bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypersonic impact properties of pristine and hybrid single and multi-layer C3N and BC3 nanosheets
Authors: Molaei Fatemeh , Eshkalak Kasra Einalipour , Sadeghzadeh Sadegh , Siavoshi Hossein
Published: April 2021

Carbon, nitrogen, and boron nanostructures are promising ballistic protection materials due to their low density and excellent mechanical properties. In this study, the ballistic properties of C3N and BC3 nanosheets against hypersonic bullets with Mach numbers greater than 6 were studied. The critical perforation conditions, and thus, the intrinsic impact strength of these 2D materials were determined by simulating ballistic curves of C3N and BC3 monolayers. Furthermore, the energy absorption scaling law with different numbers of layers and interlayer spacing was investigated, for homogeneous or hybrid configurations (alternated stacking of C3N and the BC3). Besides, we created a hybrid sheet using van der Waals bonds between two adjacent sheets based on the hypervelocity impacts of fullerene (C60) molecules utilizing molecular dynamics simulation. As a result, since the higher bond energy between N–C compared to B-C, it was shown that C3N nanosheets have higher absorption energy than BC3. In contrast, in lower impact speeds and before penetration, single-layer sheets exhibited almost similar behavior. Our findings also reveal that in hybrid structures, the C3N layers will improve the ballistic properties of BC3. The energy absorption values with a variable number of layers and variable interlayer distance (X = 3.4 Å and 4X = 13.6 Å) are investigated, for homogeneous or hybrid configurations. These results provide a fundamental understanding of ultra-light multilayered armors' design using nanocomposites based on advanced 2D materials. The results can also be used to select and make 2D membranes and allotropes for DNA sequencing and filtration.
Impact of image compression on deep learning-based mammogram classification
Authors: Jo Yong-Yeon , Choi Young Sang , Park Hyun Woo , Lee Jae Hyeok , Jung Hyojung , Kim Hyo-Eun , Ko Kyounglan , Lee Chan Wha , Cha Hyo Soung , Hwangbo Yul
Published: April 2021

Image compression is used in several clinical organizations to help address the overhead associated with medical imaging. These methods reduce file size by using a compact representation of the original image. This study aimed to analyze the impact of image compression on the performance of deep learning-based models in classifying mammograms as “malignant”—cases that lead to a cancer diagnosis and treatment—or “normal” and “benign,” non-malignant cases that do not require immediate medical intervention. In this retrospective study, 9111 unique mammograms–5672 normal, 1686 benign, and 1754 malignant cases were collected from the National Cancer Center in the Republic of Korea. Image compression was applied to mammograms with compression ratios (CRs) ranging from 15 to 11 K. Convolutional neural networks (CNNs) with three convolutional layers and three fully-connected layers were trained using these images to classify a mammogram as malignant or not malignant across a range of CRs using five-fold cross-validation. Models trained on images with maximum CRs of 5 K had an average area under the receiver operating characteristic curve (AUROC) of 0.87 and area under the precision-recall curve (AUPRC) of 0.75 across the five folds and compression ratios. For images compressed with CRs of 10 K and 11 K, model performance decreased (average 0.79 in AUROC and 0.49 in AUPRC). Upon generating saliency maps that visualize the areas each model views as significant for prediction, models trained on less compressed (CR <  = 5 K) images had maps encapsulating a radiologist’s label, while models trained on images with higher amounts of compression had maps that missed the ground truth completely. In addition, base ResNet18 models pre-trained on ImageNet and trained using compressed mammograms did not show performance improvements over our CNN model, with AUROC and AUPRC values ranging from 0.77 to 0.87 and 0.52 to 0.71 respectively when trained and tested on images with maximum CRs of 5 K. This paper finds that while training models on images with increased the robustness of the models when tested on compressed data, moderate image compression did not substantially impact the classification performance of DL-based models.
Short-range UV-LED irradiation in postmenopausal osteoporosis using ovariectomized mice
Authors: Ochiai Satoshi , Nishida Yoshihiro , Higuchi Yoshitoshi , Morita Daigo , Makida Kazuya , Seki Taisuke , Ikuta Kunihiro , Imagama Shiro
Published: April 2021

Postmenopausal osteoporosis is crucial condition that reduces the QOL of affected patients just like aged type osteoporosis. The aim of this study was to evaluate the effectiveness of short-range UV-LED irradiation in postmenopausal osteoporosis using ovariectomized mice. Preliminary experiments identified the time of onset of osteoporosis after ovariectomy (8 weeks) in our model. We have set up a total of 4 groups (n = 8/group); vitamin D-repletion with UV irradiation (Vit.D+UV+), vitamin D-repletion without UV irradiation (Vit.D+UV−), vitamin D-deficiency with UV irradiation (Vit.D-UV+), vitamin D-deficiency without UV irradiation (Vit.D-UV−), and. From 8 weeks after ovariectomy, UV was irradiated for 24 weeks. At the time of 16 and 24 weeks’ irradiation, serum Vit.D levels, various markers of bone metabolism, bone mineral density, and bone strength were evaluated, and histological analyses were performed. In addition, muscle strength was analyzed. Serum 25-hydroxyvitamin D [25 (OH) D] levels at 40 and 48 weeks of age were increased in the Vit.D-UV+ group compared to the Vit.D-UV−group. Cortical thickness evaluated with micro-CT and strength of bone were significantly higher in Vit.D-UV+ group than those in Vit.D-UV− group. There was no difference in muscle strength between Vit.D-UV+ group and Vit.D-UV− group. No obvious adverse effects were observed in UV-irradiated mice including skin findings. Short-range UV irradiation may ameliorate postmenopausal osteoporosis associated with a state of vitamin D deficiency.
Computing inelastic neutron scattering spectra from molecular dynamics trajectories
Authors: Harrelson Thomas F. , Dettmann Makena , Scherer Christoph , Andrienko Denis , Moulé Adam J. , Faller Roland
Published: April 2021

