bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in wood physical properties and effects of climate for different geographic sources of Chinese fir in subtropical area of China
Authors: You Ren , Zhu Ninghua , Deng Xiangwen , Wang Jing , Liu Fei
Published: February 2021

Chinese fir is one of the most important commercial timber species in China, with many geographic sources. However, little is known of the variation in wood physical properties among them. To explore the differences in wood physical properties and their influencing factors, five geographic sources of Chinese fir were selected. The variance inflation factor, stepwise regression, and principle component analysis were used to reduce multicollinearity and dimensions of the 19 wood physical properties (including density, shrinkage, and mechanical properties). The results showed that the wood density differed significantly among five geographic sources. The tangential shrinkage rate and radial shrinkage rate reached maximum values in black-heart Chinese fir (HNYX-T) but accompanied by the lowest value for difference dry shrinkage. The wood density and mechanical properties of HNYX-T was exceeded to that of others geographic sources. Fast-growth Chinese fir (FJYK-P) had the lowest value for all mechanical properties. The precipitation and temperature had significant correlations with the wood physical properties of this five geographic sources. The temperature in summer was mainly positive correlated with physical properties, while precipitation was negatively correlated with them. HNYX-T had the highest comprehensive score of PCA, followed by JXCS-R, emerged as higher-quality geographic source, which is important for selecting and utilizing geographic sources in forest management.
A spatiotemporal analysis of opioid poisoning mortality in Ohio from 2010 to 2016
Authors: Park Chihyun , Clemenceau Jean R. , Seballos Anna , Crawford Sara , Lopez Rocio , Coy Tyler , Atluri Gowtham , Hwang Tae Hyun
Published: February 2021

Opioid-related deaths have severely increased since 2000 in the United States. This crisis has been declared a public health emergency, and among the most affected states is Ohio. We used statewide vital statistic data from the Ohio Department of Health (ODH) and demographics data from the U.S. Census Bureau to analyze opioid-related mortality from 2010 to 2016. We focused on the characterization of the demographics from the population of opioid-related fatalities, spatiotemporal pattern analysis using Moran’s statistics at the census-tract level, and comorbidity analysis using frequent itemset mining and association rule mining. We found higher rates of opioid-related deaths in white males aged 25–54 compared to the rest of Ohioans. Deaths tended to increasingly cluster around Cleveland, Columbus and Cincinnati and away from rural regions as time progressed. We also found relatively high co-occurrence of cardiovascular disease, anxiety or drug abuse history, with opioid-related mortality. Our results demonstrate that state-wide spatiotemporal and comorbidity analysis of the opioid epidemic could provide novel insights into how the demographic characteristics, spatiotemporal factors, and/or health conditions may be associated with opioid-related deaths in the state of Ohio.
Microfluidic Overhauser DNP chip for signal-enhanced compact NMR
Authors: Kiss Sebastian Z. , MacKinnon Neil , Korvink Jan G.
Published: February 2021

Nuclear magnetic resonance at low field strength is an insensitive spectroscopic technique, precluding portable applications with small sample volumes, such as needed for biomarker detection in body fluids. Here we report a compact double resonant chip stack system that implements in situ dynamic nuclear polarisation of a 130 nL sample volume, achieving signal enhancements of up to − 60 w.r.t. the thermal equilibrium level at a microwave power level of 0.5 W. This work overcomes instrumental barriers to the use of NMR detection for point-of-care applications.
Thermal reaction norms of key metabolic enzymes reflect divergent physiological and behavioral adaptations of closely related amphipod species
Authors: Jakob Lena , Vereshchagina Kseniya P. , Tillmann Anette , Rivarola-Duarte Lorena , Axenov-Gribanov Denis V. , Bedulina Daria S. , Gurkov Anton N. , Drozdova Polina , Timofeyev Maxim A. , Stadler Peter F. , Luckenbach Till , Pörtner Hans-Otto , Sartoris Franz J. , Lucassen Magnus
Published: February 2021

Lake Baikal is inhabited by more than 300 endemic amphipod species, which are narrowly adapted to certain thermal niches due to the high interspecific competition. In contrast, the surrounding freshwater fauna is commonly represented by species with large-scale distribution and high phenotypic thermal plasticity. Here, we investigated the thermal plasticity of the energy metabolism in two closely-related endemic amphipod species from Lake Baikal (Eulimnogammarus verrucosus; stenothermal andEulimnogammarus cyaneus; eurythermal) and the ubiquitous Holarctic amphipodGammarus lacustris(eurythermal) by exposure to a summer warming scenario (6–23.6 °C; 0.8 °C d−1). In concert with routine metabolic rates, activities of key metabolic enzymes increased strongly with temperature up to 15 °C inE. verrucosus, whereupon they leveled off (except for lactate dehydrogenase). In contrast, exponential increases were seen inE. cyaneusandG. lacustristhroughout the thermal trial (Q10-values: 1.6–3.7). Cytochrome-c-oxidase, lactate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase activities were found to be higher inG. lacustristhan inE. cyaneus, especially at the highest experimental temperature (23.6 °C). Decreasing gene expression levels revealed some thermal compensation inE. cyaneusbut not inG. lacustris. In all species, shifts in enzyme activities favored glycolytic energy generation in the warmth. The congruent temperature-dependencies of enzyme activities and routine metabolism inE. verrucosusindicate a strong feedback-regulation of enzymatic activities by whole organism responses. The species-specific thermal reaction norms reflect the different ecological niches, including the spatial distribution, distinct thermal behavior such as temperature-dependent migration, movement activity, and mating season.
Systematic and computational identification of Androctonus crassicauda long non-coding RNAs
Authors: Salabi Fatemeh , Jafari Hedieh , Navidpour Shahrokh , Sadr Ayeh Sadat
Published: February 2021

