bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between clinical outcomes and empirical antibiotic therapy in patients with community-onset Gram-negative bloodstream infections: a cohort study from a large teaching hospital
Authors: Aryee A. , Rockenschaub P. , Gill M. J. , Hayward A. , Shallcross L.
Published: September 2020

Antibiotic-resistant Gram-negative bacteraemias (GNB) are increasing in incidence. We aimed to investigate the impact of empirical antibiotic therapy on clinical outcomes by carrying out an observational 6-year cohort study of patients at a teaching hospital with community-onset Escherichia coli bacteraemia (ECB), Klebsiella pneumoniae bacteraemia (KPB) and Pseudomonas aeruginosa bacteraemia (PsAB). Antibiotic therapy was considered concordant if the organism was sensitive in vitro and discordant if resistant. We estimated the association between concordant vs. discordant empirical antibiotic therapy on odds of in-hospital death and ICU admission for KPB and ECB. Of 1380 patients, 1103 (79.9%) had ECB, 189 (13.7%) KPB and 88 (6.4%) PsAB. Discordant therapy was not associated with increased odds of either outcome. For ECB, severe illness and non-urinary source were associated with increased odds of both outcomes (OR of in-hospital death for non-urinary source 3.21, 95% CI 1.73–5.97). For KPB, discordant therapy was associated with in-hospital death on univariable but not multivariable analysis. Illness severity was associated with increased odds of both outcomes. These findings suggest broadening of therapy for low-risk patients with community-onset GNB is not warranted. Future research should focus on the relationship between patient outcomes, clinical factors, infection focus and causative organism and resistance profile.
Ecologic association between influenza and COVID-19 mortality rates in European countries
Authors: Petti S. , Cowling B. J.
Published: September 2020

Ecologic studies investigating COVID-19 mortality determinants, used to make predictions and design public health control measures, generally focused on population-based variable counterparts of individual-based risk factors. Influenza is not causally associated with COVID-19, but shares population-based determinants, such as similar incidence/mortality trends, transmission patterns, efficacy of non-pharmaceutical interventions, comorbidities and underdiagnosis. We investigated the ecologic association between influenza mortality rates and COVID-19 mortality rates in the European context. We considered the 3-year average influenza (2014–2016) and COVID-19 (31 May 2020) crude mortality rates in 34 countries using EUROSTAT and ECDC databases and performed correlation and regression analyses. The two variables – log transformed, showed significant Spearman's correlation ρ = 0.439 (P = 0.01), and regression coefficients, b = 0.743 (95% confidence interval, 0.272–1.214; R2 = 0.244; P = 0.003), b = 0.472 (95% confidence interval, 0.067–0.878; R2 = 0.549; P = 0.02), unadjusted and adjusted for confounders (population size and cardiovascular disease mortality), respectively. Common significant determinants of both COVID-19 and influenza mortality rates were life expectancy, influenza vaccination in the elderly (direct associations), number of hospital beds per population unit and crude cardiovascular disease mortality rate (inverse associations). This analysis suggests that influenza mortality rates were independently associated with COVID-19 mortality rates in Europe, with implications for public health preparedness, and implies preliminary undetected SARS-CoV-2 spread in Europe.
Being an Archdeacon: A Coaching Model
Authors: Boakes Norman
Published: September 2020

Considering the importance of their role in the life of the Church of England and the Church in Wales, there is not much written about the role of archdeacons. In her recent article in the January 2019 issue of thisJournal, Jane Steen focused on the legal aspect of the role of archdeacons, and reflected on how they play a key role in shaping the Church and its ministry, delighting in its beauty and rejoicing in its well-being. In this article, the recently retired training, development and support officer for archdeacons reflects on the nature of the role and, in the light of that, on the way in which it might best be carried out. Believing that process is at least as important as outcome, and that good processes lead to better outcomes, he argues that coaching provides a useful model to enable archdeacons to exercise their ministries most effectively and promote both the mission and the well-being of the Church. It is also, he argues, a better reflection of Anglican theology.
Do We Still Need the Faculty System?
Authors: George Charles
Published: September 2020

Following a brief history and explanation of the extent and role of the faculty jurisdiction, the article considers various reviews of its working, and that of the ecclesiastical exemption, starting with the Report of the Faculty Jurisdiction Commission in 1984 and the Newman Report in 1997. The Department for Culture, Media and Sport stated in 2005 that the operation of the ecclesiastical exemption would be monitored periodically, and in 2010 that it would be kept under review to ensure the required standards of protection were maintained. The article argues that a no-holds-barred review of the faculty system would now be appropriate, with a view to achieving a less cumbrous structural apparatus, with a markedly less restrictive approach to changes within unlisted churches and a more rigorous and expert approach to changes affecting listed churches.
February–May 2020
Authors: Cranmer Frank
Published: September 2020

Much of the period under review was dominated by the impact of the Coronavirus (COVID-19) pandemic. Advice both from the Government and from the Churches was at first fairly muted. On 10 February the Government introduced the Health Protection (Coronavirus) Regulations 2020, which applied to England only and which made provision for detention for screening for the virus under certain conditions and imposing restrictions on individuals to limit the risk of those with the infection contaminating others; however, at the same time, the Prime Minister was urging people to remain ‘confident and calm’. Similarly, an Ad Clerum on hygiene at Holy Communion issued by the Bishop of Peterborough on 20 February deprecated the practices of intinction and of receiving the bread directly on to the tongue but did not recommend the ending of communion in both kinds.
Papageorgiou and Others v Greece: Exemption from a Mandatory Course in Religion and the Art of Reading between the Lines
Authors: Brzozowski Wojciech
Published: September 2020

