bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic resistance genes and class 1 integron: Evidence of fecal pollution as a major driver for their abundance in water and sediments impacted by metal contamination and wastewater in the Andean region of Bolivia
Authors: Agramont Jorge , Gutierrez-Cortez Sergio , Joffré Enrique , Sjöling Åsa , Toledo Carla Calderon
Published: March 2020

Water and sediment samples affected by mining activities were collected from three lakes in Bolivia, the pristine Andean lake Pata Khota, the Milluni Chico lake directly impacted by acid mine drainage, and the Uru-Uru lake located close to Oruro city and highly polluted by mining activities and human wastewater discharges. Physicochemical parameters, including metal compositions, were analyzed in water and sediment samples. Antibiotic resistance genes (ARGs), were screened for, and verified by quantitative PCR together with the mobile element class 1 integron (intl1) as well as crAssphage, a marker of human fecal pollution. The geneintl1showed a positive correlation withsul1, sul2, tetAandblaOXA-2. CrAssphage was only detected in Uru-Uru lake and its tributaries and significantly higher abundance of ARGs were found in these sites. Multivariate analysis showed that crAssphage abundance, electrical conductivity and pH were positively correlated with higher levels ofintl1and ARGs. Taken together our results suggest that fecal pollution is the major driver of higher ARGs andintl1in wastewater and mining contaminated environments.
Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes
Authors: Szpirer Claude
Published: March 2020

The rat has been used for a long time as the model of choice in several biomedical disciplines. Numerous inbred strains have been isolated, displaying a wide range of phenotypes and providing many models of human traits and diseases. Rat genome mapping and genomics was considerably developed in the last decades. The availability of these resources has stimulated numerous studies aimed at discovering disease genes by positional identification. Numerous rat genes have now been identified that underlie monogenic or complex diseases and remarkably, these results have been translated to the human in a significant proportion of cases, leading to the identification of novel human disease susceptibility genes, helping in studying the mechanisms underlying the pathological abnormalities and also suggesting new therapeutic approaches. In addition, reverse genetic tools have been developed. Several genome-editing methods were introduced to generate targeted mutations in genes the function of which could be clarified in this manner [generally these are knockout (KO) mutations]. Furthermore, even when the human gene causing a disease is identified, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis. Today, about 300 rat genes have been identified as underlying diseases or playing a key role in critical biological processes that are altered in diseases. This article provides the reader with an inventory of these genes.
Hypersilencing of SRRM4 suppresses basal microexon inclusion and promotes tumor growth across cancers
Authors: Head Sarah A. , Hernandez-Alias Xavier , Yang Jae-Seong , Beltran-Sastre Violeta , Torres-Méndez Antonio , Irimia Manuel , Schaefer Martin H. , Serrano Luis
Published: March 2020

RNA splicing is widely dysregulated in cancer, frequently due to altered expression or activity of splicing factors. Microexons are extremely small exons (3-27 nucleotides long) that are highly evolutionarily conserved and play critical roles in promoting neuronal differentiation and development. Inclusion of microexons in mRNA transcripts is mediated by the splicing factor SRRM4, whose expression is largely restricted to neural tissues. However, microexons have been largely overlooked in prior analyses of splicing in cancer, as their small size necessitates specialized computational approaches for their detection. Here we demonstrate that despite having low expression in normal non-neural tissues, SRRM4 is hypersilenced in tumors, resulting in the suppression of basal microexon inclusion. Remarkably, SRRM4 is the most consistently silenced splicing factor across all tumor types analyzed, implying a general advantage of microexon downregulation in cancer independent of its tissue of origin. We show that this silencing is favorable for tumor growth, as decreased SRRM4 expression in tumors is correlated with an increase in mitotic gene expression, and upregulation of SRRM4 in cancer cell lines dose-dependently inhibits proliferationin vitroand in a mouse xenograft model. Further, this proliferation inhibition is accompanied by induction of neural-like expression and splicing patterns in cancer cells, suggesting that SRRM4 expression shifts the cell state away from proliferation and towards differentiation. We therefore conclude that SRRM4 acts as a proliferation brake, and tumors gain a selective advantage by cutting off this brake.

Significance

Microexons are extremely small exons enriched in the brain that play important roles in neural development. Their inclusion is mediated by the splicing factor SRRM4, also predominantly expressed in the brain. Surprisingly, we find that low expression of SRRM4 outside of the brain is further decreased in tumors, and in fact SRRM4 is the most consistently silenced splicing factor in tumors across tissue types. We demonstrate that SRRM4 inhibits cancer cell proliferationin vitroandin vivoby inducing a neuronal differentiation program. Our findings add a new element to the overall picture of splicing dysregulation in cancer, reveal an antiproliferative function for SRRM4 and microexons outside of the brain, and may present a common therapeutic intervention point across cancer types.
The glycolysis regulator PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma
Authors: Sittewelle Méghane , Kappès Vincent , Lécuyer Déborah , Monsoro-Burq Anne H.
Published: March 2020

Cell migration is a complex process, tightly regulated during embryonic development and abnormally activated during cancer metastasis. RAS-dependent signaling is a major nexus controlling essential cell parameters including proliferation, survival and migration, utilizing downstream effectors such as the PI3K/AKT signaling pathway. In melanoma, oncogenic mutations frequently enhance RAS, PI3K/AKT or MAP kinase signaling, and trigger other cancer hallmarks among which the activation of metabolism regulators. PFKFB4 is one of these critical regulators of glycolysis and of the Warburg effect. Here however, we explore a novel function of PFKFB4 in melanoma cell migration. We find that PFKFB4 interacts with ICMT, a post-translational modifier of RAS. PFKFB4 promotes ICMT/RAS interaction, controls RAS localization at the plasma membrane, activates AKT signaling and enhances cell migration. We thus provide evidence of a novel and glycolysis-independent function of PFKFB4 in human cancer cells. This unconventional activity links the metabolic regulator PFKFB4 to RAS-AKT signaling and impacts melanoma cell migration.

