bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative real-time PCR (qPCR) for the detection and quantification of dactylogyrid parasites infectingLutjanus guttatus
Authors: Soler-Jiménez L.C. , García-Gasca A. , Fajer-Ávila E.J.
Published: March 2017

Severe infections of the spotted rose snapperLutjanus guttatusresulting from dactylogyrid monogeneans present a risk to aquaculture. Currently, the diagnosis of this infection requires the morphological identification and manual quantification of parasites. Based on the characterization of the 28S rRNA gene of dactylogyrid species present inL. guttatus, specific primers were designed for real-time polymerase chain reaction (qPCR) using EvaGreen® chemistry. The standard curve method estimated the number of dactylogyrids accurately. A total of 85 gill samples from cage-cultured fish infected with dactylogyrids were analysed. The estimated number of dactylogyrids using this molecular method was very similar to the manual count that was performed initially. The standardized qPCR approach will be helpful as a complementary method for the early routine monitoring of dactylogyrid infections and for epidemiological studies in which a high number of fish must be studied.
Non-State Armed Groups, Detention Authority in Non-International Armed Conflict, and the Coherence of International Law: Searching for a Way Forward
Authors: MURRAY DARAGH
Published: March 2017

International humanitarian law establishes explicit safeguards applicable to detention occurring in non-international armed conflict. However, debate exists as to whether these treaty provisions establish an implicit legal basis for detention. This article approaches this debate in light of the application of international humanitarian law to non-state armed groups. It examines the principal arguments against implicit detention authority and then applies the law of treaty interpretation to international humanitarian law's detention-related provisions. On the basis of current understandings of international law – and the prohibition of arbitrary detention in particular – it is concluded that international humanitarian law must be interpreted as establishing implicit detention authority, in order to ensure the continued regulation of armed groups. Although, perhaps, problematic from certain states’ perspective, this conclusion is reflective of the current state of international law. However, this is not necessarily the end of the story. A number of potential ‘ways forward’ are identified: implicit detention authority may be (i) rejected; (ii) accepted; or (iii) re-examined in light of the non-state status of armed groups, and what this means for the content of the prohibition of arbitrary detention. These scenarios are examined in light of the desire to ensure: the coherency of international law including recognition of the role of armed groups, the continued effectiveness of international humanitarian law, and state sovereignty. An emphasis is placed on understanding the non-state status of armed groups and what this means for international regulation and the content of imposed obligations.
Formulating a list of sites of waterbird conservation significance to contribute to China’s Ecological Protection Red Line
Authors: ZHANG LU , WANG XIN , ZHANG JUNJIAN , OUYANG ZHIYUN , CHAN SIMBA , CROSBY MIKE , WATKINS DOUG , MARTINEZ JONATHAN , SU LIYING , YU YAT-TUNG , SZABO JUDIT , CAO LEI , FOX ANTHONY D.
Published: March 2017

China makes a unique and vital contribution to maintaining global and regional waterbird diversity and conservation. Despite considerable historical conservation efforts, the continued loss of waterbird diversity and abundance necessitates a contemporary review of Chinese sites of conservation significance. The Ecological Protection Red Line (EPRL) was proposed by China’s Central Government in 2013 to protect areas providing crucial ecosystem services and provides the opportunity for such a review to enhance waterbird conservation in China. By incorporating various sources of data, surveys and information, we identified a suite of sites of waterbird conservation significance in China, following the Ramsar Site Criteria/Important Bird and Biodiversity Area (IBA) Criteria. In total, we identified 422 sites, of which the existing 286 IBA sites formed the basis of the site safeguard network. Altogether, these sites of waterbird conservation significance constitute over 727,000 km2(7.6% of China’s land surface). Over half of the area of these sites is outside China’s national nature reserves, thus confirming the importance and urgency of including them in the EPRL for the effective conservation of waterbird sites. We suggest that this assessment of sites of waterbird importance offers a useful model to apply to other taxa, such as terrestrial birds and mammals.
Supplementation of sperm media with zinc, D-aspartate and co-enzyme Q10 protects bull sperm against exogenous oxidative stress and improves their ability to support embryo development
Authors: Barbato Vincenza , Talevi Riccardo , Braun Sabrina , Merolla Anna , Sudhakaran Sam , Longobardi S. , Gualtieri Roberto
Published: March 2017

High levels of reactive oxygen species in the semen of infertile patients or spontaneously generated during in vitro sperm handling may impair sperm quality, fertilization and embryo developmental competence. We recently reported that zinc, d-aspartate and co-enzyme Q10, contained in the dietary supplement Genadis® (Merck Serono), have protective effects on human and bull sperm motility, lipid peroxidation and DNA fragmentation in vitro; furthermore, in bovine, treated spermatozoa had an improved ability to support embryo development. However, only a few studies have investigated the protective role of antioxidants during in vitro sperm handling in the presence of an exogenous oxidative stress. Herein, to simulate such conditions in an animal model, we induced exogenous oxidative stress on spermatozoa through the xanthine–xanthine oxidase system and investigated its effects on sperm function and subsequent embryo developmental competence in the presence of zinc, d-Asp and CoQ10 protection. The main results showed that exogenous oxidative stress decreased sperm motility, increased sperm DNA fragmentation, and reduced fertilization and blastocyst rates and quality. Pre-treatment with zinc, d-aspartate and co-enzyme Q10 before exogenous oxidative stress was able to prevent these effects. Supplementation of sperm culture media with zinc, d-aspartate and co-enzyme Q10 could protect sperm from oxidative stress damage during in vitro handling in assisted reproductive technologies.
Emerging trends: I did it, I did it, I did it, but. . .
Authors: CHURCH KENNETH WARD
Published: March 2017

