bluuebunny/crossref_metadata_2025 huggingface dataset:
Indicators of the molecular pathogenesis of virulent Newcastle disease virus in chickens revealed by transcriptomic profiling of spleen
Authors: Rabiei Mohammad , Low Wai Yee , Ren Yan , Cahyono Mohamad Indro , Doan Phuong Thi Kim , Dharmayanti Indi , Grande Eleonora Dal , Hemmatzadeh Farhid
Published: September 2021

Newcastle disease virus (NDV) has caused significant outbreaks in South-East Asia, particularly in Indonesia in recent years. Recently emerged genotype VII NDVs (NDV-GVII) have shifted their tropism from gastrointestinal/respiratory tropism to a lymphotropic virus, invading lymphoid organs including spleen and bursa of Fabricius to cause profound lymphoid depletion. In this study, we aimed to identify candidate genes and biological pathways that contribute to the disease caused by this velogenic NDV-GVII. A transcriptomic analysis based on RNA-Seq of spleen was performed in chickens challenged with NDV-GVII and a control group. In total, 6361 genes were differentially expressed that included 3506 up-regulated genes and 2855 down-regulated genes. Real-Time PCR of ten selected genes validated the RNA-Seq results as the correlation between them is 0.98. Functional and network analysis of Differentially Expressed Genes (DEGs) showed altered regulation of ElF2 signalling, mTOR signalling, proliferation of cells of the lymphoid system, signalling by Rho family GTPases and synaptogenesis signalling in spleen. We have also identified modified expression of IFIT5, PI3K, AGT and PLP1 genes in NDV-GVII infected chickens. Our findings in activation of autophagy-mediated cell death, lymphotropic and synaptogenesis signalling pathways provide new insights into the molecular pathogenesis of this newly emerged NDV-GVII.
Serum protein electrophoretic pattern in piglets during the early postnatal period
Authors: Tóthová Csilla , Link Robert , Kyzeková Petronela , Nagy Oskar
Published: September 2021

The pattern of serum proteins, the typical features of the electrophoretogram in newborn piglets and during their postnatal development is not completely described. Therefore, the aim of this study was to characterize the changes in serum protein electrophoretic pattern and features of the electrophoretograms during the early postnatal period. Significant changes during the monitored period were found in all evaluated parameters (P < 0.001). The most marked changes were observed mainly in the period before weaning. The concentrations of total proteins, albumin and γ-globulins were before colostrum intake low, γ-globulins represented the smallest proportion of protein fractions. The proportion of α1-globulins was after birth a dominant protein fraction. Significant increase of total proteins, α2-, β- and γ-globulins and decrease of α1-globulins was found 2 days after colostrum intake. The albumin and A/G values increased after birth gradually until weaning. After weaning a significant changes were found in absolute concentrations of total protein and albumin, and in relative values of β-globulin fractions. Presented results showed marked developmental alterations in the serum protein pattern in piglets along with the age. The study also brings new knowledge in the field of description of typical features of electrophoretograms in the observed period of piglet’s life.
Amplified spontaneous emission and gain in highly concentrated Rhodamine-doped peptide derivative
Authors: Machnev Andrey , Ofer Daniel , Shishkin Ivan , Kozlov Vitali , Diaferia Carlo , Accardo Antonella , Morelli Giancarlo , Apter Boris , Inberg Alexandra , Rosenman Gil , Ginzburg Pavel
Published: September 2021

Bioinspired fluorescence, being widely explored for imaging purposes, faces challenges in delivering bright biocompatible sources. While quite a few techniques have been developed to reach this goal, encapsulation of high-quantum yield fluorescent dyes in natural biological forms suggest achieving superior light-emitting characteristics, approaching amplified spontaneous emission and even lasing. Here we compare gain capabilities of highly concentrated Rhodamine B solutions with a newly synthesized biocompatible peptide derivative hybrid polymer/peptide material, RhoB-PEG1300-F6, which contains the fluorescent covalently bound dye. While concentration quenching effects limit the maximal achievable gain of dissolved Rhodamine B, biocompatible conjugation allows elevating amplification coefficients towards moderately high values. In particular, Rhodamine B, anchored to the peptide derivative material, demonstrates gain of 22–23 cm−1 for a 10−2 M solution, while a pure dye solution possesses 25% smaller values at the same concentration. New biocompatible fluorescent agents pave ways to demonstrate lasing in living organisms and can be further introduced to therapeutic applications, if proper solvents are found.
Age and sex effects in physical fitness components of 108,295 third graders including 515 primary schools and 9 cohorts
Authors: Fühner Thea , Granacher Urs , Golle Kathleen , Kliegl Reinhold
Published: September 2021

