bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperbaric oxygen therapy in malignant otitis externa: A systematic review of the literature
Authors: Byun Young Jae , Patel Jaimin , Nguyen Shaun A. , Lambert Paul R.
Published: May 2020

Objective

To review the role of adjuvant hyperbaric oxygen therapy (HBOT) in the treatment of malignant otitis externa (MOE).

Data sources

PubMed, Scopus, Web of Science, Science Direct, and Cochrane Library were searched for the following concepts: “hyperbaric oxygen” and “malignant or necrotizing otitis externa.”

Methods

Studies were included if they contained (1) patients with reported evidence of MOE, (2) employment of adjuvant HBOT, (3) details on patients’ medical condition, and (4) documented survival outcomes. Extracted information included patient demographics, underlying medical conditions, infectious etiology, signs and symptoms, medical and surgical treatments, duration of medical treatment, mean follow up time, HBOT setting, number of HBOT sessions, complications, survival rate, and all‐cause mortality.

Results

A total of 16 studies comprising 58 patients (mean age 68.0 years) were included. Diabetes was present in 94.7% of cases and Pseudomonas spp (64.3%) was the most common infectious agent. Cranial nerve VII was involved in 55.2% of cases. Overall, the disease cure rate with adjuvant HBOT was 91.4% and all‐cause mortality was 8.6%. Among those who had cranial nerve VII involvement, 72.0% had return of function and 93.8% of them survived.

Conclusion

HBOT may be an effective treatment option for refractory or advanced MOE but its efficacy remains unproven due to lack of strong scientific evidence. However, its therapeutic value should not be underestimated given good results and few adverse events reported in this study.
The post-politics of public-private security governance: An ideology critique of the complaints about Facebook
Authors: Jacobsen Jeppe T.
Published: May 2020

How do public protests emerge and become impotent? Inspired by Žižek's ideology critique, the article examines the ideological underpinnings of contemporary public-private security governance and suggests that worried, complaining subjects are a product of a dominant discourse of expert knowledge and technification. It then introduces three Žižekian dynamics that prevent protests from challenging the prevailing discourse – particularisation, ultra-politics, and cynicism – and illustrates these dynamic through a case study of the history of public complaints about Facebook. The article suggests that Facebook communicates through a discourse of technification whereby it constantly invents technological fixes unable to satisfy the complaints. The article further suggests that Facebook turning into a national security partner in the fight against terrorism online prevents complaints from becoming universalised by rendering even particularised privacy contestations illegitimate. This is reinforced, the article argues, by the subject's cynical enjoyment; that is, the ‘letting off steam’ on Facebook while criticising it.
Always in control? Sovereign states in cyberspace
Authors: Mainwaring Sarah
Published: May 2020

For well over twenty years, we have witnessed an intriguing debate about the nature of cyberspace. Used for everything from communication to commerce, it has transformed the way individuals and societies live. But how has it impacted the sovereignty of states? An initial wave of scholars argued that it had dramatically diminished centralised control by states, helped by a tidal wave of globalisation and freedom. These libertarian claims were considerable. More recently, a new wave of writing has argued that states have begun to recover control in cyberspace, focusing on either the police work of authoritarian regimes or the revelations of Edward Snowden. Both claims were wide of the mark. By contrast, this article argues that we have often misunderstood the materiality of cyberspace and its consequences for control. It not only challenges the libertarian narrative of freedom, it suggests that the anarchic imaginary of the Internet as a ‘Wild West’ was deliberately promoted by states in order to distract from the reality. The Internet, like previous forms of electronic connectivity, consists mostly of a physical infrastructure located in specific geographies and jurisdictions. Rather than circumscribing sovereignty, it has offered centralised authority new ways of conducting statecraft. Indeed, the Internet, high-speed computing, and voice recognition were all the result of security research by a single information hegemon and therefore it has always been in control.
Are Epistemic Norms Fundamentally Social Norms?
Authors: Henderson David
Published: May 2020

People develop and deploy epistemic norms – normative sensibilities in light of which they regulate both their individual and community epistemic practice. There is a similarity to folk's epistemic normative sensibilities – and it is by virtue of this that folk commonly can rely on each other, and even work jointly to produce systems of true beliefs – a kind of epistemic common good. Agents not only regulate their belief forming practices in light of these sensitivities, but they make clear to others that they approve or disapprove of practices as these accord with their sensibilities – they thus regulate the belief forming practices of others in an interdependent pursuit of a good – something on the order of a community stock of true beliefs. Such general observations suggest ways in which common epistemic norms function as social norms, as these are characterized by Cristina Bicchieri's (2006) discussion of various kinds of norms. I draw on this framework – together with an important elaboration in Bicchieri (2017) – as it affords an analysis of the various related ways in which normative sensibilities function in communities of interdependent agents. The framework allows one to probe how these normative sensibilities function in the various associated choice situations. I argue that epistemic norms are fundamentally social norms, and, at the same time, they also are widely shared sensibilities about state-of-the-art ways of pursuing projects of individual veritistic value. The two foundations suggest the analogy of an arch.
Framing the concept of invasive species “impact” within a management context
Authors: Barney Jacob N. , Tekiela Daniel R.
Published: May 2020