There has been a trend for publications to report better and better numbers, but less and less insight. The literature is turning into a giant leaderboard, where publication depends on numbers and little else (such as insight and explanation). It is considered a feature that machine learning has become so powerful (and so opaque) that it is no longer necessary (or even relevant) to talk about how it works. Insight is not only not required any more, but perhaps, insight is no longer even considered desirable.

Transparency is good and opacity is bad. A recent best seller, Weapons of Math Destruction, is concerned that big data (and WMDs) increase inequality and threaten democracy largely because of opacity. Algorithms are being used to make lots of important decisions like who gets a loan and who goes to jail. If we tell the machine to maximize an objective function like making money, it will do exactly that, for better and for worse. Who is responsible for the consequences? Does it make it ok for machines to do bad things if no one knows what’s happening and why, including those of us who created the machines?
Listening for Context: Interpretation, abstraction and the real
Authors: Hill Andrew
Published: March 2017

This article seeks to explore the proposed notion of ‘context-based composition’ by examining the nature of ‘real-world’ context. It does this by studying the way in which listeners interpret sounds, working towards a deeper understanding of what it is that we mean by ‘real-world’ sound and context-based composition. These discussions are then utilised to explore the concept of what it means to compose context-based works and suggests that new potentials are opened up by a closer examination of the definition of context-based composition, one which liberates itself from a concern over an absolute physical nature of sounds and which embraces the use of both abstract and referential sounds. This journey highlights the importance of memory and experience within processes of interpretation and the creation of context-based compositions, and questions divisions between the virtual and the real.
Ecological Sound Art: Steps towards a new field
Authors: Gilmurray Jonathan
Published: March 2017

The years since the turn of the millennium have seen an increasing number of sound artists engaging with contemporary environmental issues such as biodiversity loss, sustainability and climate change through their work, forming a growing movement of environmentally concerned sound art; however, their work has yet to achieve the recognition enjoyed by comparable environmentalist practices in almost every other art form. This article argues that this increasingly significant area of sound arts practice should be recognised as a distinct field in its own right, and proposes that it be termed ‘ecological sound art’, reflecting its equivalent in the visual arts. After establishing its current absence from both ecocritical and sound arts scholarship, it proceeds to outline some of the core approaches which characterise works of ecological sound art, as the first step towards its establishment as a coherent field of practice. The final section draws from key works of contemporary ecological theory, examining the fundamental accord that exists between the new modes of thought they propose and the ways in which we experience and relate to sound art, demonstrating that ecological sound art represents not only a significant new field of sound arts practice, but also a powerful ecological art form.
Sound Art Situations
Authors: Groth Sanne Krogh , Samson Kristine
Published: March 2017

This article is an analysis of two sound art performances that took place in June 2015 in outdoor public spaces at the social housing areaUrbanplanenin Copenhagen, Denmark. The two performances wereOn the Productions of a Poor Acousticsby Brandon LaBelle andGreen Interactive Biofeedback Environments (GIBE)by Jeremy Woodruff. In order to investigate the complex situation that arises when sound art is staged in such contexts, the authors of this article suggest exploring the events through approaching them as ‘situations’ (Doherty 2009). With this approach it becomes possible to engage and combine theories from several fields. Aspects of sound art studies, performance studies and contemporary art studies are presented in order to theoretically explore the very diverse dimensions of the two sound art pieces. Visual, auditory, performative, social, spatial and durational dimensions become integrated within the analysis in our pursuit of the most comprehensive interpretation of the pieces possible.
Testing the feasibility of using the Edmonton Symptom Assessment System (ESAS) to assess caregiver symptom burden
Authors: Tanco Kimberson , Vidal Marieberta , Arthur Joseph , Delgado Guay Marvin , Hui David , Liu Diane , Chisholm Gary , Bruera Eduardo
Published: March 2017

Objective:

Caregiver symptom assessment is not part of regular clinical cancer care. The ESAS (Edmonton Symptom Assessment System) is a multidimensional tool regularly used to measure symptom burden in patients but not caregivers. The objectives of the present study were to determine the feasibility of the ESAS in caregiver completion (defined as ≥ 9 of 12 items) and determine its concurrent validity with the Zarit Burden Interview–12 (ZBI–12).

Method:

We conducted a prospective study on 90 patient–primary caregiver dyads seen in an outpatient supportive care center in a cancer center. The 12 item ESAS–FS (financial–spiritual) was completed by the dyads along with other clinical and psychosocial measures.