Highlights

-

PFKFB4, a known regulator of glycolysis, also displays an unconventional role in melanoma cell migration.

-

PFKFB4 interacts with ICMT and promotes RAS localization at the plasma membrane.

-

PFKFB4 and ICMT cooperation modulates AKT signaling and controls melanoma cell migration.
Benchmarking accuracy and precision of intensity-based absolute quantification of protein abundances inSaccharomyces cerevisiae
Authors: Sánchez Benjamín J. , Lahtvee Petri-Jaan , Campbell Kate , Kasvandik Sergo , Yu Rosemary , Domenzain Iván , Zelezniak Aleksej , Nielsen Jens
Published: March 2020

Protein quantification via label-free mass spectrometry (MS) has become an increasingly popular method for determining genome-wide absolute protein abundances. A known caveat of this approach is the poor technical reproducibility, i.e. how consistent the estimations are when the same sample is measured repeatedly. Here, we measured proteomics data forSaccharomyces cerevisiaewith both biological and inter-batch technical triplicates, to analyze both accuracy and precision of protein quantification via MS. Moreover, we analyzed how these metrics vary when applying different methods for converting MS intensities to absolute protein abundances. We found that a simple normalization and rescaling approach performs as accurately yet more precisely than methods that rely on external standards. Additionally, we show that inter-batch reproducibility is worse than biological reproducibility for all evaluated methods. These results subsequently serve as a benchmark for assessing MS data quality for protein quantification, whilst also underscoring current limitations in this approach.
The impact of characteristics of intra-organizational environment on entrepreneurial marketing intensity and performance in Egypt
Authors: Mahrous Abeer , Genedy Mohamed Ashraf , Kalliny Morris
Published: March 2020

Purpose

The purpose of this paper is to contribute to the entrepreneurial marketing (EM) paradigm by empirically investigating the relationship between intra-organizational environment, EM intensity (EMI) and organizational performance in an emerging market context. Specifically, the paper identifies the elements of the intra-organizational environment that enhances EMI and also examines the impact of EMI on organizational performance.

Design/methodology/approach

The data were collected from large-sized companies in Egypt. Data were analyzed by using path analysis on Smart-PLS.

Findings

The findings suggest that the characteristics of the intra-organizational environment that support developing and increasing EMI in large-sized companies in emerging markets are cooperative competency, deep locus of planning and institutional support. Also, it was found that the long planning horizon hinders EMI. Finally, it was found that EMI is positively related to organizational performance and competitive advantage.

Practical implications

The study provides guidelines for managers of large-sized organizations, especially in emerging economies, on how to develop the intra-organizational environment to enhance EMI.

Originality/value

The study of EMI received little or no attention in previous research. Also, there is a paucity of empirical research on the impact of the intra-organizational environment on EMI and also on the impact of EMI on the organizational performance of large-sized companies in emerging markets. Therefore, the results of this research are a step toward filling these gaps.
Islamic financial institutions: conduits for money laundering?
Authors: Jabbar Siti Faridah Abdul
Published: March 2020

Purpose

The purpose of this paper is to discuss various situations in the Islamic financial services industry that are asserted to facilitate money laundering and the counter-arguments to the assertions.

Design/methodology/approach

The approach adopted by this paper is a review of literature and of several practices of Islamic financial institutions in a number of countries.

Findings

There is no evidence to support the contentions that Islamic financial institutions facilitate money laundering. Further, Islamic financial institutions are not any more susceptible to money laundering than conventional financial institutions are.

Originality/value

This paper demonstrates that Islamic financial institutions are not conduits for money laundering.
Genome‐resolved metagenomics to study co‐occurrence patterns and intraspecific heterogeneity among plant pathogen metapopulations
Authors: Newberry Eric , Bhandari Rishi , Kemble Joseph , Sikora Edward , Potnis Neha
Published: March 2020

Assessment of pathogen diversity in agricultural fields is essential for informing management decisions and the development of resistant plant varieties. However, many population genomic studies have relied on culture‐based approaches that do not provide quantitative assessment of pathogen populations at the field‐level or the associated host microbiome. Here, we applied whole‐genome shotgun sequencing of microbial DNA extracted directly from the washings of pooled leaf samples, collected from individual tomato and pepper fields in Alabama that displayed the classical symptoms of bacterial spot disease caused by Xanthomonas spp. Our results revealed that while the occurrence of both X. perforans and X. euvesicatoria within fields was limited, evidence of co‐occurrence of up to three distinct X. perforans genotypes was obtained in 7 of 10 tomato fields sampled. These population dynamics were accompanied by the corresponding type 3 secreted effector repertoires associated with the co‐occurring X. perforans genotypes, indicating that metapopulation structure within fields should be considered when assessing the adaptive potential of X. perforans. Finally, analysis of microbial community composition revealed that co‐occurrence of the bacterial spot pathogens Pseudomonas cichorii and Xanthomonas spp. is common in Alabama fields and provided evidence for the non‐random association of several other human and plant opportunists.
ASERNIP‐S: unusual acronym, outstanding results
Authors: Maddern Guy J. , Babidge Wendy J. , Faulkner Kingsley W.
Published: March 2020

