bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy
Authors: Chen Chen-Yun , Lee Desy S. , Choong Oi Kuan , Chang Sheng-Kai , Hsu Tien , Nicholson Martin W. , Liu Li-Wei , Lin Po-Ju , Ruan Shu-Chian , Lin Shu-Wha , Hu Chung-Yi , Hsieh Patrick C. H. 
Published: January 2021

AbstractMicroRNA-125b, the first microRNA to be identified, is known to promote cardiomyocyte maturation from embryonic stem cells; however, its physiological role remains unclear. To investigate the role of miR-125b in cardiovascular biology, cardiac-specific miR-125b-1 knockout mice were generated. We found that cardiac-specific miR-125b-1 knockout mice displayed half the miR-125b expression of control mice resulting in a 60% perinatal death rate. However, the surviving mice developed hearts with cardiac hypertrophy. The cardiomyocytes in both neonatal and adult mice displayed abnormal mitochondrial morphology. In the deficient neonatal hearts, there was an increase in mitochondrial DNA, but total ATP production was reduced. In addition, both the respiratory complex proteins in mitochondria and mitochondrial transcription machinery were impaired. Mechanistically, using transcriptome and proteome analysis, we found that many proteins involved in fatty acid metabolism were significantly downregulated in miR-125b knockout mice which resulted in reduced fatty acid metabolism. Importantly, many of these proteins are expressed in the mitochondria. We conclude that miR-125b deficiency causes a high mortality rate in neonates and cardiac hypertrophy in adult mice. The dysregulation of fatty acid metabolism may be responsible for the cardiac defect in the miR-125b deficient mice.
Modelling quantum aspects of disruption of a white dwarf star by a black hole
Authors: Karpiuk Tomasz , Nikołajuk Marek , Gajda Mariusz , Brewczyk Mirosław 
Published: January 2021

AbstractWe study the final stages of the evolution of a binary system consisted of a black hole and a white dwarf star. We implement the quantum hydrodynamic equations and carry out numerical simulations. As a model of a white dwarf star we consider a zero temperature droplet of attractively interacting degenerate atomic bosons and spin-polarized atomic fermions. Such mixtures are investigated experimentally nowadays. We find that the white dwarf star is stripped off its mass while passing the periastron. Due to nonlinear effects, the accretion disk originated from the white dwarf becomes fragmented and the onset of a quantum turbulence with giant quantized vortices present in the bosonic component of the accretion disk is observed. The binary system ends its life in a spectacular way, revealing quantum features underlying the white dwarf star’s structure. We find a charged mass, falling onto a black hole, could be responsible for recently discovered ultraluminous X-ray bursts. The simulations show that final passage of a white dwarf near a black hole can cause a gamma-ray burst.
Atomic scale displacements detected by optical image cross-correlation analysis and 3D printed marker arrays
Authors: Frenzel Tobias , Köpfler Julian , Naber Andreas , Wegener Martin 
Published: January 2021

AbstractFor analyzing displacement-vector fields in mechanics, for example to characterize the properties of 3D printed mechanical metamaterials, routine high-precision position measurements are indispensable. For this purpose, nanometer-scale localization errors have been achieved by wide-field optical-image cross-correlation analysis. Here, we bring this approach to atomic-scale accuracy by combining it with well-defined 3D printed marker arrays. By using an air-lens with a numerical aperture of$$0.4$$0.4and a free working distance of$$11.2\, \mathrm{mm}$$11.2mm, and an$$8\times 8$$8×8array of markers with a diameter of$$2\, \upmu\mathrm{m}$$2μmand a period of$$5\,\upmu \mathrm{ m}$$5μm, we obtain 2D localization errors as small as$$0.9\, \AA$$0.9Åin$$12.5\, \mathrm{ms}$$12.5msmeasurement time ($$80\, \mathrm{frames}/\mathrm{s}$$80frames/s). The underlying experimental setup is simple, reliable, and inexpensive, and the marker arrays can easily be integrated onto and into complex architectures during their 3D printing process.
Comparison of pelvic C-clamp and pelvic binder for emergency stabilization and bleeding control in type-C pelvic ring fractures
Authors: Audretsch Christof K. , Mader Daniel , Bahrs Christian , Trulson Alexander , Höch Andreas , Herath Steven C. , Küper Markus A. ,   Working Group on Pelvic Fractures of the German Trauma Society
Published: January 2021

