bluuebunny/crossref_metadata_2025 huggingface dataset:
Lorentzian Filter Correction of Turbulence Measurements on Oscillating Floating Platforms: Impact on Wind Spectra and Eddy‐Covariance Fluxes
Authors: Ezraty R. , Mor Z. , Bodzin R. , Assouline S. , Tanny J. , Fratini G. , Griessbaum F. , Lensky N. G.
Published: January 2021

Turbulence and eddy‐covariance measurements on a floating platform over water surfaces can be contaminated by platform oscillations, which may affect the calculated air‐water exchange. The conventional method for decontamination of the platform oscillations from the wind velocity measurements requires the installation of an additional sensitive, and often costly, motion sensor. This paper examines a new mathematical decontamination method, termed Lorentzian filter, which avoids the need for such an instrument. The method, based on the Lorentzian function, capitalizes on the pseudo‐harmonic behavior of the platform oscillations and reduces the amplitude of turbulent wind velocity data detected as artifacts at the specific natural frequencies of the platform. The Lorentzian filter was applied to wind velocity data measured by sonic anemometer and eddy‐covariance system over the Dead Sea, Israel, for 30 days. We examined two approaches of dealing with motion contamination: Lorentzian filter decontamination and motion sensor decontamination. Both approaches were compared to nonfiltered raw wind velocity as well. Using the 3D wind velocity series, we examined the wind spectra, the cospectra of water vapor concentration and horizontal wind speed with vertical wind speed, and H2O and momentum fluxes. The Lorentzian filter performed very well in decontaminating the wind spectrum, meaning that it efficiently identified the contamination in the natural oscillation frequency and returned a decontaminated wind velocity time series. The cospectra and fluxes were less prone to the contamination of platform oscillations, presumably due to low correlations between the spurious wind velocity components and other measured scalars, such as water vapor.
Risk assessment analysis for maternal autoantibody-related autism (MAR-ASD): a subtype of autism
Authors: Ramirez-Celis Alexandra , Becker Martin , Nuño Miriam , Schauer Joseph , Aghaeepour Nima , Van de Water Judy
Published: January 2021

The incidence of autism spectrum disorder (ASD) has been rising, however ASD-risk biomarkers remain lacking. We previously identified the presence of maternal autoantibodies to fetal brain proteins specific to ASD, now termed maternal autoantibody-related (MAR) ASD. The current study aimed to create and validate a serological assay to identify ASD-specific maternal autoantibody patterns of reactivity against eight previously identified proteins (CRMP1, CRMP2, GDA, NSE, LDHA, LDHB, STIP1, and YBOX) that are highly expressed in developing brain, and determine the relationship of these reactivity patterns with ASD outcome severity. We used plasma from mothers of children diagnosed with ASD (n = 450) and from typically developing children (TD, n = 342) to develop an ELISA test for each of the protein antigens. We then determined patterns of reactivity a highly significant association with ASD, and discovered several patterns that were ASD-specific (18% in the training set and 10% in the validation set vs. 0% TD). The three main patterns associated with MAR ASD are CRMP1 + GDA (ASD% = 4.2 vs. TD% = 0, OR 31.04, p = <0.0001), CRMP1 + CRMP2 (ASD% = 3.6 vs. TD% = 0, OR 26.08, p = 0.0005) and NSE + STIP1 (ASD% = 3.1 vs. TD% = 0, OR 22.82, p = 0.0001). Additionally, we found that maternal autoantibody reactivity to CRMP1 significantly increases the odds of a child having a higher Autism Diagnostic Observation Schedule (ADOS) severity score (OR 2.3; 95% CI: 1.358–3.987, p = 0.0021). This is the first report that uses machine learning subgroup discovery to identify with 100% accuracy MAR ASD-specific patterns as potential biomarkers of risk for a subset of up to 18% of ASD cases in this study population.
Essential role for autophagy protein VMP1 in maintaining neuronal homeostasis and preventing axonal degeneration
Authors: Wang Panpan , Chen Xi , Wang Yuanyuan , Jia Congcong , Liu Xinyao , Wang Ying , Wu Haifeng , Cai Huaibin , Shen Han-Ming , Le Weidong
Published: January 2021