The potential function of long non-coding RNAs in regulating neighbor protein-coding genes has attracted scientists’ attention. Despite the important role of lncRNAs in biological processes, a limited number of studies focus on non-model animal lncRNAs. In this study, we used a stringent step-by-step filtering pipeline and machine learning-based tools to identify the specific Androctonus crassicauda lncRNAs and analyze the features of predicted scorpion lncRNAs. 13,401 lncRNAs were detected using pipeline in A. crassicauda transcriptome. The blast results indicated that the majority of these lncRNAs sequences (12,642) have no identifiable orthologs even in closely related species and those considered as novel lncRNAs. Compared to lncRNA prediction tools indicated that our pipeline is a helpful approach to distinguish protein-coding and non-coding transcripts from RNA sequencing data of species without reference genomes. Moreover, analyzing lncRNA characteristics in A. crassicauda uncovered that lower protein-coding potential, lower GC content, shorter transcript length, and less number of isoform per gene are outstanding features of A. crassicauda lncRNAs transcripts.
High diversity, inbreeding and a dynamic Pleistocene demographic history revealed by African buffalo genomes
Authors: de Jager Deon , Glanzmann Brigitte , Möller Marlo , Hoal Eileen , van Helden Paul , Harper Cindy , Bloomer Paulette
Published: February 2021

Genomes retain records of demographic changes and evolutionary forces that shape species and populations. Remnant populations of African buffalo (Syncerus caffer) in South Africa, with varied histories, provide an opportunity to investigate signatures left in their genomes by past events, both recent and ancient. Here, we produce 40 low coverage (7.14×) genome sequences of Cape buffalo (S. c. caffer) from four protected areas in South Africa. Genome-wide heterozygosity was the highest for any mammal for which these data are available, while differences in individual inbreeding coefficients reflected the severity of historical bottlenecks and current census sizes in each population. PSMC analysis revealed multiple changes in Ne between approximately one million and 20 thousand years ago, corresponding to paleoclimatic changes and Cape buffalo colonisation of southern Africa. The results of this study have implications for buffalo management and conservation, particularly in the context of the predicted increase in aridity and temperature in southern Africa over the next century as a result of climate change.
Investigating the effect of a nap following experimental trauma on analogue PTSD symptoms
Authors: Wilhelm Ines , Azza Yasmine , Brennwald Karin , Ehrt-Schäfer Yamina , Seifritz Erich , Kleim Birgit
Published: February 2021

Cognitive models assume that the incomplete integration of a traumatic experience into the autobiographical memory results in typical symptoms associated with post-traumatic stress disorder (PTSD) such as intrusive re-experiencing. Sleep supports the integration of new experiences into existing memory networks through memory consolidation. In fifty-six females, we investigated whether a 90-min daytime nap (n = 33) compared to a wake period (n = 23) after being exposed to an experimental trauma (i.e. a trauma film) prevents PTSD analogue symptoms. Intrusive memories were recorded for seven days using a diary, overall PTSD symptoms were assessed using the Impact of Event Scale (IES-R) and affective response to trauma cues were measured one week after experimental trauma. The two groups did not differ in any of the analogue PTSD symptoms. However, participants obtaining rapid eye movement (REM) sleep in the nap experienced less distressing intrusive memories. Moreover, the duration of REM sleep and slow wave activity was negatively correlated with analogue PTSD symptoms. Our findings suggest that even a short sleep period after experimental trauma can play a protective role in trauma memory formation but only if the nap contains REM sleep. Our data provide additional evidence for a critical role of REM sleep in PTSD development.
Chimpanzees balance resources and risk in an anthropogenic landscape of fear
Authors: Bersacola Elena , Hill Catherine M. , Hockings Kimberley J.
Published: February 2021

Human-wildlife coexistence is possible when animals can meet their ecological requirements while managing human-induced risks. Understanding how wildlife balance these trade-offs in anthropogenic environments is crucial to develop effective strategies to reduce risks of negative interactions, including bi-directional aggression and disease transmission. For the first time, we use a landscape of fear framework with Bayesian spatiotemporal modelling to investigate anthropogenic risk-mitigation and optimal foraging trade-offs in Critically Endangered western chimpanzees (Pan troglodytes verus). Using 12 months of camera trap data (21 camera traps, 6722 camera trap days) and phenology on wild and cultivated plant species collected at Caiquene–Cadique, Cantanhez National Park (Guinea-Bissau), we show that humans and chimpanzees broadly overlapped in their use of forest and anthropogenic parts of the habitat including villages and cultivated areas. The spatiotemporal model showed that chimpanzee use of space was predicted by the availability of naturalised oil-palm fruit. Chimpanzees used areas away from villages and agriculture more intensively, but optimised their foraging strategies by increasing their use of village areas with cultivated fruits when wild fruits were scarce. Our modelling approach generates fine-resolution space–time output maps, which can be scaled-up to identify human-wildlife interaction hotspots at the landscape level, informing coexistence strategy.
Bio-inspired synthesis of palladium nanoparticles fabricated magnetic Fe3O4 nanocomposite over Fritillaria imperialis flower extract as an efficient recyclable catalyst for the reduction of nitroarenes
Authors: Veisi Hojat , Karmakar Bikash , Tamoradi Taiebeh , Tayebee Reza , Sajjadifar Sami , Lotfi Shahram , Maleki Behrooz , Hemmati Saba
Published: February 2021