Results:

The caregiver ESAS was found to be feasible (90/90 caregivers, 100% completed ≥ 9/12 items) and useful (66/90 caregivers, 73%) by caregivers to report their symptom burden. Some 68 of 90 (76%) caregivers had symptom distress scores ≥ 4 on at least one symptom. A significant association was found between the ESAS scores of caregivers and patients for fatigue (0.03), depression (<0.01), anxiety (<0.01), sleep (0.05), well-being (<0.01), financial distress (<0.01), spiritual pain (<0.01), and total ESAS score (<0.01). Concurrent validity with the ZBI–12 was not achieved (r = 0.53, p = 0.74). A significant correlation was found between caregiver ESAS scores and time spent feeding, housekeeping, total combined caregiver activities, and total ZBI–12 scores.

Significance of results:

The caregiver ESAS is a feasible tool and was found useful by our caregivers. Further research is needed to modify the ESAS based on caregivers' recommendations, and further psychometric studies need to be conducted.
Factors associated with patient-reported subjective well-being among advanced lung or non-colonic gastrointestinal cancer patients
Authors: Yennurajalingam Sriram , Kim Yu Jung , Zhang Yi , Park Jichan , Arthur Joseph , Chisholm Gary B. , Williams Janet L. , Bruera Eduardo
Published: March 2017

Objective:

The aim of this study was to determine the factors associated with a feeling of well-being using the Edmonton Symptom Assessment Scale (ESAS)–Feeling of Well-Being item (ESAS–FWB; where 0 = best and 10 = worst) among advanced lung or non-colonic gastrointestinal cancer patients who were referred to an outpatient palliative care clinic (OPCC). We also examined the association of performance on the ESAS–FWB with overall survival (OS).

Method:

We reviewed the records of consecutive patients with incurable advanced lung cancer and non-colonic gastrointestinal cancer presenting to an OPCC from 1 January 2008 through to 31 December 2013. Descriptive statistics were employed to summarize patient characteristics. Multivariate regression analysis was used to determine the factors associated with ESAS–FWB severity. We also examined the association of ESAS–FWB scores and survival using Kaplan–Meier survival analysis.

Results:

A total of 826 evaluable patients were analyzed (median age = 62 years, 57% male). Median ESAS–FWB scores were five times the interquartile range (5 ×IQR; 3–7). ESAS–FWB score was found to be significantly associated with ESAS fatigue (OR= 2.31,p< 0.001); anxiety (OR= 1.98,p< 0.001); anorexia (OR= 2.31,p< 0.001); cut down, annoyed, guilty, eye opener (CAGE) score (hazard ratio [HR] = 1.80,p= 0.008); and family caregiver distress (HR= 1.93,p= 0.002). A worse ESAS–FWB score was significantly associated with decreased OS (r= –0.18,p< 0.001). However, ESAS–FWB score was not independently associated with OS in the final multivariate model (p= 0.35), which included known major clinical prognostic factors.

Conclusions:

Worse ESAS–FWB scores were significantly associated with high scores on ESAS fatigue, anorexia, anxiety, CAGE, and family caregiver distress. More research is necessary to understand how palliative care interventions are capable of improving the contributory factors related to ESAS–FWB score.
Loss of ERα induces amoeboid-like migration of breast cancer cells by downregulating vinculin
Authors: Gao Yuan , Wang Zhaowei , Hao Qiang , Li Weina , Xu Yujin , Zhang Juliang , Zhang Wangqian , Wang Shuning , Liu Shuo , Li Meng , Xue Xiaochang , Zhang Wei , Zhang Cun , Zhang Yingqi
Published: March 2017

Oestrogen receptor alpha (ERα) is a well-known target of endocrine therapy for ERα-positive breast cancer. ERα-negative cells, which are enriched during endocrine therapy, are associated with metastatic relapse. Here we determine that loss of ERα in the invasive front and in lymph node metastasis in human breast cancer is significantly correlated with lymphatic metastasis. Using in vivo and in vitro experiments, we demonstrate that ERα inhibits breast cancer metastasis. Furthermore, we find that ERα is a novel regulator of vinculin expression in breast cancer. Notably, ERα suppresses the amoeboid-like movement of breast cancer cells by upregulating vinculin in 3D matrix, which in turn promotes cell–cell and cell–matrix adhesion and inhibits the formation of amoeboid-like protrusions. A positive association between ERα and vinculin expression is found in human breast cancer tissues. The results show that ERα inhibits breast cancer metastasis and suggest that ERα suppresses cell amoeboid-like movement by upregulating vinculin.
Misrouting of v-ATPase subunit V0a1 dysregulates lysosomal acidification in a neurodegenerative lysosomal storage disease model
Authors: Bagh Maria B. , Peng Shiyong , Chandra Goutam , Zhang Zhongjian , Singh Satya P. , Pattabiraman Nagarajan , Liu Aiyi , Mukherjee Anil B.
Published: March 2017

