bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of dexmedetomidine on renal microcirculation in ischemia/reperfusion-induced acute kidney injury in rats
Authors: Yang Szu-Jen , Fan Chia-Ning , Wang Ming-Jiuh , Fan Shou-Zen , Tsai Jui-Chang , Sun Wei-Zen , Chan Wing-Sum , Yeh Yu-Chang ,   NTUH Center of Microcirculation Medical Research (NCMMR), Cheng Ya-Jung , Yeh Yu-Chang , Liu Chih-Min , Shih Po-Yuan , Chen Shih-Hong , Chiu Ching-Tang , Chao Anne , Wu Chun-Yu
Published: January 2021

Microcirculatory dysfunction plays a crucial role in renal ischemia/reperfusion (IR)-induced injury. Dexmedetomidine was reported to ameliorate IR-induced acute kidney injury. This study investigated the effects of dexmedetomidine on renal microcirculation after IR-induced acute kidney injury in rats. In total, 50 rats were randomly allocated to the following five groups (10 in each group): Sham, Control‒IR, Dex (dexmedetomidine) ‒Sham, Dex‒IR, and IR‒Dex group. The microcirculation parameters included total small vessel density, perfused small vessel density (PSVD), proportion of perfused small vessels, microvascular flow index, and tissue oxygen saturation (StO2) were recorded. The repeated measures analysis showed that PSVD on renal surface was higher in the Dex‒IR group than in the Control‒IR group (3.5 mm/mm2, 95% confidence interval [CI] 0.6 to 6.4 mm/mm2, P = 0.01). At 240 min, StO2 on renal surface was lower in the Control‒IR group than in the Sham group (– 7%, 95% CI − 13 to − 1%, P = 0.021), but StO2 did not differ significantly among the Sham, Dex‒IR, and IR‒Dex groups. Our results showed that pretreatment with dexmedetomidine improved renal microcirculation in rats with IR-induced acute kidney injury. However, the adverse effects of low mean arterial pressure and heart rate might offset the protective effect of dexmedetomidine on organ injury.
Specific egg yolk immunoglobulin as a promising non-antibiotic biotherapeutic product against Acinetobacter baumannii pneumonia infection
Authors: Jahangiri Abolfazl , Owlia Parviz , Rasooli Iraj , Salimian Jafar , Derakhshanifar Ehsan , Aghajani Zahra , Abdollahi Sajad , Khalili Saeed , Talei Daryush , Eslam Elham Darzi
Published: January 2021

Acinetobacter baumannii is a serious health threat with a high mortality rate. We have already reported prophylactic effects of IgYs raised against OmpA and Omp34 as well as against inactivated whole-cell (IWC) of A. baumannii in a murine pneumonia model. However, the infection was exacerbated in the mice group that received IgYs raised against the combination of OmpA and Omp34. The current study was conducted to propose reasons for the observed antibody-dependent enhancement (ADE) in addition to the therapeutic effect of specific IgYs in the murine pneumonia model. This phenomenon was hypothetically attributed to topologically inaccessible similar epitopes of OmpA and Omp34 sharing similarity with peptides of mice proteins. In silico analyses revealed that some inaccessible peptides of OmpA shared similarity with peptides of Omp34 and Mus musculus. Specific anti-OmpA and anti-Omp34 IgYs cross-reacted with Omp34 and OmpA respectively. Specific IgYs showed different protectivity against A. baumannii AbI101 in the murine pneumonia model. IgYs triggered against OmpA or IWC of A. baumannii were the most protective antibodies. IgY triggered against Omp34 is ranked next after those against OmpA. The lowest protection was observed in mice received IgYs raised against the combination of rOmpA and rOmp34. In conclusion, specific IgYs against OmpA, Omp34, and IWC of A. baumannii could serve as novel biotherapeutics against A. baumannii pneumonia.
Rapid and efficient immunomagnetic isolation of endothelial cells from human peripheral nerves
Authors: Dömer Patrick , Kayal Janine , Janssen-Bienhold Ulrike , Kewitz Bettina , Kretschmer Thomas , Heinen Christian
Published: January 2021

Endothelial cells (ECs) have gained an increased scientific focus since they were reported to provide guidance for Schwann cells and subsequently following axons after nerve injuries. However, previous protocols for the isolation of nerve-derived ECs from human nerves are ineffective regarding time and yield. Therefore, we established a novel and efficient protocol for the isolation of ECs from human peripheral nerves by means of immunomagnetic CD31-antibody conjugated Dynabeads and assessed the purity of the isolated cells. The easy-to-follow and time-effective isolation method allows the isolation of > 95% pure ECs. The isolated ECs were shown to express highly specific EC marker proteins and revealed functional properties by formation of CD31 and VE-cadherin positive adherens junctions, as well as ZO-1 positive tight-junctions. Moreover, the formation of capillary EC-tubes was observed in-vitro. The novel protocol for the isolation of human nerve-derived ECs allows and simplifies the usage of ECs in research of the human blood-nerve-barrier and peripheral nerve regeneration. Additionally, a potential experimental application of patient-derived nerve ECs in the in-vitro vascularization of artificial nerve grafts is feasible.
Analysis of SteraMist ionized hydrogen peroxide technology in the sterilization of N95 respirators and other PPE
Authors: Cramer Avilash K. , Plana Deborah , Yang Helen , Carmack Mary M. , Tian Enze , Sinha Michael S. , Krikorian David , Turner David , Mo Jinhan , Li Ju , Gupta Rajiv , Manning Heather , Bourgeois Florence T. , Yu Sherry H. , Sorger Peter K. , LeBoeuf Nicole R.
Published: January 2021