This current research is based on a bio-inspired procedure for the synthesis of biomolecule functionalized hybrid magnetic nanocomposite with the Fe3O4 NPs at core and Pd NPs at outer shell. The central idea was the initial modification of magnetic NP by the phytochemicals from Fritillaria imperialis flower extract, which was further exploited in the green reduction of Pd2+ ions into Pd NPs, in situ. The flower extract also acted as a capping agent for the obtained Pd/Fe3O4 composite without the need of additional toxic reagents. The as-synthesized Fe3O4@Fritillaria/Pd nanocomposite was methodically characterized over different physicochemical measures like FT-IR, ICP-AES, FESEM, EDX, TEM, XPS and VSM analysis. Thereafter, its catalytic potential was evaluated in the reduction of various nitrobenzenes to arylamines applying hydrazine hydrate as reductant in ethanol/water (1:2) medium under mild conditions. Furthermore, the nanocatalyst was retrieved using a bar magnet and recycled several times without considerable leaching or loss of activity. This green, bio-inspired ligand-free protocol has remarkable advantages like environmental friendliness, high yields, easy workup and reusability of the catalyst.
Helicobacter pylori type 4 secretion systems as gastroduodenal disease markers
Authors: Phuc Bui Hoang , Tuan Vo Phuoc , Dung Ho Dang Quy , Binh Tran Thanh , Tung Pham Huu , Tri Tran Dinh , Thuan Ngo Phuong Minh , Van Khien Vu , Trang Tran Thi Huyen , Akada Junko , Matsumoto Takeshi , Yamaoka Yoshio
Published: February 2021

Although the type 4 secretion system of the integrating and conjugative elements (tfs ICE) is common in Helicobacter pylori, its clinical association with the cag pathogenicity island (cagPAI) have not yet been well-investigated. In this study, Vietnamese patient H. pylori samples (46 duodenal ulcer (DU), 51 non-cardia gastric cancer (NCGC), 39 chronic gastritis (CG)) were fully sequenced using next-generation sequencing and assembled into contigs. tfs3, tfs4, and cagPAI genes were compared with the public database. Most (94%) H. pylori strains possessed a complete cagPAI, which was the greatest risk factor for clinical outcomes, while the prevalences of tfs3 and tfs4 were 45% and 77%, respectively. Complete tfs3 and tfs4 were found in 18.3% and 17.6% of strains, respectively. The prevalence of H. pylori strains with complete tfs3 ICE in DU patients was significantly higher than that in NCGC patients (30.4% vs 11.7%, P < 0.05). In addition, the prevalence of strains with complete tfs3 ICE and cagPAI was significantly higher in DU patients than that in NCGC (28.4% vs 9.8%, P = 0.038) and CG patients (28.2% vs 7.7%, P = 0.024). cagPAI and complete tfs3 increased the risk of DU compared to NCGC (OR = 3.56, 95%CI: 1.1–14.1, P = 0.038) and CG (OR = 4.64, 95%CI: 1.1–27.6, P = 0.024). A complete cluster of tfs3 ICE was associated with gastroduodenal diseases in Vietnam. However, there was a low prevalence of the dupA/complete dupA cluster (15.4%) in the Vietnam strains. The prevalence of cagPAI in Vietnam strains was significantly higher than in US (P = 0.01) and Indonesia (P < 0.0001); the prevalence of the dupA cluster was also higher in the Vietnam strains than in the Indonesian strains (P < 0.05). In addition, the prevalence of ctkA, an accessory gene of tfs3, was significantly different between Vietnam and US strains (28% vs 2%, P = 0.0002). In summary, the acquisition of tfs3/4 ICE was common in H. pylori strains in patients with gastroduodenal disease in Vietnam, and the complete cluster of tfs3 ICE was a reliable marker for the severity of disease in the H. pylori infected population.
Three-dimensional imaging of xylem at cell wall level through near field nano holotomography
Authors: Koddenberg Tim , Greving Imke , Hagemann Johannes , Flenner Silja , Krause Andreas , Laipple Daniel , Klein Kim C. , Schmitt Uwe , Schuster Max , Wolf Andreas , Seifert Maria , Ludwig Veronika , Funk Stefan , Militz Holger , Nopens Martin
Published: February 2021

Detailed imaging of the three-dimensionally complex architecture of xylary plants is important for studying biological and mechanical functions of woody plants. Apart from common two-dimensional microscopy, X-ray micro-computed tomography has been established as a three-dimensional (3D) imaging method for studying the hydraulic function of wooden plants. However, this X-ray imaging method can barely reach the resolution needed to see the minute structures (e.g. pit membrane). To complement the xylem structure with 3D views at the nanoscale level, X-ray near-field nano-holotomography (NFH) was applied to analyze the wood speciesPinus sylvestrisandFagus sylvatica. The demanded small specimens required focused ion beam (FIB) application. The FIB milling, however, influenced the image quality through gallium implantation on the cell-wall surfaces. The measurements indicated that NFH is appropriate for imaging wood at nanometric resolution. With a 26 nm voxel pitch, the structure of the cell-wall surface inPinus sylvestriscould be visualized in genuine detail. In wood ofFagus sylvatica, the structure of a pit pair, including the pit membrane, between two neighboring fibrous cells could be traced tomographically.
Prokaryotic Argonaute from Archaeoglobus fulgidus interacts with DNA as a homodimer
Authors: Golovinas Edvardas , Rutkauskas Danielis , Manakova Elena , Jankunec Marija , Silanskas Arunas , Sasnauskas Giedrius , Zaremba Mindaugas
Published: February 2021