Inelastic neutron scattering (INS) provides a weighted density of phonon modes. Currently, INS spectra can only be interpreted for perfectly crystalline materials because of high computational cost for electronic simulations. INS has the potential to provide detailed morphological information if sufficiently large volumes and appropriate structural variety are simulated. Here, we propose a method that allows direct comparison between INS data with molecular dynamics simulations, a simulation method that is frequently used to simulate semicrystalline/amorphous materials. We illustrate the technique by analyzing spectra of a well-studied conjugated polymer, poly(3-hexylthiophene-2,5-diyl) (P3HT) and conclude that our technique provides improved volume and structural variety, but that the classical force field requires improvement before the morphology can be accurately interpreted.
A highly prevalent SINE mutation in the myostatin (MSTN) gene promoter is associated with low circulating myostatin concentration in Thoroughbred racehorses
Authors: O’Hara Victoria , Cowan Amélie , Riddell Dominique , Massey Claire , Martin John , Piercy Richard J.
Published: April 2021

Horse racing is a popular and financially important industry worldwide and researchers and horse owners are interested in genetic and training influences that maximise athletic performance. An association has been found between the presence of a short interspersed nuclear element (SINE) mutation in the myostatin (MSTN) gene promoter and optimal race distance in Thoroughbred horses. There is previous laboratory evidence that this mutation reduces MSTN expression in a cell culture model and influences skeletal muscle fibre type proportions in horses. Manipulating MSTN expression has been proposed for illicit gene doping in human and equine athletes and already, researchers have generated homozygous and heterozygous MSTN-null horse embryos following CRISPR/Cas9 editing at the equine MSTN locus and nuclear transfer, aiming artificially to enhance performance. To date however, the role of the naturally-occurring equine MSTN SINE mutation in vivo has remained unclear; here we hypothesised that it reduces, but does not ablate circulating myostatin expression. Following validation of an ELISA for detection of myostatin in equine serum and using residual whole blood and serum samples from 176 Thoroughbred racehorses under identical management, horses were genotyped for the SINE mutation by PCR and their serum myostatin concentrations measured. In our population, the proportions of SINE homozygotes, heterozygotes and normal horses were 27%, 46% and 27% respectively. Results indicated that horses that are homozygous for the SINE mutation have detectable, but significantly lower (p < 0.0001) serum myostatin concentrations (226.8 pg/ml; 69.3–895.4 pg/ml; median; minimum–maximum) than heterozygous (766 pg/ml; 64.6–1182 pg/ml) and normal horses (1099 pg/ml; 187.8–1743 pg/ml). Heterozygotes have significantly lower (p < 0.0001) myostatin concentrations than normal horses. Variation in serum myostatin concentrations across horses was not influenced by age or sex. This is the first study to reveal the direct functional effect of a highly prevalent mutation in the equine MSTN gene associated with exercise performance. Determining the reason for variation in expression of myostatin within SINE-genotyped groups might identify additional performance-associated environmental or genetic influences in Thoroughbreds. Understanding the mechanism by which altered myostatin expression influences skeletal muscle fibre type remains to be determined.
Preference of Proteomonas sulcata anion channelrhodopsin for NO3− revealed using a pH electrode method
Authors: Kikuchi Chihiro , Kurane Hina , Watanabe Takuma , Demura Makoto , Kikukawa Takashi , Tsukamoto Takashi
Published: April 2021

Ion channel proteins are physiologically important molecules in living organisms. Their molecular functions have been investigated using electrophysiological methods, which enable quantitative, precise and advanced measurements and thus require complex instruments and experienced operators. For simpler and easier measurements, we measured the anion transport activity of light-gated anion channelrhodopsins (ACRs) using a pH electrode method, which has already been established for ion pump rhodopsins. Using that method, we successfully measured the anion transport activity and its dependence on the wavelength of light, i.e. its action spectra, and on the anion species, i.e. its selectivity or preference, of several ACRs expressed in yeast cells. In addition, we identified the strong anion transport activity and the preference for NO3− of an ACR from a marine cryptophyte algae Proteomonas sulcata, named PsuACR_353. Such a preference was discovered for the first time in microbial pump- or channel-type rhodopsins. Nitrate is one of the most stable forms of nitrogen and is used as a nitrogen source by most organisms including plants. Therefore, PsuACR_353 may play a role in NO3− transport and might take part in NO3−-related cellular functions in nature. Measurements of a mutant protein revealed that a Thr residue in the 3rd transmembrane helix, which corresponds to Cys102 in GtACR1, contributed to the preference for NO3−. These findings will be helpful to understand the mechanisms of anion transport, selectivity and preference of PsuACR_353.
Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients
Authors: Neuzillet Cindy , Marchais Manon , Vacher Sophie , Hilmi Marc , Schnitzler Anne , Meseure Didier , Leclere Renaud , Lecerf Charlotte , Dubot Coraline , Jeannot Emmanuelle , Klijanienko Jerzy , Mariani Odette , Calugaru Valentin , Hoffmann Caroline , Lesnik Maria , Badois Nathalie , Borcoman Edith , Piaggio Eliane , Kamal Maud , Le Tourneau Christophe , Bieche Ivan
Published: April 2021

Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features, relapse, and overall survival (OS) in two independent cohorts of patients with OSCC, and to explore the interplay with immune-related genes. We retrospectively analyzed tissue samples from a first cohort of 122 patients with head and neck squamous cell carcinoma, including 61 OSCC (cohort #1), and a second cohort of 90 additional OSCC (cohort #2). We then performed a sensitivity analysis on the merged cohort of OSCC patients (N = 151). F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. The presence of gram-negative bacteria and macrophages was confirmed by LPS and CD163 immunostainings, respectively. F. nucleatum positivity was associated with older age, less alcohol and combined alcohol plus tobacco consumption, and less frequent lymph node invasion. There was a trend for a lower recurrence rate in F. nucleatum-positive cases, with less metastatic relapses compared to F. nucleatum-negative tumors, and significantly longer OS, relapse-free and metastasis-free survival. F. nucleatum status was independently associated with OS in multivariate analysis. Immune-related gene and immunohistochemistry analyses showed that gram-negative bacteria load inversely correlated with M2 macrophages. F. nucleatum-associated OSCC has a specific immune microenvironment, is more frequent in older, non-drinking patients, and associated with a favorable prognosis.
A robust nitridation technique for fabrication of disordered superconducting TiN thin films featuring phase slip events
Authors: Yadav Sachin , Kaushik Vinay , Saravanan M. P. , Aloysius R. P. , Ganesan V. , Sahoo Sangeeta
Published: April 2021

Disorder induced phase slip (PS) events appearing in the current voltage characteristics (IVCs) are reported for two-dimensional TiN thin films produced by a robust substrate mediated nitridation technique. Here, high temperature annealing of Ti/Si3N4 based metal/substrate assembly is the key to produce majority phase TiN accompanied by TiSi2 & elemental Si as minority phases. The method itself introduces different level of disorder intrinsically by tuning the amount of the non-superconducting minority phases that are controlled by annealing temperature (Ta) and the film thickness. The superconducting critical temperature (Tc) strongly depends on Ta and the maximum Tc obtained from the demonstrated technique is about 4.8 K for the thickness range ~ 12 nm and above. Besides, the dynamics of IVCs get modulated by the appearance of intermediated resistive steps for decreased Ta and the steps get more prominent for reduced thickness. Further, the deviation in the temperature dependent critical current (Ic) from the Ginzburg–Landau theoretical limit varies strongly with the thickness. Finally, the Tc, intermediate resistive steps in the IVCs and the depairing current are observed to alter in a similar fashion with Ta and the thickness indicating the robustness of the synthesis process to fabricate disordered nitride-based superconductor.
An anisotropic pore-network model to estimate the shale gas permeability
Authors: Zhang Di , Zhang Xinghao , Guo Haohao , Lin Dantong , Meegoda Jay N. , Hu Liming
Published: April 2021

The permeability of shale is a significant and important design parameter for shale gas extraction. The shale gas permeability is usually obtained based on Darcy flow using standard laboratory permeability tests done on core samples, that do not account for different transport mechanisms at high pressures and anisotropic effects in shales due to nano-scale pore structure. In this study, the permeability of shale is predicted using a pore network model. The characteristics of pore structure can be described by specific parameters, including porosity, pore body and pore throat sizes and distributions and coordination numbers. The anisotropy was incorporated into the model using a coordination number ratio, and an algorithm that was developed for connections of pores in the shale formation. By predicting hydraulic connectivity and comparing it with several high-pressure permeability tests, the proposed three-dimensional pore network model was verified. Results show that the prediction from the anisotropic pore network model is closer to the test results than that based on the isotropic pore network model. The predicted permeability values from numerical simulation using anisotropic pore network model for four shales from Qaidam Basin, China are quite similar to those measured from laboratory tests. This study confirmed that the developed anisotropic three-dimensional pore network model could reasonably represent the natural gas flow in the actual shale formation so that it can be used as a prediction tool.
Penetration mechanics of elongated female and male genitalia of earwigs
Authors: Matsumura Yoko , Kamimura Yoshitaka , Lee Chow-Yang , Gorb Stanislav N. , Rajabi Hamed
Published: April 2021

We unveiled the penile penetration mechanics of two earwig species,Echinosoma horridum, whose intromittent organ, termed virga, is extraordinarily long, andE. denticulatum, whose virga is conversely short. We characterised configuration, geometry, material and bending stiffness for both virga and spermatheca. The short virga ofE. denticulatumhas a material gradient with the stiffer base, whereas the long virga ofE. horridumand the spermathecae of both species are homogeneously sclerotised. The long virga ofE. horridumhas a lower bending stiffness than the spermatheca. The virga ofE. denticulatumis overall less flexible than the spermatheca. We compared our results to a previous study on the penetration mechanics of elongated beetle genitalia. Based on the comparison, we hypothesised that the lower stiffness of the male intromittent organ comparing to the corresponding female structure is a universal prerequisite for the penetration mechanics of the elongated intromittent organ in insects.
A derivative of vitamin B3 applied several days after exposure reduces lethality of severely irradiated mice
Authors: Cheda Aneta , Nowosielska Ewa M. , Gebicki Jerzy , Marcinek Andrzej , Chlopicki Stefan , Janiak Marek K.
Published: April 2021