In the late 1990s, concerns regarding the introduction of new surgical procedures arose following the rapid uptake of some minimally invasive procedures. At that time, the evidence was not clear on the safety and effectiveness of these new procedures, and it was recommended that data be collected to look at both short‐ and long‐term outcomes. Based on a UK group, ‘the Safety and Efficacy Register of New Interventional Procedures (SERNIP)’, the Australian SERNIP was born under the auspices of the Royal Australasian College of Surgeons, with ‘‐S’ added to the acronym to highlight the focus on surgery. ASERNIP‐S was established to review the evidence on new interventional procedures before their introduction into the Australian healthcare system. The programme operated with initial national government funding for 7 years. Following establishment of the Medical Services Advisory Committee, ASERNIP‐S became a contractor and remains so today. ASERNIP‐S was an also an early adopter of Horizon Scanning, a key activity informing of new procedures/technologies on the verge of introduction into our healthcare system. A strong international reputation of ASERNIP‐S is recognised, both by lead roles of international networks and in working relationships with overseas agencies. In recent years the remit of ASERNIP‐S has expanded to include research and evaluation services across the Royal Australasian College of Surgeons (including committees) and for Specialty Surgical Societies. Externally funded work is growing, including for the Federal Office of Public Health in Switzerland and the Ludwig Boltzmann Institute in Austria. It is unknown what the future will be for this unusually titled programme, but its long history in promoting and supporting surgical evidence and innovation is clear.
Does early surgery imply a critical risk for patients with Grade III acute cholecystitis?
Authors: Kohga Atsushi , Okumura Takuya , Yamashita Kimihiro , Isogaki Jun , Kawabe Akihiro , Kimura Taizo
Published: March 2020

Background

For patients with Grade III acute cholecystitis (AC), several factors have been proposed in the 2018 Tokyo guidelines as caution signs in performing early surgery. However, these factors have not been externally validated in detail.

Methods

This retrospective study examined 35 patients who had been diagnosed with Grade III AC and treated with laparoscopic cholecystectomy between January 2008 and July 2019. The patients were allocated into an early group (patients who underwent surgery within 7 days of admission, n = 28) and a delayed group (patients who underwent surgery at least 8 days after admission, n = 7). Comparisons were made between these groups.

Results

No patients died. Significantly more patients required a conversion to open surgery (0% vs 28.5%, P = .003) or conversion to subtotal cholecystectomy (25.0% vs 71.4%, P = .020) in the delayed group than in the early group, and the total length of postoperative stay was significantly longer in the delayed group (11.4 vs 27.2 days, P = .001). The presence of negative predictive factors or risk factors listed in the 2018 Tokyo guidelines was not associated with death or postoperative complications.

Conclusions

Early surgery was considered appropriate and feasible for select patients who had Grade III AC and preoperative risk factors.
Effects of dietary dihydroartemisinin supplementation on growth performance, hepatic inflammation, and lipid metabolism in weaned piglets with intrauterine growth retardation
Authors: Zhao Yongwei , Niu Yu , He Jintian , Gan Zhending , Ji Shuli , Zhang Lili , Wang Chao , Wang Tian
Published: March 2020

The aims of this study were to investigate the effects of dietary supplementation with dihydroartemisinin (DHA) on growth performance, hepatic inflammation, and lipid metabolism in intrauterine growth retardation (IUGR)‐affected weaned piglets. Eight piglets with normal birth weight (NBW) and 16 IUGR‐affected piglets were selected and fed either a basal diet (NBW and IUGR groups) or the basal diet supplemented with 80 mg/kg DHA (IUGR‐DHA group) from 21 to 49 day of age. Blood and liver samples were collected on day 49. DHA supplementation significantly alleviated the compromised growth performance and liver damage in IUGR‐affected piglets. Additionally, DHA supplementation decreased the activities of alanine aminotransferase and aspartate aminotransferase, as well as the serum levels of non‐esterified fatty acids (NEFA), very‐low‐density lipoprotein, and total cholesterol. In the liver, the concentrations of interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, triglycerides, and NEFA were decreased. Fatty acid synthesis was decreased by DHA supplementation, whereas the activities of lipoprotein lipase, hepatic lipase, and total lipase were increased. Dietary DHA supplementation led to upregulation of the expression of AMPK/SIRT1 signaling pathway‐related genes, whereas that of inflammatory factor‐related genes were downregulated. In conclusion, dietary inclusion of 80 mg/kg DHA can alleviate IUGR‐induced impairments in piglets.
Promoting dementia‐friendly communities to improve the well‐being of individuals with and without dementia
Authors: Maki Yohko , Takao Makiko , Hattori Hideyuki , Suzuki Takao
Published: March 2020