Argonaute (Ago) proteins are found in all three domains of life. The best-characterized group is eukaryotic Argonautes (eAgos), which are the core of RNA interference. The best understood prokaryotic Ago (pAgo) proteins are full-length pAgos. They are composed of four major structural/functional domains (N, PAZ, MID, and PIWI) and thereby closely resemble eAgos. It was demonstrated that full-length pAgos function as prokaryotic antiviral systems, with the PIWI domain performing cleavage of invading nucleic acids. However, the majority of identified pAgos are shorter and catalytically inactive (encode just MID and inactive PIWI domains), thus their action mechanism and function remain unknown. In this work we focus on AfAgo, a short pAgo protein encoded by an archaeon Archaeoglobus fulgidus. We find that in all previously solved AfAgo structures, its two monomers form substantial dimerization interfaces involving the C-terminal β-sheets. Led by this finding, we have employed various biochemical and biophysical assays, including SEC-MALS, SAXS, single-molecule FRET, and AFM, to show that AfAgo is indeed a homodimer in solution, which is capable of simultaneous interaction with two DNA molecules. This finding underscores the diversity of prokaryotic Agos and broadens the range of currently known Argonaute-nucleic acid interaction mechanisms.
Osteopathy modulates brain–heart interaction in chronic pain patients: an ASL study
Authors: Cerritelli Francesco , Chiacchiaretta Piero , Gambi Francesco , Saggini Raoul , Perrucci Mauro Gianni , Ferretti Antonio
Published: February 2021

In this study we used a combination of measures including regional cerebral blood flow (rCBF) and heart rate variability (HRV) to investigate brain–heart correlates of longitudinal baseline changes of chronic low back pain (cLBP) after osteopathic manipulative treatment (OMT). Thirty-two right-handed patients were randomised and divided into 4 weekly session of OMT (N = 16) or Sham (N = 16). Participants aged 42.3 ± 7.3 (M/F: 20/12) with cLBP (duration: 14.6 ± 8.0 m). At the end of the study, patients receiving OMT showed decreased baseline rCBF within several regions belonging to the pain matrix (left posterior insula, left anterior cingulate cortex, left thalamus), sensory regions (left superior parietal lobe), middle frontal lobe and left cuneus. Conversely, rCBF was increased in right anterior insula, bilateral striatum, left posterior cingulate cortex, right prefrontal cortex, left cerebellum and right ventroposterior lateral thalamus in the OMT group as compared with Sham. OMT showed a statistically significant negative correlation between baseline High Frequency HRV changes and rCBF changes at T2 in the left posterior insula and bilateral lentiform nucleus. The same brain regions showed a positive correlation between rCBF changes and Low Frequency HRV baseline changes at T2. These findings suggest that OMT can play a significant role in regulating brain–heart interaction mechanisms.
A novel technology to integrate imaging and clinical markers for non-invasive diagnosis of lung cancer
Authors: Shaffie Ahmed , Soliman Ahmed , Fu Xiao-An , Nantz Michael , Giridharan Guruprasad , van Berkel Victor , Khalifeh Hadil Abu , Ghazal Mohammed , Elmaghraby Adel , El-baz Ayman
Published: February 2021

This study presents a non-invasive, automated, clinical diagnostic system for early diagnosis of lung cancer that integrates imaging data from a single computed tomography scan and breath bio-markers obtained from a single exhaled breath to quickly and accurately classify lung nodules. CT imaging and breath volatile organic compounds data were collected from 47 patients. Spherical Harmonics-based shape features to quantify the shape complexity of the pulmonary nodules, 7th-Order Markov Gibbs Random Field based appearance model to describe the spatial non-homogeneities in the pulmonary nodule, and volumetric features (size) of pulmonary nodules were calculated from CT images. 27 VOCs in exhaled breath were captured by a micro-reactor approach and quantied using mass spectrometry. CT and breath markers were input into a deep-learning autoencoder classifier with a leave-one-subject-out cross validation for nodule classification. To mitigate the limitation of a small sample size and validate the methodology for individual markers, retrospective CT scans from 467 patients with 727 pulmonary nodules, and breath samples from 504 patients were analyzed. The CAD system achieved 97.8% accuracy, 97.3% sensitivity, 100% specificity, and 99.1% area under curve in classifying pulmonary nodules.
CIBERSORT analysis of TCGA and METABRIC identifies subgroups with better outcomes in triple negative breast cancer
Authors: Craven Kelly E. , Gökmen-Polar Yesim , Badve Sunil S.
Published: February 2021