Children’s physical fitness development and related moderating effects of age and sex are well documented, especially boys’ and girls’ divergence during puberty. The situation might be different during prepuberty. As girls mature approximately two years earlier than boys, we tested a possible convergence of performance with five tests representing four components of physical fitness in a large sample of 108,295 eight-year old third-graders. Within this single prepubertal year of life and irrespective of the test, performance increased linearly with chronological age, and boys outperformed girls to a larger extent in tests requiring muscle mass for successful performance. Tests differed in the magnitude of age effects (gains), but there was no evidence for an interaction between age and sex. Moreover, “physical fitness” of schools correlated at r = 0.48 with their age effect which might imply that "fit schools” promote larger gains; expected secular trends from 2011 to 2019 were replicated.
Eukaryotic Box C/D methylation machinery has two non-symmetric protein assembly sites
Authors: Höfler Simone , Lukat Peer , Blankenfeldt Wulf , Carlomagno Teresa
Published: September 2021

Box C/D ribonucleoprotein complexes are RNA-guided methyltransferases that methylate the ribose 2’-OH of RNA. The central ‘guide RNA’ has box C and D motifs at its ends, which are crucial for activity. Archaeal guide RNAs have a second box C’/D’ motif pair that is also essential for function. This second motif is poorly conserved in eukaryotes and its function is uncertain. Conflicting literature data report that eukaryotic box C’/D’ motifs do or do not bind proteins specialized to recognize box C/D-motifs and are or are not important for function. Despite this uncertainty, the architecture of eukaryotic 2’-O-methylation enzymes is thought to be similar to that of their archaeal counterpart. Here, we use biochemistry, X-ray crystallography and mutant analysis to demonstrate the absence of functional box C’/D’ motifs in more than 80% of yeast guide RNAs. We conclude that eukaryotic Box C/D RNPs have two non-symmetric protein assembly sites and that their three-dimensional architecture differs from that of archaeal 2’-O-methylation enzymes.
Ultra slow acoustic energy transport in dense fish aggregates
Authors: Tallon Benoit , Roux Philippe , Matte Guillaume , Guillard Jean , Page John H. , Skipetrov Sergey E.
Published: September 2021

A dramatic slowing down of acoustic wave transport in dense fish shoals is observed in open-sea fish cages. By employing a multi-beam ultrasonic antenna, we observe the coherent backscattering phenomenon. We extract key parameters of wave transport such as the transport mean free path and the energy transport velocity of diffusive waves from diffusion theory fits to the experimental data. The energy transport velocity is found to be about 10 times smaller than the speed of sound in water, a value that is exceptionally low compared with most observations in acoustics. By studying different models of the fish body, we explain the basic mechanism responsible for the observed very slow transport of ultrasonic waves in dense fish shoals. Our results show that, while the fish swim bladder plays an important role in wave scattering, other organs have to be considered to explain ultra-low energy transport velocities.
A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma
Authors: Peng Yang , Yu Haochen , Zhang Yingzi , Qu Fanli , Tang Zhenrong , Qu Chi , Tian Jiao , Zong Beige , Wang Yu , Ren Haoyu , Liu Shengchun
Published: September 2021

Ferroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients. We downloaded the mRNA expression profiles and corresponding clinical data of BRCA patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) databases. Then, we built a prognostic multigene signature with ferroptosis-related differentially expressed genes (DEGs) in the METABRIC cohort and validated it in the TCGA cohort. The predictive value of this signature was investigated in terms of the immune microenvironment and the probability of a response to immunotherapy and chemotherapy. The patients were divided into a high-risk group and a low-risk group according to the ferroptosis-associated gene signature, and the high-risk group had a worse overall survival (OS). The risk score based on the 10 ferroptosis-related gene-based signature was determined to be an independent prognostic predictor in both the METABRIC and TCGA cohorts (HR, 1.41, 95% CI, 1.14–1.76, P = 0.002; HR, 2.19, 95% CI, 1.13–4.26, P = 0.02). Gene set enrichment analysis indicated that the term “cytokine-cytokine receptor interaction” was enriched in the high-risk score subgroup. Moreover, the immune infiltration scores of most immune cells were significantly different between the two groups, the low-risk group was much more sensitive to immunotherapy, and six drugs might have potential therapeutic implications in the high-risk group. Finally, a nomogram incorporating a classifier based on the 10 ferroptosis-related genes, tumor stage, age and histologic grade was established. This nomogram showed favorable discriminative ability and could help guide clinical decision-making for luminal-type breast carcinoma.
ApoE4 attenuates autophagy via FoxO3a repression in the brain
Authors: Sohn Hee-Young , Kim Seong-Ik , Park Jee-Yun , Park Sung-Hye , Koh Young Ho , Kim Joon , Jo Chulman
Published: September 2021

Apolipoprotein E (ApoE) plays multiple roles in lipid transport, neuronal signaling, glucose metabolism, mitochondrial function, and inflammation in the brain. It is also associated with neurodegenerative diseases, and its influence differs depending on the isoform. In particular, the ε4 allele of APOE is the highest genetic risk factor for developing late-onset Alzheimer’s disease (AD). However, the mechanism by which ApoE4 contributes to the pathogenesis of AD remains unclear. We investigated the effect of ApoE4 on autophagy in the human brains of ApoE4 carriers. Compared to non-carriers, the expression of FoxO3a regulating autophagy-related genes was significantly reduced in ApoE4 carriers, and the phosphorylation level of FoxO3a at Ser253 increased in ApoE4 carriers, indicating that FoxO3a is considerably repressed in ApoE4 carriers. As a result, the protein expression of FoxO3a downstream genes, such as Atg12, Beclin-1, BNIP3, and PINK1, was significantly decreased, likely leading to dysfunction of both autophagy and mitophagy in ApoE4 carriers. In addition, phosphorylated tau accumulated more in ApoE4 carriers than in non-carriers. Taken together, our results suggest that ApoE4 might attenuate autophagy via the repression of FoxO3a in AD pathogenesis. The regulation of the ApoE4-FoxO3a axis may provide a novel therapeutic target for the prevention and treatment of AD with the APOE4 allele.
Fanless, porous graphene-copper composite heat sink for micro devices
Authors: Rho Hokyun , Jang Yea Sol , Bae Hyojung , Cha An-Na , Lee Sang Hyun , Ha Jun-Seok
Published: September 2021