Religious education is probably one of the most attractive topics in law and religious studies – a truly bottomless pit which, every now and then, reveals new questions and new challenges. The most recent judgment of the European Court of Human Rights (ECtHR) concerning this matter is the one delivered on 31 October 2019 in the case of Papageorgiou and others. The judgment only became final at the end of January 2020, under Article 44(2) of the European Convention of Human Rights (ECHR), so as yet it has not received much scholarly attention. However, it should be expected that there will be no lack of such attention, as the judgment deserves it for at least two reasons.
Individual differences in bilingual experience modulate executive control network and performance: behavioral and structural neuroimaging evidence
Authors: Gallo Federico , Novitskiy Nikolay , Myachykov Andriy , Shtyrov Yury
Published: September 2020

Dual/multiple language use has been shown to affect cognition and its neural substrate, although the replicability of such findings varies, partially due to neglecting the role of interindividual variability in bilingual experience. To address this, we operationalized the main bilingual experience factors as continuous variables, investigating their effects on executive control performance and neural substrate deploying a Flanker task and structural magnetic resonance imaging. First, higher L2 proficiency predicted better executive performance. Second, neuroimaging results indicated that bilingualism-related neuroplasticity may peak at a certain stage of bilingual experience and eventually revert, possibly following functional specialization. Importantly, experienced bilinguals optimized behavioral performance independently of volumetric variations, suggesting a degree of performance gain even with lower GMV. Hence, the effects of bilingualism on cognition may evolve with experience, with improvements in functional efficiency eventually replacing structural changes. We conclude that individual differences in bilingual experience modulate cognitive and neural consequences of bilingualism.
Comparison of food and beverage products’ availability, variety, price and quality in German and US supermarkets
Authors: Stroebele-Benschop Nanette , Wolf Kerstin , Palmer Katharine , Kelley Casey J , Jilcott Pitts Stephanie B
Published: September 2020

Objective:

To assess availability, variety, price and quality of different food products in a convenience sample of supermarkets in Germany and the USA.

Design:

Cross-sectional study using an adapted version of the Bridging the Gap Food Store Observation Form.

Setting:

Information on availability, quality, price and variety of selected food products in eight German and seven US supermarkets (discount and full service) was obtained and compared by country.

Results:

A general tendency for lower prices of fruits and vegetables in Germany was observed, while produce quality and variety did not seem to differ between countries, with the exception of the variety of some vegetables such as tomatoes. Chips and cereals did not differ significantly in variety nor price. In both countries, high energy-dense foods were lower in energy costs than lower energy-dense foods.

Conclusions:

The influence of food prices and availability on consumption should be further explored, including the impact of country differences.
Factors influencing the recruitment and retention of registered nurses in adult community nursing services: an integrative literature review
Authors: Chamanga Edwin , Dyson Judith , Loke Jennifer , McKeown Eamonn
Published: September 2020

Background:

Adult community nursing services are evolving around the world in response to government policies and changing patient demographics. Amidst these changes, recruitment and retention of community nursing staff are proving a challenge. An integrative literature review has identified multiple factors that influence nurse retention in adult community nursing with sparse information on recruitment factors. Although factors impacting retention of community nurses have been identified, their generalisability around the world is a challenge as they are context and co-dependent. Indicating the need for this area of study to be explored at a local level, as the same factors present with different findings globally.

Aim:

To establish factors influencing recruitment and retention of registered nurses in adult community nursing services.

Design:

Integrative literature review.

Data sources:

Four electronic databases were searched in August 2019 from January 2008 to December 2018: CINAHL Complete, Web of Science, MEDLINE and PROQUEST. Both qualitative and quantitative studies focusing on factors influencing community nursing recruitment and retention were included.

Review methods:

An integrative literature review methodology by Whittemore and Knafl (The integrative review: updated methodology. Journal of Advanced Nursing 52, 546–553) was followed, supported by Cochrane guidelines on data synthesis and analysis using a narrative synthesis method. The Center for Evidence-Based Management (CEBMa) critical appraisal tools were used for study quality assessment.

Results:

Ten papers met the study inclusion criteria. Data synthesis and analysis revealed individual and organisational factors influencing the retention of community nurses with the following three dominant themes: (1) work pressure, (2) working conditions and (3) lack of appreciation by managers.