A community is the totality of human relationships, in which individuals live with and for others. This article discusses promoting dementia‐friendly community from the perspective of human relationships within a community. Improving the social well‐being of aging people is important; it is especially important for people with dementia, as dementia is a life‐changing syndrome that affects all aspects of one's life, including human relationships. Dementia‐friendly community requires support from the community in improving the social adaptation of people with dementia, as they experience greater difficulties in social interaction as a result of cognitive decline, especially deterioration of social cognition. They need to be empowered to stay motivated for the opportunity to maintain an active and meaningful life, despite dementia. Flexible provisions of such tailored support can be effective to improve the support network in the community to meet the individual's needs. As social and human resources are limited, it is also necessary to discuss how to share socioeconomic burdens to meet both social sustainability demands and the welfare of aging adults. More discussions that include people with dementia and their family members are required to achieve the purpose of dementia‐friendly community. This is important to enhance the well‐being of individuals with and without dementia, as well as the society as a whole, through dementia support and dementia prevention activities. Geriatr Gerontol Int 2020; ••: ••–••.
Effect of probiotics during vonoprazan‐containing triple therapy on gut microbiota in Helicobacter pylori infection: A randomized controlled trial
Authors: Kakiuchi Toshihiko , Mizoe Akihiko , Yamamoto Kentaroh , Imamura Ichiro , Hashiguchi Kazutoshi , Kawakubo Hiroharu , Yamaguchi Daisuke , Fujioka Yasuhiko , Nakayama Aiko , Okuda Masumi , Matsuo Muneaki
Published: March 2020

Background

Probiotics are beneficial to patients with Helicobacter pylori infections by modulating the gut microbiota. Biofermin‐R (BFR) is a multiple antibiotic‐resistant lactic acid bacteria preparation of Enterococcus faecium 129 BIO 3B‐R and is effective in normalizing the gut microbiota when used in combination with antibiotics. This study aimed to determine the effect of BFR in combination with vonoprazan (VPZ)‐based therapy on gut microbiota.

Methods

Patients with positive urinary anti‐H pylori antibody test (primary test) and fecal H pylori antigen test (secondary test) were examined. Patients in group 1 (BFR−) received VPZ (20 mg twice daily), amoxicillin (750 mg twice daily), and clarithromycin (400 mg twice daily) for 7 days. Patients in group 2 (BFR+) received BFR (3 tablets/day) for 7 days, in addition to the aforementioned treatments. Following treatment, the relative abundance, α‐diversity, and β‐diversity of gut microbiota were assessed.

Results

Supplementation with BFR prevented the decrease in a‐diversity after eradication therapy (Day 7). β‐diversity was similar between groups. The incidence rate of diarrhea was non‐significantly higher in the BFR− than in the BFR+ group (73.1% vs 56.5%; P = .361). Stool consistency was comparable in the BFR+ group on Days 7 and 1 (3.86 ± 0.95 vs 3.86 ± 1.46; P = .415).

Conclusion

Biofermin‐R combined with VPZ‐based therapy resulted in higher microbial α‐strain diversity and suppressed stool softening during H pylori eradication therapy.
Rethinking student participation in the college classroom: Can commitment and self‐affirmation enhance oral participation?
Authors: Sereno Ken , Walter Nathan , Brooks John J.
Published: March 2020

The literature suggests that in‐class oral participation is associated with various positive outcomes that directly contribute to academic success. The goal of the current study was to investigate the role played by psychological barriers to oral participation, focusing on commitment and self‐affirmation as methods to bypass barriers to participation. The results of the semester‐long experiment (N = 157) demonstrate that committed individuals who had an opportunity to self‐affirm outperformed both committed students and affirmed students, as well as members of the control group. Interestingly, the interplay between self‐affirmation and commitment increased oral participation, irrespective of whether students had high or low self‐esteem and high or low self‐efficacy. The current results offer some room for cautious optimism, as they highlight the importance of self‐affirmation and commitment as a route to academic success.
The Other Person’s Choices
Authors: Stuart, H. W.
Published: March 2020

This note analyzes a critical moment in a trade negotiation from a game‐theoretic perspective. The critical moment occurred in a U.S.‐China negotiation and required remarkable presence of mind from the leader of the U.S. side, Charlene Barshefsky. The analysis illustrates the importance of creating moves for other players when confronted with a situation that offers you no acceptable options. This tactic involves real‐time perspective taking skills to create a move that benefits both parties.
Making Connection as Critical Moves in Negotiation
Authors: Kolb Deborah M.
Published: March 2020

Using transcripts from the Program on Negotiation’s Great Negotiator Award seminars, as well as teaching cases based on the work of the Great Negotiators, this article analyzes how several of these Great Negotiators worked to make connections and establish good working relationships with their negotiating counterparts. Connection requires taking on a stance of curiosity about one's counterparts, cultivating good relationships as a way to learn about them and their priorities, using moves that facilitate their ability and willingness to negotiate, and helping them save face in front of their key constituencies. Making connected moves at the moment can lead to turning points in a negotiation.
Low temperature ALD growth optimization of ZnO, TiO2, and Al2O3 to be used as a buffer layer in perovskite solar cells
Authors: Rajbhandari Pravakar P. , Dhakal Tara P.
Published: March 2020