Thermal management in devices directly affects their performance, but it is difficult to apply conventional cooling methods such as the use of cooling liquids or fans to micro devices owing to the small size of micro devices. In this study, we attempted to solve this problem by employing a heat sink fabricated using copper with porous structures consisting of single-layer graphene on the surface and graphene oxide inside the pores. The porous copper/single-layer graphene/graphene oxide composite (p-Cu/G/rGO) had a porosity of approximately 35%, and the measured pore size was approximately 10 to 100 µm. The internal GO was reduced at a temperature of 1000 °C. On observing the heat distribution in the structure using a thermal imaging camera, we could observe that the p-Cu/G/rGO was conducting heat faster than the p-Cu, which was consistent with the simulation. Furthermore, the thermal resistance of p-Cu/G/rGO was lower than those of the p-Cu and pure Cu. When the p-Cu/G/rGO was fabricated into a heat sink to mount the light emitting diode (LED) chip, the measured temperature of the LED was 31.04 °C, which was less than the temperature of the pure Cu of 40.8 °C. After a week of being subjected to high power (1000 mA), the light intensity of p-Cu/G/rGO decreased to 95.24%. However, the pure Cu decreased significantly to 66.04%. The results of this study are expected to be applied to micro devices for their effective thermal management.
Simulating the impacts of interregional mobility restriction on the spatial spread of COVID-19 in Japan
Authors: Kondo Keisuke
Published: September 2021

A spatial susceptible–exposed–infectious–recovered (SEIR) model is developed to analyze the effects of restricting interregional mobility on the spatial spread of the coronavirus disease 2019 (COVID-19) infection in Japan. National and local governments have requested that residents refrain from traveling between prefectures during the state of emergency. However, the extent to which restricting interregional mobility prevents infection expansion is unclear. The spatial SEIR model describes the spatial spread pattern of COVID-19 infection when people commute or travel to a prefecture in the daytime and return to their residential prefecture at night. It is assumed that people are exposed to an infection risk during their daytime activities. The spatial spread of COVID-19 infection is simulated by integrating interregional mobility data. According to the simulation results, interregional mobility restrictions can prevent the geographical expansion of the infection. On the other hand, in urban prefectures with many infectious individuals, residents are exposed to higher infection risk when their interregional mobility is restricted. The simulation results also show that interregional mobility restrictions play a limited role in reducing the total number of infected individuals in Japan, suggesting that other non-pharmaceutical interventions should be implemented to reduce the epidemic size.
Effect of the strain on spin-valley transport properties in MoS2 superlattice
Authors: Sattari Farhad , Mirershadi Soghra
Published: September 2021

The effect of the strain on the spin and valley dependent transport properties, including the conductance and polarization, through a monolayer MoS2 superlattice under Rashba spin–orbit coupling is theoretically investigated. It is found that the conductance strongly depends on the spin and valley degrees of freedom, and spin-inversion can be achieved by MoS2 superlattice. Also, the spin and valley dependent conductance in a monolayer MoS2 superlattice can be efficiently adjusted via strain and the number of the superlattice barriers. Moreover, it is demonstrated that both the magnitude and sign of the spin and valley polarization depend on the strain strength, the number of barriers, and electrostatic barrier height. Both full spin and valley polarized current (with 100% or − 100% efficiency) can be realized in a MoS2 superlattice under strain.
Exposure to COVID-19 is associated with increased altruism, particularly at the local level
Authors: Grimalda Gianluca , Buchan Nancy R. , Ozturk Orgul D. , Pinate Adriana C. , Urso Giulia , Brewer Marilynn B.
Published: September 2021

Theory posits that situations of existential threat will enhance prosociality in general and particularly toward others perceived as belonging to the same group as the individual (parochial altruism). Yet, the global character of the COVID-19 pandemic may blur boundaries between ingroups and outgroups and engage altruism at a broader level. In an online experiment, participants from the U.S. and Italy chose whether to allocate a monetary bonus to a charity active in COVID-19 relief efforts at the local, national, or international level. The purpose was to address two important questions about charitable giving in this context: first, what influences the propensity to give, and second, how is charitable giving distributed across different levels of collective welfare? We found that personal exposure to COVID-19 increased donations relative to those not exposed, even as levels of environmental exposure (numbers of cases locally) had no effect. With respect to targets of giving, we found that donors predominantly benefitted the local level; donations toward country and world levels were half as large. Social identity was found to influence charity choice in both countries, although an experimental manipulation of identity salience did not have any direct effect.
Histology to 3D in vivo MR registration for volumetric evaluation of MRgFUS treatment assessment biomarkers
Authors: Zimmerman Blake E. , Johnson Sara L. , Odéen Henrik A. , Shea Jill E. , Factor Rachel E. , Joshi Sarang C. , Payne Allison H.
Published: September 2021