Conclusion:

The review identified context-dependent factors that influence adult community nurses’ retention with limited generalisability. There is a lack of data on factors influencing recruitment into adult community nursing; further research is needed to explore factors affiliated to community nursing recruitment.
Evaluation of resistance to stemphylium blight in interspecific recombinant inbred lines derived from Lens culinaris × Lens ervoides
Authors: Adobor Stanley , Podder Rajib , Banniza Sabine , Vandenberg Albert
Published: September 2020

Cultivated lentil suffers yield loss from stemphylium blight, caused by Stemphylium botryosum Wallr. Identification of sources of stemphylium blight resistance and knowledge of the mode of inheritance of resistance are important for developing resistant cultivars. The interspecific recombinant inbred line (RIL) population developed from a cross between the moderately resistant parent Lens culinaris cv. ‘Eston’ and the resistant parent L. ervoides (Brign.) Grande accession IG 72815 was evaluated for stemphylium blight resistance under controlled conditions at the University of Saskatchewan, Saskatoon, Canada, and under field conditions at the Pulses Research Centre (PRC), Ishurdi, Bangladesh. We hypothesized that resistance from both parents will lead to transgressive segregation indicative of pyramiding of resistance genes from the same. However, no resistant transgressive segregants were observed in the RIL population. A large proportion (50%) of the RILs had disease severity levels similar to the resistant parent IG 72815 in experiments conducted under natural disease pressure in Bangladesh. Under controlled conditions in Saskatoon, 38% of RILs had resistance levels similar to IG 72815. Across all environments, 14 RILs consistently had resistance levels similar to IG 72815. The distribution of disease severity scores for all RILs indicated polygenic inheritance of stemphylium blight resistance in the population. RILs with consistent resistant reactions should prove useful for lentil improvement programmes. This will contribute to increasing the productivity of lentil crops in North America and the Indo-Gangetic region, which account for more than 68% of world lentil production.
Social Welfare Attitudes and Immigrants as a Target Population: Experimental Evidence
Authors: Haselswerdt Jake
Published: September 2020

What makes some Americans assume that social welfare programs will benefit immigrants rather than native-born Americans? How do these assumptions shape their attitudes about policy? Recent observational research has shown that immigration attitudes and social welfare attitudes are strongly correlated, but we lack evidence of exactly how this relationship works. In this pre-registered survey experiment, I study respondents’ assumptions about beneficiaries of a generic social welfare policy, and test the effects of different “threat” primes on the assumption that the policy benefits immigrants rather than native-born Americans. I find that a prime constructing immigrants as a fiscal threat increases the likelihood that a respondent will make this assumption, while a prime emphasizing cultural or demographic threat has no significant effect. These effects vary by geographic context, but not by relevant attitudes. Attitudes about immigration become an important predictor of policy approval when this assumption is triggered.
Getting the Message? Choice, Self-Selection, and the Efficacy of Social Movement Arguments
Authors: Testa Paul F. , Williams Tarah , Britzman Kylee , Hibbing Matthew V.
Published: September 2020

The dynamics of choice and self-selection are central features of politics but absent from most experimental designs. We show how designs that incorporate choice, by allowing some subjects the option to receive or avoid treatment, can be extended by randomizing conditional on subjects’ treatment choices to answer further questions of interest while preserving statistical power. We apply this design to study how the gender of messengers for the #MeToo social movement conditions who receives the movement’s message and how they respond. Our results, from both convenience and nationally representative samples, suggest that #MeToo movement’s message reaches a wide audience with the intended effect. The potential for backlash in response to the message appears limited but more likely when this message is delivered by a woman.
Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA
Authors: Chen Guofang , Liu Binya , Yin Shasha , Li Shuangdi , Guo Yu’e , Wang Mengfei , Wang Kai , Wan Xiaoping
Published: September 2020

Endometrial cancer stem cells (ECSCs) are stem-like cells endowed with self-renewal and differentiation abilities, and these cells are essential for cancer progression in endometrial cancer (EC). As hallmarks of the tumour microenvironment (TME), hypoxia and hypoxia-inducing factors (HIFs) give rise to the dysregulation of tumour stemness genes, such as SOX2. Against this backdrop, we investigated the regulatory mechanisms regulated by HIFs and SOX2 in ECSCs during EC development. Here, ECSCs isolated from EC cell lines and tissues were found to express stemness genes (CD133 and aldehyde dehydrogenase, ALDH1) following the induction of their ECSC expansion. Notably, m6A methylation of RNA and HIF-1α/2α-dependent AlkB homologue 5 (ALKBH5) participate in the regulation of HIFs and SOX2 in EC, as confirmed by the observations that mRNA levels of m6A demethylases and ALKBH5 significantly increase under hypoxic conditions in ECSCs. Moreover, hypoxia and high ALKBH5 levels restore the stem-like state of differentiated ECSCs and increase the ECSC-like phenotype, whereas the knockdown of HIFs or ALKBH5 significantly reduces their tumour initiation capacity. In addition, our findings validate the role of ALKBH5 in promoting SOX2 transcription via mRNA demethylation, thereby maintaining the stem-like state and tumorigenicity potential of ECSCs. In conclusion, these observations demonstrate a critical role for m6A methylation-mediated regulation of the HIF-ALKBH5-SOX2 axis during ECSC expansion in hypoxic TMEs.
A single-cell polony method reveals low levels of infected Prochlorococcus in oligotrophic waters despite high cyanophage abundances
Authors: Mruwat Noor , Carlson Michael C G , Goldin Svetlana , Ribalet François , Kirzner Shay , Hulata Yotam , Beckett Stephen J , Shitrit Dror , Weitz Joshua S , Armbrust E Virginia , Lindell Debbie
Published: September 2020