Studies have shown that the presence of tumor infiltrating lymphocytes (TILs) in Triple Negative Breast Cancer (TNBC) is associated with better prognosis. However, the molecular mechanisms underlying these immune cell differences are not well delineated. In this study, analysis of hematoxylin and eosin images from The Cancer Genome Atlas (TCGA) breast cancer cohort failed to show a prognostic benefit of TILs in TNBC, whereas CIBERSORT analysis, which quantifies the proportion of each immune cell type, demonstrated improved overall survival in TCGA TNBC samples with increased CD8 T cells or CD8 plus CD4 memory activated T cells and in Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) TNBC samples with increased gamma delta T cells. Twenty-five genes showed mutational frequency differences between the TCGA high and low T cell groups, and many play important roles in inflammation or immune evasion (ATG2B, HIST1H2BC, PKD1, PIKFYVE, TLR3, NOTCH3, GOLGB1, CREBBP). Identification of these mutations suggests novel mechanisms by which the cancer cells attract immune cells and by which they evade or dampen the immune system during the cancer immunoediting process. This study suggests that integration of mutations with CIBERSORT analysis could provide better prediction of outcomes and novel therapeutic targets in TNBC cases.
Enhancement in external quantum efficiency of AlGaInP red μ-LED using chemical solution treatment process
Authors: Jung Byung Oh , Lee Wonyong , Kim Jeomoh , Choi Myungshin , Shin Hui-Youn , Joo Minho , Jung Sukkoo , Choi Yoon-Ho , Kim Moon J.
Published: February 2021

To investigate the effects of their surface recovery and optical properties, extremely small sized (12 µm × 12 µm mesa area) red AlGaInP micro light emitting diodes ($$\upmu$$
μ
LED) were fabricated using a diluted hydrofluoric acid (HF) surface etch treatment. After the chemical treatment, the external quantum efficiencies (EQEs) of $$\upmu$$
μ
-LED at low and high injection current regions have been improved by 35.48% and 12.86%, respectively. The different phenomena of EQEs have a complex relationship between the suppression of non-radiative recombination originating from the etching damage of the surface and the improvement of light extraction of the sidewalls. The constant enhancement of EQE at a high injection current it is attributed to the expansion of the active region’s sidewall surface area by the selective etching of AlInP layers. The improved EQE at a low injection current is related to the minimization of the surface recombination caused by plasma damage from the surface. High-resolution transmission electron microscopy (HR-TEM) revealed physical defects on the sidewall surface, such as plasma-induced lattice disorder and impurity contamination damage, were eliminated using chemical treatment. This study suggests that chemical surface treatment using diluted HF acid can be an effective method for enhancing the $$\upmu$$
μ
-LED performance.
Iohexol plasma clearance simplified by Dried Blood Spot (DBS) sampling to measure renal function in conscious mice
Authors: Rodríguez-Rodríguez Ana Elena , Luis-Lima Sergio , Donate-Correa Javier , Diaz-Martín Laura , Arnau María Rosa , Jiménez-Sosa Alejandro , Gaspari Flavio , Ortiz Alberto , Porrini Esteban
Published: February 2021

There is no simple method to measure glomerular filtration rate (GFR) in mice, which limits the use of mice in models of renal diseases. We aimed at simplifying the plasma clearance of iohexol in mice, using dried blood spot (DBS) sampling in order to reduce the amount of blood taken for analysis. GFR was measured simultaneously by a reference method in total blood—as described before—and tested method using DBS in fifteen male and six female C57BL/6J mice. Total blood extraction was 50 μL for the reference methods and 25μL for the tested methods, distributed in 5 samples. The agreement of GFR values between both methods was analyzed with the concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). The agreement between both methods was excellent, showing a TDI = 8.1%, which indicates that 90% of the GFR values obtained with DBS showed an error ranging from − 8 to + 8% of the reference method; a CCC of 0.996 (CI: 0.992), reflecting high precision and accuracy and a CP of 94 (CI: 83), indicating that 6% of the GFR values obtained with DBS had an error greater than 10% of the method in blood. So, both methods are interchangeable. DBS represent a major simplification of GFR measurement in mice. Also, DBS improves animal welfare by reducing the total blood required and refining the procedure.
Immunoinformatic based identification of cytotoxic T lymphocyte epitopes from the Indian isolate of SARS-CoV-2
Authors: Mulpuru Viswajit , Mishra Nidhi
Published: February 2021

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has turned into a pandemic with about thirty million confirmed cases worldwide as of September 2020. Being an airborne infection, it can be catastrophic to populous countries like India. This study sets to identify potential cytotoxic T lymphocyte (CTL) epitopes in the SARS-CoV-2 Indian isolate which can act as an effective vaccine epitope candidate for the majority of the Indian population. The immunogenicity and the foreignness of the epitopes towards the human body have to be studied to further confirm their candidacy. The top-scoring epitopes were subjected to molecular docking studies to study their interactions with the corresponding human leukocyte antigen (HLA) system. The CTL epitopes were observed to bind at the peptide-binding groove of the corresponding HLA system, indicating their potency as an epitope candidate. The candidacy was further analyzed using sequence conservation studies and molecular dynamics simulation. The identified epitopes can be subjected to further studies for the development of the SARS-CoV-2 vaccine.
Dispersion as a waste-clearance mechanism in flow through penetrating perivascular spaces in the brain
Authors: Troyetsky Daniel E. , Tithof Jeffrey , Thomas John H. , Kelley Douglas H.
Published: February 2021