Governments and conservation organizations worldwide are motivated to manage invasive species due to quantified and perceived negative ecological and economic impacts invasive species impose. Thus, determining which species cause significant negative impacts, as well as clear articulation of those impacts, is critical to meet conservation priorities. This process of determining which species warrant management can be straightforward when there are clear negative impacts, such as dramatic reductions in native diversity. However, the majority of changes to ecosystem pools and fluxes cannot be readily categorized as ecologically negative or positive (e.g., lower soil pH). Additionally, diverse stakeholders may not all agree on impacts as negative. This complexity challenges our ability to simply and uniformly determine which species cause negative impact, and thus which species merit management, especially as we expand invader impacts to encompass a more holistic ecosystem perspective beyond biodiversity and consider stakeholder perspectives and priorities. Thus, we suggest impact be evaluated in a context that is dictated by governing policies or conservation/land management missions with the support of scientists. In other words, within each jurisdiction, populations are identified as causing negative impact based on the hierarchical governing policies and mission of that parcel. Framing negative impact in a management context has the advantages of (1) easily scaling from individual landscapes to geopolitical states; (2) better representing how managers practice, (3) reflecting invasive species as spatially contextual, not universal, and (4) allowing for flexibility with dynamic ecosystems undergoing global change. We hope that framing negative impact in an applied context aids management prioritization and achieving conservation goals.
The Effect of Rotation on Propagation of Rayleigh Wave in an Incompressible Monoclinic Elastic Solid
Authors: Kaur Baljinder , Singh Baljeet
Published: May 2020

In this paper, the Rayleigh wave propagation is investigated in rotating half-space of incompressible monoclinic elastic materials which are subjected to the impedance boundary conditions. In particular, the explicit secular equation of the Rayleigh wave is obtained. The main objective of this paper is to illustrate the dependence of dimensionless speed of Rayleigh wave on rotation, anisotropy and impedance parameters. An algorithm in MATLAB software is developed to solve the secular equation of Rayleigh wave. The speed of Rayleigh wave is plotted against rotation, anisotropy and impedance parameters.
Strong convergence of multivariate maxima
Authors: Falk Michael , Padoan Simone A. , Rizzelli Stefano
Published: May 2020

It is well known and readily seen that the maximum of n independent and uniformly on [0, 1] distributed random variables, suitably standardised, converges in total variation distance, as n increases, to the standard negative exponential distribution. We extend this result to higher dimensions by considering copulas. We show that the strong convergence result holds for copulas that are in a differential neighbourhood of a multivariate generalised Pareto copula. Sklar’s theorem then implies convergence in variational distance of the maximum of n independent and identically distributed random vectors with arbitrary common distribution function and (under conditions on the marginals) of its appropriately normalised version. We illustrate how these convergence results can be exploited to establish the almost-sure consistency of some estimation procedures for max-stable models, using sample maxima.
Branching processes in a random environment with immigration stopped at zero
Authors: Dyakonova Elena , Li Doudou , Vatutin Vladimir , Zhang Mei
Published: May 2020

A critical branching process with immigration which evolves in a random environment is considered. Assuming that immigration is not allowed when there are no individuals in the population, we investigate the tail distribution of the so-called life period of the process, i.e. the length of the time interval between the moment when the process is initiated by a positive number of particles and the moment when there are no individuals in the population for the first time.
A functional limit theorem for general shot noise processes
Authors: Iksanov Alexander , Rashytov Bohdan
Published: May 2020

By a general shot noise process we mean a shot noise process in which the counting process of shots is arbitrary locally finite. Assuming that the counting process of shots satisfies a functional limit theorem in the Skorokhod space with a locally Hölder continuous Gaussian limit process, and that the response function is regularly varying at infinity, we prove that the corresponding general shot noise process satisfies a similar functional limit theorem with a different limit process and different normalization and centering functions. For instance, if the limit process for the counting process of shots is a Brownian motion, then the limit process for the general shot noise process is a Riemann–Liouville process. We specialize our result for five particular counting processes. Also, we investigate Hölder continuity of the limit processes for general shot noise processes.
Great expectations: millennial lawyers and the structures of contemporary legal practice
Authors: Bleasdale Lydia , Francis Andrew
Published: May 2020

This paper presents the findings of the first empirical study of the experiences of young lawyers who have entered an increasingly uncertain profession following a highly competitive education and recruitment process. These ‘millennial lawyers’ are framed by a narrative of ‘difference’. This ‘difference’ is commonly articulated negatively and as a challenge to organisational and professional norms. However, our findings suggest a more complex reality. In its synthesis of work on structure and agency, with the temporal focus required by generational sociology, this paper advances an original approach to the analysis of organisational and professional change within contemporary legal practice. Drawing on new empirical research, it demonstrates that although our sample shares many field-level expectations, there is also considerable stress, unhappiness and discomfort. This is generated by a complex interaction between the lawyers’ expectations of practice, and the structuring properties of the field. Thus, the capacity for organisational and professional change is more comprehensively understood within a temporal frame. This paper challenges academic and professional paradigms of generational change within the legal field. It concludes with recommendations for legal educators and the profession which foreground the complexity of millennial lawyers’ expectations of practice.
A Populist Paradox? How Brexit Softened Anti-Immigrant Attitudes
Authors: Schwartz Cassilde , Simon Miranda , Hudson David , van-Heerde-Hudson Jennifer
Published: May 2020