Long-term stability of picocyanobacteria in the open oceans is maintained by a balance between synchronous division and death on daily timescales. Viruses are considered a major source of microbial mortality, however, current methods to measure infection have significant methodological limitations. Here we describe a method that pairs flow-cytometric sorting with a PCR-based polony technique to simultaneously screen thousands of taxonomically resolved individual cells for intracellular virus DNA, enabling sensitive, high-throughput, and direct quantification of infection by different virus lineages. Under controlled conditions with picocyanobacteria-cyanophage models, the method detected infection throughout the lytic cycle and discriminated between varying infection levels. In North Pacific subtropical surface waters, the method revealed that only a small percentage of Prochlorococcus (0.35–1.6%) were infected, predominantly by T4-like cyanophages, and that infection oscillated 2-fold in phase with the diel cycle. This corresponds to 0.35–4.8% of Prochlorococcus mortality daily. Cyanophages were 2–4-fold more abundant than Prochlorococcus, indicating that most encounters did not result in infection and suggesting infection is mitigated via host resistance, reduced phage infectivity and inefficient adsorption. This method will enable quantification of infection for key microbial taxa across oceanic regimes and will help determine the extent that viruses shape microbial communities and ecosystem level processes.
Intriguing size distribution of the uncultured and globally widespread marine non-cyanobacterial diazotroph Gamma-A
Authors: Cornejo-Castillo Francisco M , Zehr Jonathan P
Published: September 2020

Non-cyanobacterial diazotrophs (NCDs) have recently emerged as potentially important contributors to marine nitrogen fixation. One of the most widely distributed NCDs is Gamma-A, yet information about its autecology is still scarce and solely relies on the PCR-based detection of its nitrogenase (nifH) gene in seawater, since previous metagenomic surveys targeting free-living planktonic size fractions (<3 μm) have not detected it. Here, we explore the diversity, biogeography, size-distribution, and nitrogenase gene expression of Gamma-A across four larger planktonic size-fractions (0.8–5, 5–20, 20–180, and 180–2000 μm) using metagenomes and metatranscriptomes from the Tara Oceans. We detected a single variant of a complete Gamma-A nifH gene along with other nitrogenase-related genes (nifKDT) within a metatranscriptomic-based contig of the Marine Atlas of Tara Ocean Unigenes. Gamma-A was detected in tropical and subtropical oceanic regions across all the size-fractions. However, the highest gene and transcript abundances were found in the 0.8–5 and 5–20 μm size-fractions at the surface, whereas abundances at the deep chlorophyll maximum were lower and similar across all size-fractions. The ubiquitous presence of active Gamma-A in large planktonic size-fractions suggests a filamentous or particle-attached lifestyle and places its potential to fix nitrogen in larger planktonic compartments.
Exosomal lncRNA DOCK9-AS2 derived from cancer stem cell-like cells activated Wnt/β-catenin pathway to aggravate stemness, proliferation, migration, and invasion in papillary thyroid carcinoma
Authors: Dai Wencheng , Jin Xiaoxia , Han Liang , Huang Haijing , Ji Zhenhua , Xu Xinjiang , Tang Mingming , Jiang Bin , Chen Weixian
Published: September 2020

Exosomal long non-coding RNAs (lncRNAs) are crucial factors that mediate the extracellular communication in tumor microenvironment. DOCK9 antisense RNA2 (DOCK9-AS2) is an exosomal lncRNA which has not been investigated in papillary thyroid carcinoma (PTC). Based on the result of differentially expressed lncRNAs in PTC via bioinformatics databases, we discovered that DOCK9-AS2 was upregulated in PTC, and presented elevation in plasma exosomes of PTC patients. Functionally, DOCK9-AS2 knockdown reduced proliferation, migration, invasion, epithelial-to-mesenchymal (EMT) and stemness in PTC cells. PTC-CSCs transmitted exosomal DOCK9-AS2 to improve stemness of PTC cells. Mechanistically, DOCK9-AS2 interacted with SP1 to induce catenin beta 1 (CTNNB1) transcription and sponged microRNA-1972 (miR-1972) to upregulate CTNNB1, thereby activating Wnt/β-catenin pathway in PTC cells. In conclusion, PTC-CSCs-derived exosomal lncRNA DOCK9-AS2 activated Wnt/β-catenin pathway to aggravate PTC progression, indicating that DOCK9-AS2 was a potential target for therapies in PTC.
LIN28B-AS1-IGF2BP1 binding promotes hepatocellular carcinoma cell progression
Authors: Zhang Jian , Hu Kewei , Yang Yong-qiang , Wang Yin , Zheng Yu-fan , Jin Yong , Li Ping , Cheng Long
Published: September 2020