The COVID-19 pandemic has led to widespread shortages of personal protective equipment (PPE) for healthcare workers, including of N95 masks (filtering facepiece respirators; FFRs). These masks are intended for single use but their sterilization and subsequent reuse has the potential to substantially mitigate shortages. Here we investigate PPE sterilization using ionized hydrogen peroxide (iHP), generated by SteraMist equipment (TOMI; Frederick, MD), in a sealed environment chamber. The efficacy of sterilization by iHP was assessed using bacterial spores in biological indicator assemblies. After one or more iHP treatments, five models of N95 masks from three manufacturers were assessed for retention of function based on their ability to form an airtight seal (measured using a quantitative fit test) and filter aerosolized particles. Filtration testing was performed at a university lab and at a National Institute for Occupational Safety and Health (NIOSH) pre-certification laboratory. The data demonstrate that N95 masks sterilized using SteraMist iHP technology retain filtration efficiency up to ten cycles, the maximum number tested to date. A typical iHP environment chamber with a volume of ~ 80 m3 can treat ~ 7000 masks and other items (e.g. other PPE, iPADs), making this an effective approach for a busy medical center.
Predictive modeling of depression and anxiety using electronic health records and a novel machine learning approach with artificial intelligence
Authors: Nemesure Matthew D. , Heinz Michael V. , Huang Raphael , Jacobson Nicholas C.
Published: January 2021

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are highly prevalent and impairing problems, but frequently go undetected, leading to substantial treatment delays. Electronic health records (EHRs) collect a great deal of biometric markers and patient characteristics that could foster the detection of GAD and MDD in primary care settings. We approached the problem of predicting MDD and GAD using a novel machine learning pipeline to re-analyze data from an observational study. The pipeline constitutes an ensemble of algorithmically distinct machine learning methods, including deep learning. A sample of 4,184 undergraduate students completed the study, undergoing a general health screening and completing a psychiatric assessment for MDD and GAD. After explicitly excluding all psychiatric information, 59 biomedical and demographic features from the general health survey in addition to a set of engineered features were used for model training. We assessed the model's performance on a held-out test set and found an AUC of 0.73 (sensitivity: 0.66, specificity: 0.7) and 0.67 (sensitivity: 0.55, specificity: 0.7) for GAD, and MDD, respectively. Additionally, we used advanced techniques (SHAP values) to illuminate which features had the greatest impact on prediction for each disease. The top predictive features for MDD were being satisfied with living conditions and having public health insurance. The top predictive features for GAD were vaccinations being up to date and marijuana use. Our results indicate moderate predictive performance for the application of machine learning methods in detection of GAD and MDD based on EHR data. By identifying important predictors of GAD and MDD, these results may be used in future research to aid in the early detection of MDD and GAD.
Electrocardiogram lead selection for intelligent screening of patients with systolic heart failure
Authors: Chiou Yu-An , Syu Jhen-Yang , Wu Sz-Ying , Lin Lian-Yu , Yi Li Tzu , Lin Ting-Tse , Lin Shien-Fong
Published: January 2021

Electrocardiogram (ECG)-based intelligent screening for systolic heart failure (HF) is an emerging method that could become a low-cost and rapid screening tool for early diagnosis of the disease before the comprehensive echocardiographic procedure. We collected 12-lead ECG signals from 900 systolic HF patients (ejection fraction, EF < 50%) and 900 individuals with normal EF in the absence of HF symptoms. The 12-lead ECG signals were converted by continuous wavelet transform (CWT) to 2D spectra and classified using a 2D convolutional neural network (CNN). The 2D CWT spectra of 12-lead ECG signals were trained separately in 12 identical 2D-CNN models. The 12-lead classification results of the 2D-CNN model revealed that Lead V6 had the highest accuracy (0.93), sensitivity (0.97), specificity (0.89), and f1 scores (0.94) in the testing dataset. We designed four comprehensive scoring methods to integrate the 12-lead classification results into a key diagnostic index. The highest quality result among these four methods was obtained when Leads V5 and V6 of the 12-lead ECG signals were combined. Our new 12-lead ECG signal–based intelligent screening method using straightforward combination of ECG leads provides a fast and accurate approach for pre-screening for systolic HF.
Towards validation of combined-accelerated stress testing through failure analysis of polyamide-based photovoltaic backsheets
Authors: Owen-Bellini Michael , Moffitt Stephanie L. , Sinha Archana , Maes Ashley M. , Meert Joseph J. , Karin Todd , Takacs Chris , Jenket Donald R. , Hartley James Y. , Miller David C. , Hacke Peter , Schelhas Laura T.
Published: January 2021