Organic materials provide a very small thermal budget for any postfabrication treatment or for a subsequent layer in a device fabrication. This demand for the low-temperature process has driven the focus of this study to obtain atomic layer deposited oxide layer at a low temperature suitable for a buffer layer in perovskite solar cells. The buffer layer will assist in blocking holes, effectively extract electrons, provide better shunt protection, and act as a sputter protection layer for organic perovskites. Three different oxide layers, Al2O3, ZnO, and TiO2, are grown at 100 °C and studied for this purpose using synchronous modulated flow draw atomic layer deposition (ALD) technology optimized in a commercial 200 mm ALD reactor from Sundew Technologies. It allows greater precursor utilization and shorter deposition cycle times that in turn reduces thermal processing time compared to traditional ALD processes. These thin films have been shown to enhance the fill factor and high charge extraction from the solar cell. Three oxides are compared on all aspects, among which ZnO (3 nm) along with Al2O3 (1 nm) on top of the perovskite layer have shown excellent performance improvement in the device’s power conversion efficiency.
Autoproducts in and near acoustic shadow zones created by barriers
Authors: Worthmann Brian M. , Dowling David R.
Published: March 2020

The autoproducts are nonlinear mathematical constructs developed from acoustic fields with non-zero bandwidth. When averaged through the field's bandwidth, the autoproducts may mimic a genuine acoustic field at frequencies that are lower or higher than the original field's bandwidth. The resulting opportunity to extend signal processing to user-selectable below- or above-band frequencies is intriguing for many signal processing algorithms. Based on prior work, the limitations of the autoproducts' mimicry of out-of-band fields are understood when the in-band acoustic field is well-represented by ray acoustics. Thus, the focus in this study is on autoproducts in acoustic shadow zones behind barriers containing only diffracted acoustic fields where a sum of ray-path contributions is not an adequate field description. Diffraction is expected to be a detriment to autoproduct techniques due to its sensitivity to frequency. Two ideal shadow-zone environments with exact analytic Helmholtz-equation solutions are considered: Sommerfeld's half-plane problem, also known as knife-edge diffraction, and Mie scattering from a sphere with ka = 40, where k is the wavenumber and a is the sphere's radius. With the exception of the shadow regions, autoproducts experience only mild degradation in field-mimicry performance when compared to what the ray-based theory would predict.
Noncanonical STAT1 phosphorylation expands its transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 production
Authors: Metwally Hozaifa , Tanaka Toshio , Li Songling , Parajuli Gyanu , Kang Sujin , Hanieh Hamza , Hashimoto Shigeru , Chalise Jaya P. , Gemechu Yohannes , Standley Daron M. , Kishimoto Tadamitsu
Published: March 2020

TLR4-dependent proinflammatory cytokine production still occurs when the receptor is endocytosed.
Destroying tumors with pyroptosis
Authors: Foley John F.
Published: March 2020

Gasdermin E suppresses tumor growth by stimulating antitumor immunity in a pyroptosis-dependent manner.
Mutations in ArgS Arginine-tRNA Synthetase Confer Additional Antibiotic Tolerance Protection to Extended-Spectrum-β-Lactamase-Producing Burkholderia thailandensis
Authors: Yi Hyojeong , Park Jongwook , Cho Kwang-Hwi , Kim Heenam Stanley
Published: March 2020

Highly conserved PenI-type class A β-lactamase in pathogenic members of
Burkholderia
species can evolve to extended-spectrum β-lactamase (ESBL), which exhibits hydrolytic activity toward third-generation cephalosporins, while losing its activity toward the original penicillin substrates. We describe three single-amino-acid-substitution mutations in the ArgS arginine-tRNA synthetase that confer extra antibiotic tolerance protection to ESBL-producing
Burkholderia thailandensis
.
Characterization of the Efflux Capability and Substrate Specificity of Aspergillus fumigatus PDR5-like ABC Transporters Expressed in Saccharomyces cerevisiae
Authors: Esquivel Brooke D. , Rybak Jeffrey M. , Barker Katherine S. , Fortwendel Jarrod R. , Rogers P. David , White Theodore C.
Published: March 2020

One mechanism behind drug resistance is altered export out of the cell. This work is a multifaceted analysis of membrane efflux transporters in the human fungal pathogen
A. fumigatus
. Bioinformatics evidence infers that there is a relatively large number of genes in
A. fumigatus
that encode ABC efflux transporters. However, very few of these transporters have been directly characterized and analyzed for their potential role in drug resistance.
Our objective was to determine if these undercharacterized proteins function as efflux transporters and then to better define whether their efflux substrates include antifungal drugs used to treat fungal infections. We chose six
A. fumigatus
potential plasma membrane ABC transporter genes for analysis and found that all six genes produced functional transporter proteins. We used two fungal systems to look for correlations between transporter function and drug resistance. These transporters have the potential to produce drug-resistant phenotypes in
A. fumigatus
. Continued characterization of these and other transporters may assist in the development of efflux inhibitor drugs.
The Hypercomplex Genome of an Insect Reproductive Parasite Highlights the Importance of Lateral Gene Transfer in Symbiont Biology
Authors: Frost Crystal L. , Siozios Stefanos , Nadal-Jimenez Pol , Brockhurst Michael A. , King Kayla C. , Darby Alistair C. , Hurst Gregory D. D.
Published: March 2020