IGF2BP1 overexpression promotes hepatocellular carcinoma (HCC) progression. Long non-coding RNA LIN28B-AS1 directly binds to IGF2BP1. In the present study, LIN28B-AS1 and IGF2BP1 expression and their potential functions in HCC cells were tested. Genetic strategies were applied to interfere their expression, and cell survival, proliferation and apoptosis were analyzed. We show that LIN28B-AS1 is expressed in established/primary human HCC cells and HCC tissues. RNA-immunoprecipitation (RIP) and RNA pull-down results confirmed that LIN28B-AS1 directly associated with IGF2BP1 protein in HCC cells. LIN28B-AS1 silencing (by targeted siRNAs) or knockout (KO, by CRISPR-Cas9 method) depleted IGF2BP1-dependent mRNAs (IGF2, Gli1, and Myc), inhibiting HCC cell growth, proliferation, migration, and invasion. Conversely, ectopic overexpression of LIN28B-AS1 upregulated IGF2BP1-dependent mRNAs and promoted HCC cell progression in vitro. Importantly, ectopic IGF2BP1 overexpression failed to rescue LIN28B-AS1-KO HepG2 cells. LIN28B-AS1 siRNA and overexpression were ineffective in IGF2BP1-KO HepG2 cells. In vivo, LIN28B-AS1 KO-HepG2 xenograft tumors grew significantly slower than the control tumors in the nude mice. Taken together, we conclude that LIN28B-AS1 associates with IGF2BP1 to promote human HCC cell progression in vitro and in vivo.
Kidney GATA3+ regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury
Authors: Sakai Ryota , Ito Minako , Komai Kyoko , Iizuka-Koga Mana , Matsuo Kazuhiko , Nakayama Takashi , Yoshie Osamu , Amano Koichi , Nishimasu Hiroshi , Nureki Osamu , Kubo Masato , Yoshimura Akihiko
Published: September 2020

FoxP3+ regulatory T cells (Tregs) play crucial roles in peripheral immune tolerance. In addition, Tregs that reside or accumulate in nonlymphoid tissues, called tissue Tregs, exhibit tissue-specific functions and contribute to the maintenance of tissue homeostasis and repair. In an experimental mouse model of crescentic glomerulonephritis induced by an anti-glomerular basement membrane antibody, Tregs started to accumulate in the kidney on day 10 of disease onset and remained at high levels (~30–35% of CD4+ T cells) during the late stage (days 21–90), which correlated with stable disease control. Treg depletion on day 21 resulted in the relapse of renal dysfunction and an increase in Th1 cells, suggesting that Tregs are essential for disease control during the convalescence stage. The Tregs that accumulated in the kidney showed tissue Treg phenotypes, including high expression of GATA3, ST2 (the IL33 receptor subunit), amphiregulin (Areg), and PPARγ. Although T-bet+ Tregs and RORγt+ Tregs were observed in the kidney, GATA3+ Tregs were predominant during the convalescence stage, and a PPARγ agonist enhanced the accumulation of GATA3+ Tregs in the kidney. To understand the function of specific genes in kidney Tregs, we developed a novel T cell transfer system to T cell-deficient mice. This experiment demonstrates that ST2, Areg, and CCR4 in Tregs play important roles in the accumulation of GATA3+ Tregs in the kidney and in the amelioration of renal injury. Our data suggest that GATA3 is important for the recruitment of Tregs into the kidney, which is necessary for convalescence after renal tissue destruction.
Signature of local stress states in the deformation behavior of metallic glasses
Authors: Bian Xilei , Şopu Daniel , Wang Gang , Sun Baoan , Bednarčik Jozef , Gammer Christoph , Zhai Qijie , Eckert Jürgen
Published: September 2020

The design of ductile heterogeneous metallic glasses (MGs) with enhanced deformability by purposely controlling the shear-band dynamics via modulation of the atomic-scale structures and local stress states remains a significant challenge. Here, we correlate the changes in the local atomic structure when cooling to cryogenic temperature with the observed improved shear stability. The enhanced atomic-level structural and elastic heterogeneities related to the nonaffine thermal contraction of the short-range order (SRO) and medium-range order (MRO) change the characteristics of the activation process of the shear transformation zones (STZs). The experimental observations corroborated by Eshelby inclusion analysis and molecular dynamics simulations disclose the correlation between the structural fluctuations and the change in the stress field around the STZ. The variations in the inclination axes of the STZs alter their percolation mechanism, affect the shear-band dynamics and kinetics, and consequently delay shear failure. These results expand the understanding of the correlation between the atomic-level structure and elementary plastic events in monolithic MGs and thereby pave the way for the design of new ductile metallic alloys.
Methane emissions from natural gas vehicles in China
Authors: Da Pan  , Tao Lei , Sun Kang , Golston Levi M. , Miller David J. , Zhu Tong , Qin Yue , Zhang Yan , Mauzerall Denise L. , Zondlo Mark A.
Published: September 2020

Natural gas vehicles (NGVs) have been promoted in China to mitigate air pollution, yet our measurements and analyses show that NGV growth in China may have significant negative impacts on climate change. We conducted real-world vehicle emission measurements in China and found high methane emissions from heavy-duty NGVs (90% higher than current emission limits). These emissions have been ignored in previous emission estimates, leading to biased results. Applying our observations to life-cycle analyses, we found that switching to NGVs from conventional vehicles in China has led to a net increase in greenhouse gas (GHG) emissions since 2000. With scenario analyses, we also show that the next decade will be critical for China to reverse the trend with the upcoming China VI standard for heavy-duty vehicles. Implementing and enforcing the China VI standard is challenging, and the method demonstrated here can provide critical information regarding the fleet-level CH4 emissions from NGVs.
Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology
Authors: Elouej Sahar , Harhouri Karim , Le Mao Morgane , Baujat Genevieve , Nampoothiri Sheela , Kayserili Hϋlya , Menabawy Nihal Al , Selim Laila , Paneque Arianne Llamos , Kubisch Christian , Lessel Davor , Rubinsztajn Robert , Charar Chayki , Bartoli Catherine , Airault Coraline , Deleuze Jean-François , Rötig Agnes , Bauer Peter , Pereira Catarina , Loh Abigail , Escande-Beillard Nathalie , Muchir Antoine , Martino Lisa , Gruenbaum Yosef , Lee Song-Hua , Manivet Philippe , Lenaers Guy , Reversade Bruno , Lévy Nicolas , De Sandre-Giovannoli Annachiara
Published: September 2020