Defective lysosomal acidification contributes to virtually all lysosomal storage disorders (LSDs) and to common neurodegenerative diseases like Alzheimer’s and Parkinson’s. Despite its fundamental importance, the mechanism(s) underlying this defect remains unclear. The v-ATPase, a multisubunit protein complex composed of cytosolic V1-sector and lysosomal membrane-anchored V0-sector, regulates lysosomal acidification. Mutations in the CLN1 gene, encoding PPT1, cause a devastating neurodegenerative LSD, INCL. Here we report that in Cln1−/− mice, which mimic INCL, reduced v-ATPase activity correlates with elevated lysosomal pH. Moreover, v-ATPase subunit a1 of the V0 sector (V0a1) requires palmitoylation for interacting with adaptor protein-2 (AP-2) and AP-3, respectively, for trafficking to the lysosomal membrane. Notably, treatment of Cln1−/− mice with a thioesterase (Ppt1)-mimetic, NtBuHA, ameliorated this defect. Our findings reveal an unanticipated role of Cln1 in regulating lysosomal targeting of V0a1 and suggest that varying factors adversely affecting v-ATPase function dysregulate lysosomal acidification in other LSDs and common neurodegenerative diseases.
Electrically controlled terahertz magneto-optical phenomena in continuous and patterned graphene
Authors: Poumirol Jean-Marie , Liu Peter Q. , Slipchenko Tetiana M. , Nikitin Alexey Y. , Martin-Moreno Luis , Faist Jérôme , Kuzmenko Alexey B.
Published: March 2017

The magnetic circular dichroism and the Faraday rotation are the fundamental phenomena of great practical importance arising from the breaking of the time reversal symmetry by a magnetic field. In most materials, the strength and the sign of these effects can be only controlled by the field value and its orientation. Furthermore, the terahertz range is lacking materials having the ability to affect the polarization state of the light in a non-reciprocal manner. Here we demonstrate, using broadband terahertz magneto-electro-optical spectroscopy, that in graphene both the magnetic circular dichroism and the Faraday rotation can be modulated in intensity, tuned in frequency and, importantly, inverted using only electrostatic doping at a fixed magnetic field. In addition, we observe strong magneto-plasmonic resonances in a patterned array of graphene antidots, which potentially allows exploiting these magneto-optical phenomena in a broad THz range.
Bioaerosol generation by raindrops on soil
Authors: Joung Young Soo , Ge Zhifei , Buie Cullen R.
Published: March 2017

Aerosolized microorganisms may play an important role in climate change, disease transmission, water and soil contaminants, and geographic migration of microbes. While it is known that bioaerosols are generated when bubbles break on the surface of water containing microbes, it is largely unclear how viable soil-based microbes are transferred to the atmosphere. Here we report a previously unknown mechanism by which rain disperses soil bacteria into the air. Bubbles, tens of micrometres in size, formed inside the raindrops disperse micro-droplets containing soil bacteria during raindrop impingement. A single raindrop can transfer 0.01% of bacteria on the soil surface and the bacteria can survive more than one hour after the aerosol generation process. This work further reveals that bacteria transfer by rain is highly dependent on the regional soil profile and climate conditions.
Complement C3 of the innate immune system secreted by muscle adipogenic cells promotes myogenic differentiation
Authors: Rouaud Thierry , Siami Nader , Dupas Tanaelle , Gervier Pascal , Gardahaut Marie-France , Auda-Boucher Gwenola , Thiriet Christophe
Published: March 2017

Myogenic differentiation results in different cell type cooperation, but the molecules involved in the myogenic cell activation remain elusive. Here, we show that muscle-resident pre-adipocytes promote myogenic differentiation through the secretion of factors. Using proteomic and transcriptomic analyses, we identified that proliferative adipogenic lineage cells produce and secrete a key factor of the innate immune system, the complement C3. Cell culture experiments revealed that C3 promotes the differentiation of myogenic progenitors following internalisation of the immune molecule. These data demonstrate that the third component of the complement system, which is a pivotal factor in the immune response to pathogens, is also involved in the differentiation of myogenic progenitor cells.
Germination of Seeds and Seedling Growth of Amaranthus retroflexus L. Following Sublethal Exposure of Parent Plants to Herbicides
Authors: Qi Yue , Yan Bing , Fu Gang , Guan Xiao , Du Leshan , Li Junsheng
Published: March 2017

Herbicides have long-term effects on the vegetative parts and reproduction of plants; however, the carry-over effects of herbicides on the F1 generation of invasive plants remain unclear. The objectives of this work were to investigate the germination and growth of the F1 generation of A. retroflexus, an invasion plant, treated by sublethal herbicides. The results demonstrated that atrazine or tribenuron-methyl had carry-over effects on the F1 generation of A. retroflexus. Atrazine or tribenuron-methyl exposure during the vegetative and reproductive periods significantly inhibited the germination and growth of the F1 generation; a lower sublethal dose of atrazine or tribenuron-methyl did not weaken the inhibition of germination or growth of the F1 generation. Our results suggest that although herbicides have a carry-over inhibition effect on the F1 generation of invasive plants, they may have a more serious carry-over effect on native plants and cause changes in weed species composition and weed diversity.
New sedimentary evidence reveals a unique history of C4 biomass in continental East Asia since the early Miocene
Authors: Zhou Bin , Bird Michael , Zheng Hongbo , Zhang Enlou , Wurster Christopher M. , Xie Luhua , Taylor David
Published: March 2017