Novel methods for advancing reliability testing of photovoltaic (PV) modules and materials have recently been developed. Combined-accelerated stress testing (C-AST) is one such method which has demonstrated reliable reproduction of some field-failures which were not reproducible by standard certification tests. To increase confidence and assist in the development of C-AST, and other new testing protocols, it is important to validate that the failure modes observed and mechanisms induced are representative of those observed in the field, and not the product of unrealistic stress conditions. Here we outline a method using appropriate materials characterization and modelling to validate the failure mechanisms induced in C-AST such that we can increase confidence in the test protocol. The method is demonstrated by applying it to a known cracking failure of a specific polyamide (PA)-based backsheet material. We found that the failure of the PA-based backsheet was a result of a combination of stress factors. Photo-oxidation from ultra-violet (UV) radiation exposure caused a reduction in fracture toughness, which ultimately lead to the cracking failure. We show that the chemical and structural changes observed in the backsheet following C-AST aging were also observed in field-aged samples. These results increase confidence that the conditions applied in C-AST are representative of the field and demonstrates our approach to validating the failure mechanisms induced.
A new mouse model for retinal degeneration due to Fam161a deficiency
Authors: Beryozkin Avigail , Matsevich Chen , Obolensky Alexey , Kostic Corinne , Arsenijevic Yvan , Wolfrum Uwe , Banin Eyal , Sharon Dror
Published: January 2021

FAM161A mutations are the most common cause of inherited retinal degenerations in Israel. We generated a knockout (KO) mouse model, Fam161atm1b/tm1b, lacking the major exon #3 which was replaced by a construct that include LacZ under the expression of the Fam161a promoter. LacZ staining was evident in ganglion cells, inner and outer nuclear layers and inner and outer-segments of photoreceptors in KO mice. No immunofluorescence staining of Fam161a was evident in the KO retina. Visual acuity and electroretinographic (ERG) responses showed a gradual decrease between the ages of 1 and 8 months. Optical coherence tomography (OCT) showed thinning of the whole retina. Hypoautofluorescence and hyperautofluorescence pigments was observed in retinas of older mice. Histological analysis revealed a progressive degeneration of photoreceptors along time and high-resolution transmission electron microscopy (TEM) analysis showed that photoreceptor outer segment disks were disorganized in a perpendicular orientation and outer segment base was wider and shorter than in WT mice. Molecular degenerative markers, such as microglia and CALPAIN-2, appear already in a 1-month old KO retina. These results indicate that a homozygous Fam161a frameshift mutation affects retinal function and causes retinal degeneration. This model will be used for gene therapy treatment in the future.
Autumn COVID-19 surge dates in Europe correlated to latitudes, not to temperature-humidity, pointing to vitamin D as contributing factor
Authors: Walrand Stephan
Published: January 2021

To determine the factor triggering the sudden surge of daily new COVID-19 cases arising in most European countries during the autumn of 2020. The dates of the surge were determined using a fitting of the two last months of reported daily new cases in 18 European countries with latitude ranging from 39° to 62°. The study proves no correlation between the country surge date and the 2 weeks preceding temperature or humidity but shows an impressive linear correlation with latitude. The country surge date corresponds to the time when its sun UV daily dose drops below ≈ 34% of that of 0° latitude. Introducing reported seasonal blood 25-hydroxyvitamin D (25(OH)D) concentration variation into the reported link between acute respiratory tract infection risk and 25(OH)D concentration quantitatively explains the surge dynamics. Several studies have already substantiated a 25(OH)D concentration impact on COVID-19 severity. However, by comparing different patient populations, discriminating whether a low 25(OH)D concentration is a real factor underlying COVID-19 severity or only a marker of another weakness that is the primary severity factor can be challenging. The date of the surge is an intrapopulation observation and has the benefit of being triggered only by a parameter globally affecting the population, i.e. decreases in the sun UV daily dose. The results indicate that a low 25(OH)D concentration is a contributing factor to COVID-19 severity, which, combined with previous studies, provides a convincing set of evidence.
Remote liver ischemic preconditioning attenuates myocardial ischemia/reperfusion injury in streptozotocin-induced diabetic rats
Authors: Liu Xinhao , Chen Hui , Yan Zhibing , Du Lei , Huang Dou , Gao Wei Dong , Hu Zhaoyang
Published: January 2021

Diabetes mellitus (DM) exhibits a higher sensitivity to myocardial ischemia/reperfusion (I/R) injury and may compromise the effectiveness of cardioprotective interventions, including ischemic preconditioning. We previously found that liver ischemic preconditioning (RLIPC) could limit infarct size post I/R in non-diabetic rat hearts and further exerted anti-arrhythmic effects in diabetic or non-diabetic rats after myocardial I/R, however, little is known regarding the effect of RLIPC on infarct-sparing in diabetic hearts. In this study, we evaluated the protective effects of RLIPC on I/R injury in streptozotocin-induced type 1 diabetic rats. Type 1 diabetes mellitus was induced by one-time intraperitoneal injection of streptozotocin in Sprague–Dawley rats. Rats were exposed to 45 min of left anterior descend in (LAD) coronary artery occlusion, followed by 3 h of reperfusion. For liver ischemic preconditioning, four cycles of 5 min of liver I/R stimuli were performed before LAD occlusion. The cardioprotective effect of RLIPC was determined in diabetic rats. Compared to non-RLIPC treated DM rats, RLIPC treatment significantly reduced infarct size and cardiac tissue damage, inhibited apoptosis in diabetic hearts post I/R. RLIPC also improved cardiac functions including LVESP, LVEDP, dp/dtmax, and − dp/dtmax. In addition, RLIPC preserved cardiac morphology by reducing the pathological score post I/R in diabetic hearts. Finally, Westernblotting showed that RLIPC stimulated phosphorylation of ventricular GSK-3β and STAT-5, which are key components of RISK and SAFE signaling pathways. Our study showed that liver ischemic preconditioning retains strong cardioprotective properties in diabetic hearts against myocardial I/R injury via GSK-3β/STAT5 signaling pathway.
Fully integrated rapid microfluidic device translated from conventional 96-well ELISA kit
Authors: Uddin M. Jalal , Bhuiyan Nabil H. , Shim Joon S.
Published: January 2021