Mandibuloacral dysplasia syndromes are mainly due to recessiveLMNAorZMPSTE24mutations, with cardinal nuclear morphological abnormalities and dysfunction. We report five homozygous null mutations inMTX2, encoding Metaxin-2 (MTX2), an outer mitochondrial membrane protein, in patients presenting with a severe laminopathy-like mandibuloacral dysplasia characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis and severe hypertension. Loss of MTX2 in patients’ primary fibroblasts leads to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients’ fibroblasts are resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Interestingly, secondary nuclear morphological defects are observed in bothMTX2-mutant fibroblasts and mtx-2-depletedC. elegans. We thus report the identification of a severe premature aging syndrome revealing an unsuspected link between mitochondrial composition and function and nuclear morphology, establishing a pathophysiological link with premature aging laminopathies and likely explaining common clinical features.
Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway
Authors: Aksenova Vasilisa , Smith Alexandra , Lee Hangnoh , Bhat Prasanna , Esnault Caroline , Chen Shane , Iben James , Kaufhold Ross , Yau Ka Chun , Echeverria Carlos , Fontoura Beatriz , Arnaoutov Alexei , Dasso Mary
Published: September 2020

Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature and the slow turnover of NPC components complicates investigations of how individual nucleoporins act in these diverse processes. To address this question, we apply an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins NUP153, NUP50 and TPR. Acute depletion of TPR causes rapid and pronounced changes in transcriptomic profiles. These changes are dissimilar to shifts observed after loss of NUP153 or NUP50, but closely related to changes caused by depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) to NPCs and results in abnormal RNA transcription and export. Our findings demonstrate a unique and pivotal role of TPR in gene expression through TREX-2- and/or NXF1-dependent mRNA turnover.
Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function
Authors: Fox Sierra , Myers Jacquelyn A. , Davidson Christina , Getman Michael , Kingsley Paul D. , Frankiewicz Nicholas , Bulger Michael
Published: September 2020

Stratification of enhancers by signal strength in ChIP-seq assays has resulted in the establishment of super-enhancers as a widespread and useful tool for identifying cell type-specific, highly expressed genes and associated pathways. We examine a distinct method of stratification that focuses on peak breadth, termed hyperacetylated chromatin domains (HCDs), which classifies broad regions exhibiting histone modifications associated with gene activation. We find that this analysis serves to identify genes that are both more highly expressed and more closely aligned to cell identity than super-enhancer analysis does using multiple data sets. Moreover, genetic manipulations of selected gene loci suggest that some enhancers located within HCDs work at least in part via a distinct mechanism involving the modulation of histone modifications across domains and that this activity can be imported into a heterologous gene locus. In addition, such genetic dissection reveals that the super-enhancer concept can obscure important functions of constituent elements.
Seafloor evidence for pre-shield volcanism above the Tristan da Cunha mantle plume
Authors: Geissler Wolfram H. , Wintersteller Paul , Maia Marcia , Strack Tonke , Kammann Janina , Eagles Graeme , Jegen Marion , Schloemer Antje , Jokat Wilfried
Published: September 2020

Tristan da Cunha is assumed to be the youngest subaerial expression of the Walvis Ridge hot spot. Based on new hydroacoustic data, we propose that the most recent hot spot volcanic activity occurs west of the island. We surveyed relatively young intraplate volcanic fields and scattered, probably monogenetic, submarine volcanoes with multibeam echosounders and sub-bottom profilers. Structural and zonal GIS analysis of bathymetric and backscatter results, based on habitat mapping algorithms to discriminate seafloor features, revealed numerous previously-unknown volcanic structures. South of Tristan da Cunha, we discovered two large seamounts. One of them, Isolde Seamount, is most likely the source of a 2004 submarine eruption known from a pumice stranding event and seismological analysis. An oceanic core complex, identified at the intersection of the Tristan da Cunha Transform and Fracture Zone System with the Mid-Atlantic Ridge, might indicate reduced magma supply and, therefore, weak plume-ridge interaction at present times.
Efficient rational modification of non-ribosomal peptides by adenylation domain substitution
Authors: Calcott Mark J. , Owen Jeremy G. , Ackerley David F.
Published: September 2020