Advances in imaging and early cancer detection have increased interest in magnetic resonance (MR) guided focused ultrasound (MRgFUS) technologies for cancer treatment. MRgFUS ablation treatments could reduce surgical risks, preserve organ tissue and function, and improve patient quality of life. However, surgical resection and histological analysis remain the gold standard to assess cancer treatment response. For non-invasive ablation therapies such as MRgFUS, the treatment response must be determined through MR imaging biomarkers. However, current MR biomarkers are inconclusive and have not been rigorously evaluated against histology via accurate registration. Existing registration methods rely on anatomical features to directly register in vivo MR and histology. For MRgFUS applications in anatomies such as liver, kidney, or breast, anatomical features that are not caused by the treatment are often insufficient to drive direct registration. We present a novel MR to histology registration workflow that utilizes intermediate imaging and does not rely on anatomical MR features being visible in histology. The presented workflow yields an overall registration accuracy of 1.00 ± 0.13 mm. The developed registration pipeline is used to evaluate a common MRgFUS treatment assessment biomarker against histology. Evaluating MR biomarkers against histology using this registration pipeline will facilitate validating novel MRgFUS biomarkers to improve treatment assessment without surgical intervention. While the presented registration technique has been evaluated in a MRgFUS ablation treatment model, this technique could be potentially applied in any tissue to evaluate a variety of therapeutic options.
Synergistic effect of drought and rainfall events of different patterns on watershed systems
Authors: Qiu Jiali , Shen Zhenyao , Leng Guoyong , Wei Guoyuan
Published: September 2021

The increase in extreme climate events such as flooding and droughts predicted by the general circulation models (GCMs) is expected to significantly affect hydrological processes, erosive dynamics, and their associated nonpoint source (NPS) pollution, resulting in a major challenge to water availability for human life and ecosystems. Using the Hydrological Simulation Program–Fortran model, we evaluated the synergistic effects of droughts and rainfall events on hydrology and water quality in an upstream catchment of the Miyun Reservoir based on the outputs of five GCMs. It showed substantial increases in air temperature, precipitation intensity, frequency of heavy rains and rainstorms, and drought duration, as well as sediment and nutrient loads in the RCP 8.5 scenario. Sustained droughts followed by intense precipitation could cause complex interactions and mobilize accumulated sediment, nutrients and other pollutants into surface water that pose substantial risks to the drinking water security, with the comprehensive effects of soil water content, antecedent drought duration, precipitation amount and intensity, and other climate characteristics, although the effects varied greatly under different rainfall patterns. The Methods and findings of this study evidence the synergistic impacts of droughts and heavy rainfall on watershed system and the significant effects of initial soil moisture conditions on water quantity and quality, and help to guide a robust adaptive management system for future drinking water supply.
Resolving early obesity leads to a cardiometabolic profile within normal ranges at 23 years old in a two-decade prospective follow-up study
Authors: Correa-Burrows Paulina , Rogan José , Blanco Estela , East Patricia , Lozoff Betsy , Gahagan Sheila , Burrows Raquel
Published: September 2021

Obesity is the most important predisposing factor for cardiovascular disease and type-2 diabetes. We explored the relationship between the age at onset of obesity and selected cardiometabolic parameters in young adults. Longitudinal study of n = 1,039 participants (48% males) in their early twenties. BMI was measured at birth, 1–5–10–12–14–16–23 years. BMI trajectories were interpolated. Five groups were identified: never obese (never-OB); early childhood obesity transitioning to non-obesity before adolescence (former-OB); obesity starting in preadolescence transitioning to non-obesity as adolescents (transient-OB); obesity from adolescence into early adulthood (recent-onset-OB); participants who were obese in early childhood and remained obese into adulthood (persistent-OB). Waist circumference (WC), blood pressure, lipids, glucose, and insulin were measured at 23 years. HOMA-IR and the Metabolic Syndrome Risk Z-Score were estimated. In the sample, 47% were obese during at least one time-point. Mean obesity duration was 20.7 years, 8.5 years, 6.2 years, and 3.3 years in persistent-OBs, recent-onset-OBs, former-OBs, and transient-OBs, respectively. The cardiometabolic profile was more adverse in recent-onset-OBs (12%) and persistent-OBs (15%) compared to never-OB participants (53%). Although former-OBs (15%) and transient-OBs (4%) had higher WC values than never-OBs, no differences were seen in other biomarkers. Both persistent and recent-onset obesity led to a cardiometabolic profile of risk in early adulthood, as suggested by values of WC, HOMA-IR, and hs-CRP above normal limits and HDL-chol values below normal limits. Participants who had obesity in early childhood or preadolescence but transitioned to a non-obesity status had a cardiometabolic profile similar to participants who were never obese and within normal limits. Obesity leads to risky values in a number of cardiometabolic biomarkers in young adulthood independent of age at obesity onset. Likewise, overcoming obesity during the pediatric age leads to a cardiometabolic profile within normal ranges at 23 years of age.
Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation
Authors: Hegre Siv Anita , Samdal Helle , Klima Antonin , Stovner Endre B. , Nørsett Kristin G. , Liabakk Nina Beate , Olsen Lene Christin , Chawla Konika , Aas Per Arne , Sætrom Pål
Published: September 2021