Accumulation of metabolic wastes in the brain is correlated with several neurodegenerative disorders, including Alzheimer’s disease. Waste transport and clearance occur via dispersion, the combined effect of diffusion and advection by flow of fluid. We examine the relative contributions of diffusion and advection in the perivascular spaces (PVSs) that surround penetrating cortical blood vessels and are filled with cerebrospinal fluid (CSF). To do so, we adapt prior analytic predictions of dispersion to the context of PVSs. We also perform advection-diffusion simulations in PVS-like geometries with parameters relevant to transport of amyloid-$$\beta$$
β
(associated with Alzheimer’s) in a variety of flows, motivated by in vivo measurements. Specifically, we examine solute transport in steady and unsteady Poiseuille flows in an open (not porous) concentric circular annulus. We find that a purely oscillatory flow enhances dispersion only weakly and does not produce significant transport, whereas a steady flow component, even if slow, clears waste more effectively.
Machine learning based predictors for COVID-19 disease severity
Authors: Patel Dhruv , Kher Vikram , Desai Bhushan , Lei Xiaomeng , Cen Steven , Nanda Neha , Gholamrezanezhad Ali , Duddalwar Vinay , Varghese Bino , Oberai Assad A
Published: February 2021

Predictors of the need for intensive care and mechanical ventilation can help healthcare systems in planning for surge capacity for COVID-19. We used socio-demographic data, clinical data, and blood panel profile data at the time of initial presentation to develop machine learning algorithms for predicting the need for intensive care and mechanical ventilation. Among the algorithms considered, the Random Forest classifier performed the best with $$\text {AUC} = 0.80$$

AUC
=
0.80

for predicting ICU need and $$\text {AUC} = 0.82$$

AUC
=
0.82

for predicting the need for mechanical ventilation. We also determined the most influential features in making this prediction, and concluded that all three categories of data are important. We determined the relative importance of blood panel profile data and noted that the AUC dropped by 0.12 units when this data was not included, thus indicating that it provided valuable information in predicting disease severity. Finally, we generated RF predictors with a reduced set of five features that retained the performance of the predictors trained on all features. These predictors, which rely only on quantitative data, are less prone to errors and subjectivity.
An asymmetric protoplast fusion and screening method for generating celeriac cybrids
Authors: Bruznican Silvia , Eeckhaut Tom , Van Huylenbroeck Johan , De Keyser Ellen , De Clercq Hervé , Geelen Danny
Published: February 2021

Celeriac F1 hybrid seed production is currently complicated due to the instability of cytoplasmic male sterile lines. To develop alternative alloplasmic CMS lines, an asymmetric protoplast fusion and hybrid screening methodology was established. Celeriac suspension cells protoplasts were used as the acceptor and carrot, coriander and white celery mesophyll protoplasts as the donor for protoplast fusion experiments. Acceptor cytoplasmic inheritance was inhibited by iodoacetamide treatment and donor nuclear genome inheritance was prevented by UV exposure. Protoplasts were selectively stained and fused using electroporation and polyethylene glycol, and candidate hybrid shoots were obtained. One chloroplast and three mitochondrial markers that could distinguish acceptor and donors organelles were used to characterize over 600 plants obtained after fusion events, without identifying any cybrid. In order to increase the testing efficiency a high number of micro plantlets were pooled and hence the presence of the carrot specific Atp1 marker in one of the pooled samples was detected. We demonstrated that fusion took place between celeriac and a carrot indicating that the creation of viable hybrids is possible although at a very low frequency. These findings open the path for new cytoplasmic hybridization and the isolation of novel CMS lines of celeriac.
Signatures of white-matter microstructure degradation during aging and its association with cognitive status
Authors: Coelho Ana , Fernandes Henrique M. , Magalhães Ricardo , Moreira Pedro Silva , Marques Paulo , Soares José M. , Amorim Liliana , Portugal-Nunes Carlos , Castanho Teresa , Santos Nadine Correia , Sousa Nuno
Published: February 2021

Previous studies have shown an association between cognitive decline and white matter integrity in aging. This led to the formulation of a “disconnection hypothesis” in the aging-brain, which states that the disruption in cortical network communication may explain the cognitive decline during aging. Although some longitudinal studies have already investigated the changes occurring in white matter microstructure, most focused on specific white matter tracts. Our study aims to characterize the longitudinal whole-brain signatures of white matter microstructural change during aging. Furthermore, we assessed the relationship between distinct longitudinal alterations in white matter integrity and cognition. White matter microstructural properties were estimated from diffusion magnetic resonance imaging, and cognitive status characterized from extensive neurocognitive testing. The same individuals were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24) between first and last assessment. Our results show that age is associated with a decline in cognitive performance and a degradation in white matter integrity. Additionally, significant associations were found between diffusion measures and different cognitive dimensions (memory, executive function and general cognition). Overall, these results suggest that age-related cognitive decline is related to white matter alterations, and thus give support to the “disconnected hypothesis” of the aging brain.
Comparative genomics of MRSA strains from human and canine origins reveals similar virulence gene repertoire
Authors: Penna Bruno , Silva Marcella B. , Soares André E. R. , Vasconcelos Ana T. R. , Ramundo Mariana S. , Ferreira Fabienne A. , Silva-Carvalho Maria C. , de Sousa Viviane S. , Rabello Renata F. , Bandeira Paula T. , de Souza Viviane S. , Planet Paul J. , Vieira-da-Motta Olney , Botelho Ana M. N. , Figueiredo Agnes M. S.
Published: February 2021