Non-ribosomal peptide synthetase (NRPS) enzymes form modular assembly-lines, wherein each module governs the incorporation of a specific monomer into a short peptide product. Modules are comprised of one or more key domains, including adenylation (A) domains, which recognise and activate the monomer substrate; condensation (C) domains, which catalyse amide bond formation; and thiolation (T) domains, which shuttle reaction intermediates between catalytic domains. This arrangement offers prospects for rational peptide modification via substitution of substrate-specifying domains. For over 20 years, it has been considered that C domains play key roles in proof-reading the substrate; a presumption that has greatly complicated rational NRPS redesign. Here we present evidence from both directed and natural evolution studies that any substrate-specifying role for C domains is likely to be the exception rather than the rule, and that novel non-ribosomal peptides can be generated by substitution of A domains alone. We identify permissive A domain recombination boundaries and show that these allow us to efficiently generate modified pyoverdine peptides at high yields. We further demonstrate the transferability of our approach in the PheATE-ProCAT model system originally used to infer C domain substrate specificity, generating modified dipeptide products at yields that are inconsistent with the prevailing dogma.
Middle-aged individuals may be in a perpetual state of H3N2 influenza virus susceptibility
Authors: Gouma Sigrid , Kim Kangchon , Weirick Madison E. , Gumina Megan E. , Branche Angela , Topham David J. , Martin Emily T. , Monto Arnold S. , Cobey Sarah , Hensley Scott E.
Published: September 2020

Influenza virus exposures in childhood can establish long-lived memory B cell responses that can be recalled later in life. Here, we complete a large serological survey to elucidate the specificity of antibodies against contemporary H3N2 viruses in differently aged individuals who were likely primed with different H3N2 strains in childhood. We find that most humans who were first infected in childhood with H3N2 viral strains from the 1960s and 1970s possess non-neutralizing antibodies against contemporary 3c2.A H3N2 viruses. We find that 3c2.A H3N2 virus infections boost non-neutralizing H3N2 antibodies in middle-aged individuals, potentially leaving many of them in a perpetual state of 3c2.A H3N2 viral susceptibility.
Prediction of hydrogenated group IV–V hexagonal binary monolayers
Authors: Mohebpour Mohammad Ali , Mozvashi Shobair Mohammadi , Vishkayi Sahar Izadi , Tagani Meysam Bagheri
Published: September 2020

Group IV and V monolayers are very crucial 2D materials for their high carrier mobilities, tunable band gaps, and optical linear dichroism. Very recently, a novel group IV–V binary compound, $${\hbox {Sn}}_2{\hbox {Bi}}$$

Sn
2

Bi

, has been synthesized on silicon substrate, and has shown very interesting electronic properties. Further investigations have revealed that the monolayer would be stable in freestanding form by hydrogenation. Inspired by this, by means of first-principles calculations, we systematically predict and investigate eight counterparts of $${\hbox {Sn}}_2{\hbox {Bi}}$$

Sn
2

Bi

, namely $${\hbox {Si}}_2{\hbox {P}}$$

Si
2

P

, $${\hbox {Si}}_2{\hbox {As}}$$

Si
2

As

, $${\hbox {Si}}_2{\hbox {Sb}}$$

Si
2

Sb

, $${\hbox {Si}}_2{\hbox {Bi}}$$

Si
2

Bi

, $${\hbox {Ge}}_2{\hbox {P}}$$

Ge
2

P

, $${\hbox {Ge}}_2{\hbox {As}}$$

Ge
2

As

, $${\hbox {Ge}}_2{\hbox {Sb}}$$

Ge
2

Sb

, and $${\hbox {Ge}}_2{\hbox {Bi}}$$

Ge
2

Bi

. The cohesive energies, phonon dispersions, and AIMD calculations show that, similar to $${\hbox {Sn}}_2{\hbox {Bi}}$$

Sn
2

Bi

, all of these freestanding monolayers are stable in hydrogenated form. These hydrogenated monolayers are semiconductors with wide band gaps, which are favorable for opto-electronic purposes. The $${\hbox {Si}}_2{\hbox {YH}}_2$$

Si
2

YH
2

and $${\hbox {Ge}}_2{\hbox {YH}}_2$$

Ge
2

YH
2

structures possess indirect and direct band gaps, respectively. They represent very interesting optical characteristics, such as good absorption in the visible region and linear dichroism, which are crucial for solar cell and beam-splitting devices, respectively. Finally, the $${\hbox {Si}}_2{\hbox {SbH}}_2$$

Si
2

SbH
2

and $${\hbox {Si}}_2{\hbox {BiH}}_2$$

Si
2

BiH
2

monolayers have suitable band gaps and band edge positions for photocatalytic water splitting. Summarily, our investigations offer very interesting and promising properties for this family of binary compounds. We hope that our predictions open ways to new experimental studies and fabrication of suitable 2D materials for next generation opto-electronic and photocatalytic devices.
Genetic variation regulates opioid-induced respiratory depression in mice
Authors: Bubier Jason A. , He Hao , Philip Vivek M. , Roy Tyler , Hernandez Christian Monroy , Bernat Rebecca , Donohue Kevin D. , O’Hara Bruce F. , Chesler Elissa J.
Published: September 2020