Recent political contests across Europe and North America have been propelled by a wave of populist, anti-immigrant resentment, and it was widely expected that these populist victories would further fan the flames of xenophobia. This article reports the results of an experiment around the Brexit referendum, designed to test how populist victories shape anti-immigrant attitudes. The study finds that anti-immigrant attitudes actuallysoftenedafter the Brexit referendum, among both Leave and Remain supporters, and these effects persisted for several months. How could a right-wing, populist victory soften anti-immigrant attitudes? The authors use causal mediation analysis to understand this ‘populist paradox’. Among Leavers, a greater sense of control over immigration channelled the effects of the Brexit outcome onto anti-immigrant attitudes. Individuals' efforts to distance themselves from accusations of xenophobia and racism explains the softening of attitudes towards immigration observed amongbothLeavers and Remainers.
A simple and efficient transfection protocol for Cryptosporidium parvum using Polyethylenimine (PEI) and Octaarginine
Authors: Nguyen-Ho-Bao Tran , Berberich Maxi , Zheng Wanpeng , Seebach Dieter , Daugschies Arwid , Kamena Faustin
Published: May 2020

The transfection of Cryptosporidium represents a major challenge, and current protocols are based on electroporation of freshly excysted sporozoites using a rather large amount of plasmid DNA which typically has a very poor yield. In this study, we report a fast and simple protocol for transfection of Cryptosporidium parvum that takes advantage of the DNA condensing power of the poly cationic polymer polyethylenimine (PEI) and the gene delivery property of the short cell-penetrating peptide octaarginine. Our novel protocol requires a very low amount of plasmid DNA and does not necessitate special laboratory equipment to be performed. Transfection appears to be more efficient in oocysts just triggered for excystation than the excysted sporozoites. Altogether, the application of octaarginine with PEI allows efficient transfection. To the best of our knowledge, this is the first report on an electroporation-free protocol for transfection of sporozoites of a Cryptosporidium species.
Intestinal parasites in rural communities in Nan Province, Thailand: changes in bacterial gut microbiota associated with minute intestinal fluke infection
Authors: Prommi Ajala , Prombutara Pinidphon , Watthanakulpanich Dorn , Adisakwattana Poom , Kusolsuk Teera , Yoonuan Tippayarat , Poodeepiyasawat Akkarin , Homsuwan Nirundorn , Prummongkol Samreong , Tanita Malee , Rattanapikul Sungkhom , Thinphovong Chuanphot , Kritiyakan Anamika , Morand Serge , Chaisiri Kittipong
Published: May 2020

Gastrointestinal helminth infection likely affects the gut microbiome, in turn affecting host health. To investigate the effect of intestinal parasite status on the gut microbiome, parasitic infection surveys were conducted in communities in Nan Province, Thailand. In total, 1047 participants submitted stool samples for intestinal parasite examination, and 391 parasite-positive cases were identified, equating to an infection prevalence of 37.3%. Intestinal protozoan species were less prevalent (4.6%) than helminth species. The most prevalent parasite was the minute intestinal fluke Haplorchis taichui (35.9%). Amplicon sequencing of 16S rRNA was conducted to investigate the gut microbiome profiles of H. taichui-infected participants compared with those of parasite-free participants. Prevotella copri was the dominant bacterial operational taxonomic unit (OTU) in the study population. The relative abundance of three bacterial taxa, Ruminococcus, Roseburia faecis and Veillonella parvula, was significantly increased in the H. taichui-infected group. Parasite-negative group had higher bacterial diversity (α diversity) than the H. taichui-positive group. In addition, a significant difference in bacterial community composition (β diversity) was found between the two groups. The results suggest that H. taichui infection impacts the gut microbiome profile by reducing bacterial diversity and altering bacterial community structure in the gastrointestinal tract.
Long-term (35 years) cryopreservation of Echinococcus multilocularis metacestodes
Authors: Laurimäe Teivi , Kronenberg Philipp A. , Alvarez Rojas Cristian A. , Ramp Theodor W. , Eckert Johannes , Deplazes Peter
Published: May 2020

The metacestode of Echinococcus multilocularis is the etiological agent of alveolar echinococcosis. The metacestode stage used for research is maintained in rodents by serial passages. In order to determine whether cryopreservation of E. multilocularis metacestodes would be suitable for long-term maintenance and replace serial passages, isolates of different geographic origin were cryopreserved in 1984–1986. The aim of the current study was to test the viability of cryopreserved isolates following long-term cryopreservation (up to 35 years) and to determine the phylogenetic clades these isolates belonged to. Cryopreserved isolates were tested for viability in vitro and in vivo in gerbils. In vitro results of 5 isolates indicated protoscolex survival in 13 of 17 experiments (76%) and metacestode survival in 5 of 12 (42%) in vivo experiments. In vivo results showed ‘abortive lesions’ in 13 of the 36 animals, 15 were negative and 8 harboured proliferating metacestode tissue containing protoscoleces. Genetic analysis confirmed the isolates belonged to European, Asian and North-American clades. In conclusion, the results of the current study indicate that metacestodes of E. multilocularis are able to survive long-term cryopreservation. Therefore, cryopreservation is a suitable method for long-term storage of E. multilocularis metacestode isolates and reduces the number of experimental animals.
Remembering the past, enhancing the present and sharing the future: a qualitative study of the impact of film screenings in care home communities
Authors: Breckenridge Jenna P. , Kroll Thilo , Wylie Gavin , Salzberg Ana
Published: May 2020