Proper regulation of the cell cycle is necessary for normal growth and development of all organisms. Conversely, altered cell cycle regulation often underlies proliferative diseases such as cancer. Long non-coding RNAs (lncRNAs) are recognized as important regulators of gene expression and are often found dysregulated in diseases, including cancers. However, identifying lncRNAs with cell cycle functions is challenging due to their often low and cell-type specific expression. We present a highly effective method that analyses changes in promoter activity, transcription, and RNA levels for identifying genes enriched for cell cycle functions. Specifically, by combining RNA sequencing with ChIP sequencing through the cell cycle of synchronized human keratinocytes, we identified 1009 genes with cell cycle-dependent expression and correlated changes in RNA polymerase II occupancy or promoter activity as measured by histone 3 lysine 4 trimethylation (H3K4me3). These genes were highly enriched for genes with known cell cycle functions and included 57 lncRNAs. We selected four of these lncRNAs—SNHG26, EMSLR, ZFAS1, and EPB41L4A-AS1—for further experimental validation and found that knockdown of each of the four lncRNAs affected cell cycle phase distributions and reduced proliferation in multiple cell lines. These results show that many genes with cell cycle functions have concomitant cell-cycle dependent changes in promoter activity, transcription, and RNA levels and support that our multi-omics method is well suited for identifying lncRNAs involved in the cell cycle.
Avoidance of different durations, colours and intensities of artificial light by adult seabirds
Authors: Syposz Martyna , Padget Oliver , Willis Jay , Van Doren Benjamin M. , Gillies Natasha , Fayet Annette L. , Wood Matt J. , Alejo Aarón , Guilford Tim
Published: September 2021

There is increasing evidence for impacts of light pollution on the physiology and behaviour of wild animals. Nocturnally active Procellariiform seabirds are often found grounded in areas polluted by light and struggle to take to the air again without human intervention. Hence, understanding their responses to different wavelengths and intensities of light is urgently needed to inform mitigation measures. Here, we demonstrate how different light characteristics can affect the nocturnal flight of Manx shearwatersPuffinus puffinusby experimentally introducing lights at a colony subject to low levels of light pollution due to passing ships and coastal developments. The density of birds in flight above the colony was measured using a thermal imaging camera. We compared number of flying shearwaters under dark conditions and in response to an artificially introduced light, and observed fewer birds in flight during ‘light-on’ periods, suggesting that adult shearwaters were repelled by the light. This effect was stronger with higher light intensity, increasing duration of ‘light-on’ periods and with green and blue compared to red light. Thus, we recommend lower light intensity, red colour, and shorter duration of ‘light-on’ periods as mitigation measures to reduce the effects of light at breeding colonies and in their vicinity.
Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches
Authors: Liao S. Y. , Casanova N. G. , Bime C. , Camp S. M. , Lynn H. , Garcia Joe G. N.
Published: September 2021

The lack of successful clinical trials in acute respiratory distress syndrome (ARDS) has highlighted the unmet need for biomarkers predicting ARDS mortality and for novel therapeutics to reduce ARDS mortality. We utilized a systems biology multi-“omics” approach to identify predictive biomarkers for ARDS mortality. Integrating analyses were designed to differentiate ARDS non-survivors and survivors (568 subjects, 27% overall 28-day mortality) using datasets derived from multiple ‘omics’ studies in a multi-institution ARDS cohort (54% European descent, 40% African descent). ‘Omics’ data was available for each subject and included genome-wide association studies (GWAS, n = 297), RNA sequencing (n = 93), DNA methylation data (n = 61), and selective proteomic network analysis (n = 240). Integration of available “omic” data identified a 9-gene set (TNPO1, NUP214, HDAC1, HNRNPA1, GATAD2A, FOSB, DDX17, PHF20, CREBBP) that differentiated ARDS survivors/non-survivors, results that were validated utilizing a longitudinal transcription dataset. Pathway analysis identified TP53-, HDAC1-, TGF-β-, and IL-6-signaling pathways to be associated with ARDS mortality. Predictive biomarker discovery identified transcription levels of the 9-gene set (AUC-0.83) and Day 7 angiopoietin 2 protein levels as potential candidate predictors of ARDS mortality (AUC-0.70). These results underscore the value of utilizing integrated “multi-omics” approaches in underpowered datasets from racially diverse ARDS subjects.
A new qualitative RT-PCR assay detecting SARS-CoV-2
Authors: Favaro Marco , Mattina Walter , Pistoia Enrico Salvatore , Gaziano Roberta , Di Francesco Paolo , Middleton Simon , D’Angelo Silvia , Altarozzi Tullio , Fontana Carla
Published: September 2021