In the U.S., opioid prescription for treatment of pain nearly quadrupled from 1999 to 2014. The diversion and misuse of prescription opioids along with increased use of drugs like heroin and fentanyl, has led to an epidemic in addiction and overdose deaths. The most common cause of opioid overdose and death is opioid-induced respiratory depression (OIRD), a life-threatening depression in respiratory rate thought to be caused by stimulation of opioid receptors in the inspiratory-generating regions of the brain. Studies in mice have revealed that variation in opiate lethality is associated with strain differences, suggesting that sensitivity to OIRD is genetically determined. We first tested the hypothesis that genetic variation in inbred strains of mice influences the innate variability in opioid-induced responses in respiratory depression, recovery time and survival time. Using the founders of the advanced, high-diversity mouse population, the Diversity Outbred (DO), we found substantial sex and genetic effects on respiratory sensitivity and opiate lethality. We used DO mice treated with morphine to map quantitative trait loci for respiratory depression, recovery time and survival time. Trait mapping and integrative functional genomic analysis in GeneWeaver has allowed us to implicateGalnt11, anN-acetylgalactosaminyltransferase, as a gene that regulates OIRD.
Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals
Authors: Vaga Stefania , Lee Sunjae , Ji Boyang , Andreasson Anna , Talley Nicholas J. , Agréus Lars , Bidkhori Gholamreza , Kovatcheva-Datchary Petia , Park Junseok , Lee Doheon , Proctor Gordon , Ehrlich Stanislav Dusko , Nielsen Jens , Engstrand Lars , Shoaie Saeed
Published: September 2020

Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities’ compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
Anterior pituitary gland T1 signal intensity is influenced by time delay after injection of gadodiamide
Authors: Mallio Carlo A. , Messina Laura , Parillo Marco , Lo Vullo Gianguido , Beomonte Zobel Bruno , Parizel Paul M. , Quattrocchi Carlo C.
Published: September 2020

To test the hypothesis of washout from the anterior pituitary (AP) gland after serial injections of gadodiamide. We included 59 patients with history of at least 5 injections of gadodiamide. Values of mean signal intensity of the AP and of the central pons were measured on unenhanced sagittal T1-weighted images. AP-to-pons signal intensity ratios were calculated dividing the values of the AP by those of the pons. The measurements were performed using MR images acquired at four different time points including baseline (prior to any gadodiamide injection), minimum post-injection time delay, maximum post-injection time delay, and last available MR scans. Normalized ratios (i.e. ratios divided total volume of injected gadodiamide) were also calculated. To assess the difference between ratios, non-parametric Wilcoxon signed-rank test was applied. The correlations were tested with non-parametric Spearman correlation coefficient. A p-value < 0.05 was considered as statistically significant. A statistically significant increase of AP signal intensity was found by comparing the baseline scans with both the minimum time delay (p = 0.003) and maximum time delay scans (p = 0.005). We found significant higher normalized ratios for minimum post-injection time delay with respect to maximum post-injection time delay (p < 0.001). The normalized ratios demonstrated a statistically significant negative correlation with the post-injection time delay (r = − 0.31; p = 0.006). The findings of this study suggest that washout phenomena of retained/deposited gadolinium from the AP are influenced by the total injected volume and post-injection time delay.
Bleb plication: a minimally invasive repair method for a leaking ischemic bleb after trabeculectomy
Authors: Sugimoto Koichiro , Murata Hiroshi , Yamashita Takehiro , Asaoka Ryo
Published: September 2020

Bleb leakage is a serious complication of glaucoma filtering surgery. This study describes the method and the results of a new repair method for ischemic bleb leaks. The subjects were consecutive eleven eyes of 11 patients with bleb leakage who underwent the bleb plication surgery. The bleb plication surgery consisted of two steps: 1) bleb needle redirection to float the conjunctiva away from the sclera as extensively as possible around the ischemic conjunctiva; and 2) multiple “O-shaped” sutures were applied between the non-ischemic conjunctiva just outside the ischemic conjunctiva and corneal limbus. The ischemic conjunctiva was not removed, but undermined beneath the advanced non-ischemic conjunctiva. This bleb plication method was repeated until the leakage was sealed. All patients were followed up for at least 6 months after final bleb plication. After final bleb plication, no recurrence of bleb leakage was observed. Moreover, ischemic changes were no longer observed in the advanced non-ischemic conjunctiva. Pre-operative and final intraocular pressure was 3.2 ± 4.1 and 11.9 ± 2.8 mmHg, respectively. This new repair method of bleb plication was safe and effective in sealing the leakage. The conjunctiva is not excised, and hence it does not run out.
Information transfer via temporal convolution in nonlinear optics
Authors: Lassonde Philippe , Ibrahim Heide , Leblanc Adrien , Azaña José , Schmidt Bruno E. , Légaré François
Published: September 2020

Nonlinear parametric processes involving ultrashort pulses are typically carried out in time domain, which mathematically corresponds to a convolution of their frequency spectra. In contrast, this spectral convolution changes into a multiplication operation when performing the nonlinear interaction in frequency domain. Here, we extend the scope of frequency-domain nonlinear optics by demonstrating its ability to perform a temporal convolution. Through this approach, nonlinear optical operations that are inaccessible in time domain can be realised: specific optical information can be coherently advanced by picoseconds within a pulse sequence—a newly generated second harmonic pulse carries the amplitude and phase information of two input pulses. This central pulse is isolated when using an input field consisting of two cross-polarized input pulses in combination with type-II second harmonic generation. The effects of nonlinear temporal convolution can be viewed from the aspect of signal processing and pulse shaping, where the nonlinear interaction in the parametric crystal plays the role of a dynamic linear optical filter—in contrast to conventional static filters—with a shaping mask instantaneously adapting to the laser field.