Many care home residents lack opportunities for meaningful activity and social connection, resulting in poor physical and emotional wellbeing. Providing residents with varied activities and social opportunities can improve their quality of life. In this paper, we examine the potential for film to provide a meaningful, social activity. The limited existing research on film in care homes has predominantly examined the use of film clips and materials in stimulating reminiscence for people with dementia. In this paper, we adopt a broader, trans-disciplinary perspective of film, drawing on evidence from Film Studies that shared spectatorship has social and emotional benefits for the viewer. We offer the first qualitative study of care home residents’ social, emotional and embodied engagement with feature-length film and identify the key benefits of film in this setting. We ran social film screenings in two Scottish care homes over six weeks. Underpinned by psycho-cinematic theory, we collected and analysed observational data alongside interviews with care home staff and discussion groups with residents. Our findings identified three ways in which film screenings benefit residents and supports social connection: prompting reminiscence; enhancing residents’ experiences in the present; and creating a shared future and intergenerational connections. The paper offers useful insights into the rich potential for film to enhance the care home community, facilitate social connectivity and promote resident wellbeing.
Migrant aged-care workers in Australia: do they have poorer-quality jobs than their locally born counterparts?
Authors: Charlesworth Sara , Isherwood Linda
Published: May 2020

Migrants make up a significant and growing proportion of the aged-care workforce in Australia. Using data from the 2016 National Aged Care Workforce Census and Survey, we investigate employment conditions for Australian-born and overseas-born frontline workers working in residential and home-based aged care, focusing on two key poor job quality indicators. We find that migrant home care workers from non-English-speaking background (NESB) countries are the most likely to be employed on a casual basis and to report hours-related underemployment. Migrant residential care workers from English-speaking background (ESB) countries are more likely to be casual while NESB migrants are more likely to be underemployed. Controlling for a range of employment and socio-demographic characteristics, we find that being an NESB migrant is significantly associated with both casual status and underemployment. Generally, while this association lessens with years spent in Australia, exposure to casual employment is amplified over time for NESB migrants in the residential sector. Holding a temporary visa increased the likelihood of casual employment for residential care workers and underemployment for home care workers. Working for a for-profit employer was also associated with poorer job quality. Further policy shifts in Australia towards temporary migration and increased marketisation of aged care may impact on the working conditions of migrant aged-care workers.
Staging Discord: Nordic Corporatism in the European Conservation Year 1970
Authors: Notaker Hallvard
Published: May 2020

This article shows how corporatism in the Nordic countries helped shape the ‘ecological turn’ as governments and conservationist associations co-organised the Council of Europe's ‘European Conservation Year 1970’. The national programmes came to present highly diverging levels of discord, as this nascent policy field channeled challenges to the premise of economic growth. Cross-national comparisons highlight the importance of variations in the institutional maturity of environmental administrations as well as in the power afforded to industrial representatives. Danish, Swedish and Norwegian archival sources illuminate negotiations between governments and private associations, contributing to an in-depth analysis of a rarely researched transnational event.
Saving for retirement: rules of thumb
Authors: Hyams S. D. , Smith A. E. , Squirrell C. M. , Warren G. J. , Warren O. H. , Willetts P. J.
Published: May 2020

Rules of thumb (RoTs) are proposed as a means of promoting higher levels of Defined Contribution (DC) pension saving and to help stimulate debate about the high and uncertain cost of pension provision, leading to the development of solutions. The Lifetime Pension Contribution (LPC) tells young people what pension contribution is required over a full working life to achieve a decent retirement income, calculated as 23% of average UK earnings. Another RoT is that each 1% of earnings provides a pension of 1.5% of earnings. Other RoTs show how costs vary by retirement age and if the saverʼs retirement planning is on track. The current high cost of pensions is partly due to low interest rates and the inefficiencies of the DC market, with inadequate bulk purchasing power and risk sharing. RoTs might help encourage higher employer contributions, either through automatic enrolment or on a voluntary basis.
Dicamba translocation in soybean and accumulation in seed
Authors: Zaccaro Maria Leticia M. , Norsworthy Jason K. , Brabham Chad B.
Published: May 2020