The world is facing an exceptional pandemic caused by SARS-CoV-2. To allow the diagnosis of COVID-19 infections, several assays based on the real-time PCR technique have been proposed. The requests for diagnosis are such that it was immediately clear that the choice of the most suitable method for each microbiology laboratory had to be based, on the one hand, on the availability of materials, and on the other hand, on the personnel and training priorities for this activity. Unfortunately, due to high demand, the shortage of commercial diagnostic kits has also become a major problem. To overcome these critical issues, we have developed a new qualitative RT-PCR probe. Our system detects three genes—RNA-dependent RNA polymerase (RdRp), envelope (E) and nucleocapsid (N)—and uses the β-actin gene as an endogenous internal control. The results from our assay are in complete agreement with the results obtained using a commercially available kit, except for two samples that did not pass the endogenous internal control. The coincidence rate was 0.96. The LoD of our assay was 140 cp/reaction for N and 14 cp/reaction for RdRp and E. Our kit was designed to be open, either for the nucleic acid extraction step or for the RT-PCR assay, and to be carried out on several instruments. Therefore, it is free from the industrial production logics of closed systems, and conversely, it is hypothetically available for distribution in large quantities to any microbiological laboratory. The kit is currently distributed worldwide (called MOLgen-COVID-19; Adaltis). A new version of the kit for detecting the S gene is also available.
Analysis of a gene family for PDF-like peptides from Arabidopsis
Authors: Omidvar Reza , Vosseler Nadine , Abbas Amjad , Gutmann Birgit , Grünwald-Gruber Clemens , Altmann Friedrich , Siddique Shahid , Bohlmann Holger
Published: September 2021

Plant defensins are small, basic peptides that have a characteristic three-dimensional folding pattern which is stabilized by four disulfide bridges. We show here that Arabidopsis contains in addition to the proper plant defensins a group of 9 plant defensin-like (PdfL) genes. They are all expressed at low levels while GUS fusions of the promoters showed expression in most tissues with only minor differences. We produced two of the encoded peptides in E. coli and tested the antimicrobial activity in vitro. Both were highly active against fungi but had lower activity against bacteria. At higher concentrations hyperbranching and swollen tips, which are indicative of antimicrobial activity, were induced in Fusarium graminearum by both peptides. Overexpression lines for most PdfL genes were produced using the 35S CaMV promoter to study their possible in planta function. With the exception of PdfL4.1 these lines had enhanced resistance against F. oxysporum. All PDFL peptides were also transiently expressed in Nicotiana benthamiana leaves with agroinfiltration using the pPZP3425 vector. In case of PDFL1.4 this resulted in complete death of the infiltrated tissues after 7 days. All other PDFLs resulted only in various degrees of small necrotic lesions. In conclusion, our results show that at least some of the PdfL genes could function in plant resistance.
High levels of osteoprotegerin are associated with coronary artery calcification in patients suspected of a chronic coronary syndrome
Authors: Dekker Mirthe , Waissi Farahnaz , Silvis Max J. M. , Bennekom Joelle V. , Schoneveld Arjan H. , de Winter Robbert J. , Isgum Ivana , Lessmann Nikolas , Velthuis Birgitta K. , Pasterkamp Gerard , Mosterd Arend , Timmers Leo , de Kleijn Dominique P. V.
Published: September 2021

Plasma osteoprotegerin (OPG) and vascular smooth muscle cell (VSMC) derived extracellular vesicles (EVs) are important regulators in the process of vascular calcification (VC). In population studies, high levels of OPG are associated with events. In animal studies, however, high OPG levels result in reduction of VC. VSMC-derived EVs are assumed to be responsible for OPG transport and VC but this role has not been studied. For this, we investigated the association between OPG in plasma and circulating EVs with coronary artery calcium (CAC) as surrogate for VC in symptomatic patients. We retrospectively assessed 742 patients undergoing myocardial perfusion imaging (MPI). CAC scores were determined on the MPI-CT images using a previously developed automated algorithm. Levels of OPG were quantified in plasma and two EV-subpopulations (LDL and TEX), using an electrochemiluminescence immunoassay. Circulating levels of OPG were independently associated with CAC scores in plasma; OR 1.39 (95% CI 1.17–1.65), and both EV populations; EV-LDL; OR 1.51 (95% CI 1.27–1.80) and EV-TEX; OR 1.21 (95% CI 1.02–1.42). High levels of OPG in plasma were independently associated with CAC scores in this symptomatic patient cohort. High levels of EV-derived OPG showed the same positive association with CAC scores, suggesting that EV-derived OPG mirrors the same pathophysiological process as plasma OPG.
The complete genome of 2,6-dichlorobenzamide (BAM) degrader Aminobacter sp. MSH1 suggests a polyploid chromosome, phylogenetic reassignment, and functions of plasmids
Authors: Nielsen Tue Kjærgaard , Horemans Benjamin , Lood Cédric , T’Syen Jeroen , van Noort Vera , Lavigne Rob , Ellegaard-Jensen Lea , Hylling Ole , Aamand Jens , Springael Dirk , Hansen Lars Hestbjerg
Published: September 2021