AbstractSevere bleeding is the major cause of death in unstable pelvic ring fractures. Therefore, a quick and efficient emergency stabilization and bleeding control is inevitable. C-clamp and pelvic binder are efficient tools for temporary bleeding control, especially from the posterior pelvic ring. Yet the C-clamp requires more user knowledge, training and equipment. However, whether this makes up for a more efficient bleeding control, is still under debate. Patients with a type-C pelvic ring fracture were identified from the German Pelvic Registry (GPR) and divided into three groups of 40 patients (1. no emergency stabilization, 2. pelvic binder, 3. C-clamp). The matching occurred according to the parameters age, gender, initial RR and initial HB. Complication—and mortality rates were compared especially regarding bleeding control. Regarding ISS and fracture dislocation there was no difference. The use of the C-clamp resulted in more complications, a higher mortality rate due to severe bleeding and more blood transfusions were admitted. Moreover the pelvic binder was established noticeably faster. However, the C-clamp was more often rated as effective. There is no evidence of advantage comparing the C-clamp to the pelvic binder, regarding bleeding control in type-C pelvic ring fractures. In fact, using the pelvic binder even showed better results, as the time until established bleeding control was significantly shorter. Therefore, the pelvic binder should be the first choice. The C-clamp should remain a measure for selected cases only, if an adequate bleeding control cannot be achieved by the pelvic binder.
Purification of Crimean–Congo hemorrhagic fever virus nucleoprotein and its utility for serological diagnosis
Authors: Lombe Boniface Pongombo , Miyamoto Hiroko , Saito Takeshi , Yoshida Reiko , Manzoor Rashid , Kajihara Masahiro , Shimojima Masayuki , Fukushi Shuetsu , Morikawa Shigeru , Yoshikawa Tomoki , Kurosu Takeshi , Saijo Masayuki , Tang Qing , Masumu Justin , Hawman David , Feldmann Heinz , Takada Ayato 
Published: January 2021

AbstractCrimean–Congo hemorrhagic fever virus (CCHFV) causes a zoonotic disease, Crimean–Congo hemorrhagic fever (CCHF) endemic in Africa, Asia, the Middle East, and Southeastern Europe. However, the prevalence of CCHF is not monitored in most of the endemic countries due to limited availability of diagnostic assays and biosafety regulations required for handling infectious CCHFV. In this study, we established a protocol to purify the recombinant CCHFV nucleoprotein (NP), which is antigenically highly conserved among multiple lineages/clades of CCHFVs and investigated its utility in an enzyme-linked immunosorbent assay (ELISA) to detect CCHFV-specific antibodies. The NP gene was cloned into the pCAGGS mammalian expression plasmid and human embryonic kidney 293 T cells were transfected with the plasmid. The expressed NP molecule was purified from the cell lysate using cesium-chloride gradient centrifugation. Purified NP was used as the antigen for the ELISA to detect anti-CCHFV IgG. Using the CCHFV NP-based ELISA, we efficiently detected CCHFV-specific IgG in anti-NP rabbit antiserum and CCHFV-infected monkey serum. When compared to the commercially available Blackbox CCHFV IgG ELISA kit, our assay showed equivalent performance in detecting CCHFV-specific IgG in human sera. These results demonstrate the usefulness of our CCHFV NP-based ELISA for seroepidemiological studies.
Distinct epigenetic signatures between adult-onset and late-onset depression
Authors: Yamagata Hirotaka , Ogihara Hiroyuki , Matsuo Koji , Uchida Shusaku , Kobayashi Ayumi , Seki Tomoe , Kobayashi Masaaki , Harada Kenichiro , Chen Chong , Miyata Shigeo , Fukuda Masato , Mikuni Masahiko , Hamamoto Yoshihiko , Watanabe Yoshifumi , Nakagawa Shin 
Published: January 2021

AbstractThe heterogeneity of major depressive disorder (MDD) is attributed to the fact that diagnostic criteria (e.g., DSM-5) are only based on clinical symptoms. The discovery of blood biomarkers has the potential to change the diagnosis of MDD. The purpose of this study was to identify blood biomarkers of DNA methylation by strategically subtyping patients with MDD by onset age. We analyzed genome-wide DNA methylation of patients with adult-onset depression (AOD; age ≥ 50 years, age at depression onset < 50 years; N = 10) and late-onset depression (LOD; age ≥ 50 years, age at depression onset ≥ 50 years; N = 25) in comparison to that of 30 healthy subjects. The methylation profile of the AOD group was not only different from that of the LOD group but also more homogenous. Six identified methylation CpG sites were validated by pyrosequencing and amplicon bisulfite sequencing as potential markers for AOD in a second set of independent patients with AOD and healthy control subjects (N = 11). The combination of three specific methylation markers achieved the highest accuracy (sensitivity, 64%; specificity, 91%; accuracy, 77%). Taken together, our findings suggest that DNA methylation markers are more suitable for AOD than for LOD patients.
Integrative analysis of transcriptomic data for identification of T-cell activation-related mRNA signatures indicative of preterm birth
Authors: Yoo Jae Young , Hyeon Do Young , Shin Yourae , Kim Soo Min , You Young-Ah , Kim Daye , Hwang Daehee , Kim Young Ju 
Published: January 2021