In this work, a fully integrated active microfluidic device transforming a conventional 96-well kit into point-of-care testing (POCT) device was implemented to improve the performance of traditional enzyme-linked immunosorbent assay (ELISA). ELISA test by the conventional method often requires the collection of 96 samples for its operation as well as longer incubation time from hours to overnight, whereas our proposed device conducts ELISA immediately individualizing a 96-well for individual patients. To do that, a programmable and disposable on-chip pump and valve were integrated on the device for precise control and actuation of microfluidic reagents, which regulated a reaction time and reagent volume to support the optimized protocols of ELISA. Due to the on-chip pump and valve, ELISA could be executed with reduced consumption of reagents and shortening the assay time, which are crucial for conventional ELISA using 96-well microplate. To demonstrate highly sensitive detection and easy-to-use operation, this unconventional device was successfully applied for the quantification of cardiac troponin I (cTnI) of 4.88 pg/mL using a minimum sample volume of 30 µL with a shorter assay time of 15 min for each ELISA step. The limit of detection (LOD) thus obtained was significantly improved than the conventional 96-well platform.
Caloric restriction reduces sympathetic activity similar to beta-blockers but conveys additional mitochondrio-protective effects in aged myocardium
Authors: Niemann Bernd , Li Ling , Simm Andreas , Molenda Nicole , Kockskämper Jens , Boening Andreas , Rohrbach Susanne
Published: January 2021

Increased activation of sympathetic nervous system contributes to congestive heart failure (CHF) progression, and inhibition of sympathetic overactivation by beta-blockers is successful in CHF patients. Similarly, caloric restriction (CR) reduces sympathetic activity but mediates additional effects. Here, we compared the cardiac effects of CR (− 40% kcal, 3 months) with beta-blocker therapy (BB), diuretic medication (DF) or control diet in 18-months-old Wistar rats. We continuously recorded blood pressure, heart rate, body temperature and activity with telemetric devices and analysed cardiac function, activated signalling cascades and markers of apoptosis and mitochondrial biogenesis. During our study, left ventricular (LV) systolic function improved markedly (CR), mildly (BB) or even deteriorated (DF; control). Diastolic function was preserved by CR and BB but impaired by DF. CR reduced blood pressure identical to DF and BB and heart rate identical to BB. Plasma noradrenaline was decreased by CR and BB but increased by DF. Only CR reduced LV oxidative damage and apoptosis, induced AMPK and Akt phosphorylation and increased mitochondrial biogenesis. Thus, additive to the reduction of sympathetic activity, CR achieves protective effects on mitochondria and improves LV function and ROS damage in aged hearts. CR mechanisms may provide additional therapeutic targets compared to traditional CHF therapy.
The impact of number of repeats N on the interlayer exchange in $$[\text {Fe/MgO}]_{N} $$(001) superlattices
Authors: Warnatz Tobias , Magnus Fridrik , Strandqvist Nanny , Sanz Sarah , Ali Hasan , Leifer Klaus , Vorobiev Alexei , Hjörvarsson Björgvin
Published: January 2021

The strength of the interlayer exchange coupling in [Fe/MgO]$$_N$$

N

(001) superlattices with 2 ≤ N ≤ 10 depends on the number of bilayer repeats (N). The exchange coupling is antiferromagnetic for all the investigated thicknesses while being nine times larger in a sample with N = 4 as compared to N = 2. The sequence of the magnetic switching in two of the samples (N = 4, N = 8) is determined using polarized neutron reflectometry. The outermost layers are shown to respond at the lowest fields, consistent with having the weakest interlayer exchange coupling. The results are consistent with the existence of quantum well states defined by the thickness of the Fe and the MgO layers as well as the number of repeats (N) in [Fe/MgO]$$ _{N}$$

N

(001)superlattices.
Estimating worldwide effects of non-pharmaceutical interventions on COVID-19 incidence and population mobility patterns using a multiple-event study
Authors: Askitas Nikolaos , Tatsiramos Konstantinos , Verheyden Bertrand
Published: January 2021

Various non-pharmaceutical interventions were adopted by countries worldwide in the fight against the COVID-19 pandemic with adverse socioeconomic side effects, which raises the question about their differential effectiveness. We estimate the average dynamic effect of each intervention on the incidence of COVID-19 and on people’s whereabouts by developing a statistical model that accounts for the contemporaneous adoption of multiple interventions. Using daily data from 175 countries, we show that, even after controlling for other concurrent lockdown policies, cancelling public events, imposing restrictions on private gatherings and closing schools and workplaces had significant effects on reducing COVID-19 infections. Restrictions on internal movement and public transport had no effects because the aforementioned policies, imposed earlier on average, had already de facto reduced human mobility. International travel restrictions, although imposed early, had a short-lived effect failing to prevent the epidemic from turning into a pandemic because they were less stringent. We interpret the impact of each intervention on containing the pandemic using a conceptual framework which relies on their effects on human mobility behaviors in a manner consistent with time-use and epidemiological factors.
Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19
Authors: De Toma Ilario , Dierssen Mara
Published: January 2021

SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection or poorer clinical outcomes. In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we identified the genes associated with the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We then analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) and created a DS-SARS-CoV-2 network. We detected COVID-19 protective and risk factors among HSA21 genes and interactors and/or DS deregulated genes that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome. Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells. However, as the anti-viral interferon I signaling is also upregulated in DS, this might increase the initial anti-viral response, inhibiting viral genome release, viral replication and viral assembly. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.
Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression
Authors: You Mi-Hyeon , Jeon Min Ji , Kim Seong ryeong , Lee Woo Kyung , Cheng Sheue-yann , Jang Goo , Kim Tae Yong , Kim Won Bae , Shong Young Kee , Kim Won Gu
Published: January 2021

Here, we investigated the potential roles of Mitofusin-2 (MFN2) in thyroid cancer progression. MFN2 regulates mitochondrial fusion/division in cells and plays an important role in various aspects of cell metabolism. MFN2 might involve in cell cycle regulation, apoptosis, and differentiation, and it might play a role as a tumor suppressor in carcinogenesis. We evaluated the prognostic impacts of MFN2 expression in thyroid cancer by analyzing TCGA data. In vitro and in vivo, MFN2 was knocked out using CRISPR/Cas9 or siRNA, and MFN2 was stably overexpressed in two thyroid cancer cell lines (Cal62 and HTH83). TCGA analysis revealed that MFN2 expression was lower in thyroid cancer than in normal tissues and significantly associated with a degree of differentiation, RAS mutations, and less lymph node metastasis. MFN2 expression was significantly correlated with cell adhesion molecules and epithelial to mesenchymal transition (EMT) in a gene-set enrichment assay. MFN2 knock-out (KO) in Cal62 and HTH83 cells using CRISPR/Cas9 or siRNA significantly promoted cell migration and invasion in vitro. The same trends were observed in MFN2 KO mouse embryonic fibroblasts (MEFs) compared to those in the controls (MFN2 WT MEFs). Conversely, MFN2 overexpression in cancer cell lines greatly inhibited cell migration and invasion. However, there was no difference in colony formation and proliferation in Cal62 and HTH83 cells after modulating MFN2, although there were significant differences between MFN KO and WT MEFs. EMT-associated protein expression was induced after MFN2 KO in both cancer cell lines. The mechanistic results suggest that MFN2 might modulate EMT through inducing the AKT signaling pathway. EMT-associated changes in protein expression were also confirmed by modulating MFN2 in xenograft tumors. Thus, MFN2 acts as a tumor suppressor in thyroid cancer progression and metastasis by modulating EMT.
Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle
Authors: Reijneveld Josephine F. , Holzheimer Mira , Young David C. , Lopez Kattya , Suliman Sara , Jimenez Judith , Calderon Roger , Lecca Leonid , Murray Megan B. , Ishikawa Eri , Yamasaki Sho , Minnaard Adriaan J. , Moody D. Branch , Van Rhijn Ildiko
Published: January 2021

The cell wall of Mycobacterium tuberculosis is composed of diverse glycolipids which potentially interact with the human immune system. To overcome difficulties in obtaining pure compounds from bacterial extracts, we recently synthesized three forms of mycobacterial diacyltrehalose (DAT) that differ in their fatty acid composition, DAT1, DAT2, and DAT3. To study the potential recognition of DATs by human T cells, we treated the lipid-binding antigen presenting molecule CD1b with synthetic DATs and looked for T cells that bound the complex. DAT1- and DAT2-treated CD1b tetramers were recognized by T cells, but DAT3-treated CD1b tetramers were not. A T cell line derived using CD1b-DAT2 tetramers showed that there is no cross-reactivity between DATs in an IFN-γ release assay, suggesting that the chemical structure of the fatty acid at the 3-position determines recognition by T cells. In contrast with the lack of recognition of DAT3 by human T cells, DAT3, but not DAT1 or DAT2, activates Mincle. Thus, we show that the mycobacterial lipid DAT can be both an antigen for T cells and an agonist for the innate Mincle receptor, and that small chemical differences determine recognition by different parts of the immune system.
Predominance of eyes and surface information for face race categorization
Authors: Bülthoff Isabelle , Jung Wonmo , Armann Regine G. M. , Wallraven Christian
Published: January 2021

Faces can be categorized in various ways, for example as male or female or as belonging to a specific biogeographic ancestry (race). Here we tested the importance of the main facial features for race perception. We exchanged inner facial features (eyes, mouth or nose), face contour (everything but those) or texture (surface information) between Asian and Caucasian faces. Features were exchanged one at a time, creating for each Asian/Caucasian face pair ten facial variations of the original face pair. German and Korean participants performed a race classification task on all faces presented in random order. The results show that eyes and texture are major determinants of perceived biogeographic ancestry for both groups of participants and for both face types. Inserting these features in a face of another race changed its perceived biogeographic ancestry. Contour, nose and mouth, in that order, had decreasing and much weaker influence on race perception for both participant groups. Exchanging those features did not induce a change of perceived biogeographic ancestry. In our study, all manipulated features were imbedded in natural looking faces, which were shown in an off-frontal view. Our findings confirm and extend previous studies investigating the importance of various facial features for race perception.
Susceptibility of Pimephales promelas and Carassius auratus to a strain of koi herpesvirus isolated from wild Cyprinus carpio in North America
Authors: Tolo Isaiah E. , Padhi Soumesh K. , Williams Keiffer , Singh Vikash , Halvorson Sophie , Mor Sunil K. , Phelps Nicholas B. D.
Published: January 2021