The biology of many bacteria is critically dependent on genes carried on plasmid and phage mobile elements. These elements shuttle between microbial species, thus providing an important source of biological innovation across taxa. It has recently been recognized that mobile elements are also important in symbiotic bacteria, which form long-lasting interactions with their host. In this study, we report a bacterial symbiont genome that carries a highly complex array of these elements.
Arsenophonus nasoniae
is the son-killer microbe of the parasitic wasp
Nasonia vitripennis
and exists with the wasp throughout its life cycle. We completed its genome with the aid of recently developed long-read technology. This assembly contained over 50 chromosomal regions of phage origin and 17 extrachromosomal elements within the genome, encoding many important traits at the host-microbe interface. Thus, the biology of this symbiont is enabled by a complex array of mobile elements.
Shotgun Metagenomics of Gut Microbiota in Humans with up to Extreme Longevity and the Increasing Role of Xenobiotic Degradation
Authors: Rampelli Simone , Soverini Matteo , D’Amico Federica , Barone Monica , Tavella Teresa , Monti Daniela , Capri Miriam , Astolfi Annalisa , Brigidi Patrizia , Biagi Elena , Franceschi Claudio , Turroni Silvia , Candela Marco
Published: March 2020

The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging.
Effectiveness of a guided online mindfulness-focused intervention in a student population: Study protocol for a randomised control trial
Authors: Schultchen Dana , Küchler Ann-Marie , Schillings Christine , Weineck Felicitas , Karabatsiakis Alexander , Ebert David D. , Baumeister Harald , Pollatos Olga
Published: March 2020

Background

Previous studies show that university students experience higher psychological stress than the general population, resulting in increased vulnerability for mental disorders for the student population. Online mindfulness interventions will be delivered to students as a potentially promising and more flexible approach compared to face-to-face interventions with the aim of improving their mental health. This study purposes to investigate the effectiveness of a guided online mindfulness-focused intervention for university students by using both self-reported and psychobiological measures.

Methods and analyses

In this multicentre, two-armed randomised controlled trial with a parallel design, a guided version of the online mindfulness-focused intervention ‘StudiCare Mindfulness’ will be compared with a waitlist control group. In total, 120 participants will be recruited at different universities (of Applied Sciences) in (Neu-) Ulm. Data will be assessed prior to randomisation, after eight weeks (post-intervention) and six months after randomisation (follow-up). The primary outcome measure is mindfulness. The secondary outcome measures include depression, anxiety and stress levels, well-being, interoceptive sensibility, emotion regulation and alexithymia. Psychobiological parameters comprise interoceptive accuracy, hair cortisol and FKBP5 genotype. Sociodemographic variables, treatment expectations, side and adverse side effects, as well as intervention satisfaction and adherence will be assessed. All data analyses will be conducted according to the intention-to-treat principle.

Ethics and dissemination

All study procedures have been approved by the Ethics Committee of Ulm University (application No. 48/18). The findings will be disseminated widely through peer-reviewed publications and conference presentations.

Trial registration number

DRKS00014701.
Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study
Authors: Kim Minseok Albert , Kim Seung Up , Sinn Dong Hyun , Jang Jeong Won , Lim Young-Suk , Ahn Sang Hoon , Shim Jae-Jun , Seo Yeon Seok , Baek Yang Hyun , Kim Sang Gyune , Kim Young Seok , Kim Ji Hoon , Choe Won Hyeok , Yim Hyung Joon , Lee Hyun Woong , Kwon Jung Hyun , Lee Sung Won , Jang Jae Young , Kim Hwi Young , Park Yewan , Kim Gi-Ae , Yang Hyun , Lee Han Ah , Koh Myeongseok , Lee Young-Sun , Kim Minkoo , Chang Young , Kim Yoon Jun , Yoon Jung-Hwan , Zoulim Fabien , Lee Jeong-Hoon
Published: March 2020

Objective

Direct comparison of the clinical outcomes between nucleos(t)ide analogue (NA) discontinuation versus NA continuation has not been performed in patients with chronic hepatitis B who achieved HBsAg-seroclearance. Whether NA discontinuation was as safe as NA continuation after NA-induced surface antigen of HBV (HBsAg) seroclearance was investigated in the present study.

Designs

This multicentre study included 276 patients from 16 hospitals in Korea who achieved NA-induced HBsAg seroclearance: 131 (47.5%) discontinued NA treatment within 6 months after HBsAg seroclearance (NA discontinuation group) and 145 (52.5%) continued NA treatment (NA continuation group). Primary endpoint was HBsAg reversion and secondary endpoints included serum HBV DNA redetection and development of hepatocellular carcinoma (HCC).