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen associated with a wide variety of infections in humans. The ability of MRSA to infect companion animals has gained increasing attention in the scientific literature. In this study, 334 dogs were screened for MRSA in two cities located in Rio de Janeiro State. The prevalence of MRSA in dogs was 2.7%. Genotyping revealed isolates from sequence types (ST) 1, 5, 30, and 239 either colonizing or infecting dogs. The genome of the canine ST5 MRSA (strain SA112) was compared with ST5 MRSA from humans—the main lineage found in Rio de Janeiro hospitals—to gain insights in the origin of this dog isolate. Phylogenetic analysis situated the canine genome and human strain CR14-035 in the same clade. Comparative genomics revealed similar virulence profiles for SA112 and CR14-035. Both genomes carry S. aureus genomic islands νSAα, νSAβ, and νSAγ. The virulence potential of the canine and human strains was similar in a Caenorhabditis elegans model. Together, these results suggest a potential of canine MRSA to infect humans and vice versa. The circulation in community settings of a MRSA lineage commonly found in hospitals is an additional challenge for public health surveillance authorities.
Evolutionary conservation of the DRACH signatures of potential N6-methyladenosine (m6A) sites among influenza A viruses
Authors: Bayoumi Mahmoud , Munir Muhammad
Published: February 2021

The addition of a methyl group to the N6-position of adenosine (m6A) is considered one of the most prevalent internal post-transcriptional modifications and is attributed to virus replication and cell biology. Viral epitranscriptome sequencing analysis has revealed that hemagglutinin (HA) mRNA of H1N1 carry eight m6A sites which are primarily enriched in 5′-DRACH-3′ sequence motif. Herein, a large-scale comparative m6A analysis was conducted to investigate the conservation patterns of the DRACH motifs that corresponding to the reference m6A sites among influenza A viruses. A total of 70,030 complete HA sequences that comprise all known HA subtypes (H1–18) collected over several years, countries, and affected host species were analysed on both mRNA and vRNA strands. The bioinformatic analysis revealed the highest degree of DRACHs conservation among all H1 sequences that clustered largely in the middle and in the vicinity to 3′ end with at least four DRACH motifs were conserved in all mRNA sequences. The major HA-containing subtypes displayed a modest DRACH motif conservation located either in the middle region of HA transcript (H3) or at the 3′ end (H5) or were distributed across the length of HA sequence (H9). The lowest conservation was demonstrated in HA subtypes that infect mostly the wild type avian species and bats. Interestingly, the total number and the conserved DRACH motifs in the vRNA were found to be much lower than those observed in the mRNA. Collectively, the identification of putative m6A topology provides a foundation for the future intervention of influenza infection, replication, and pathobiology in susceptible hosts.
Mechanism of autonomous synchronization of the circadian KaiABC rhythm
Authors: Sasai Masaki
Published: February 2021

The cyanobacterial circadian clock can be reconstituted by mixing three proteins, KaiA, KaiB, and KaiC, in vitro. In this protein mixture, oscillations of the phosphorylation level of KaiC molecules are synchronized to show the coherent oscillations of the ensemble of many molecules. However, the molecular mechanism of this synchronization has not yet been fully elucidated. In this paper, we explain a theoretical model that considers the multifold feedback relations among the structure and reactions of KaiC. The simulated KaiC hexamers show stochastic switch-like transitions at the level of single molecules, which are synchronized in the ensemble through the sequestration of KaiA into the KaiC–KaiB–KaiA complexes. The proposed mechanism quantitatively reproduces the synchronization that was observed by mixing two solutions oscillating in different phases. The model results suggest that biochemical assays with varying concentrations of KaiA or KaiB can be used to test this hypothesis.
Specific domain V reduction of beta-2-glycoprotein I induces protein flexibility and alters pathogenic antibody binding
Authors: Buchholz Ina , McDonnell Thomas , Nestler Peter , Tharad Sudarat , Kulke Martin , Radziszewska Anna , Ripoll Vera M. , Schmidt Frank , Hammer Elke , Toca-Herrera Jose L. , Rahman Anisur , Delcea Mihaela
Published: February 2021

Beta-2-glycoprotein I (β2GPI) is a blood protein and the major antigen in the autoimmune disorder antiphospholipid syndrome (APS). β2GPI exists mainly in closed or open conformations and comprises of 11 disulfides distributed across five domains. The terminal Cys288/Cys326 disulfide bond at domain V has been associated with different cysteine redox states. The role of this disulfide bond in conformational dynamics of this protein has not been investigated so far. Here, we report on the enzymatic driven reduction by thioredoxin-1 (recycled by Tris(2-carboxyethyl)phosphine; TCEP) of β2GPI. Specific reduction was demonstrated by Western blot and mass spectrometry analyses confirming majority targeting to the fifth domain of β2GPI. Atomic force microscopy images suggested that reduced β2GPI shows a slightly higher proportion of open conformation and is more flexible compared to the untreated protein as confirmed by modelling studies. We have determined a strong increase in the binding of pathogenic APS autoantibodies to reduced β2GPI as demonstrated by ELISA. Our study is relevant for understanding the effect of β2GPI reduction on the protein structure and its implications for antibody binding in APS patients.
Comparative evaluation of expiratory airflow limitation between patients with COPD and BE using IOS
Authors: dos Santos Daniele Oliveira , Perossi Larissa , Perossi Jéssica , de Souza Simoni Letícia Helena , Holtz Mayara , Moroli Ricardo Grassi , Baddini-Martinez José Antônio , Gastaldi Ada Clarice
Published: February 2021