Cyprinid herpesvirus-3 (CyHV-3, syn. koi herpesvirus) is an important pathogen worldwide and a common cause of mass mortality events of wild common carp (Cyprinus carpio) in North America, however, reference strains and genomes obtained from wild carp are not available. Additionally, it is unclear if fishes in North America are susceptible to CyHV-3 infection due to incomplete susceptibility testing. Here we present the first North American type strain and whole-genome sequence of CyHV-3 isolated from wild carp collected from a lake with a history and recent incidence of carp mortality. Additionally, the strain was used in an in-vivo infection model to test the susceptibility of a common native minnow (Pimephales promelas) and goldfish (Carrasius auratus) which is invasive in North America. Detection of CyHV-3 DNA was confirmed in the tissues of a single fathead minnow but the same tissues were negative for CyHV-3 mRNA and samples from exposed fathead minnows were negative on cell culture. There was no detection of CyHV-3 DNA or mRNA in goldfish throughout the experiment. CyHV-3 DNA in carp tissues was reproducibly accompanied by the detection of CyHV-3 mRNA and isolation on cell culture. Additionally, environmental CyHV-3 DNA was detected on all tank filters during the study. These findings suggest that fathead minnows and goldfish are not susceptible to CyHV-3 infection and that detection of CyHV-3 DNA alone in host susceptibility trials should be interpreted with caution.
Quantification of serum C-mannosyl tryptophan by novel assay to evaluate renal function and vascular complications in patients with type 2 diabetes
Authors: Morita Shuhei , Inai Yoko , Minakata Shiho , Kishimoto Shohei , Manabe Shino , Iwahashi Naoyuki , Ino Kazuhiko , Ito Yukishige , Akamizu Takashi , Ihara Yoshito
Published: January 2021

C-Mannosyl tryptophan (CMW) is a unique glycosylated amino acid, and a candidate novel biomarker of renal function. In type 2 diabetes (T2D), a combination of metabolites including CMW has recently been the focus of novel biomarkers for the evaluation of renal function and prediction of its decline. However, previous quantification methods for serum CMW have several limitations. We recently established a novel assay for quantifying serum CMW. Serum CMW from 99 Japanese patients with T2D was quantified by this assay using hydrophilic interaction liquid chromatography. The serum CMW levels were cross-sectionally characterized in relation to clinical features, including renal function and vascular complications. Serum CMW level was more strongly correlated with serum creatinine and cystatin C levels and with eGFR than with albumin urea level. The ROC curve to detect eGFR < 60 ml/min/1.73 m2 revealed that the cutoff serum CMW level was 337.5 nM (AUC 0.883). Serum CMW levels were higher in patients with a history of macroangiopathy than in those without history. They correlated with ankle-brachial pressure index, whereas cystatin C did not. Serum CMW levels quantified by the novel assay could be useful in evaluation of glomerular filtration of renal function and peripheral arterial disease in T2D.
High waist circumference rather than high body mass index may be a predictive risk factor for the longer disease duration of chronic spontaneous urticaria
Authors: Kim Yeong Ho , Do Han Kyung , Bang Chul Hwan , Lee Ji Hyun , Lee Jun Young , Park Yong Gyu , Park Young Min
Published: January 2021

In a previous study, we found that higher waist circumference (WC) and higher body mass index (BMI) both increase the risk of chronic spontaneous urticaria (CSU). The aim of this study was to determine whether WC and BMI also increase the duration of CSU. We used multivariable Cox proportional hazards models to determine the hazard ratio (HR) for longer disease duration (longer than 3 years) according to WC and BMI. A total of 52,667 subjects were enrolled and their mean age was 54.5. After adjustments for other confounding variables the high WC/high BMI group had 1.062 times higher HR (95% CI, 1.028–1.098) than the normal WC/normal BMI group. Interestingly, the high WC/normal BMI group showed a significantly higher HR (1.053; 95% CI, 1.008–1.101) than the normal WC/normal BMI group, but not the normal WC/high BMI group (0.998; 95% CI, 0.951–1.046). Taken together, our results suggest that high WC rather than high BMI is a predictive risk factor for the longer disease duration of CSU.
A KHz frequency cold atmospheric pressure argon plasma jet for the emission of O(1S) auroral lines in ambient air
Authors: Jaiswal S. , Aguirre E. M. , Prakash G. Veda
Published: January 2021

Creation of the “auroral” green line, a fascinating occurrence commonly observed in the upper atmosphere, has long been a difficult endeavor, especially at atmospheric pressure. Here we report strong emission of the “auroral” green line for the first time in a kHz frequency, linear field atmospheric pressure plasma jet system. The device used 99.999% pure argon as a working gas for the plasma generation. Optical emission spectroscopy measurements of the after discharge region show the existence of 557.7 nm emission which corresponds to the transition O($$^1$$