Vacuole membrane protein 1 (VMP1), the endoplasmic reticulum (ER)-localized autophagy protein, plays a key role during the autophagy process in mammalian cells. To study the impact of VMP1-deficiency on midbrain dopaminergic (mDAergic) neurons, we selectively deleted VMP1 in the mDAergic neurons of VMP1fl/fl/DATCreERT2 bigenic mice using a tamoxifen-inducible CreERT2/loxp gene targeting system. The VMP1fl/fl/DATCreERT2 mice developed progressive motor deficits, concomitant with a profound loss of mDAergic neurons in the substantia nigra pars compacta (SNc) and a high presynaptic accumulation of α-synuclein (α-syn) in the enlarged terminals. Mechanistic studies showed that VMP1 deficiency in the mDAergic neurons led to the increased number of microtubule-associated protein 1 light chain 3-labeled (LC3) puncta and the accumulation of sequestosome 1/p62 aggregates in the SNc neurons, suggesting the impairment of autophagic flux in these neurons. Furthermore, VMP1 deficiency resulted in multiple cellular abnormalities, including large vacuolar-like structures (LVSs), damaged mitochondria, swollen ER, and the accumulation of ubiquitin+ aggregates. Together, our studies reveal a previously unknown role of VMP1 in modulating neuronal survival and maintaining axonal homeostasis, which suggests that VMP1 deficiency might contribute to mDAergic neurodegeneration via the autophagy pathway.
Circ-NOLC1 promotes epithelial ovarian cancer tumorigenesis and progression by binding ESRP1 and modulating CDK1 and RhoA expression
Authors: Chen Shuo , Wu Wu , Li Qian-hui , Xie Bu-min , Shen Fan , Du Yu-ping , Zong Zhi-hong , Wang Li-li , Wei Xiao-qing , Zhao Yang
Published: January 2021

Circular RNAs (circRNAs) play important roles in cancer tumorigenesis and progression, representing prognostic biomarkers and therapeutic targets. In this case, we demonstrated the role of circ-NOLC1 in epithelial ovarian cancer (EOC). Our results have shown that Circ-NOLC1 expression was higher in EOC tissues than in normal tissues, and was positively associated with FIGO stage, differentiation. Among ovarian cancer cell lines, circ-NOLC1 expression was the highest in A2780, and lowest in CAOV3. Overexpression of circ-NOLC1 in CAOV3 cells increased cell proliferation, migration, and invasion ability, whereas silencing of circ-NOLC1 in A2780 cells had the opposite effect: however, neither circ-NOLC1 downregulation nor overexpression influenced NOLC1 mRNA expression. In nude mice with subcutaneous tumors, circ-NOLC1 downregulation decreased tumor growth. Bioinformatic analysis and RNA-binding protein immunoprecipitation showed that circ-NOLC1 could bind to ESRP1. In addition, the overexpression of circ-NOLC1 significantly increased ESRP1, RhoA, and CDK1 protein and mRNA expression level; circ-NOLC1 downregulation had the opposite effects. The tumor-promoting effect of circ-NOLC1 was inhibited by knockdown of ESRP1, CDK1, or RhoA expression in circ-NOLC1-overexpressing cells, which might act by modulating RhoA and CDK1 expression. In conclusion, our study demonstrated that Circ-NOLC1 might promote EOC tumorigenesis and development by binding ESRP1 and modulating CDK1 and RhoA expression.
Phosphorus(III)-assisted regioselective C–H silylation of heteroarenes
Authors: Wang Dingyi , Chen Xiangyang , Wong Jonathan J. , Jin Liqun , Li Mingjie , Zhao Yue , Houk K. N. , Shi Zhuangzhi
Published: January 2021

Heteroarenes containing carbon–silicon (C–Si) bonds are important building blocks that play an important role in the construction of natural products, pharmaceuticals, and organic materials. In this context, the C–H silylation of heteroarenes is a topic of intense interest. Indole C–H silylation can preferentially occur at the nucleophilic C3 and C2 position (pyrrole core), while accessing the C4-C7 positions (benzene core) of the indole remains highly challenging. Here, we show a general strategy for the regioselective C7-H silylation of indole derivatives. Mainly, the regioselectivity is determined by strong coordination of the palladium catalyst with phosphorus (III) directing group. Using this expedient synthetic strategy, the diverse C7-silylated indoles are synthesized effectively which exhibits the broad functional group compatibility. Moreover, this protocol also been extended to other heteroarenes such as carbazoles. The obtained silylated indoles have been employed in various transformations to enable the corresponding differently functionalized indole derivatives. Significantly, a cyclopalladated intermediate is successfully synthesized to test the hypothesis about the P(III)-directed C–H metalation event. A series of mechanistic experiments and density functional theory (M06-2X) calculations has shown the preferred pathway of this directed C–H silylation process.
Profiling serum antibodies with a pan allergen phage library identifies key wheat allergy epitopes
Authors: Monaco Daniel R. , Sie Brandon M. , Nirschl Thomas R. , Knight Audrey C. , Sampson Hugh A. , Nowak-Wegrzyn Anna , Wood Robert A. , Hamilton Robert G. , Frischmeyer-Guerrerio Pamela A. , Larman H. Benjamin
Published: January 2021