Most, if not all, of the hitherto tested substances exert more or less pronounced pro-survival effects when applied before or immediately after the exposure to high doses of ionizing radiation. In the present study we demonstrate for the first time that 1-methyl nicotinamide (MNA), a derivative of vitamin B3, significantly (1.6 to 1.9 times) prolonged survival of BALB/c mice irradiated at LD30/30 (6.5 Gy), LD50/30 (7.0 Gy) or LD80/30 (7.5 Gy) of γ-rays when the MNA administration started as late as 7 days post irradiation. A slightly less efficient and only after the highest dose (7.5 Gy) of γ-rays was another vitamin B3 derivative, 1-methyl-3-acetylpyridine (1,3-MAP) (1.4-fold prolonged survival). These pro-survival effects did not seem to be mediated by stimulation of haematopoiesis, but might be related to anti-inflammatory and/or anti-thrombotic properties of the vitamin B3 derivatives. Our results show that MNA may represent a prototype of a radioremedial agent capable of mitigating the severity and/or progression of radiation-induced injuries when applied several hours or days after exposure to high doses of ionizing radiation.
Publisher Correction: A machine learning approach for reliable prediction of amino acid interactions and its application in the directed evolution of enantioselective enzymes
Authors: Cadet Frédéric , Fontaine Nicolas , Li Guangyue , Sanchis Joaquin , Chong Matthieu Ng Fuk , Pandjaitan Rudy , Vetrivel Iyanar , Offmann Bernard , Reetz Manfred T.
Published: April 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Tick defensin γ-core reduces Fusarium graminearum growth and abrogates mycotoxins production with high efficiency
Authors: Leannec-Rialland Valentin , Cabezas-Cruz Alejandro , Atanasova Vessela , Chereau Sylvain , Ponts Nadia , Tonk Miray , Vilcinskas Andreas , Ferrer Nathalie , Valdés James J. , Richard-Forget Florence
Published: April 2021

Fusarium graminearum is a major fungal pathogen affecting crops of worldwide importance. F. graminearum produces type B trichothecene mycotoxins (TCTB), which are not fully eliminated during food and feed processing. Therefore, the best way to minimize TCTB contamination is to develop prevention strategies. Herein we show that treatment with the reduced form of the γ-core of the tick defensin DefMT3, referred to as TickCore3 (TC3), decreases F. graminearum growth and abrogates TCTB production. The oxidized form of TC3 loses antifungal activity, but retains anti-mycotoxin activity. Molecular dynamics show that TC3 is recruited by specific membrane phospholipids in F. graminearum and that membrane binding of the oxidized form of TC3 is unstable. Capping each of the three cysteine residues of TC3 with methyl groups reduces its inhibitory efficacy. Substitutions of the positively-charged residues lysine (Lys) 6 or arginine 7 by threonine had the highest and the lesser impact, respectively, on the anti-mycotoxin activity of TC3. We conclude that the binding of linear TC3 to F. graminearum membrane phospholipids is required for the antifungal activity of the reduced peptide. Besides, Lys6 appears essential for the anti-mycotoxin activity of the reduced peptide. Our results provide foundation for developing novel and environment-friendly strategies for controlling F. graminearum.
CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer
Authors: Uzor Simon , Porazinski Sean R. , Li Ling , Clark Bethany , Ajiro Masahiko , Iida Kei , Hagiwara Masatoshi , Alqasem Abdullah A. , Perks Claire M. , Wilson Ian D. , Oltean Sebastian , Ladomery Michael R.
Published: April 2021

Dysregulation of alternative splicing is a feature of cancer, both in aetiology and progression. It occurs because of mutations in splice sites or sites that regulate splicing, or because of the altered expression and activity of splice factors and of splice factor kinases that regulate splice factor activity. Recently the CDC2-like kinases (CLKs) have attracted attention due to their increasing involvement in cancer. We measured the effect of the CLK inhibitor, the benzothiazole TG003, on two prostate cancer cell lines. TG003 reduced cell proliferation and increased apoptosis in PC3 and DU145 cells. Conversely, the overexpression of CLK1 in PC3 cells prevented TG003 from reducing cell proliferation. TG003 slowed scratch closure and reduced cell migration and invasion in a transwell assay. TG003 decisively inhibited the growth of a PC3 cell line xenograft in nude mice. We performed a transcriptomic analysis of cells treated with TG003. We report widespread and consistent changes in alternative splicing of cancer-associated genes including CENPE, ESCO2, CKAP2, MELK, ASPH and CD164 in both HeLa and PC3 cells. Together these findings suggest that targeting CLKs will provide novel therapeutic opportunities in prostate cancer.
STORM imaging reveals the spatial arrangement of transition zone components and IFT particles at the ciliary base in Tetrahymena
Authors: Hazime Khodor S. , Zhou Zhu , Joachimiak Ewa , Bulgakova Natalia A. , Wloga Dorota , Malicki Jarema J.
Published: April 2021

