bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquitin ligation to F-box protein targets by SCF–RBR E3–E3 super-assembly
Authors: Horn-Ghetko Daniel , Krist David T. , Prabu J. Rajan , Baek Kheewoong , Mulder Monique P. C. , Klügel Maren , Scott Daniel C. , Ovaa Huib , Kleiger Gary , Schulman Brenda A. 
Published: February 2021

AbstractE3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates1,2. However, rather than functioning individually, many neddylated cullin–RING E3 ligases (CRLs) and RBR-type E3 ligases in the ARIH family—which together account for nearly half of all ubiquitin ligases in humans—form E3–E3 super-assemblies3–7. Here, by studying CRLs in the SKP1–CUL1–F-box (SCF) family, we show how neddylated SCF ligases and ARIH1 (an RBR-type E3 ligase) co-evolved to ubiquitylate diverse substrates presented on various F-box proteins. We developed activity-based chemical probes that enabled cryo-electron microscopy visualization of steps in E3–E3 ubiquitylation, initiating with ubiquitin linked to the E2 enzyme UBE2L3, then transferred to the catalytic cysteine of ARIH1, and culminating in ubiquitin linkage to a substrate bound to the SCF E3 ligase. The E3–E3 mechanism places the ubiquitin-linked active site of ARIH1 adjacent to substrates bound to F-box proteins (for example, substrates with folded structures or limited length) that are incompatible with previously described conventional RING E3-only mechanisms. The versatile E3–E3 super-assembly may therefore underlie widespread ubiquitylation.
Allergic rhinitis, asthma and laryngopharyngeal reflux disease: a cross-sectional study on their reciprocal relations
Authors: Kakaje Ameer , Alhalabi Mohammad Marwan , Alyousbashi Ayham , Ghareeb Ayham 
Published: February 2021

AbstractAllergic rhinitis (AR) is a common medical condition worldwide. It is an inflammation in the nasal mucosa due to allergen exposure throughout the year. Laryngopharyngeal reflux (LPR) is another medical condition that can overlap with AR. LPR can be considered an extra oesophageal manifestation of gastro-oesophageal reflux disease (GORD) or a different entity. Its diagnosis imposes a real challenge as it has a wide range of unspecific symptoms. Although AR and LPR are not life-threatening, they can severely affect the quality of life for years and cause substantial distress. Moreover, having AR is associated with having asthma which is also in turn associated with GORD. This is a cross-sectional study which used surveys distributed online on Social Media and targeted people across Syria. All participants who responded to the key questions were included. Reflux symptom index (RSI) was used for LPR, and score for allergic rhinitis (SFAR) was used for AR. Demographic questions and whether the participant had asthma were also included in the survey. We found that there was an association between the symptoms of LPR and AR p < 0.0001 (OR, 2.592; 95% CI 1.846–3.639), and their scores were significantly correlated (r = 0.334). Having asthma was associated with LPR symptoms p = 0.0002 (OR 3.096; 95% CI 1.665–5.759) and AR p < 0.0001 (OR 6.772; 95% CI 2.823–16.248). We concluded that there was a significant association between having LPR, AR, and asthma. We need more studies to distinguish between their common symptoms and aetiologies.
Influenza-associated disease burden in mainland China: a systematic review and meta-analysis
Authors: Li Jing , Chen Yinzi , Wang Xiling , Yu Hongjie 
Published: February 2021