Pyrogenic carbon (PyC) and n-alkane data from sediments in the northern South China Sea reveal variations in material from C4 plants in East Asia over the last ~19 Ma. These data indicate the likely presence of C4 taxa during the earliest part of the record analysed, with C4 species also prominent during the mid and late Miocene and especially the mid Quaternary. Notably the two records diverge after the mid Quaternary, when PyC data indicate a reduced contribution of C4 taxa to biomass burning, whereas plant-derived n-alkanes indicate a greater abundance of C4 plants. This divergence likely reflects differences in the predominant source areas of organic materials accumulating at the coring site, with PyC representing a larger source area that includes material transported in the atmosphere from more temperate (relatively cooler and drier) parts of East Asia. Variations in the relative abundances of C3 and C4 taxa appear to be linked to a combination of environmental factors that have varied temporally and geographically and that are unique to East Asia. A major expansion of C4 biomass in warmer subtropical parts of eastern Asia from ~1 Ma and particularly from ~0.4 Ma is later than other parts of the world.
Correction: Corrigendum: Relationship between nanotopographical alignment and stem cell fate with live imaging and shape analysis
Authors: Newman Peter , Galeano Niño Jorge Luis , Graney Pamela , Razal Joselito M. , Minett Andrew I. , Ribas João , Ovalle-Robles Raquel , Biro Maté , Zreiqat Hala
Published: March 2017

Scientific Reports 6: Article number: 37909; published online: 02 December 2016; updated: 07 March 2017. The original version of this Article contained an error in the spelling of the author Jorge Luis Galeano Niño, which was incorrectly given as Jorge Luis Galenano-Niño. Additionally, there were typographical errors in Affiliation 9 which was incorrectly listed as ‘Sydney Medical School, The University of Sydney, NSW, 2006, Australia.
Important fossil source contribution to brown carbon in Beijing during winter
Authors: Yan Caiqing , Zheng Mei , Bosch Carme , Andersson August , Desyaterik Yury , Sullivan Amy P. , Collett Jeffrey L. , Zhao Bin , Wang Shuxiao , He Kebin , Gustafsson Örjan
Published: March 2017

Organic aerosol (OA) constitutes a substantial fraction of fine particles and affects both human health and climate. It is becoming clear that OA absorbs light substantially (hence termed Brown Carbon, BrC), adding uncertainties to global aerosol radiative forcing estimations. The few current radiative-transfer and chemical-transport models that include BrC primarily consider sources from biogenic and biomass combustion. However, radiocarbon fingerprinting here clearly indicates that light-absorbing organic carbon in winter Beijing, the capital of China, is mainly due to fossil sources, which contribute the largest part to organic carbon (OC, 67 ± 3%) and its sub-constituents (water-soluble OC, WSOC: 54 ± 4%, and water-insoluble OC, WIOC: 73 ± 3%). The dual-isotope (Δ14C/δ13C) signatures, organic molecular tracers and Beijing-tailored emission inventory identify that this fossil source is primarily from coal combustion activities in winter, especially from the residential sector. Source testing on Chinese residential coal combustion provides direct evidence that intensive coal combustion could contribute to increased light-absorptivity of ambient BrC in Beijing winter. Coal combustion is an important source to BrC in regions such as northern China, especially during the winter season. Future modeling of OA radiative forcing should consider the importance of both biomass and fossil sources.
Spectroscopic properties in Er3+-doped germanotellurite glasses and glass ceramics for mid-infrared laser materials
Authors: Kang Shiliang , Xiao Xiudi , Pan Qiwen , Chen Dongdan , Qiu Jianrong , Dong Guoping
Published: March 2017

Transparent Er3+-doped germanotellurite glass ceramics (GCs) with variable Te/Ge ratio were prepared by controllable heat-treated process. X-ray diffraction (XRD) and transmission electron microscope (TEM) confirmed the formation of nanocrystals in glass matrix. Raman spectra were used to investigate the evolution of glass structure and photon energy. Fourier transform infrared (FTIR) spectra were introduced to characterize the change of hydroxyl group (OH−) content. Enhanced 2.7 μm emission was achieved from Er3+-doped GCs upon excitation with a 980 nm laser diode (LD), and the influence of GeO2 concentration and heat-treated temperature on the spectroscopic properties were also discussed in detail. It is found that the present Er3+-doped GC possesses large stimulated emission cross section at around 2.7 μm (0.85 × 10−20 cm2). The advantageous spectroscopic characteristics suggest that the obtained GC may be a promising material for mid-infrared fiber lasers.
OGG1-DNA interactions facilitate NF-κB binding to DNA targets
Authors: Pan Lang , Hao Wenjing , Zheng Xu , Zeng Xianlu , Ahmed Abbasi Adeel , Boldogh Istvan , Ba Xueqing
Published: March 2017