AbstractPreterm birth (PTB), defined as birth at less than 37 weeks of gestation, is a major determinant of neonatal mortality and morbidity. Early diagnosis of PTB risk followed by protective interventions are essential to reduce adverse neonatal outcomes. However, due to the redundant nature of the clinical conditions with other diseases, PTB-associated clinical parameters are poor predictors of PTB. To identify molecular signatures predictive of PTB with high accuracy, we performed mRNA sequencing analysis of PTB patients and full-term birth (FTB) controls in Korean population and identified differentially expressed genes (DEGs) as well as cellular pathways represented by the DEGs between PTB and FTB. By integrating the gene expression profiles of different ethnic groups from previous studies, we identified the core T-cell activation pathway associated with PTB, which was shared among all previous datasets, and selected three representative DEGs (CYLD, TFRC, and RIPK2) from the core pathway as mRNA signatures predictive of PTB. We confirmed the dysregulation of the candidate predictors and the core T-cell activation pathway in an independent cohort. Our results suggest that CYLD, TFRC, and RIPK2 are potentially reliable predictors for PTB.
Development of a target identification approach using native mass spectrometry
Authors: Liu Miaomiao , Van Voorhis Wesley C. , Quinn Ronald J. 
Published: January 2021

AbstractA key step in the development of new pharmaceutical drugs is the identification of the molecular target and distinguishing this from all other gene products that respond indirectly to the drug. Target identification remains a crucial process and a current bottleneck for advancing hits through the discovery pipeline. Here we report a method, that takes advantage of the specific detection of protein–ligand complexes by native mass spectrometry (MS) to probe the protein partner of a ligand in an untargeted method. The key advantage is that it uses unmodified small molecules for binding and, thereby, it does not require labelled ligands and is not limited by the chemistry required to tag the molecule. We demonstrate the use of native MS to identify known ligand–protein interactions in a protein mixture under various experimental conditions. A protein–ligand complex was successfully detected between parthenolide and thioredoxin (PfTrx) in a five-protein mixture, as well as when parthenolide was mixed in a bacterial cell lysate spiked with PfTrx. We provide preliminary data that native MS could be used to identify binding targets for any small molecule.
Associated factors of white matter hyperintensity volume: a machine-learning approach
Authors: Grosu Sergio , Rospleszcz Susanne , Hartmann Felix , Habes Mohamad , Bamberg Fabian , Schlett Christopher L. , Galie Franziska , Lorbeer Roberto , Auweter Sigrid , Selder Sonja , Buelow Robin , Heier Margit , Rathmann Wolfgang , Mueller-Peltzer Katharina , Ladwig Karl-Heinz , Grabe Hans J. , Peters Annette , Ertl-Wagner Birgit B. , Stoecklein Sophia 
Published: January 2021

AbstractTo identify the most important parameters associated with cerebral white matter hyperintensities (WMH), in consideration of potential collinearity, we used a data-driven machine-learning approach. We analysed two independent cohorts (KORA and SHIP). WMH volumes were derived from cMRI-images (FLAIR). 90 (KORA) and 34 (SHIP) potential determinants of WMH including measures of diabetes, blood-pressure, medication-intake, sociodemographics, life-style factors, somatic/depressive-symptoms and sleep were collected. Elastic net regression was used to identify relevant predictor covariates associated with WMH volume. The ten most frequently selected variables in KORA were subsequently examined for robustness in SHIP. The final KORA sample consisted of 370 participants (58% male; age 55.7 ± 9.1 years), the SHIP sample comprised 854 participants (38% male; age 53.9 ± 9.3 years). The most often selected and highly replicable parameters associated with WMH volume were in descending order age, hypertension, components of the social environment (i.e. widowed, living alone) and prediabetes. A systematic machine-learning based analysis of two independent, population-based cohorts showed, that besides age and hypertension, prediabetes and components of the social environment might play important roles in the development of WMH. Our results enable personal risk assessment for the development of WMH and inform prevention strategies tailored to the individual patient.
Magnetism and magnetoresistance in the critical region of a dilute ferromagnet
Authors: Wang M. , Howells B. , Marshall R. A. , Taylor J. M. , Edmonds K. W. , Rushforth A. W. , Campion R. P. , Gallagher B. L. 
Published: January 2021