The dicamba-resistant cropping system was developed to be used as a tool to control multiple-resistant weed species, particularly Palmer amaranth (Amaranthus palmeri S. Watson). However, dicamba applications have resulted in off-target movement of the herbicide to susceptible neighboring vegetation, with frequent damage to non–dicamba resistant soybean [Glycine max (L.) Merr.]. Pod malformation and subsequent auxin-like injury to progeny is common when parent soybean plants are exposed to the herbicide post-flowering. Yet no publication to date has conveyed the presence of dicamba in seed. The objective of this study was to determine whether dicamba exists and at what quantities inside soybean seed following a low-dose exposure in the pod-filling stage using radiolabeled herbicide as a tracer. Non–dicamba resistant soybean plants were grown in the greenhouse until the pod-filling growth stage and then treated with 2.8 g ae ha−1 of dicamba (1/200 of the recommended rate of 560 g ae ha−1). Immediately afterward, [14C]dicamba (approximately 6.4 kBq per plant) was applied to the adaxial surface of one trifoliate leaf located in the midportion of each plant. The greatest amount of [14C]dicamba recovered was in seeds and in pods, and these plant parts accumulated 44% and 38% of the total absorbed, respectively. Chromatography results showed that the totality of the [14C]dicamba present in the soybean seeds was in the phytotoxic form, except for a single sample, in which one metabolite was detected (possibly 5-hydroxy dicamba). Precautions should be taken to avoid dicamba exposure to sensitive soybean fields, especially those dedicated to seed production, as this may result in low seed quality and symptomology on progeny plants.
High‐Resolution Proxy Records From Two Simultaneously Grown Stalagmites From Zoolithencave (Southeastern Germany) and their Potential for Palaeoclimate Reconstruction
Authors: Riechelmann Dana F. C. , Riechelmann Sylvia , Wassenburg Jasper A. , Fohlmeister Jens , Schöne Bernd R. , Jochum Klaus Peter , Richter Detlev K. , Scholz Denis
Published: May 2020

Two small annually laminated stalagmites from Zoolithencave (southeastern Germany) grew between CE 1821 and 1970 (Zoo‐rez‐1) and CE 1835 and 1970 (Zoo‐rez‐2), respectively. Trace element concentrations were determined by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA‐ICP‐MS). Samples for δ13C and δ18O analyses were micromilled on annual and subannual resolution. Soil and host rock samples were analyzed by X‐Ray Diffraction (XRD) and their elemental concentrations determined via inductively coupled plasma optical emission spectrometer (ICP‐OES). Trace element concentrations in the stalagmites show two groups in the principal component analyses: one with Mg, Ba, and Sr and another with Y, P, and Al, respectively. The second group reflects the content of detrital material. Increased weathering of soil minerals seems to have a strong influence on the silicate/carbonate weathering ratio controlling the variability of Mg, Ba, and Sr. Meteorological and Global Network of Isotopes in Precipitation (GNIP) station data were used to calculate the δ18O values of the drip water (infiltration‐weighted, mean annual, and the mean of the winter precipitation δ18O values) as well as the corresponding speleothem calcite. The δ18O values calculated by the infiltration‐weighted model show similar patterns and amplitudes as the measured δ18O values of the two stalagmites. This suggests that the δ18O values of speleothem calcite reflect the δ18O values of infiltration‐weighted annual precipitation, which zis related to mean annual temperature, resulting in a significant correlation between mean annual temperature and the measured δ18O values of stalagmite Zoo‐rez‐2. This relationship could potentially be used for quantitative climate reconstruction in the future by extending the time series back in time with further stalagmites from Zoolithencave.
On Parameterizing Soil Evaporation in a Direct Remote Sensing Model of ET: PT‐JPL
Authors: Marshall Michael , Tu Kevin , Andreo Veronica
Published: May 2020

Remote sensing models that measure evapotranspiration directly from the Penman‐Monteith or Priestley‐Taylor equations typically estimate the soil evaporation component over large areas using coarse spatial resolution relative humidity (RH) from geospatial climate datasets. As a result, the models tend to underperform in dry areas at local scales where moisture status is not well represented by surrounding areas. Earth observation sensors that monitor large‐scale global dynamics (e.g., MODIS) afford comparable spatial coverage and temporal frequency, but at a higher spatial resolution than geospatial climate datasets. In this study, we compared soil evaporation parameterized with optical and thermal indices derived from MODIS to RH‐based soil evaporation as implemented in the Priestley Taylor‐Jet Propulsion Laboratory (PT‐JPL) model. We evaluated the parameterizations by subtracting PT‐JPL transpiration from observation‐based flux tower evapotranspiration in agricultural fields across the contiguous United States. We compared the apparent thermal inertia (ATI) index, land surface water index (LSWI), normalized difference water index (NDWI), and a new index derived from red and shortwave infrared bands (soil moisture divergence index [SMDI]). Relationships were significant at the 95% confidence band. LSWI and SMDI explained 18–33% of variance in 8‐day soil evaporation. This led to a 3–11% increase in explained ET variance. LSWI and SMDI tended to perform better at the irrigated sites than RH. LSWI and SMDI led to markedly better performance over other indices at a seasonal time step. L‐band microwave backscatter can penetrate clouds and can distinguish soil from canopy moisture content. We are presently fusing red‐SWIR‐RADAR to improve soil evaporation estimation.
Bayesian modeling reveals host genetics associated with rumen microbiota jointly influence methane emission in dairy cows
Authors: Zhang Qianqian , Difford Gareth , Sahana Goutam , Løvendahl Peter , Lassen Jan , Lund Mogens Sandø , Guldbrandtsen Bernt , Janss Luc
Published: May 2020