Aminobacter sp. MSH1 (CIP 110285) can use the pesticide dichlobenil and its recalcitrant transformation product, 2,6-dichlorobenzamide (BAM), as sole source of carbon, nitrogen, and energy. The concentration of BAM in groundwater often exceeds the threshold limit for drinking water, requiring additional treatment in drinking water treatment plants or closure of the affected abstraction wells. Biological treatment with MSH1 is considered a potential sustainable alternative to remediate BAM-contamination in drinking water production. We present the complete genome of MSH1, which was determined independently in two institutes at Aarhus University and KU Leuven. Divergences were observed between the two genomes, i.e. one of them lacked four plasmids compared to the other. Besides the circular chromosome and the two previously described plasmids involved in BAM catabolism, pBAM1 and pBAM2, the genome of MSH1 contained two megaplasmids and three smaller plasmids. The MSH1 substrain from KU Leuven showed a reduced genome lacking a megaplasmid and three smaller plasmids and was designated substrain MK1, whereas the Aarhus variant with all plasmids was designated substrain DK1. A plasmid stability experiment indicate that substrain DK1 may have a polyploid chromosome when growing in R2B medium with more chromosomes than plasmids per cell. Finally, strain MSH1 is reassigned as Aminobacter niigataensis MSH1.
Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin
Authors: Gradin Robin , Forreryd Andy , Mattson Ulrika , Jerre Anders , Johansson Henrik
Published: September 2021

Hundreds of chemicals have been identified as skin sensitizers. These are chemicals that possess the ability to induce hypersensitivity reactions in humans, giving rise to a condition termed allergic contact dermatitis. The capacity to limit hazardous exposure to such chemicals depends upon the ability to accurately identify and characterize their skin sensitizing potency. This has traditionally been accomplished using animal models, but their widespread use offers challenges from both an ethical and a scientific perspective. Comprehensive efforts have been made by the scientific community to develop new approach methodologies (NAMs) capable of replacing in vivo assays, which have successfully yielded several methods that can identify skin sensitizers. However, there is still a lack of new approaches that can effectively measure skin sensitizing potency. We present a novel methodology for quantitative assessment of skin sensitizing potency, which is founded on the already established protocols of the GARDskin assay. This approach analyses dose–response relationships in the GARDskin assay to identify chemical-specific concentrations that are sufficient to induce a positive response in the assay. We here compare results for 22 skin sensitizers analyzed using this method with both human and LLNA potency reference data and show that the results correlate strongly and significantly with both metrics (rLLNA = 0.81, p = 9.1 × 10–5; rHuman = 0.74, p = 1.5 × 10–3). In conclusion, the results suggest that the proposed GARDskin dose–response methodology provides a novel non-animal approach for quantitative potency assessment, which could represent an important step towards reducing the need for in vivo experiments.
Agro-productivity amidst environmental degradation and energy usage in Nigeria
Authors: Adeleye Bosede Ngozi , Daramola Praise , Onabote Ademola , Osabohien Romanus
Published: September 2021

This study revisits the 2030 United Nations Sustainable Development Goal (SDG) 2 which aims to “end hunger, achieve food security, improve nutrition and promote sustainable agriculture” by highlighting the impact of environmental degradation (proxied by carbon emissions) and non-renewable energy on agro-productivity in Nigeria. Using annual time series data from 1980 to 2018, the study engages the Johansen cointegration and impulse response functions (IRFs) techniques within the vector autoregressive (VAR) framework. Evidence reveals that carbon emissions significantly reduce agro-productivity by 0.23% while non-renewable energy boosts agro-productivity by 5.38%, on average, ceteris paribus. Other results reveal that domestic credit, rural population and arable land exert asymmetric effects. These outcomes are consistent and align with a priori expectations. Policy recommendations are discussed.
A novel lncRNA–protein interaction prediction method based on deep forest with cascade forest structure
Authors: Tian Xiongfei , Shen Ling , Wang Zhenwu , Zhou Liqian , Peng Lihong
Published: September 2021

Long noncoding RNAs (lncRNAs) regulate many biological processes by interacting with corresponding RNA-binding proteins. The identification of lncRNA–protein Interactions (LPIs) is significantly important to well characterize the biological functions and mechanisms of lncRNAs. Existing computational methods have been effectively applied to LPI prediction. However, the majority of them were evaluated only on one LPI dataset, thereby resulting in prediction bias. More importantly, part of models did not discover possible LPIs for new lncRNAs (or proteins). In addition, the prediction performance remains limited. To solve with the above problems, in this study, we develop a Deep Forest-based LPI prediction method (LPIDF). First, five LPI datasets are obtained and the corresponding sequence information of lncRNAs and proteins are collected. Second, features of lncRNAs and proteins are constructed based on four-nucleotide composition and BioSeq2vec with encoder-decoder structure, respectively. Finally, a deep forest model with cascade forest structure is developed to find new LPIs. We compare LPIDF with four classical association prediction models based on three fivefold cross validations on lncRNAs, proteins, and LPIs. LPIDF obtains better average AUCs of 0.9012, 0.6937 and 0.9457, and the best average AUPRs of 0.9022, 0.6860, and 0.9382, respectively, for the three CVs, significantly outperforming other methods. The results show that the lncRNA FTX may interact with the protein P35637 and needs further validation.
Network neighbors of viral targets and differentially expressed genes in COVID-19 are drug target candidates
Authors: Zambrana Carme , Xenos Alexandros , Böttcher René , Malod-Dognin Noël , Pržulj Nataša
Published: September 2021