DNA repair protein counteracting oxidative promoter lesions may modulate gene expression. Oxidative DNA bases modified by reactive oxygen species (ROS), primarily as 7, 8-dihydro-8-oxo-2′-deoxyguanosine (8-oxoG), which is repaired by 8-oxoguanine DNA glycosylase1 (OGG1) during base excision repair (BER) pathway. Because cellular response to oxidative challenge is accompanied by DNA damage repair, we tested whether the repair by OGG1 is compatible with transcription factor binding and gene expression. We performed electrophoretic mobility shift assay (EMSA) using wild-type sequence deriving from Cxcl2 gene promoter and the same sequence bearing a single synthetic 8-oxoG at defined 5′ or 3′ guanine in runs of guanines to mimic oxidative effects. We showed that DNA occupancy of NF-κB present in nuclear extracts from tumour necrosis factor alpha (TNFα) exposed cells is OGG1 and 8-oxoG position dependent, importantly, OGG1 counteracting 8-oxoG outside consensus motif had a profound influence on purified NF-κB binding to DNA. Furthermore, OGG1 is essential for NF-κB dependent gene expression, prior to 8-oxoG excised from DNA. These observations imply that pre-excision step(s) during OGG1 initiated BER evoked by ROS facilitates NF-κB DNA occupancy and gene expression.
Bifidobacterium breve with α-linolenic acid alters the composition, distribution and transcription factor activity associated with metabolism and absorption of fat
Authors: Patterson Elaine , Wall Rebecca , Lisai Sara , Ross R. Paul , Dinan Timothy G. , Cryan John F. , Fitzgerald Gerald F. , Banni Sebastiano , Quigley Eamonn M. , Shanahan Fergus , Stanton Catherine
Published: March 2017

This study focused on the mechanisms that fatty acid conjugating strains - Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 - influence lipid metabolism when ingested with α-linolenic acid (ALA) enriched diet. Four groups of BALB/c mice received ALA enriched diet (3% (w/w)) either alone or in combination with B. breve NCIMB 702258 or B. breve DPC 6330 (109 CFU/day) or unsupplemented control diet for six weeks. The overall n-3 PUFA score was increased in all groups receiving the ALA enriched diet. Hepatic peroxisomal beta oxidation increased following supplementation of the ALA enriched diet with B. breve (P < 0.05) and so the ability of the strains to produce c9t11 conjugated linoleic acid (CLA) was identified in adipose tissue. Furthermore, a strain specific effect of B. breve NCIMB 702258 was found on the endocannabinoid system (ECS). Liver triglycerides (TAG) were reduced following ALA supplementation, compared with unsupplemented controls (P < 0.01) while intervention with B. breve further reduced liver TAG (P < 0.01), compared with the ALA enriched control. These data indicate that the interactions of the gut microbiota with fatty acid metabolism directly affect host health by modulating n-3 PUFA score and the ECS.
Comparative evaluation of leukocyte- and platelet-rich plasma and pure platelet-rich plasma for cartilage regeneration
Authors: Xu Zhengliang , Yin Wenjing , Zhang Yuelei , Qi Xin , Chen Yixuan , Xie Xuetao , Zhang Changqing
Published: March 2017

Platelet-rich plasma (PRP) has gained growing popularity in the treatment of articular cartilage lesions in the last decade. However, the potential harmful effects of leukocytes in PRP on cartilage regeneration have seldom been studied in vitro, and not at all in vivo yet. The objective of the present study is to compare the effects of leukocyte- and platelet-rich plasma (L-PRP) and pure platelet-rich plasma (P-PRP) on cartilage repair and NF-κB pathway, in order to explore the mechanism underlying the function of leukocytes in PRP in cartilage regeneration. The constituent analysis showed that P-PRP had significantly lower concentrations of leukocytes and pro-inflammatory cytokines compared with L-PRP. In addition, cell proliferation and differentiation assays indicated P-PRP promoted growth and chondrogenesis of rabbit bone marrow mesenchymal stem cells (rBMSC) significantly compared with L-PRP. Despite similarity in macroscopic appearance, the implantation of P-PRP combining rBMSC in vivo yielded better cartilage repair results than the L-PRP group based on histological examination. Importantly, the therapeutic effects of PRP on cartilage regeneration could be enhanced by removing leukocytes to avoid the activation of the NF-κB pathway. Thus, PRP without concentrated leukocytes may be more suitable for the treatment of articular cartilage lesions.
Observation of laser pulse propagation in optical fibers with a SPAD camera
Authors: Warburton Ryan , Aniculaesei Constantin , Clerici Matteo , Altmann Yoann , Gariepy Genevieve , McCracken Richard , Reid Derryck , McLaughlin Steve , Petrovich Marco , Hayes John , Henderson Robert , Faccio Daniele , Leach Jonathan
Published: March 2017

Recording processes and events that occur on sub-nanosecond timescales poses a difficult challenge. Conventional ultrafast imaging techniques often rely on long data collection times, which can be due to limited device sensitivity and/or the requirement of scanning the detection system to form an image. In this work, we use a single-photon avalanche detector array camera with pico-second timing accuracy to detect photons scattered by the cladding in optical fibers. We use this method to film supercontinuum generation and track a GHz pulse train in optical fibers. We also show how the limited spatial resolution of the array can be improved with computational imaging. The single-photon sensitivity of the camera and the absence of scanning the detection system results in short total acquisition times, as low as a few seconds depending on light levels. Our results allow us to calculate the group index of different wavelength bands within the supercontinuum generation process. This technology can be applied to a range of applications, e.g., the characterization of ultrafast processes, time-resolved fluorescence imaging, three-dimensional depth imaging, and tracking hidden objects around a corner.
CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis
Authors: Sun Yue , Zhang Jie , Zhai Tianhang , Li Huidan , Li Haichuan , Huo Rongfen , Shen Baihua , Wang Beiqing , Chen Xiangdong , Li Ningli , Teng Jialin
Published: March 2017