Results

During follow-up (median=26.9 months, IQR=12.2–49.2 months), 10 patients (3.6%) experienced HBsAg reversion, 6 (2.2%) showed HBV DNA redetection and 8 (2.9%) developed HCC. Compared with NA continuation, NA discontinuation was not associated with HBsAg reversion in both univariable (HR=0.45, 95% CI=0.12 to 1.76, log-rank p=0.24) and multivariable analyses (adjusted HR=0.65, 95% CI=0.16 to 2.59, p=0.54). The cumulative probabilities of HBsAg reversion at 1, 3 and 5 years were 0.8%, 2.3% and 5.0% in the NA discontinuation group, and 1.5%, 6.3% and 8.4% in the NA continuation group, respectively. NA discontinuation was not associated with higher risk of either HBV redetection (HR=0.83, 95% CI=0.16 to 4.16, log-rank p=0.82) or HCC development (HR=0.53, 95% CI=0.12 to 2.23, log-rank p=0.38).

Conclusion

The discontinuation of NA was not associated with a higher risk of either HBsAg reversion, serum HBV DNA redetection or HCC development compared with NA continuation among patients who achieved HBsAg seroclearance with NA.
Demographic variation in fit note receipt and long-term conditions in south London
Authors: Dorrington Sarah , Carr Ewan , Stevelink Sharon A M , Dregan Alexandru , Whitney David , Durbaba Stevo , Ashworth Mark , Mykletun Arnstein , Broadbent Matthew , Madan Ira , Hatch Stephani , Hotopf Matthew
Published: March 2020

Objectives

Introduced in the UK in 2010, the fit note was designed to address the problem of long-term sickness absence. We explored (1) associations between demographic variables and fit note receipt, ‘maybe fit’ use and long-term conditions, (2) whether individuals with long-term conditions receive more fit notes and are more likely to have the ‘maybe fit’ option selected and (3) whether long-term conditions explained associations between demographic variables and fit note receipt.

Methods

Data were extracted from Lambeth DataNet, a database containing electronic medical records of all 45 general practitioner (GP) practices within the borough of Lambeth. Individual-level anonymised data on GP consultations, prescriptions, Quality and Outcomes Framework diagnostic data and demographic information were analysed using survival analysis.

Results

In a sample of 326 415 people, 41 502 (12.7%) received a fit note. We found substantial differences in fit note receipt by gender, age, ethnicity and area-level deprivation. Chronic pain (HR 3.7 (95% CI 3.3 to 4.0)) and depression (HR 3.4 (95% CI 3.3 to 3.6)) had the highest rates for first fit note receipt. ‘Maybe fit’ recommendations were used least often in patients with epilepsy and serious mental illness. The presence of long-term conditions did not explain associations between demographic variables and fit note use.

Conclusions

For the first time, we show the relationships between fit note use and long-term conditions using individual-level primary care data from south London. Further research is required in order to evaluate this relatively new policy and to understand the needs of the population it was designed to support.
The optimal level of windpower that could be regulated with Norway’s existing hydroreservoirs
Authors: Hirvijoki Eero
Published: March 2020

This study estimates the optimal level of wind-generated electricity production in Nordic countries’ market region given the existing hydroreservoirs of Norway to regulate the intermittency in wind-energy production and to meet the market demand. Using realized, scaled patterns for hourly wind production and electricity demand, we perform a series of numerical simulations and find a threshold value of approximately 90 TWh for annual wind production after which surplus and deficit in the production begin to accumulate significantly, weakening the utilization factor of wind installments. In light of the ambitious climate policies in the Nordic countries, and that the existing annual capacity of installed wind in the region is approximately 41 TWh, the Nordic governments should consider investing heavily in both national and international grid infrastructure to enable private sector to double the existing wind capacity in the market region.
String theory on AdS3 × M7 in the tensionless limit
Authors: Giribet Gaston
Published: March 2020

We review old and recent results on a special limit of string theory on [Formula: see text] with pure NS–NS fluxes: the limit in which the string length [Formula: see text] equals the [Formula: see text] radius [Formula: see text]. At this point of the moduli space, the theory exhibits special properties, which we discuss. Special attention is focused on features of correlation functions that are related to the noncompactness of the boundary CFT target space, and on how these features change when the point [Formula: see text] is approached. Also, we briefly review the recent proposals for exact realizations of AdS/CFT correspondence at this special point.
A study on distance in graph complement
Authors: Chellaram Malaravan A. , Wilson Baskar A.
Published: March 2020

The aim of this paper is to determine radius and diameter of graph complements. We provide a necessary and sufficient condition for the complement of a graph to be connected, and determine the components of graph complement. Finally, we completely characterize the class of graphs [Formula: see text] for which the subgraph induced by central (respectively peripheral) vertices of its complement in [Formula: see text] is isomorphic to a complete graph [Formula: see text], for some positive integer [Formula: see text].
The kinetics of glucagon action on the liver during insulin-induced hypoglycemia
Authors: Pedersen Christina , Kraft Guillaume , Edgerton Dale S. , Scott Melanie , Farmer Ben , Smith Marta , Laneve David C. , Williams Phillip E. , Moore L. Merkle , Cherrington Alan D.
Published: March 2020