The base of the cilium comprising the transition zone (TZ) and transition fibers (TF) acts as a selecting gate to regulate the intraflagellar transport (IFT)-dependent trafficking of proteins to and from cilia. Before entering the ciliary compartment, IFT complexes and transported cargoes accumulate at or near the base of the cilium. The spatial organization of IFT proteins at the cilia base is key for understanding cilia formation and function. Using stochastic optical reconstruction microscopy (STORM) and computational averaging, we show that seven TZ, nine IFT, three Bardet–Biedl syndrome (BBS), and one centrosomal protein, form 9-clustered rings at the cilium base of a ciliate Tetrahymena thermophila. In the axial dimension, analyzed TZ proteins localize to a narrow region of about 30 nm while IFT proteins dock approximately 80 nm proximal to TZ. Moreover, the IFT-A subcomplex is positioned peripheral to the IFT-B subcomplex and the investigated BBS proteins localize near the ciliary membrane. The positioning of the HA-tagged N- and C-termini of the selected proteins enabled the prediction of the spatial orientation of protein particles and likely cargo interaction sites. Based on the obtained data, we built a comprehensive 3D-model showing the arrangement of the investigated ciliary proteins.
Abnormal myocardial work in children with Kawasaki disease
Authors: Sabatino Jolanda , Borrelli Nunzia , Fraisse Alain , Herberg Jethro , Karagadova Elena , Avesani Martina , Bucciarelli Valentina , Josen Manjit , Paredes Josefa , Piccinelli Enrico , Spada Maraisa , Krupickova Sylvia , Indolfi Ciro , Di Salvo Giovanni
Published: April 2021

Kawasaki disease (KD) can be associated with high morbidity and mortality due to coronary artery aneurysms formation and myocardial dysfunction. Aim of this study was to evaluate the diagnostic performance of non-invasive myocardial work in predicting subtle myocardial abnormalities in Kawasaki disease (KD) children with coronary dilatation (CADL). A total of 100 patients (age 8.7 ± 5 years) were included: 45 children with KD and CADL (KD/CADL) (Z-score > 2.5), 45 age-matched controls (CTRL) and, finally, an additional group of 10 children with KD in absence of coronary dilatation (KD group). Left ventricular (LV) systolic function and global longitudinal strain (GLS) were assessed. Global myocardial work index (MWI) was calculated as the area of the LV pressure-strain loops. From MWI, global Constructive Work (MCW), Wasted Work (MWW) and Work Efficiency (MWE) were estimated. Despite normal LV systolic function by routine echocardiography, KD/CADL patients had lower MWI (1433.2 ± 375.8 mmHg% vs 1752.2 ± 265.7 mmHg%, p < 0.001), MCW (1885.5 ± 384.2 mmHg% vs 2175.9 ± 292.4 mmHg%, p = 0.001) and MWE (994.0 ± 4.8% vs 95.9 ± 2.0%, p = 0.030) compared to CTRL. Furthermore, MWI was significantly reduced in children belonging to the KD group in comparison with controls (KD: 1498.3 ± 361.7 mmHg%; KD vs CTRL p = 0.028) and was comparable between KD/CADL and KD groups (KD/CADL vs KD p = 0.896). Moreover, KD/CADL patients with normal GLS (n = 38) preserved significant differences in MWI and MCW in comparison with CTRL. MWI, MCW and MWE were significantly reduced in KD children despite normal LVEF and normal GLS. These abnormalities seems independent from CADL. Thus, in KD with normal LVEF and normal GLS, estimation of MWI may be a more sensitive indicator of myocardial dysfunction.
The impact of baseline glomerular filtration rate on subsequent changes of glomerular filtration rate in patients with chronic kidney disease
Authors: Lin Yi-Chih , Lai Tai-Shuan , Lin Shuei-Liong , Chen Yung-Ming , Chu Tzong-Shinn , Tu Yu-Kang
Published: April 2021

Higher baseline glomerular filtration rate (GFR) may yield subsequent steeper GFR decline, especially in patients with diabetes mellitus (DM). However, this correlation in patients with chronic kidney disease (CKD) and the presence or absence of DM remains controversial. We conducted a longitudinal cohort study in a single medical center between 2011 and 2018. Participants with CKD stage 1 to 3A were enrolled and divided into DM groups and non-DM groups, and then followed up at least every 6 months. We used a linear mixed regression model with centering time variable to overcome the problem of mathematical coupling in the analysis of the relation between baseline GFR and the changes, and compared the results from correct and incorrect specifications of the mixed models. A total number of 1002 patients with 285 diabetic and 717 non-diabetic persons was identified. The linear mixed regression model revealed a significantly negative correlation between baseline GFR and subsequent GFR change rate in both diabetic group and non-diabetic group (r =  − 0.44 [95% confidence interval [CI], − 0.69 to − 0.09]), but no statistical significance in non-diabetic group after within-subject mean centering of time variable (r =  − 0.09 [95% CI, − 0.41 to 0.25]). Our study showed that higher baseline GFR was associated with a subsequent steeper GFR decline in the DM group but not in the non-DM group among patients with early-stage CKD. Exact model specifications should be described in detail to prevent from a spurious conclusion.
He–Ne laser accelerates seed germination by modulating growth hormones and reprogramming metabolism in brinjal
Authors: Swathy Puthanvila Surendrababu , Kiran Kodsara Ramachandra , Joshi Manjunath B , Mahato Krishna Kishore , Muthusamy Annamalai
Published: April 2021