Reducing methane emissions from livestock production is of great importance for the sustainable management of the Earth’s environment. Rumen microbiota play an important role in producing biogenic methane. However, knowledge of how host genetics influences variation in ruminal microbiota and their joint effects on methane emission is limited. We analyzed data from 750 dairy cows, using a Bayesian model to simultaneously assess the impact of host genetics and microbiota on host methane emission. We estimated that host genetics and microbiota explained 24% and 7%, respectively, of variation in host methane levels. In this Bayesian model, one bacterial genus explained up to 1.6% of the total microbiota variance. Further analysis was performed by a mixed linear model to estimate variance explained by host genomics in abundances of microbial genera and operational taxonomic units (OTU). Highest estimates were observed for a bacterial OTU with 33%, for an archaeal OTU with 26%, and for a microbial genus with 41% heritability. However, after multiple testing correction for the number of genera and OTUs modeled, none of the effects remained significant. We also used a mixed linear model to test effects of individual host genetic markers on microbial genera and OTUs. In this analysis, genetic markers inside host genes ABS4 and DNAJC10 were found associated with microbiota composition. We show that a Bayesian model can be utilized to model complex structure and relationship between microbiota simultaneously and their interaction with host genetics on methane emission. The host genome explains a significant fraction of between-individual variation in microbial abundance. Individual microbial taxonomic groups each only explain a small amount of variation in methane emissions. The identification of genes and genetic markers suggests that it is possible to design strategies for breeding cows with desired microbiota composition associated with phenotypes.
Correction: High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation
Authors: Buhler Stéphane , Baldomero Helen , Ferrari-Lacraz Sylvie , Nunes José Manuel , Sanchez-Mazas Alicia , Massouridi-Levrat Stravroula , Heim Dominik , Halter Jörg , Nair Gayathri , Chalandon Yves , Schanz Urs , Güngör Tayfun , Nicoloso Grazia , Tiercy Jean-Marie , Passweg Jakob , Villard Jean
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The heterocyclic compound Tempol inhibits the growth of cancer cells by interfering with glutamine metabolism
Authors: Ye Shuangyan , Xu Pengfei , Huang Mengqiu , Chen Xi , Zeng Sisi , Wang Qianli , Chen Jianping , Li Keyi , Gao Wenwen , Liu Ruiyuan , Liu Jingxian , Shao Yihao , Zhang Hui , Xu Yang , Zhang Qianbing , Zhong Zhuo , Wei Zibo , Wang Jiale , Hao Bingtao , Huang Wenhua , Liu Qiuzhen
Published: May 2020

Tempol (4-hydroxy-2,2,6,6-Tetramethylpiperidine-1-oxyl, TPL), a nitroxide compound, inhibits proliferation and increases the vulnerability of cancer cells to apoptosis induced by cytotoxic agents. However, the molecular mechanism of TPL inhibiting cancer cell proliferation has not been fully understood. In this study, we evaluated the metabolic effect of TPL on cancer cells and explored its cancer therapeutic potential. Extracellular flow assays showed that TPL inhibited cellular basal and maximal oxygen consumption rates of mitochondrial. 13C metabolic flux analysis showed that TPL treatment had minimal effect on glycolysis. However, we found that TPL inhibits glutamine metabolism by interfering with the oxidative tricarboxylic acid cycle (TCA) process and reductive glutamine process. We found that the inhibitory effect of TPL on metabolism occurs mainly on the step from citrate to α-ketoglutarate or vice versa. We also found that activity of isocitrate dehydrogenase IDH1 and IDH2, the key enzymes in TCA, were inhibited by TPL treatment. In xenograft mouse model, TPL treatment reduced tumor growth by inhibiting cellular proliferation of xenograft tumors. Thus, we provided a mechanism of TPL inhibiting cancer cell proliferation by interfering with glutamine utilization that is important for survival and proliferation of cancer cells. The study may help the development of a therapeutic strategy of TPL combined with other anticancer medicines.
anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells
Authors: Liu Shaochuan , Qin Tingting , Liu Zhujun , Wang Jing , Jia Yanan , Feng Yingfang , Gao Yuan , Li Kai
Published: May 2020

Aberrant vascular network is a hallmark of cancer. However, the role of vascular endothelial cells (VECs)-expressing PD-L1 in tumor immune microenvironment and antiangiogenic therapy remains unclear. In this study, we used the specimens of cancer patients for immunohistochemical staining to observe the number of PD-L1+ CD34+ VECs and infiltrated immune cells inside tumor specimens. Immunofluorescence staining and flow cytometry were performed to observe the infiltration of CD8+ T cells and FoxP3+ T cells in tumor tissues. Here, we found that PD-L1 expression on VECs determined CD8+ T cells’, FoxP3+ T cells’ infiltration, and the prognosis of patients with lung adenocarcinoma. Anlotinib downregulated PD-L1 expression on VECs through the inactivation of AKT pathway, thereby improving the ratio of CD8/FoxP3 inside tumor and remolding the immune microenvironment. In conclusion, our results demonstrate that PD-L1 high expression on VECs inhibits the infiltration of CD8+ T cells, whereas promotes the aggregation of FoxP3+ T cells into tumor tissues, thus becoming an “immunosuppressive barrier”. Anlotinib can ameliorate the immuno-microenvironment by downregulating PD-L1 expression on VECs to inhibit tumor growth.
Activation and targeting of ATG8 protein lipidation
Authors: Martens Sascha , Fracchiolla Dorotea
Published: May 2020