CCN1, an extracellular protein also known as cysteine-rich protein 61 (Cyr61), is a novel pro-inflammatory factor involved in the pathogenesis of rheumatoid arthritis. As an inflammatory disease, psoriasis is characterized by keratinocyte activation-induced epidermal hyperplasia and cytokine-mediated inflammation. We demonstrated in our previous study that CCN1 promoted keratinocyte activation in psoriasis. However, the role of CCN1 in regulating inflammation in psoriasis is still unknown. Here, we showed that CCN1 increased inflammatory cytokine IL-1β production in keratinocytes. Furthermore, endogenous ATP and caspase-1 were required for mature IL-1β production stimulated by CCN1 in keratinocytes. After binding to the receptor of integrin α6β1, CCN1 activated the downstream p38 MAPK signaling pathway, thus inducing the expression of IL-1β. In addition, we inhibited CCN1 function in mouse models of psoriasis, and decreased IL-1β production was observed in vivo. Overall, we showed that CCN1 increased IL-1β production via p38 MAPK signaling, indicating a role for CCN1 protein in regulating inflammation in psoriasis.
Efficient and rapid generation of large genomic variants in rats and mice using CRISMERE
Authors: Birling Marie-Christine , Schaeffer Laurence , André Philippe , Lindner Loic , Maréchal Damien , Ayadi Abdel , Sorg Tania , Pavlovic Guillaume , Hérault Yann
Published: March 2017

Modelling Down syndrome (DS) in mouse has been crucial for the understanding of the disease and the evaluation of therapeutic targets. Nevertheless, the modelling so far has been limited to the mouse and, even in this model, generating duplication of genomic regions has been labour intensive and time consuming. We developed the CRISpr MEdiated REarrangement (CRISMERE) strategy, which takes advantage of the CRISPR/Cas9 system, to generate most of the desired rearrangements from a single experiment at much lower expenses and in less than 9 months. Deletions, duplications, and inversions of genomic regions as large as 24.4 Mb in rat and mouse founders were observed and germ line transmission was confirmed for fragment as large as 3.6 Mb. Interestingly we have been able to recover duplicated regions from founders in which we only detected deletions. CRISMERE is even more powerful than anticipated it allows the scientific community to manipulate the rodent and probably other genomes in a fast and efficient manner which was not possible before.
ELF-MF exposure affects the robustness of epigenetic programming during granulopoiesis
Authors: Manser Melissa , Sater Mohamad R. Abdul , Schmid Christoph D. , Noreen Faiza , Murbach Manuel , Kuster Niels , Schuermann David , Schär Primo
Published: March 2017

Extremely-low-frequency magnetic fields (ELF-MF) have been classified as “possibly carcinogenic” to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia. We examined the potential of ELF-MF to influence key epigenetic modifications in leukaemic Jurkat cells and in human CD34+ haematopoietic stem cells undergoing in vitro differentiation into the neutrophilic lineage. During granulopoiesis, sensitive genome-wide profiling of multiple replicate experiments did not reveal any statistically significant, ELF-MF-dependent alterations in the patterns of active (H3K4me2) and repressive (H3K27me3) histone marks nor in DNA methylation. However, ELF-MF exposure showed consistent effects on the reproducibility of these histone and DNA modification profiles (replicate variability), which appear to be of a stochastic nature but show preferences for the genomic context. The data indicate that ELF-MF exposure stabilizes active chromatin, particularly during the transition from a repressive to an active state during cell differentiation.
ESR1 inhibits hCG-induced steroidogenesis and proliferation of progenitor Leydig cells in mice
Authors: Oh Yeong Seok , Koh Il Kyoo , Choi Bomi , Gye Myung Chan
Published: March 2017

Oestrogen is an important regulator in reproduction. To understand the role of oestrogen receptor 1 (ESR1) in Leydig cells, we investigated the expression of ESR1 in mouse Leydig cells during postnatal development and the effects of oestrogen on steroidogenesis and proliferation of progenitor Leydig cells (PLCs). In Leydig cells, the ESR1 expression was low at birth, increased until postnatal day 14 at which PLCs were predominant, and then decreased until adulthood. In foetal Leydig cells, ESR1 immunoreactivity increased from birth to postnatal day 14. These suggest that ESR1 is a potential biomarker of Leydig cell development. In PLCs, 17β-estradiol and the ESR1-selective agonist propylpyrazoletriol suppressed human chorionic gonadotropin (hCG)-induced progesterone production and steroidogenic gene expression. The ESR2-selective agonist diarylpropionitrile did not affect steroidogenesis. In PLCs fromEsr1knockout mice, hCG-stimulated steroidogenesis was not suppressed by 17β-estradiol, suggesting that oestrogen inhibits PLC steroidogenesis via ESR1. 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile decreased bromodeoxyuridine uptake in PLCs in the neonatal mice. In cultured PLCs, 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile reduced hCG-stimulatedKi67andPcnamRNA expression and the number of KI67-positive PLCs, suggesting that oestrogen inhibits PLC proliferation via both ESR1 and ESR2. In PLCs, ESR1 mediates the oestrogen-induced negative regulation of steroidogenesis and proliferation.
Experimental Evaluation of Kidney Regeneration by Organ Scaffold Recellularization
Authors: Remuzzi Andrea , Figliuzzi Marina , Bonandrini Barbara , Silvani Sara , Azzollini Nadia , Nossa Roberta , Benigni Ariela , Remuzzi Giuseppe
Published: March 2017