Glucagon’s effect on hepatic glucose production (HGP), under hyperglycemic conditions, is time dependent such that after an initial burst of HGP, it slowly wanes. It is not known whether this is also the case under hypoglycemic conditions, where an increase in HGP is essential. This question was addressed using adrenalectomized dogs to avoid the confounding effects of other counterregulatory hormones. During the study, infusions of epinephrine and cortisol were given to maintain basal levels. Somatostatin and insulin (800 µU·kg−1·min−1) were infused to induce hypoglycemia. After 30 min, glucagon was infused at a basal rate (1 ng·kg−1·min−1, baGGN group, n = 5 dogs) or a rate eightfold basal (8 ng·kg−1·min−1, hiGGN group, n = 5 dogs) for 4 h. Glucose was infused to match the arterial glucose levels between groups (≈50 mg/dL). Our data showed that glucagon has a biphasic effect on the liver despite hypoglycemia. Hyperglucagonemia stimulated a rapid, transient peak in HGP (4-fold basal production) over ~60 min, which was followed by a slow reduction in HGP to a rate 1.5-fold basal. During the last 2 h of the experiment, hiGGN stimulated glucose production at a rate fivefold greater than baGGN (2.5 vs. 0.5 mg·kg−1·min−1, respectively), indicating a sustained effect of the hormone. Of note, the hypoglycemia-induced rises in norepinephrine and glycerol were smaller in hiGGN compared with the baGGN group despite identical hypoglycemia. This finding suggests that there is reciprocity between glucagon and the sympathetic nervous system such that when glucagon is increased, the sympathetic nervous response to hypoglycemia is downregulated.
Lymph Node Metastasis and Extrathyroidal Extension in Papillary Thyroid Microcarcinoma in Cyprus: Suspicious Subcentimeter Nodules Should Undergo FNA When Multifocality is Suspected
Authors: Papaioannou Christos , Lamnisos Demetris , Kyriacou Katerina , Lyssiotis Theodoros , Constantinides Vasilis , Frangos Savvas , Economides Aliki , Economides Panayiotis A.
Published: March 2020

Objective. To determine the prevalence of lymph node (LN) metastasis and extrathyroidal extension (ETE) in patients with papillary thyroid microcarcinoma (PTMC) in Cyprus and to evaluate the role of preoperative ultrasound (U/S) examination. Methods. A retrospective study of 102 patients who underwent thyroidectomy for PTMC in a 2-year period. Preoperatively, all patients had a thyroid and neck U/S examination with LN mapping. Tumor size according to the largest diameter, number of foci, LN metastasis, and ETE data was collected from the histopathological report and was compared to the preoperative U/S reports. Results. LN metastasis was present in 23.5% of patients. 15.7% had central, 3.9% had lateral, and 3.9% had both central and lateral LN metastasis. ETE was present in 27.5% of patients. 21.6% had multifocal disease, and in this group, 40.9% had LN metastasis and 36.4% had ETE. Multifocality (p=0.03), size of tumor (p=0.05), and ETE (p≤0.001) were significantly associated with LN metastasis. The prevalence of LN metastasis in multifocal PTMC ≤5 mm was the same with multifocal PTMC >5 mm. The preoperative U/S sensitivity for the suspicious lateral neck and central LN was 100%, and the specificity was 100%. The preoperative U/S sensitivity for nodules suspicious for ETE was 53.6%, and the specificity was 100%. Conclusion. The presence of LN metastasis and ETE in our PTMC patients in Cyprus is frequent. Neck U/S mapping is a highly reliable and accurate tool in identifying metastatic nodes. LN metastasis is associated with ETE and multifocality. Suspicious subcentimeter nodules should undergo FNA irrespective of size when multifocality is suspected.
Ultra-Low-Dose Radiotherapy for Palliation of Mycosis Fungoides
Authors: Aral İpek Pınar , Göçer Gürok Neşe , Konuk Aykut Oğuz , Üçer Özlem
Published: March 2020

Introduction. Mycosis fungoides (MF) is a form of primary cutaneous T-cell lymphomas, and radiotherapy (RT) has been used to treat localized/limited lesions of MF. In this case report, the results of low-dose RT applied for palliative purpose are shared. Case Report. A 70-year-old male patient was admitted to the outpatient clinic 7 months ago with a generalized itchy rash. The result of the biopsy was reported as mycosis fungoides. Systemic treatment was not performed due to comorbid diseases. The hemibody RT was applied. 2 Gy was given per fraction, with a total dose of 6 Gy. The significant clinical relief was observed with 6 Gy RT. The patient died due to multiorgan failure 2 months later, and no recurrence was observed. Conclusion. The palliation was achieved in the advanced MF patient with fractionated 6 Gy hemibody RT for the remaining 2 months of life.
Biological Mesh Repair of a Large Incisional Hernia Containing a Kidney Transplant in the Presence of Inflammation
Authors: Sran Harkiran , Manook Miriam , Chandak Pankaj , Uwechue Raphael , Drage Martin , Loukopoulos Ioannis , Kessaris Nicos
Published: March 2020

The incidence of incisional hernia after kidney transplantation varies between 1.1% and 3.8%. These are usually repaired electively using polypropylene mesh. We present here a case where a patient presented as an emergency, with a large painful incisional hernia over his kidney transplant, and evidence of local erythema and systemic inflammation. As this could have represented either infection or rejection, the patient was started on antibiotics and subsequently underwent graft nephrectomy and hernia repair using a biological (porcine-derived) acellular dermal matrix, Strattice™, with a satisfactory outcome. In addition, histology showed evidence of allograft rejection. This is the first reported case of an incisional hernia containing a rejecting kidney allograft, managed with nephrectomy and biological mesh repair.