ATG8 family proteins are evolutionary conserved ubiquitin-like modifiers, which become attached to the headgroup of the membrane lipid phosphatidylethanolamine in a process referred to as lipidation. This reaction is carried out analogous to the conjugation of ubiquitin to its target proteins, involving the E1-like ATG7, the E2-like ATG3 and the E3-like ATG12–ATG5–ATG16 complex, which determines the site of lipidation. ATG8 lipidation is a hallmark of autophagy where these proteins are involved in autophagosome formation, the fusion of autophagosomes with lysosomes and cargo selection. However, it has become evident that ATG8 lipidation also occurs in processes that are not directly related to autophagy. Here we discuss recent insights into the targeting of ATG8 lipidation in autophagy and other pathways with special emphasis on the recruitment and activation of the E3-like complex.
Mendelian neurodegenerative disease genes involved in autophagy
Authors: Stamatakou Eleanna , Wróbel Lidia , Hill Sandra Malmgren , Puri Claudia , Son Sung Min , Fujimaki Motoki , Zhu Ye , Siddiqi Farah , Fernandez-Estevez Marian , Manni Marco M. , Park So Jung , Villeneuve Julien , Rubinsztein David Chaim
Published: May 2020

The lysosomal degradation pathway of macroautophagy (herein referred to as autophagy) plays a crucial role in cellular physiology by regulating the removal of unwanted cargoes such as protein aggregates and damaged organelles. Over the last five decades, significant progress has been made in understanding the molecular mechanisms that regulate autophagy and its roles in human physiology and diseases. These advances, together with discoveries in human genetics linking autophagy-related gene mutations to specific diseases, provide a better understanding of the mechanisms by which autophagy-dependent pathways can be potentially targeted for treating human diseases. Here, we review mutations that have been identified in genes involved in autophagy and their associations with neurodegenerative diseases.
Natural polyphenol assisted delivery of single-strand oligonucleotides by cationic polymers
Authors: Shen Wanwan , Wang Ruojun , Fan Qianqian , Li Yiwen , Cheng Yiyun
Published: May 2020

Single-strand oligonucleotides provide promising potential as new therapeutics towards various diseases. However, the efficient delivery of oligonucleotide therapeutics is still challenging due to their susceptibility to nuclease degradation and the lack of effective carriers for condensation. In this study, we reported the use of natural polyphenol to facilitate the condensation of single-strand oligonucleotides by cationic polymers. Green tea catechin complexed with single-strand oligonucleotides to form anionic nanoparticles, which were further coated by low molecular weight cationic polymers to increase their cell internalization. The resulting core-shell structured nanoparticles, so-called green nanoparticles (GNPs), showed improved cargo stability, and achieved high efficiency in the delivery of several types of single-strand oligonucleotides including antisense oligonucleotides, anti-miRNA, and DNAzyme. This study provides a facile strategy for the efficient delivery of single-strand oligonucleotides.
A human monoclonal antibody blocking SARS-CoV-2 infection
Authors: Wang Chunyan , Li Wentao , Drabek Dubravka , Okba Nisreen M. A. , van Haperen Rien , Osterhaus Albert D. M. E. , van Kuppeveld Frank J. M. , Haagmans Bart L. , Grosveld Frank , Bosch Berend-Jan
Published: May 2020

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.
Challenges in returning results in a genomic medicine implementation study: the Return of Actionable Variants Empirical (RAVE) study
Authors: Kochan David C. , Winkler Erin , Lindor Noralane , Shaibi Gabriel Q. , Olson Janet , Caraballo Pedro J. , Freimuth Robert , Pacyna Joel E. , Breitkopf Carmen Radecki , Sharp Richard R. , Kullo Iftikhar J.
Published: May 2020

To inform the process of returning results in genome sequencing studies, we conducted a quantitative and qualitative assessment of challenges encountered during the Return of Actionable Variants Empiric (RAVE) study conducted at Mayo Clinic. Participants (n = 2535, mean age 63 ± 7, 57% female) were sequenced for 68 clinically actionable genes and 14 single nucleotide variants. Of 122 actionable results detected, 118 were returnable; results were returned by a genetic counselor—86 in-person and 12 by phone. Challenges in returning actionable results were encountered in a significant proportion (38%) of the cohort and were related to sequencing and participant contact. Sequencing related challenges (n = 14), affecting 13 participants, included reports revised based on clinical presentation (n = 3); reports requiring corrections (n = 2); mosaicism requiring alternative DNA samples for confirmation (n = 3); and variant re-interpretation due to updated informatics pipelines (n = 6). Participant contact related challenges (n = 44), affecting 38 participants, included nonresponders (n = 20), decedents (n = 1), and previously known results (n = 23). These results should be helpful to investigators preparing for return of results in large-scale genomic sequencing projects.
Pairing mechanism in multiband superconductors
Authors: Huang Wen-Min , Lin Hsiu-Hau
Published: May 2020