AbstractWe present detailed experimental measurements and simulations of the field-dependent magnetization and magnetoresistance in the vicinity of the Curie temperature in the highly disordered dilute ferromagnetic semiconductor (Ga,Mn)As. The observed dependence of the magnetization on external magnetic field and temperature is consistent with three-dimensional Heisenberg equation of state calculations including a narrow distribution of critical temperatures. The magnetoresistance shows a peak at the Curie temperature due to the suppression of magnetic scattering in an applied magnetic field, which is well-described by considering changes in the square of the magnetization induced by the magnetic field.
Quantification of stroke lesion volume using epidural EEG in a cerebral ischaemic rat model
Authors: Yoo Hyun-Joon , Ham Jinsil , Duc Nguyen Thanh , Lee Boreom 
Published: January 2021

AbstractPrecise monitoring of the brain after a stroke is essential for clinical decision making. Due to the non-invasive nature and high temporal resolution of electroencephalography (EEG), it is widely used to evaluate real-time cortical activity. In this study, we investigated the stroke-related EEG biomarkers and developed a predictive model for quantifying the structural brain damage in a focal cerebral ischaemic rat model. We enrolled 31 male Sprague–Dawley rats and randomly assigned them to mild stroke, moderate stroke, severe stroke, and control groups. We induced photothrombotic stroke targeting the right auditory cortex. We then acquired EEG signal responses to sound stimuli (frequency linearly increasing from 8 to 12 kHz with 750 ms duration). Power spectral analysis revealed a significant correlation of the relative powers of alpha, theta, delta, delta/alpha ratio, and (delta + theta)/(alpha + beta) ratio with the stroke lesion volume. The auditory evoked potential analysis revealed a significant association of amplitude and latency with stroke lesion volume. Finally, we developed a multiple regression model combining EEG predictors for quantifying the ischaemic lesion (R2 = 0.938, p value < 0.001). These findings demonstrate the potential application of EEG as a valid modality for monitoring the brain after a stroke.
A hybrid broadband metalens operating at ultraviolet frequencies
Authors: Ali Farhan , Aksu Serap 
Published: January 2021

AbstractThe investigation on metalenses have been rapidly developing, aiming to bring compact optical devices with superior properties to the market. Realizing miniature optics at the UV frequency range in particular has been challenging as the available transparent materials have limited range of dielectric constants. In this work we introduce a low absorption loss and low refractive index dielectric material magnesium oxide, MgO, as an ideal candidate for metalenses operating at UV frequencies. We theoretically investigate metalens designs capable of efficient focusing over a broad UV frequency range (200–400 nm). The presented metalenses are composed of sub-wavelength MgO nanoblocks, and characterized according to the geometric Pancharatnam–Berry phase method using FDTD method. The presented broadband metalenses can focus the incident UV light on tight focal spots (182 nm) with high numerical aperture ($$\hbox {NA}\approx 0.8$$

NA
≈
0.8

). The polarization conversion efficiency of the metalens unit cell and focusing efficiency of the total metalens are calculated to be as high as 94%, the best value reported in UV range so far. In addition, the metalens unit cell can be hybridized to enable lensing at multiple polarization states. The presented highly efficient MgO metalenses can play a vital role in the development of UV nanophotonic systems and could pave the way towards the world of miniaturization.
Development of a novel hyaluronic acid membrane for the treatment of ocular surface diseases
Authors: Kim Dong Ju , Jung Mi-Young , Pak Ha-Jin , Park Joo-Hee , Kim Martha , Chuck Roy S. , Park Choul Yong 
Published: January 2021