1

S)–O($$^1$$

1

D). The intensity of the produced green line is strong enough that the entire plasma plume in the ambient air is visible as a green plasma. We provide the chemical reactions of O($$^1$$

1

S) production in the plasma and the estimation of the density of the O($$^1$$

1

S) metastable state using the kinetic reactions. Further, the O($$^1$$

1

S) emission is characterized by changing the flow rate of argon, applied voltage and electrode gap. The adequate plasma length ($$> 25 \, \hbox {mm}$$

>
25

mm

) along with the production of a variety of reactive components viz; OH, $${\hbox {N}}_{2}^{+}$$

N

2

+

and oxygen (777 nm) make this configuration useful for applications such as: blood coagulation, cancer treatment, sterilization, and waste treatment. Moreover, this setup can be potentially used as a test bed for the in-depth understanding of plasma chemistry relevant to the aurora and comet tails using a laboratory setting.
Associations between plasma clozapine/N-desmethylclozapine ratio, insulin resistance and cognitive performance in patients with co-morbid obesity and ultra-treatment resistant schizophrenia
Authors: Costa-Dookhan Kenya A. , Rajji Tarek K. , Tran Veronica N. , Bowden Sylvie , Mueller Daniel J. , Remington Gary J. , Agarwal Sri Mahavir , Hahn Margaret K.
Published: January 2021

Clozapine (CLZ), the sole antipsychotic with superior efficacy for ultra-treatment resistant schizophrenia (TRS), is limited by adverse effects, including metabolic dysregulation. Clozapine’s main metabolite, N-desmethylclozapine (NDMC), has potent 5-HT2C antagonist properties which may explain this metabolic dysfunction, thus the CLZ:NDMC ratio is of particular interest. High insulin resistance states could be associated with CYP1A2 induction and lower CLZ:NDMC ratios. Additionally, lower CLZ:NDMC ratios have been associated with better cognitive, but worse metabolic functioning. This study investigated associations between metabolic and cognitive parameters with the CLZ/NDMC ratio. Primary outcomes included relationships between the CLZ:NDMC ratio to the homeostatic model assessment for insulin resistance (HOMA-IR) and Brief Assessment of Cognition in Schizophrenia (BACS) composite z-scores. Secondary outcomes assessed relationships between CLZ:NDMC ratios to fasting insulin, BMI, weight, fasting glucose, and BACS digit sequencing z-scores. 38 patients who were overweight or obese with schizophrenia or schizoaffective disorder completed fasting bloodwork, anthropometric, psychopathological, and cognitive assessments. Multivariate regressions found a statistically significant inverse association between the CLZ/NDMC ratio and HOMA-IR (B = − 1.028, SE B = .473, β = − 0.348 p = 0.037), which may have been driven by fasting insulin levels (B = − 27.124, SE B = 12.081, β = − 0.351 p = 0.031). The CLZ/NDMC ratio may predict insulin resistance/metabolic comorbidity among patients with TRS receiving clozapine.
Development and comparison of novel multiple cross displacement amplification (MCDA) assays with other nucleic acid amplification methods for SARS-CoV-2 detection
Authors: Luu Laurence Don Wai , Payne Michael , Zhang Xiaomei , Luo Lijuan , Lan Ruiting
Published: January 2021

The development of alternative isothermal amplification assays including multiple cross displacement amplification (MCDA) may address speed and portability limitations of real-time PCR (rt-PCR) methods for SARS-CoV-2 detection. We developed a novel SARS-CoV-2 MCDA assay and compared its speed and sensitivity to loop-mediated isothermal amplification (LAMP) and rt-PCR. Two MCDA assays targeting SARS-CoV-2 N gene and ORF1ab were designed. The fastest time to detection and sensitivity of MCDA was compared to LAMP and rt-PCR using DNA standards and transcribed RNA. For the N gene, MCDA was faster than LAMP and rt-PCR by 10 and 20 min, respectively with fastest time to detection at 5.2 min. rt-PCR had the highest sensitivity with the limit of detection at 10 copies/µl compared with MCDA (100 copies/µl) and LAMP (500 copies/µl). For ORF1ab, MCDA and LAMP had similar speed with fastest time to detection at 9.7 and 8.4 min, respectively. LAMP was more sensitive for ORF1ab detection with 50 copies/µl compared to MCDA (500 copies/µl). In conclusion, different nucleic acid amplification methods provide different advantages. MCDA is the fastest nucleic acid amplification method for SARS-CoV-2 while rt-PCR is the most sensitive. These advantages should be considered when determining the most suitable nucleic acid amplification methods for different applications.
Analysis of phase noise effects in a coupled Mach–Zehnder interferometer for a much stabilized free-space optical link
Authors: Ham Byoung S.
Published: January 2021

Recently, new physics for unconditional security in a classical key distribution (USCKD) has been proposed and demonstrated in a frame of a double Mach–Zehnder interferometer (MZI) as a proof of principle, where the unconditional security is rooted in MZI channel superposition. Due to environmental phase noise caused by temperature variations, atmospheric turbulences, and mechanical vibrations, free-space optical links have been severely challenged for both classical and quantum communications. Here, the double MZI scheme of USCKD is analyzed for greatly subdued environment-caused phase noise via double unitary transformation, resulting in potential applications of free-space optical links, where the free-space optical link has been a major research area from fundamental physics of atomic clock and quantum key distribution to potential applications of geodesy, navigation, and MIMO technologies in mobile communications systems.
Role of osteogenic Dickkopf-1 in bone remodeling and bone healing in mice with type I diabetes mellitus
Authors: Hildebrandt Nick , Colditz Juliane , Dutra Caio , Goes Paula , Salbach-Hirsch Juliane , Thiele Sylvia , Hofbauer Lorenz C. , Rauner Martina
Published: January 2021