Allergic reactions occur when IgE molecules become crosslinked by antigens such as food proteins. Here we create the ‘AllerScan’ programmable phage display system to characterize the binding specificities of anti-allergen IgG and IgE antibodies in serum against thousands of allergenic proteins from hundreds of organisms at peptide resolution. Using AllerScan, we identify robust anti-wheat IgE reactivities in wheat allergic individuals but not in wheat-sensitized individuals. Meanwhile, a key wheat epitope in alpha purothionin elicits dominant IgE responses among allergic patients, and frequent IgG responses among sensitized and non-allergic patients. A double-blind, placebo-controlled trial shows that alpha purothionin reactivity, among others, is strongly modulated by oral immunotherapy in tolerized individuals. AllerScan may thus serve as a high-throughput platform for unbiased analysis of anti-allergen antibody specificities.
SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques
Authors: Shaan Lakshmanappa Yashavanth , Elizaldi Sonny R. , Roh Jamin W. , Schmidt Brian A. , Carroll Timothy D. , Weaver Kourtney D. , Smith Justin C. , Verma Anil , Deere Jesse D. , Dutra Joseph , Stone Mars , Franz Sergej , Sammak Rebecca Lee , Olstad Katherine J. , Rachel Reader J. , Ma Zhong-Min , Nguyen Nancy K. , Watanabe Jennifer , Usachenko Jodie , Immareddy Ramya , Yee JoAnn L. , Weiskopf Daniela , Sette Alessandro , Hartigan-O’Connor Dennis , McSorley Stephen J. , Morrison John H. , Tran Nam K. , Simmons Graham , Busch Michael P. , Kozlowski Pamela A. , Van Rompay Koen K. A. , Miller Christopher J. , Iyer Smita S.
Published: January 2021

CD4 T follicular helper (Tfh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center (GC) response is an important question as we investigate vaccine induced immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC Tfh cells specific for the SARS-CoV-2 spike and nucleocapsid proteins, and a corresponding early appearance of antiviral serum IgG antibodies. Collectively, the data show induction of GC responses in a rhesus model of mild COVID-19.
A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses
Authors: Tan Tiong Kit , Rijal Pramila , Rahikainen Rolle , Keeble Anthony H. , Schimanski Lisa , Hussain Saira , Harvey Ruth , Hayes Jack W. P. , Edwards Jane C. , McLean Rebecca K. , Martini Veronica , Pedrera Miriam , Thakur Nazia , Conceicao Carina , Dietrich Isabelle , Shelton Holly , Ludi Anna , Wilsden Ginette , Browning Clare , Zagrajek Adrian K. , Bialy Dagmara , Bhat Sushant , Stevenson-Leggett Phoebe , Hollinghurst Philippa , Tully Matthew , Moffat Katy , Chiu Chris , Waters Ryan , Gray Ashley , Azhar Mehreen , Mioulet Valerie , Newman Joseph , Asfor Amin S. , Burman Alison , Crossley Sylvia , Hammond John A. , Tchilian Elma , Charleston Bryan , Bailey Dalan , Tuthill Tobias J. , Graham Simon P. , Duyvesteyn Helen M. E. , Malinauskas Tomas , Huo Jiandong , Tree Julia A. , Buttigieg Karen R. , Owens Raymond J. , Carroll Miles W. , Daniels Rodney S. , McCauley John W. , Stuart David I. , Huang Kuan-Ying A. , Howarth Mark , Townsend Alain R.
Published: January 2021

There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.
Adsorption separation of heavier isotope gases in subnanometer carbon pores
Authors: Ujjain Sanjeev Kumar , Bagusetty Abhishek , Matsuda Yuki , Tanaka Hideki , Ahuja Preety , de Tomas Carla , Sakai Motomu , Vallejos-Burgos Fernando , Futamura Ryusuke , Suarez-Martinez Irene , Matsukata Masahiko , Kodama Akio , Garberoglio Giovanni , Gogotsi Yury , Karl Johnson J. , Kaneko Katsumi
Published: January 2021