AbstractInfluenza causes substantial morbidity and mortality. Many original studies have been carried out to estimate disease burden of influenza in mainland China, while the full disease burden has not yet been systematically reviewed. We did a systematic review and meta-analysis to assess the burden of influenza-associated mortality, hospitalization, and outpatient visit in mainland China. We searched 3 English and 4 Chinese databases with studies published from 2005 to 2019. Studies reporting population-based rates of mortality, hospitalization, or outpatient visit attributed to seasonal influenza were included in the analysis. Fixed-effects or random-effects model was used to calculate pooled estimates of influenza-associated mortality depending on the degree of heterogeneity. Meta-regression was applied to explore the sources of heterogeneity. Publication bias was assessed by funnel plots and Egger’s test. We identified 30 studies eligible for inclusion with 17, 8, 5 studies reporting mortality, hospitalization, and outpatient visit associated with influenza, respectively. The pooled influenza-associated all-cause mortality rates were 14.33 and 122.79 per 100,000 persons for all ages and ≥ 65 years age groups, respectively. Studies were highly heterogeneous in aspects of age group, cause of death, statistical model, geographic location, and study period, and these factors could explain 60.14% of the heterogeneity in influenza-associated mortality. No significant publication bias existed in estimates of influenza-associated all-cause mortality. Children aged < 5 years were observed with the highest rates of influenza-associated hospitalizations and ILI outpatient visits. People aged ≥ 65 years and < 5 years contribute mostly to mortality and morbidity burden due to influenza, which calls for targeted vaccination policy for older adults and younger children in mainland China.
Water column gradients beneath the summer ice of a High Arctic freshwater lake as indicators of sensitivity to climate change
Authors: Bégin Paschale N. , Tanabe Yukiko , Rautio Milla , Wauthy Maxime , Laurion Isabelle , Uchida Masaki , Culley Alexander I. , Vincent Warwick F. 
Published: February 2021

AbstractIce cover persists throughout summer over many lakes at extreme polar latitudes but is likely to become increasingly rare with ongoing climate change. Here we addressed the question of how summer ice-cover affects the underlying water column of Ward Hunt Lake, a freshwater lake in the Canadian High Arctic, with attention to its vertical gradients in limnological properties that would be disrupted by ice loss. Profiling in the deepest part of the lake under thick mid-summer ice revealed a high degree of vertical structure, with gradients in temperature, conductivity and dissolved gases. Dissolved oxygen, nitrous oxide, carbon dioxide and methane rose with depth to concentrations well above air-equilibrium, with oxygen values at > 150% saturation in a mid-water column layer of potential convective mixing. Fatty acid signatures of the seston also varied with depth. Benthic microbial mats were the dominant phototrophs, growing under a dim green light regime controlled by the ice cover, water itself and weakly colored dissolved organic matter that was mostly autochthonous in origin. In this and other polar lakes, future loss of mid-summer ice will completely change many water column properties and benthic light conditions, resulting in a markedly different ecosystem regime.
Reference values of electrographic and cardiac ultrasound parameters in Russian healthy children and adolescents
Authors: Landon Geraldine , Denjoy Isabelle , Clero Enora , Silenok Aleksandr , Kurnosova Irina , Butsenin Andrey , Gourmelon Patrick , Jourdain Jean-Rene 
Published: February 2021

AbstractBetween 2009 and 2013, a large cross-sectional study on the health consequences of the Chernobyl nuclear accident was performed in the contaminated and uncontaminated territories of the Bryansk Oblast (Russian Federation). The objective of this work was to confirm or refute a possible association between childhood cardiac arrhythmia and a chronic exposure to caesium-137. As part of this study, a large number of electrocardiographic and cardiac ultrasound parameters were collected from 18,152 children aged 2–18 years including 12,512 healthy ones not contaminated with caesium-137. It seemed therefore relevant for us to share in a second publication these medical data based on healthy and uncontaminated children with the scientific community because of the large quantities and the limited availability of such kind of data. In the present study, relating to electrocardiographic parameters, the measurements performed fully reflect the expected evolution of the paediatric electrocardiogram between 5 and 18 years of age. Thus, the median values were generally quite close to those available in the literature. In contrast, differences in the 2nd and 98th percentiles were notable and could be explained in particular by the type of equipment used, the number of subjects included in the study and racial disparities. As for echocardiographic parameters, the evolution of the measured values in age groups is consistent with what was expected considering factors such as growth. In comparison with other scientific studies that have investigated these echocardiographic parameters, some differences by age groups have been identified. The ethnic factor truly appears to be a relevant feature to consider. In view of the results, it appeared essential to the authors to approach the methodological conditions of the scientific studies already published on the topic to be truly comparable and thus to provide a reliable answer on a topic for which real expectations in terms of medical care are required.
Quenching effect of oscillating potential on anisotropic resonant transmission through a phosphorene electrostatic barrier
Authors: Biswas R. , Sinha C. 
Published: February 2021