Impulse oscillometry (IOS) allows evaluation of the compartmentalized resistance and reactance of the respiratory system, distinguishing central and peripheral obstruction. The IOS measurements are getting attention in the diagnosis and differentiation of chronic respiratory diseases. However, no data are available in the literature to differentiate between COPD and BE using IOS parameters. We aimed to evaluate the feasibility of IOS in the diagnosis of bronchiectasis non-cystic fibrosis (BE) in comparison to COPD. Whole breath, inspiration, expiration, and inspiratory-expiratory difference (Δ) were evaluated based on the IOS parameters: total resistance (R5), central airway resistance (R20), peripheral airway resistance (R5-R20), reactance (X5), reactance area (AX), and resonance frequency (Fres). Fifty-nine subjects (21 Healthy, 19 BE, and 19 COPD) participated in this study. It was observed a significant difference in the comparison of healthy and pulmonary disease groups (BE and COPD) for total breathing (R5-R20, X5, AX, and Fres), inspiratory phase (R5 and R5-R5), and expiratory phase (R5-R20 and X5). The comparison between BE and COPD groups showed significant difference in the expiratory phase for resistance at 5 and 20 Hz and, ΔR5 and ΔR20. The IOS evidenced an increase of R5, R20 and R5-R20 in patients with BE and COPD when compared to healthy subjects. Expiratory measures of IOS revealed increased airway resistance in COPD compared to BE patients who had similar FEV1 measured by spirometry, however, further studies are needed to confirm these differences.
rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis
Authors: Hitomi Yuki , Aiba Yoshihiro , Kawai Yosuke , Kojima Kaname , Ueno Kazuko , Nishida Nao , Kawashima Minae , Gervais Olivier , Khor Seik-Soon , Nagasaki Masao , Tokunaga Katsushi , Nakamura Minoru , Tsuiji Makoto
Published: February 2021

Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which intrahepatic bile ducts are destroyed by an autoimmune reaction. Our previous genome-wide association study (GWAS) identified chromosome 11q23.1 as a susceptibility gene locus for PBC in the Japanese population. Here, high-density association mapping based on single nucleotide polymorphism (SNP) imputation and in silico/in vitro functional analyses identified rs1944919 as the primary functional variant. Expression-quantitative trait loci analyses showed that the PBC susceptibility allele of rs1944919 was significantly associated with increased COLCA1/COLCA2 expression levels. Additionally, the effects of rs1944919 on COLCA1/COLCA2 expression levels were confirmed using genotype knock-in versions of cell lines constructed using the CRISPR/Cas9 system and differed between rs1944919-G/G clones and -T/T clones. To our knowledge, this is the first study to demonstrate the contribution of COLCA1/COLCA2 to PBC susceptibility.
Associations of ultrasound estimated early mid pregnancy visceral and subcutaneous fat depths and early pregnancy BMI with adverse neonatal outcomes
Authors: Lindberger Emelie , Wikström Anna-Karin , Bergman Eva , Eurenius Karin , Mulic-Lutvica Ajlana , Lindström Linda , Sundström Poromaa Inger , Ahlsson Fredrik
Published: February 2021

This study investigated whether maternal central adiposity and body mass index (BMI) were associated with neonatal hypoglycemia and adverse neonatal outcomes. A cohort study was performed at Uppsala University Hospital, Sweden, between 2015 and 2018. Visceral and subcutaneous fat depths were measured by ultrasound at the early second-trimester anomaly scan in 2771 women giving birth to singleton infants. Body mass index was assessed in early pregnancy. Logistic regression models were performed. Adjustments were made for age, BMI (not in model with BMI as exposure), smoking, maternal country of birth, and parity. Outcomes were neonatal hypoglycemia (blood glucose concentration < 2.6 mmol/l), a composite of adverse neonatal outcomes (Apgar < 7 at 5 min of age, or umbilical artery pH ≤ 7.0, or admission to neonatal intensive care unit), and the components of the composite outcome. Visceral and subcutaneous fat depths measured by ultrasound in early mid pregnancy were not associated with any of the outcomes in adjusted analyses. For every unit increase in BMI, the likelihood of neonatal hypoglycemia increased by 5% (aOR 1.05, 95% CI 1.01–1.10), the composite outcome by 5% (aOR 1.05, 95% CI 1.01–1.08), and admission to neonatal intensive care unit by 6% (aOR 1.06, 95% CI 1.02–1.10).
Memories for third-person experiences in immersive virtual reality
Authors: Iriye Heather , St. Jacques Peggy L.
Published: February 2021

We typically experience the world from a first-person perspective (1PP) but can sometimes experience events from a third-person perspective (3PP) much as an observer might see us. Little is known about how visual perspective influences the formation of memories for events. We developed an immersive virtual reality paradigm to examine how visual perspective during encoding influences memories. Across two studies, participants explored immersive virtual environments from first-person and third-person avatar perspectives while wearing an Oculus Rift headset. Memory was tested immediately (Study One and Study Two) and following a one-week delay (Study Two). We assessed the accuracy of visual memory using cued recall questions and spatial memory by asking participants to draw maps of the layout of each environment (Study One and Study Two). Additional phenomenological ratings were included to assess visual perspective during remembering (Study Two). There were no differences in the accuracy of visual information across the two studies, but 3PP experiences were found to increase spatial memory accuracy due to their wider camera field of view when compared to 1PP experiences. Our results also demonstrate that 3PP experiences create 3PP memories, as reflected by an increase in subjective ratings of observer-like perspectives during remembering. In sum, visual perspective during memory formation influences the accuracy of spatial but not visual information, and the vantage point of memories during remembering.