagnosis was 50%. HPV16-positive OPC cases were at significantly lower risk of death (aHR = 0.51, 95% CI: 0.32–0.80). A significant effect on OPC survival was apparent for female sex (aHR 0.50: 95% CI: 0.29–0.85) and being underweight at diagnosis (aHR: 2.41, 95% CI: 1.38–4.21). A 10 pack year smoking history was not associated with overall survival. Higher stage at diagnosis appeared as the only factor significantly associated with OPC recurrence (aHR: 4.88, 95% CI: 2.12–11.21). Conclusion: This study confirms that HPV16 status is an independent prognostic factor for OPC survival while female sex lowers risk of death and being underweight at diagnosis increases the risk of death. Smoking was not an independent predictor of OPC survival.</p

Novel combination of feed enzymes to improve the degradation of Chlorella vulgaris recalcitrant cell wall

Research Areas: Science & TechnologyABSTRACT - In this study, a rational combination of 200 pre-selected Carbohydrate-Active enzymes (CAZymes) and sulfatases were tested, individually or combined, according to their ability to degrade Chlorella vulgaris cell wall to access its valuable nutritional compounds. The disruption of microalgae cell walls by a four enzyme mixture (Mix) in comparison with the control, enabled to release up to 1.21g/L of reducing sugars (p<0.001), led to an eight-fold increase in oligosaccharides release (p<0.001), and reduced the fuorescence intensity by 47% after staining with Calcofuor White (p<0.001). The Mix treatment was successful in releasing proteins (p<0.001), some MUFA (p<0.05), and the benefcial 18:3n-3 fatty acid (p0.05), total carotenoids were increased in the supernatant (p<0.05) from the Mix treatment, relative to the control. Taken together, these results indicate that this four-enzyme Mix displays an efective capacity to degrade C. vulgaris cell wall. Thus, these enzymes may constitute a good approach to improve the bioavailability of C. vulgaris nutrients for monogastric diets, in particular, and to facilitate the cost-efective use of microalgae by the feed industry, in general.info:eu-repo/semantics/publishedVersio

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Evolution of hepatitis B virus surface gene and protein among Iranian chronic carriers from different provinces

Background and Objectives: Iranian chronic HBV carrier�s population has shown a unique pattern of genotype D distribution all around the country. The aim of this study was to explore more details of evolutionary history of carriers based on structural surface proteins from different provinces. Materials and Methods: Sera obtained from 360 isolates from 12 Different regions of country were used for amplification and sequencing of surface proteins. A detailed mutational analysis was undertaken. Results: The total ratio for Missense/Silent nucleotide substitutions was 0.96. Sistan and Kermanshah showed the lowest rate of evolution between provinces (P = 0.055). On the other hand, Khorasan Razavi and Khoozestan contained the highest ratio (P = 0.055). The rest of regions were laid between these two extremes. Azarbayjan and Guilan showed the highest proportion of immune epitope distribution (91.3 and 96, respectively). Conversely, Sistan and Tehran harbored the least percentage (66.6 and 68.8, respectively). Kermanshah province contained only 5.2, whereas Isfahan had 54.5 of B cell epitope distribution. In terms of T helper epitopes, all provinces showed a somehow homogeneity: 22.58 (Fars) to 46.6 (Khuzestan). On the other hand, distribution of substitutions within the CTL epitopes showed a wide range of variation between 6.6 (Khuzestan) and 63 (Kermanshah). Conclusion: Further to low selection pressure found in Iranian population, the variations between different regions designate random genetic drift within the surface proteins. These finding would have some applications in terms of specific antiviral regimen, design of more efficient vaccine and public health issues. © 2015, Tehran University of Medical Science. All rights reserved

A Survey on the Security and the Evolution of Osmotic and Catalytic Computing for 5G Networks

The 5G networks have the capability to provide high compatibility for the new applications, industries, and business models. These networks can tremendously improve the quality of life by enabling various use cases that require high data-rate, low latency, and continuous connectivity for applications pertaining to eHealth, automatic vehicles, smart cities, smart grid, and the Internet of Things (IoT). However, these applications need secure servicing as well as resource policing for effective network formations. There have been a lot of studies, which emphasized the security aspects of 5G networks while focusing only on the adaptability features of these networks. However, there is a gap in the literature which particularly needs to follow recent computing paradigms as alternative mechanisms for the enhancement of security. To cover this, a detailed description of the security for the 5G networks is presented in this article along with the discussions on the evolution of osmotic and catalytic computing-based security modules. The taxonomy on the basis of security requirements is presented, which also includes the comparison of the existing state-of-the-art solutions. This article also provides a security model, "CATMOSIS", which idealizes the incorporation of security features on the basis of catalytic and osmotic computing in the 5G networks. Finally, various security challenges and open issues are discussed to emphasize the works to follow in this direction of research.Comment: 34 pages, 7 tables, 7 figures, Published In 5G Enabled Secure Wireless Networks, pp. 69-102. Springer, Cham, 201