A plant’s ability to maximize seed germination, growth, and photosynthetic productivity depends on its aptitude to sense, evaluate, and respond to the quality, quantity, and direction of the light. Among diverse colors of light possessing different wavelengths and red light shown to have a high impact on the photosynthetic and growth responses of the plants. The use of artificial light sources where the quality, intensity, and duration of exposure can be controlled would be an efficient method to increase the efficiency of the crop plants. The coherent, collimated, and monochromatic properties of laser light sources enabled as biostimulator compared to the normal light. The present study was attempted to use the potential role of the He–Ne laser as a bio-stimulator device to improve the germination and growth of brinjal and to investigate the possible interactions of plant and laser photons. A substantial enhancement was observed in germination index, germination time and seed vigor index of laser-irradiated than control groups. The enhanced germination rate was correlated with higher GA content and its biosynthetic genes whereas decreased ABA content and its catabolic genes and GA/ABA ratio were noted in laser-irradiated groups during seed germination than control groups. Further the expression of phytochrome gene transcripts, PhyA and PhyB1 were upregulated in laser-irradiated seedlings which correlate with enhanced seed germination than control. Elevated levels of primary metabolites were noted in the early stages of germination whereas modulation of secondary metabolites was observed in later growth. Consequently, significantly increased photosynthetic rate, stomatal conductance, and transpiration rate was perceived in laser-irradiated seedlings compare with control. The current study showed hormone and phytochrome-mediated mechanisms of seed germination in laser-irradiated groups along with the enhanced photosynthetic rate, primary and secondary metabolites.
Structural comparison of Acinetobacter baumannii β-ketoacyl-acyl carrier protein reductases in fatty acid and aryl polyene biosynthesis
Authors: Lee Woo Cheol , Choi Sungjae , Jang Ahjin , Son Kkabi , Kim Yangmee
Published: April 2021

Some Gram-negative bacteria harbor lipids with aryl polyene (APE) moieties. Biosynthesis gene clusters (BGCs) for APE biosynthesis exhibit striking similarities with fatty acid synthase (FAS) genes. Despite their broad distribution among pathogenic and symbiotic bacteria, the detailed roles of the metabolic products of APE gene clusters are unclear. Here, we determined the crystal structures of the β-ketoacyl-acyl carrier protein (ACP) reductase ApeQ produced by an APE gene cluster from clinically isolated virulent Acinetobacter baumannii in two states (bound and unbound to NADPH). An in vitro visible absorption spectrum assay of the APE polyene moiety revealed that the β-ketoacyl-ACP reductase FabG from the A. baumannii FAS gene cluster cannot be substituted for ApeQ in APE biosynthesis. Comparison with the FabG structure exhibited distinct surface electrostatic potential profiles for ApeQ, suggesting a positively charged arginine patch as the cognate ACP-binding site. Binding modeling for the aryl group predicted that Leu185 (Phe183 in FabG) in ApeQ is responsible for 4-benzoyl moiety recognition. Isothermal titration and arginine patch mutagenesis experiments corroborated these results. These structure–function insights of a unique reductase in the APE BGC in comparison with FAS provide new directions for elucidating host–pathogen interaction mechanisms and novel antibiotics discovery.
The larval environment strongly influences the bacterial communities of Aedes triseriatus and Aedes japonicus (Diptera: Culicidae)
Authors: Juma Elijah O. , Allan Brian F. , Kim Chang-Hyun , Stone Christopher , Dunlap Christopher , Muturi Ephantus J.
Published: April 2021

Mosquito bacterial communities are essential in mosquito biology, and knowing the factors shaping these bacterial communities is critical to their application in mosquito-borne disease control. This study investigated how the larval environment influences the bacterial communities of larval stages of two container-dwelling mosquito species, Aedes triseriatus, and Aedes japonicus. Larval and water samples were collected from tree holes and used tires at two study sites, and their bacteria characterized through MiSeq sequencing of the 16S rRNA gene. Bacterial richness was highest in Ae. japonicus, intermediate in Ae. triseriatus, and lowest in water samples. Dysgonomonas was the dominant bacterial taxa in Ae. triseriatus larvae; the unclassified Comamonadaceae was dominant in water samples from waste tires, while Mycobacterium and Carnobacterium, dominated Ae. japonicus. The two mosquito species harbored distinct bacterial communities that were different from those of the water samples. The bacterial communities also clustered by habitat type (used tires vs. tree holes) and study site. These findings demonstrate that host species, and the larval sampling environment are important determinants of a significant component of bacterial community composition and diversity in mosquito larvae and that the mosquito body may select for microbes that are generally rare in the larval environment.
Transcriptomic analysis of human brain microvascular endothelial cells exposed to laminin binding protein (adhesion lipoprotein) and Streptococcus pneumoniae
Authors: Jiménez-Munguía Irene , Tomečková Zuzana , Mochnáčová Evelína , Bhide Katarína , Majerová Petra , Bhide Mangesh
Published: April 2021

Streptococcus pneumoniaeinvades the CNS and triggers a strong cellular response. To date, signaling events that occur in the human brain microvascular endothelial cells (hBMECs), in response to pneumococci or its surface adhesins are not mapped comprehensively. We evaluated the response of hBMECs to the adhesion lipoprotein (a laminin binding protein—Lbp) or live pneumococci. Lbp is a surface adhesin recently identified as a potential ligand, which binds to the hBMECs. Transcriptomic analysis was performed by RNA-seq of three independent biological replicates and validated with qRT-PCR using 11 genes. In total 350 differentially expressed genes (DEGs) were identified after infection withS. pneumoniae,whereas 443 DEGs when challenged with Lbp. Total 231 DEGs were common in both treatments. Integrative functional analysis revealed participation of DEGs in cytokine, chemokine, TNF signaling pathways and phagosome formation. Moreover, Lbp induced cell senescence and breakdown, and remodeling of ECM. This is the first report which maps complete picture of cell signaling events in the hBMECs triggered againstS. pneumoniaeand Lbp. The data obtained here could contribute in a better understanding of the invasion of pneumococci across BBB and underscores role of Lbp adhesin in evoking the gene expression in neurovascular unit.
How to put quantum particles on magic bullet trajectories that can hit two targets without a clear line-of-sight
Authors: Hofmann Holger F.
Published: April 2021