Type 1 diabetes mellitus (T1DM) is associated with low bone mass and a higher risk for fractures. Dickkopf-1 (Dkk1), which inhibits Wnt signaling, osteoblast function, and bone formation, has been found to be increased in the serum of patients with T1DM. Here, we investigated the functional role of Dkk1 in T1DM-induced bone loss in mice. T1DM was induced in 10-week-old male mice with Dkk1-deficiency in late osteoblasts/osteocytes (Dkk1f/f;Dmp1-Cre, cKO) and littermate control mice by 5 subsequent injections of streptozotocin (40 mg/kg). Age-matched, non-diabetic control groups received citrate buffer instead. At week 12, calvarial defects were created in subgroups of each cohort. After a total of 16 weeks, weight, fat, the femoral bone phenotype and the area of the bone defect were analyzed using µCT and dynamic histomorphometry. During the experiment, diabetic WT and cKO mice did not gain body weight compared to control mice. Further they lost their perigonadal and subcutaneous fat pads. Diabetic mice had highly elevated serum glucose levels and impaired glucose tolerance, regardless of their Dkk1 levels. T1DM led to a 36% decrease in trabecular bone volume in Cre− negative control animals, whereas Dkk1 cKO mice only lost 16%. Of note, Dkk1 cKO mice were completely protected from T1DM-induced cortical bone loss. T1DM suppressed the bone formation rate, the number of osteoblasts at trabecular bone, serum levels of P1NP and bone defect healing in both, Dkk1-deficient and sufficient, mice. This may be explained by increased serum sclerostin levels in both genotypes and the strict dependence on bone formation for bone defect healing. In contrast, the number of osteoclasts and TRACP 5b serum levels only increased in diabetic control mice, but not in Dkk1 cKO mice. In summary, Dkk1 derived from osteogenic cells does not influence the development of T1DM but plays a crucial role in T1DM-induced bone loss in male mice by regulating osteoclast numbers.
Explaining the emergence of complex networks through log-normal fitness in a Euclidean node similarity space
Authors: Smith Keith Malcolm
Published: January 2021

Networks of disparate phenomena—be it the global ecology, human social institutions, within the human brain, or in micro-scale protein interactions—exhibit broadly consistent architectural features. To explain this, we propose a new theory where link probability is modelled by a log-normal node fitness (surface) factor and a latent Euclidean space-embedded node similarity (depth) factor. Building on recurring trends in the literature, the theory asserts that links arise due to individualistic as well as dyadic information and that important dyadic information making up the so-called depth factor is obscured by this essentially non-dyadic information making up the surface factor. Modelling based on this theory considerably outperforms popular power-law fitness and hyperbolic geometry explanations across 110 networks. Importantly, the degree distributions of the model resemble power-laws at small densities and log-normal distributions at larger densities, posing a reconciliatory solution to the long-standing debate on the nature and existence of scale-free networks. Validating this theory, a surface factor inversion approach on an economic world city network and an fMRI connectome results in considerably more geometrically aligned nearest neighbour networks, as is hypothesised to be the case for the depth factor. This establishes new foundations from which to understand, analyse, deconstruct and interpret network phenomena.
Behavioral arrest and a characteristic slow waveform are hallmark responses to selective 5-HT2A receptor activation
Authors: Contreras April , Khumnark Matthew , Hines Rochelle M. , Hines Dustin J.
Published: January 2021

Perception, emotion, and mood are powerfully modulated by serotonin receptor (5-HTR) agonists including hallucinogens. The 5-HT2AR subtype has been shown to be central to hallucinogen action, yet the precise mechanisms mediating the response to 5-HT2AR activation remain unclear. Hallucinogens induce the head twitch response (HTR) in rodents, which is the most commonly used behavioral readout of hallucinogen pharmacology. While the HTR provides a key behavioral signature, less is known about the meso level changes that are induced by 5-HT2AR activation. In response to administration of the potent and highly selective 5-HT2AR agonist 25I-NBOH in mice, we observe a disorganization of behavior which includes frequent episodes of behavioral arrest that consistently precede the HTR by a precise interval. By combining behavioral analysis with electroencephalogram (EEG) recordings we describe a characteristic pattern composed of two distinctive EEG waveforms, Phase 1 and Phase 2, that map onto behavioral arrest and the HTR respectively, with the same temporal separation. Phase 1, which underlies behavioral arrest, is a 3.5–4.5 Hz waveform, while Phase 2 is slower at 2.5–3.2 Hz. Nicotine pretreatment, considered an integral component of ritualistic hallucinogen practices, attenuates 25I-NBOH induced HTR and Phase 2 waveforms, yet increases behavioral arrest and Phase 1 waveforms. Our results suggest that in addition to the HTR, behavioral arrest and characteristic meso level slow waveforms are key hallmarks of the response to 5-HT2AR activation. Increased understanding of the response to serotonergic hallucinogens may provide mechanistic insights into perception and hallucinations, as well as regulation of mood.