It has been a long-standing puzzle why electrons with repulsive interactions can form pairs in unconventional superconductors. Here we develop an analytic solution for renormalization group analysis in multiband superconductors, which agrees with the numerical results exceedingly well. The analytic solution allows us to construct soluble effective theory and answers the pairing puzzle: electrons form pairs resonating between different bands to compensate the energy penalty for bring them together, just like the resonating chemical bonds in benzene. The analytic solutions allow us to explain the peculiar features of critical temperatures, spin uctuations in unconventional superconductors and can be generalized to cuprates where the notion of multibands is replaced by multipatches in momentum space.
Snakes elicit specific neural responses in the human infant brain
Authors: Bertels J. , Bourguignon M. , de Heering A. , Chetail F. , De Tiège X. , Cleeremans A. , Destrebecqz A.
Published: May 2020

Detecting predators is essential for survival. Given that snakes are the first of primates’ major predators, natural selection may have fostered efficient snake detection mechanisms to allow for optimal defensive behavior. Here, we provide electrophysiological evidence for a brain-anchored evolved predisposition to rapidly detect snakes in humans, which does not depend on previous exposure or knowledge about snakes. To do so, we recorded scalp electrical brain activity in 7- to 10-month-old infants watching sequences of flickering animal pictures. All animals were presented in their natural background. We showed that glancing at snakes generates specific neural responses in the infant brain, that are higher in amplitude than those generated by frogs or caterpillars, especially in the occipital region of the brain. The temporal dynamics of these neural responses support that infants devote increased attention to snakes than to non-snake stimuli. These results therefore demonstrate that a single fixation at snakes is sufficient to generate a prompt and large selective response in the infant brain. They argue for the existence in humans of an inborn, brain-anchored mechanism to swiftly detect snakes based on their characteristic visual features.
Differences in intracellular localisation of ANKH mutants that relate to mechanisms of calcium pyrophosphate deposition disease and craniometaphyseal dysplasia
Authors: Vijen Sunny , Hawes Chris , Runions John , Russell R. Graham G. , Wordsworth B. Paul , Carr Andrew J. , Pink Ryan C. , Zhang Yun
Published: May 2020

ANKH mutations are associated with calcium pyrophosphate deposition disease and craniometaphyseal dysplasia. This study investigated the effects of these ANKH mutants on cellular localisation and associated biochemistry. We generated four ANKH overexpression-plasmids containing either calcium pyrophosphate deposition disease or craniometaphyseal dysplasia linked mutations: P5L, E490del and S375del, G389R. They were transfected into CH-8 articular chondrocytes and HEK293 cells. The ANKH mutants dynamic differential localisations were imaged and we investigated the interactions with the autophagy marker LC3. Extracellular inorganic pyrophosphate, mineralization, ENPP1 activity expression of ENPP1, TNAP and PIT-1 were measured. P5L delayed cell membrane localisation but once recruited into the membrane it increased extracellular inorganic pyrophosphate, mineralization, and ENPP1 activity. E490del remained mostly cytoplasmic, forming punctate co-localisations with LC3, increased mineralization, ENPP1 and ENPP1 activity with an initial but unsustained increase in TNAP and PIT-1. S375del trended to decrease extracellular inorganic pyrophosphate, increase mineralization. G389R delayed cell membrane localisation, trended to decrease extracellular inorganic pyrophosphate, increased mineralization and co-localised with LC3. Our results demonstrate a link between pathological localisation of ANKH mutants with different degrees in mineralization. Furthermore, mutant ANKH functions are related to synthesis of defective proteins, inorganic pyrophosphate transport, ENPP1 activity and expression of ENPP1, TNAP and PIT-1.
Molecular insights and cell cycle assessment upon exposure to Chaga (Inonotus obliquus) mushroom polysaccharides in zebrafish (Danio rerio)
Authors: Eid Jehane Ibrahim , Das Biswadeep
Published: May 2020

Chaga (Inonotus obliquus) mushroom is considered as one of the most powerful antioxidants across the world. Though the therapeutic effects of Chaga components are well characterized in vitro, the in vivo developmental effects are not elucidated in detail. In this study, we assessed the in vivo developmental effects of Chaga polysaccharides in zebrafish, along with revealing the effects on cell cycle and apoptosis. Chaga mushroom polysaccharides comprised xylulose, rhamnose, mannose, glucose, inositol, and galactose, in addition to phenolic compounds; zebrafish embryos exhibited normal embryonic development upon transient exposure to Chaga extract (24 hours). Most embryos (>90%) were found to be healthy even at high concentrations (5 mg/mL). In addition, staining with the DNA binding dye, acridine orange showed that Chaga polysaccharides alleviated oxidative stress. Flow cytometric analysis using H2DCFDA that specifically binds to cells with fragmented DNA showed significantly reduced levels of intracellular reactive oxygen species (ROS) (p < 0.05), which in turn reduced apoptosis in the developing embryos. Cell cycle analysis by measuring the DNA content using flow cytometry revealed that Chaga polysaccharides moderately arrested the cells at G1 stage, thereby inhibiting cell proliferation that can be further explored in cancer studies. Overall, transient exposure of Chaga polysaccharide extract reduced intracellular ROS and assisted in the normal development of zebrafish.