Quantum particles move in strange ways, even when they propagate freely in space. As a result of the uncertainty principle, it is not possible to control the initial conditions of particle emission in such a way that the particle will definitely pass through two precisely defined positions along its path, even if it is possible to line up the two positions with the emitter. However, there is also an upside to the quantum mechanical laws of motion: constructive quantum interferences can actually raise probabilities to values higher than those permitted by classical causality. Here, it is shown that conventional interferometric methods can be used to prepare photons in a quantum state in which a non-vanishing fraction of particles will hit both of two possible targets, even though the direct line-of-sight connecting the two targets is blocked at the source. The demonstration of the effect is complicated by the uncertainty principle because the physical detection of a particle at one target disturbs the motion of the particle, making it impossible to determine whether the initial state of motion would have allowed the particle to hit the other target or not. It is nonetheless possible to determine the minimal fraction of “magic bullet” particles that must have hit both targets by showing that the number of particles hitting target A is larger than the number of particles missing target B. Quantum interference effects can thus be used to optimize the path of particles in free space beyond the classical limit of motion along a straight line.
Deep brain electrical neurofeedback allows Parkinson patients to control pathological oscillations and quicken movements
Authors: Bichsel Oliver , Stieglitz Lennart H. , Oertel Markus F. , Baumann Christian R. , Gassert Roger , Imbach Lukas L.
Published: April 2021

Parkinsonian motor symptoms are linked to pathologically increased beta-oscillations in the basal ganglia. While pharmacological treatment and deep brain stimulation (DBS) reduce these pathological oscillations concomitantly with improving motor performance, we set out to explore neurofeedback as an endogenous modulatory method. We implemented real-time processing of pathological subthalamic beta oscillations through implanted DBS electrodes to provide deep brain electrical neurofeedback. Patients volitionally controlled ongoing beta-oscillatory activity by visual neurofeedback within minutes of training. During a single one-hour training session, the reduction of beta-oscillatory activity became gradually stronger and we observed improved motor performance. Lastly, endogenous control over deep brain activity was possible even after removing visual neurofeedback, suggesting that neurofeedback-acquired strategies were retained in the short-term. Moreover, we observed motor improvement when the learnt mental strategies were applied 2 days later without neurofeedback. Further training of deep brain neurofeedback might provide therapeutic benefits for Parkinson patients by improving symptom control using strategies optimized through neurofeedback.
Transcutaneous auricular vagus nerve stimulation induces stabilizing modifications in large-scale functional brain networks: towards understanding the effects of taVNS in subjects with epilepsy
Authors: von Wrede Randi , Rings Thorsten , Schach Sophia , Helmstaedter Christoph , Lehnertz Klaus
Published: April 2021

Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive brain stimulation technique considered as a potential supplementary treatment option for subjects with refractory epilepsy. Its exact mechanism of action is not yet fully understood. We developed an examination schedule to probe for immediate taVNS-induced modifications of large-scale epileptic brain networks and accompanying changes of cognition and behaviour. In this prospective trial, we applied short-term (1 h) taVNS to 14 subjects with epilepsy during a continuous 3-h EEG recording which was embedded in two standardized neuropsychological assessments. From these EEG, we derived evolving epileptic brain networks and tracked important topological, robustness, and stability properties of networks over time. In the majority of investigated subjects, taVNS induced measurable and persisting modifications in network properties that point to a more resilient epileptic brain network without negatively impacting cognition, behaviour, or mood. The stimulation was well tolerated and the usability of the device was rated good. Short-term taVNS has a topology-modifying, robustness- and stability-enhancing immediate effect on large-scale epileptic brain networks. It has no detrimental effects on cognition and behaviour. Translation into clinical practice requires further studies to detail knowledge about the exact mechanisms by which taVNS prevents or inhibits seizures.
A microfluidic approach to rapid sperm recovery from heterogeneous cell suspensions
Authors: Vasilescu Steven A. , Khorsandi Shayan , Ding Lin , Bazaz Sajad Razavi , Nosrati Reza , Gook Debra , Warkiani Majid Ebrahimi
Published: April 2021

The isolation of sperm cells from background cell populations and debris is an essential step in all assisted reproductive technologies. Conventional techniques for sperm recovery from testicular sperm extractions stagnate at the sample processing stage, where it can take several hours to identify viable sperm from a background of collateral cells such as white bloods cells (WBCs), red blood cells (RBCs), epithelial cells (ECs) and in some cases cancer cells. Manual identification of sperm from contaminating cells and debris is a tedious and time-consuming operation that can be suitably addressed through inertial microfluidics. Microfluidics has proven an effective technology for high-quality sperm selection based on motility. However, motility-based selection methods cannot cater for viable, non-motile sperm often present in testicular or epididymal sperm extractions and aspirations. This study demonstrates the use of a 3D printed inertial microfluidic device for the separation of sperm cells from a mixed suspension of WBCs, RBCs, ECs, and leukemic cancer cells. This technology presents a 36-fold time improvement for the recovery of sperm cells (> 96%) by separating sperm, RBCS, WBCs, ECs and cancer cells into tight bands in less than 5 min. Furthermore, microfluidic processing of sperm has no impact on sperm parameters; vitality, motility, morphology, or DNA fragmentation of sperm. Applying inertial microfluidics for non-motile sperm recovery can greatly improve the current processing procedure of testicular sperm extractions, simplifying the fertility outcomes for severe forms of male infertility that warrant the surgery.
Evolutionary diversification of cytokinin-specific glucosyltransferases in angiosperms and enigma of missing cis-zeatin O-glucosyltransferase gene in Brassicaceae
Authors: Záveská Drábková Lenka , Honys David , Motyka Václav
Published: April 2021