AbstractThe anisotropy in resonant tunneling transport through an electrostatic barrier in monolayer black phosphorus either in presence or in absence of an oscillating potential is studied. Non-perturbative Floquet theory is applied to solve the time dependent problem and the results obtained are discussed thoroughly. The resonance spectra in field free transmission are Lorentzian in nature although the width of the resonance for the barrier along the zigzag (Г–Y) direction is too thinner than that for the armchair (Г–X) one. Resonant transmission is suppressed for both the cases by the application of oscillating potential that produces small oscillations in the transmission around the resonant energy particularly at low frequency range. Sharp asymmetric Fano resonances are noted in the transmission spectrum along the armchair direction while a distinct line shape resonance is noted for the zigzag direction at higher frequency of the oscillating potential. Even after the angular average, the conductance along the Г–X direction retains the characteristic Fano features that could be observed experimentally. The present results are supposed to suggest that the phosphorene electrostatic barrier could be used successfully as switching devices and nano detectors.
Elevated serum TREM-1 is associated with periodontitis and disease activity in rheumatoid arthritis
Authors: Inanc Nevsun , Mumcu Gonca , Can Meryem , Yay Meral , Silbereisen Angelika , Manoil Daniel , Direskeneli Haner , Bostanci Nagihan 
Published: February 2021

AbstractThe triggering receptor expressed on myeloid cells 1 (TREM-1) and peptidoglycan recognition protein 1 (PGLYRP1) are involved in the propagation of inflammatory responses. This study investigated whether serum levels of TREM-1 and PGLYRP1 correlate with periodontitis in rheumatoid arthritis (RA) patients. A total of 154 non-smoking participants with RA (n = 55, F/M: 41/14), Behçet´s disease (BD, n = 41, F/M: 30/11) and healthy controls (HC, n = 58, F/M: 40/18) were recruited. Serum and saliva were collected, the 28-joint disease activity score (DAS-28) was calculated and dental/periodontal measurements were recorded. Serum TREM-1 and PGLYRP1 levels were measured by ELISA and salivary bacterial DNA counts by quantitative polymerase chain reaction. TREM-1 and PGLYRP1 levels were higher in RA (166.3 ± 94.3; 155.5 ± 226.9 pg/ml) than BD (102.3 ± 42.8; 52.5 ± 26.3 pg/ml) and HCs (89.8 ± 55.7; 67.4 ± 37.3 pg/ml) (p < 0.05). In RA, periodontitis was associated with increased TREM-1 and PGLYRP1 levels (p < 0.05), yet in patients under methotrexate TREM-1 levels were lower. TREM-1 correlated with C-reactive protein (CRP) levels, DAS-28 and erythrocyte sedimentation rate, whereas PGLYRP1 positively correlated with CRP. RA patients displayed 3.5-fold higher salivary bacterial DNA counts than HCs. Increased serum TREM-1 levels correlated with PGLYRP1, CRP and DAS-28-ESR in RA patients with periodontitis.
First finding of free-living representatives of Prokinetoplastina and their nuclear and mitochondrial genomes
Authors: Tikhonenkov Denis V. , Gawryluk Ryan M. R. , Mylnikov Alexander P. , Keeling Patrick J. 
Published: February 2021