AbstractOcular surface diseases (OSD) can cause serious visual deterioration and discomfort. Commercial artificial tear solution containing hyaluronic acid (HA) show excellent biocompatibility and unique viscoelastic characteristics. Here, we developed a novel HA membrane (HAM) by chemical crosslinking using 1,4-butanediol diglycidyl ether for the effective treatment of OSDs. The main purpose of HAMs is to provide sustained release of HA to modulate the wound healing response in OSDs. The safety and efficacy of HAMs were investigated using primary cultured human corneal epithelial cells and various OSD rabbit models. In the dry state, the HAM is firm, transparent, and easy to manipulate. When hydrated, it swells rapidly with high water retention and over 90% transmission of visible light. Human corneal epithelial cells and rabbit eyes showed no toxic response to HAM. Addition of HAMs to the culture medium enhanced human corneal epithelial cell viability and expression of cell proliferation markers. Investigation of HAM wound healing efficacy using mechanical or chemical corneal trauma and conjunctival surgery in rabbits revealed that application of HAMs to the ocular surface enhanced healing of corneal epithelium and reduced corneal limbal vascularization, opacity and conjunctival fibrosis. The therapeutic potential of HAMs in various OSDs was successfully demonstrated.
The RGS-RhoGEFs control the amplitude of YAP1 activation by serum
Authors: Lane Brandon S. , Heller Brigitte , Hollenberg Morley D. , Wells Clark D. 
Published: January 2021

AbstractActin-dependent mechanisms drive the nuclear translocation of Yap1 to enable its co-activation of transcription factors that induce pro-growth and survival programs. While Rho GTPases are necessary for the nuclear import of YAP1, the relevant Guanine Exchange Factors (GEFs) and GTPase Activating Proteins (GAPs) that connect this process to upstream signaling are not well defined. To this end, we measured the impact of expressing sixty-seven RhoGEFs and RhoGAPs on the YAP1 dependent activity of a TEAD element transcriptional reporter. Robust effects by all three members of the regulator of G-protein signaling (RGS) domain containing RhoGEFs (ArhGEF1, ArhGEF11 and ArhGEF12) prompted studies relating their known roles in serum signaling onto the regulation of Yap1. Under all conditions examined, ArhGEF12 preferentially mediated the activation of YAP1/TEAD by serum versus ArhGEF1 or ArhGEF11. Conversely, ArhGEF1 in multiple contexts inhibited both basal and serum elevated YAP1 activity through its GAP activity for Gα13. The sensitivity of such inhibition to cellular density and to low states of serum signaling supports that ArhGEF1 is a context dependent regulator of YAP1. Taken together, the relative activities of the RGS-RhoGEFs were found to dictate the degree to which serum signaling promotes YAP1 activity.
The carboxy terminal coiled-coil modulates Orai1 internalization during meiosis
Authors: Hodeify Rawad , Dib Maya , Alcantara-Adap Ethel , Courjaret Raphael , Nader Nancy , Reyes Cleo Z. , Hammad Ayat S. , Hubrack Satanay , Yu Fang , Machaca Khaled 
Published: January 2021

AbstractRegulation of Ca2+ signaling is critical for the progression of cell division, especially during meiosis to prepare the egg for fertilization. The primary Ca2+ influx pathway in oocytes is Store-Operated Ca2+ Entry (SOCE). SOCE is tightly regulated during meiosis, including internalization of the SOCE channel, Orai1. Orai1 is a four-pass membrane protein with cytosolic N- and C-termini. Orai1 internalization requires a caveolin binding motif (CBM) in the N-terminus as well as the C-terminal cytosolic domain. However, the molecular determinant for Orai1 endocytosis in the C-terminus are not known. Here we show that the Orai1 C-terminus modulates Orai1 endocytosis during meiosis through a structural motif that is based on the strength of the C-terminal intersubunit coiled coil (CC) domains. Deletion mutants show that a minimal C-terminal sequence after transmembrane domain 4 (residues 260–275) supports Orai1 internalization. We refer to this region as the C-terminus Internalization Handle (CIH). Access to CIH however is dependent on the strength of the intersubunit CC. Mutants that increase the stability of the coiled coil prevent internalization independent of specific mutation. We further used human and Xenopus Orai isoforms with different propensity to form C-terminal CC and show a strong correlation between the strength of the CC and Orai internalization. Furthermore, Orai1 internalization does not depend on clathrin, flotillin or PIP2. Collectively these results argue that Orai1 internalization requires both the N-terminal CBM and C-terminal CIH where access to CIH is controlled by the strength of intersubunit C-terminal CC.
Entanglement of formation and monogamy of multi-party quantum entanglement
Authors: Kim Jeong San 
Published: January 2021

AbstractWe provide a sufficient condition for the monogamy inequality of multi-party quantum entanglement of arbitrary dimensions in terms of entanglement of formation. Based on the classical–classical–quantum(ccq) states whose quantum parts are obtained from the two-party reduced density matrices of a three-party quantum state, we show the additivity of the mutual information of the ccq states guarantees the monogamy inequality of the three-party pure state in terms of EoF. After illustrating the result with some examples, we generalize our result of three-party systems into any multi-party systems of arbitrary dimensions.