The rising number of patients needing renal replacement therapy, alongside the significant clinical and economic limitations of current therapies, creates an imperative need for new strategies to treat kidney diseases. Kidney bioengineering through the production of acellular scaffolds and recellularization with stem cells is one potential strategy. While protocols for obtaining organ scaffolds have been developed successfully, scaffold recellularization is more challenging. We evaluated the potential of in vivo and in vitro kidney scaffold recellularization procedures. Our results show that acellular scaffolds implanted in rats cannot be repopulated with host cells, and in vitro recellularization is necessary. However, we obtained very limited and inconsistent cell seeding when using different infusion protocols, regardless of injection site. We also obtained experimental and theoretical data indicating that uniform cell delivery into the kidney scaffolds cannot be obtained using these infusion protocols, due to the permeability of the extracellular matrix of the scaffold. Our results highlight the major physical barriers that limit in vitro recellularization of acellular kidney scaffolds and the obstacles that must be investigated to effectively advance this strategy for regenerative medicine.
Human NDE1 splicing and mammalian brain development
Authors: Mosca S. , Raponi M. , Meneghello A. , Buratti E. , Woods C. G. , Baralle D.
Published: March 2017

Exploring genetic and molecular differences between humans and other close species may be the key to explain the uniqueness of our brain and the selective pressures under which it evolves. Recent discoveries unveiled the involvement of Nuclear distribution factor E-homolog 1 (NDE1) in human cerebral cortical neurogenesis and suggested a role in brain evolution; however the evolutionary changes involved have not been investigated. NDE1 has a different gene structure in human and mouse resulting in the production of diverse splicing isoforms. In particular, mouse uses the terminal exon 8 T, while Human uses terminal exon 9, which is absent in rodents. Through chimeric minigenes splicing assay we investigated the unique elements regulating NDE1 terminal exon choice. We found that selection of the terminal exon is regulated in a cell dependent manner and relies on gain/loss of splicing regulatory sequences across the exons. Our results show how evolutionary changes in cis as well as trans acting signals have played a fundamental role in determining NDE1 species specific splicing isoforms supporting the notion that alternative splicing plays a central role in human genome evolution, and possibly human cognitive predominance.
Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection
Authors: Lee Hyojin , Jeong Moonsup , Oh Jooyeon , Cho Youngran , Shen Xuefei , Stone John , Yan Jian , Rothkopf Zachary , Khan Amir S. , Cho Byung Mun , Park Young K. , Weiner David B. , Son Woo-Chan , Maslow Joel N.
Published: March 2017

Direct-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14th vaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection.
Edge magnetism of Heisenberg model on honeycomb lattice
Authors: Huang Wen-Min , Hikihara Toshiya , Lee Yen-Chen , Lin Hsiu-Hau
Published: March 2017

Edge magnetism in graphene sparks intense theoretical and experimental interests. In the previous study, we demonstrated the existence of collective excitations at the zigzag edge of the honeycomb lattice with long-ranged Néel order. By employing the Schwinger-boson approach, we show that the edge magnons remain robust even when the long-ranged order is destroyed by spin fluctuations. Furthermore, in the effective field-theory limit, the dynamics of the edge magnon is captured by the one-dimensional relativistic Klein-Gordon equation. It is intriguing that the boundary field theory for the edge magnon is tied up with its bulk counterpart. By performing density-matrix renormalization group calculations, we show that the robustness may be attributed to the closeness between the ground state and the Néel state. The existence of edge magnon is not limited to the honeycomb structure, as demonstrated in the rotated-square lattice with zigzag edges as well. The universal behavior indicates that the edge magnons may attribute to the uncompensated edges and can be detected in many two-dimensional materials.
Large-scale human skin lipidomics by quantitative, high-throughput shotgun mass spectrometry
Authors: Sadowski Tomasz , Klose Christian , Gerl Mathias J. , Wójcik-Maciejewicz Anna , Herzog Ronny , Simons Kai , Reich Adam , Surma Michal A.
Published: March 2017

The lipid composition of human skin is essential for its function; however the simultaneous quantification of a wide range of stratum corneum (SC) and sebaceous lipids is not trivial. We developed and validated a quantitative high-throughput shotgun mass spectrometry-based platform for lipid analysis of tape-stripped SC skin samples. It features coverage of 16 lipid classes; total quantification to the level of individual lipid molecules; high reproducibility and high-throughput capabilities. With this method we conducted a large lipidomic survey of 268 human SC samples, where we investigated the relationship between sampling depth and lipid composition, lipidome variability in samples from 14 different sampling sites on the human body and finally, we assessed the impact of age and sex on lipidome variability in 104 healthy subjects. We found sebaceous lipids to constitute an abundant component of the SC lipidome as they diffuse into the topmost SC layers forming a gradient. Lipidomic variability with respect to sampling depth, site and subject is considerable, and mainly accredited to sebaceous lipids, while stratum corneum lipids vary less. This stresses the importance of sampling design and the role of sebaceous lipids in skin studies.