AbstractKinetoplastids are heterotrophic flagellated protists, including important parasites of humans and animals (trypanosomatids), and ecologically important free-living bacterial consumers (bodonids). Phylogenies have shown that the earliest-branching kinetoplastids are all parasites or obligate endosymbionts, whose highly-derived state makes reconstructing the ancestral state of the group challenging. We have isolated new strains of unusual free-living flagellates that molecular phylogeny shows to be most closely related to endosymbiotic and parasitic Perkinsela and Ichthyobodo species that, together with unidentified environmental sequences, form the clade at the base of kinetoplastids. These strains are therefore the first described free-living prokinetoplastids, and potentially very informative in understanding the evolution and ancestral states of morphological and molecular characteristics described in other kinetoplastids. Overall, we find that these organisms morphologically and ultrastructurally resemble some free-living bodonids and diplonemids, and possess nuclear genomes with few introns, polycistronic mRNA expression, high coding density, and derived traits shared with other kinetoplastids. Their genetic repertoires are more diverse than the best-studied free-living kinetoplastids, which is likely a reflection of their higher metabolic potential. Mitochondrial RNAs of these new species undergo the most extensive U insertion/deletion editing reported so far, and limited deaminative C-to-U and A-to-I editing, but we find no evidence for mitochondrial trans-splicing.
Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer
Authors: Osman Muhammad Afiq , Neoh Hui-min , Ab Mutalib Nurul-Syakima , Chin Siok-Fong , Mazlan Luqman , Raja Ali Raja Affendi , Zakaria Andee Dzulkarnaen , Ngiu Chai Soon , Ang Mia Yang , Jamal Rahman 
Published: February 2021

AbstractDysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.
Accurate and confident prediction of electron beam longitudinal properties using spectral virtual diagnostics
Authors: Hanuka A. , Emma C. , Maxwell T. , Fisher A. S. , Jacobson B. , Hogan M. J. , Huang Z. 
Published: February 2021

AbstractLongitudinal phase space (LPS) provides a critical information about electron beam dynamics for various scientific applications. For example, it can give insight into the high-brightness X-ray radiation from a free electron laser. Existing diagnostics are invasive, and often times cannot operate at the required resolution. In this work we present a machine learning-based Virtual Diagnostic (VD) tool to accurately predict the LPS for every shot using spectral information collected non-destructively from the radiation of relativistic electron beam. We demonstrate the tool’s accuracy for three different case studies with experimental or simulated data. For each case, we introduce a method to increase the confidence in the VD tool. We anticipate that spectral VD would improve the setup and understanding of experimental configurations at DOE’s user facilities as well as data sorting and analysis. The spectral VD can provide confident knowledge of the longitudinal bunch properties at the next generation of high-repetition rate linear accelerators while reducing the load on data storage, readout and streaming requirements.
Genetic patterns in Mugil cephalus and implications for fisheries and aquaculture management
Authors: Cossu Piero , Mura Laura , Scarpa Fabio , Lai Tiziana , Sanna Daria , Azzena Ilenia , Fois Nicola , Casu Marco 
Published: February 2021

AbstractExploitation of fisheries and aquaculture practices are exposing marine fish populations to increasing genetic risks. Therefore, the integration of genetic information into fisheries and aquaculture management is becoming crucial to ensure species’ long-term persistence. The raising commercial value of grey mullet (Mugil cephalus) and its roe represents a growing challenge to the sustainable management of this economically important fishery resource. Here, microsatellites were used to investigate patterns of genetic variation in a Mediterranean area that harbor flourishing fisheries and practice semi-intensive farming of grey mullet. Genetic diversity within populations is smaller than values reported in previous studies as a result of the lower polymorphism displayed by the new microsatellite loci. Lack of genetic structuring points to the existence of a unique genetic stock, which is consistent with the species’ high dispersal capabilities. Nonetheless, differences in local population effective size as well as the excess of related individuals do not completely fit the picture of a large panmictic population. Baseline genetic information here gathered will allow to set up the genetic monitoring of regional fish stocks, which is needed to assess the impact of both harvesting and aquaculture on the genetic integrity of Mugil cephalus wild populations.
Detection of selection signatures for response to Aleutian mink disease virus infection in American mink
Authors: Karimi Karim , Farid A. Hossain , Myles Sean , Miar Younes 
Published: February 2021