The COVID-19 pandemic is raging. It revealed the importance of rapid scientific advancement towards understanding and treating new diseases. To address this challenge, we adapt an explainable artificial intelligence algorithm for data fusion and utilize it on new omics data on viral–host interactions, human protein interactions, and drugs to better understand SARS-CoV-2 infection mechanisms and predict new drug–target interactions for COVID-19. We discover that in the human interactome, the human proteins targeted by SARS-CoV-2 proteins and the genes that are differentially expressed after the infection have common neighbors central in the interactome that may be key to the disease mechanisms. We uncover 185 new drug–target interactions targeting 49 of these key genes and suggest re-purposing of 149 FDA-approved drugs, including drugs targeting VEGF and nitric oxide signaling, whose pathways coincide with the observed COVID-19 symptoms. Our integrative methodology is universal and can enable insight into this and other serious diseases.
Agreement between commercially available ELISA and in-house Luminex SARS-CoV-2 antibody immunoassays
Authors: Santano Rebeca , Barrios Diana , Crispi Fàtima , Crovetto Francesca , Vidal Marta , Chi Jordi , Izquierdo Luis , Gratacós Eduard , Moncunill Gemma , Dobaño Carlota
Published: September 2021

Serological diagnostic of the severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2) is a valuable tool for the determination of immunity and surveillance of exposure to the virus. In the context of an ongoing pandemic, it is essential to externally validate widely used tests to assure correct diagnostics and epidemiological estimations. We evaluated the performance of the COVID-19 ELISA IgG and the COVID-19 ELISA IgM/A (Vircell, S.L.) against a highly specific and sensitive in-house Luminex immunoassay in a set of samples from pregnant women and cord blood. The agreement between both assays was moderate to high for IgG but low for IgM/A. Considering seropositivity by either IgG and/or IgM/A, the technical performance of the ELISA was highly imbalanced, with 96% sensitivity at the expense of 22% specificity. As for the clinical performance, the negative predictive value reached 87% while the positive predictive value was 51%. Our results stress the need for highly specific and sensitive assays and external validation of diagnostic tests with different sets of samples to avoid the clinical, epidemiological and personal disturbances derived from serological misdiagnosis.
Robust squeezed light against mode mismatch using a self imaging optical parametric oscillator
Authors: Roh Chan , Gwak Geunhee , Ra Young-Sik
Published: September 2021

We present squeezed light that is robust against spatial mode mismatch (beam displacement, tilt, and beam-size difference), which is generated from a self-imaging optical parametric oscillator below the threshold. We investigate the quantum properties of the generated light when the oscillator is detuned from the ideal self-imaging condition for stable operation. We find that the generated light is more robust to mode mismatch than single-mode squeezed light having the same squeezing level, and it even outperforms the single-mode infinitely squeezed light as the strength of mode mismatch increases.
Risk and outcomes of diabetes in patients with epilepsy
Authors: Li Chun-Cheng , Chang Chuen-Chau , Cherng Yih-Giun , Lin Chao-Shun , Yeh Chun-Chieh , Chang Yi-Cheng , Hu Chaur-Jong , Shih Chun-Chuan , Chen Ta-Liang , Liao Chien-Chang
Published: September 2021

The risk and outcomes of diabetes in patients with epilepsy remains unclear. We evaluated these risks using an epilepsy cohort analysis and a diabetes admission analysis. In the epilepsy cohort analysis, we identified 2854 patients with newly diagnosed epilepsy in 2000–2008 from the research data of National Health Insurance in Taiwan. Using Propensity-score matching by sociodemographic factors and medical conditions, we selected 22,832 people without epilepsy as a non-exposed cohort for comparison. Follow-up events of diabetes from January 1, 2000 until December 31, 2013 were ascertained from medical claims. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of diabetes associated with epilepsy were calculated using multiple Cox proportional hazard models. In the diabetes admission analysis, we identified 92,438 hospitalized diabetes patients, 930 of whom had a history of epilepsy. Adjusted odds ratios (ORs) and 95% CIs of adverse events after diabetes associated with previous epilepsy were calculated using multiple logistic regressions. The adjusted HR of diabetes in the cohort with epilepsy was 1.31 (95% CI 1.14–1.50) compared to the non-epilepsy cohort. Previous epilepsy was associated with post-diabetes adverse events, such as pneumonia (OR 1.68, 95% CI 1.37–2.07), urinary tract infection (OR 1.83, 95% CI 1.55–2.16), and septicemia (OR 1.34, 95% CI 1.09–1.65). In conclusion, epilepsy was associated with higher risk of diabetes and adverse post-diabetes outcomes. Diabetes prevention and attention to post-diabetes adverse events are needed for this susceptible population.