In the complex process of homeostasis of phytohormones cytokinins (CKs),O-glucosylation catalyzed by specificO-glucosyltransferases represents one of important mechanisms of their reversible inactivation. The CKO-glucosyltransferases belong to a highly divergent and polyphyletic multigene superfamily of glycosyltransferases, of which subfamily 1 containing UDP-glycosyltransferases (UGTs) is the largest in the plant kingdom. It contains recently discovered O and P subfamilies present in higher plant species but not inArabidopsis thaliana. Thecis-zeatinO-glucosyltransferase (cisZOG) genes belong to the O subfamily encoding a stereo-specificO-glucosylation ofcis-zeatin-type CKs. We studied different homologous genes, their domains and motifs, and performed a phylogenetic reconstruction to elucidate the plant evolution of thecisZOG gene. We found that thecisZOG homologs do not form a clear separate clade, indicating that diversification of thecisZOG gene took place after the diversification of the main angiosperm families, probably within genera or closely related groups. We confirmed that the gene(s) from group O is(are) not present inA. thalianaand is(are) also missing in the family Brassicaceae. However,cisZOG or its metabolites are found among Brassicaceae clade, indicating that remaining genes from other groups (UGT73—group D and UGT85—group G) are able, at least in part, to substitute the function of group O lost during evolution. This study is the first detailed evolutionary evaluation of relationships among different plant ZOGs within angiosperms.
Carbohydrate binding module-fused antibodies improve the performance of cellulose-based lateral flow immunoassays
Authors: Elter Adrian , Bock Tina , Spiehl Dieter , Russo Giulio , Hinz Steffen C. , Bitsch Sebastian , Baum Eva , Langhans Markus , Meckel Tobias , Dörsam Edgar , Kolmar Harald , Schwall Gerhard
Published: April 2021

Since the pandemic outbreak of Covid-19 in December 2019, several lateral flow assay (LFA) devices were developed to enable the constant monitoring of regional and global infection processes. Additionally, innumerable lateral flow test devices are frequently used for determination of different clinical parameters, food safety, and environmental factors. Since common LFAs rely on non-biodegradable nitrocellulose membranes, we focused on their replacement by cellulose-composed, biodegradable papers. We report the development of cellulose paper-based lateral flow immunoassays using a carbohydrate-binding module-fused to detection antibodies. Studies regarding the protein binding capacity and potential protein wash-off effects on cellulose paper demonstrated a 2.7-fold protein binding capacity of CBM-fused antibody fragments compared to the sole antibody fragment. Furthermore, this strategy improved the spatial retention of CBM-fused detection antibodies to the test area, which resulted in an enhanced sensitivity and improved overall LFA-performance compared to the naked detection antibody. CBM-assisted antibodies were validated by implementation into two model lateral flow test devices (pregnancy detection and the detection of SARS-CoV-2 specific antibodies). The CBM-assisted pregnancy LFA demonstrated sensitive detection of human gonadotropin (hCG) in synthetic urine and the CBM-assisted Covid-19 antibody LFA was able to detect SARS-CoV-2 specific antibodies present in serum. Our findings pave the way to the more frequent use of cellulose-based papers instead of nitrocellulose in LFA devices and thus potentially improve the sustainability in the field of POC diagnostics.
The first record of exceptionally-preserved spiral coprolites from the Tsagan-Tsab formation (lower cretaceous), Tatal, western Mongolia
Authors: Rummy Paul , Halaclar Kazim , Chen He
Published: April 2021

In this paper, seven coprolites from the Lower Cretaceous of Tsagan-Tsab formation have been described. Thus, producing a significant contribution to what we perceived as the first detailed study of coprolites from the Mesozoic deposits in Mongolia. The collected coprolites encompass a total of six spiral amphipolar and one scroll coprolites. We prominently identified four new coprolite ichnotaxa, such as:Hyronocoprus tsagantsabensisandHyronocoprus hunti, to which both are ichnosp. nov.; followed byMegakalocoprus barremianensisandScrollocoprus tatalensis, where both are ichnogen. et ichnosp. nov. Notably, CT scans revealed that all specimens showed various amounts of bony inclusions and scales, hence, deducing that the producers could have had a low acidic digestive track and were unable to dissolve bone matters. Moreover, SEM–EDS analysis concluded its carnivorous nature, thus, pointing towards piscivorous diet. The small sizedScrollocoprusis considered to be the second findings of Mesozoic era’s scroll coprolites, which contain possible plant pollens, a complete infraorbital bone, clusters of bone fragments and rhomboidal-shaped ganoid scales of the prey; and bioerosional scars have been observed on the surface. We suggest those amphipolar spiral ichnotaxa were produced by Asipenceriformes, with Pholidophoriformes as the prey, whileScrollocoprusrepresents fecal excrement of underived fish, possibly of sarcopterygian origins.