AbstractAleutian disease (AD) is the most significant health issue for farmed American mink. The objective of this study was to identify the genomic regions subjected to selection for response to infection with Aleutian mink disease virus (AMDV) in American mink using genotyping by sequencing (GBS) data. A total of 225 black mink were inoculated with AMDV and genotyped using a GBS assay based on the sequencing ofApeKI-digested libraries. Five AD-characterized phenotypes were used to assign animals to pairwise groups. Signatures of selection were detected using integrated measurement of fixation index (FST) and nucleotide diversity (θπ), that were validated by haplotype-based (hap-FLK) test. The total of 99 putatively selected regions harbouring 63 genes were detected in different groups. The gene ontology revealed numerous genes related to immune response (e.g.TRAF3IP2,WDR7,SWAP70,CBFB, andGPR65), liver development (e.g.SULF2,SRSF5) and reproduction process (e.g.FBXO5,CatSperβ,CATSPER4, andIGF2R). The hapFLK test supported two strongly selected regions that contained five candidate genes related to immune response, virus–host interaction, reproduction and liver regeneration. This study provided the first map of putative selection signals of response to AMDV infection in American mink, bringing new insights into genomic regions controlling the AD phenotypes.
Macrophages enhance lipopolysaccharide induced apoptosis via Ang1 and NF-κB pathways in human umbilical vein endothelial cells
Authors: Cai Guo-Long , Yang Zhou-Xin , Guo Dong-Yang , Hu Cai-Bao , Yan Mo-Lei , Yan Jing 
Published: February 2021

AbstractLipopolysaccharide (LPS) could induce apoptosis and dysfunction of endothelial cells. We aimed to reveal the effects of macrophages on cell proliferation and apoptosis in LPS induced human umbilical vein endothelial cells (HUVECs). THP-1 derived macrophages and HUVECs were co-cultured in the presence of LPS. Cell viability was measured by Cell Counting Kit-8 and apoptosis was analyzed by flow cytometry. Expression of Ang1, the NF-κB component p65 was evaluated by western blot and quantitative PCR. Small interfering RNAs (siRNAs) were used to knockdown the expression of proinflammatory cytokines and p65 in HUVECs. Plasmid transfection-mediated overexpression of Ang1 was employed to see its effects on cell proliferation and apoptosis in HUVECs. Macrophages enhanced LPS-induced proliferation impairments and apoptosis in HUVECs, which could be attenuated by siRNA-mediated knockdown of cytokines TNF-α, IL-1β, IL-6 and IL-12p70 in macrophages. The dysfunction of HUVECs was tightly associated with reduced Ang1 expression and increased phosphorylated p65 (p-65). Overexpression of Ang1 in HUVECs significantly decreased p-p65, suggesting negatively regulation of p-p65 by Ang1. Overexpression of Ang1, adding recombinant Ang1 or silencing of p65 substantially attenuated the dysfunction of HUVECs in terms of cell proliferation and apoptosis. In conclusions, THP-1-derived macrophages enhance LPS induced dysfunction of HUVECs via Ang1 and NF-κB pathways, suggesting new therapeutic targets for sepsis.
The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues
Authors: Staniszewska Magdalena , Bronowicka-Szydełko Agnieszka , Gostomska-Pampuch Kinga , Szkudlarek Jerzy , Bartyś Arkadiusz , Bieg Tadeusz , Gamian Elżbieta , Kochman Agata , Picur Bolesław , Pietkiewicz Jadwiga , Kuropka Piotr , Szeja Wiesław , Wiśniewski Jerzy , Ziółkowski Piotr , Gamian Andrzej 
Published: February 2021

AbstractNon-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (mel-derived AGEs) synthesized in vitro under anhydrous conditions with bovine serum albumin and myoglobin. Using nuclear magnetic resonance spectroscopy we have identified MAGEs as a set of isomers, with open-chain and cyclic structures, of the fructosamine moiety. We generated a mouse anti-MAGE monoclonal antibody and show for the first time that the native and previously undescribed analogous glycation product exists in living organisms and is naturally present in tissues of both invertebrates and vertebrates, including humans. We also report MAGE cross-reactive auto-antibodies in patients with diabetes. We anticipate our approach for modeling glycation in vivo will be a foundational methodology in cell biology. Further studies relevant to the discovery of MAGE may contribute to clarifying disease mechanisms and to the development of novel therapeutic options for diabetic complications, neuropathology, and cancer.