Isotopes of heavier gases including carbon (13C/14C), nitrogen (13N), and oxygen (18O) are highly important because they can be substituted for naturally occurring atoms without significantly perturbing the biochemical properties of the radiolabelled parent molecules. These labelled molecules are employed in clinical radiopharmaceuticals, in studies of brain disease and as imaging probes for advanced medical imaging techniques such as positron-emission tomography (PET). Established distillation-based isotope gas separation methods have a separation factor (S) below 1.05 and incur very high operating costs due to high energy consumption and long processing times, highlighting the need for new separation technologies. Here, we show a rapid and highly selective adsorption-based separation of 18O2 from 16O2 with S above 60 using nanoporous adsorbents operating near the boiling point of methane (112 K), which is accessible through cryogenic liquefied-natural-gas technology. A collective-nuclear-quantum effect difference between the ordered 18O2 and 16O2 molecular assemblies confined in subnanometer pores can explain the observed equilibrium separation and is applicable to other isotopic gases.
An integrative multiomic network model links lipid metabolism to glucose regulation in coronary artery disease
Authors: Cohain Ariella T. , Barrington William T. , Jordan Daniel M. , Beckmann Noam D. , Argmann Carmen A. , Houten Sander M. , Charney Alexander W. , Ermel Raili , Sukhavasi Katyayani , Franzen Oscar , Koplev Simon , Whatling Carl , Belbin Gillian M. , Yang Jialiang , Hao Ke , Kenny Eimear E. , Tu Zhidong , Zhu Jun , Gan Li-Ming , Do Ron , Giannarelli Chiara , Kovacic Jason C. , Ruusalepp Arno , Lusis Aldons J. , Bjorkegren Johan L. M. , Schadt Eric E.
Published: January 2021

Elevated plasma cholesterol and type 2 diabetes (T2D) are associated with coronary artery disease (CAD). Individuals treated with cholesterol-lowering statins have increased T2D risk, while individuals with hypercholesterolemia have reduced T2D risk. We explore the relationship between lipid and glucose control by constructing network models from the STARNET study with sequencing data from seven cardiometabolic tissues obtained from CAD patients during coronary artery by-pass grafting surgery. By integrating gene expression, genotype, metabolomic, and clinical data, we identify a glucose and lipid determining (GLD) regulatory network showing inverse relationships with lipid and glucose traits. Master regulators of the GLD network also impact lipid and glucose levels in inverse directions. Experimental inhibition of one of the GLD network master regulators, lanosterol synthase (LSS), in mice confirms the inverse relationships to glucose and lipid levels as predicted by our model and provides mechanistic insights.
Structural basis of ribosomal RNA transcription regulation
Authors: Shin Yeonoh , Qayyum M. Zuhaib , Pupov Danil , Esyunina Daria , Kulbachinskiy Andrey , Murakami Katsuhiko S.
Published: January 2021

Ribosomal RNA (rRNA) is most highly expressed in rapidly growing bacteria and is drastically downregulated under stress conditions by the global transcriptional regulator DksA and the alarmone ppGpp. Here, we determined cryo-electron microscopy structures of the Escherichia coli RNA polymerase (RNAP) σ70 holoenzyme during rRNA promoter recognition with and without DksA/ppGpp. RNAP contacts the UP element using dimerized α subunit carboxyl-terminal domains and scrunches the template DNA with the σ finger and β’ lid to select the transcription start site favorable for rapid promoter escape. Promoter binding induces conformational change of σ domain 2 that opens a gate for DNA loading and ejects σ1.1 from the RNAP cleft to facilitate open complex formation. DksA/ppGpp binding also opens the DNA loading gate, which is not coupled to σ1.1 ejection and impedes open complex formation. These results provide a molecular basis for the exceptionally active rRNA transcription and its vulnerability to DksA/ppGpp.
A functional family of fluorescent nucleotide analogues to investigate actin dynamics and energetics
Authors: Colombo Jessica , Antkowiak Adrien , Kogan Konstantin , Kotila Tommi , Elliott Jenna , Guillotin Audrey , Lappalainen Pekka , Michelot Alphée
Published: January 2021

Actin polymerization provides force for vital processes of the eukaryotic cell, but our understanding of actin dynamics and energetics remains limited due to the lack of high-quality probes. Most current probes affect dynamics of actin or its interactions with actin-binding proteins (ABPs), and cannot track the bound nucleotide. Here, we identify a family of highly sensitive fluorescent nucleotide analogues structurally compatible with actin. We demonstrate that these fluorescent nucleotides bind to actin, maintain functional interactions with a number of essential ABPs, are hydrolyzed within actin filaments, and provide energy to power actin-based processes. These probes also enable monitoring actin assembly and nucleotide exchange with single-molecule microscopy and fluorescence anisotropy kinetics, therefore providing robust and highly versatile tools to study actin dynamics and functions of ABPs.
Spin blockade and phonon bottleneck for hot electron relaxation observed in n-doped colloidal quantum dots
Authors: Wang Junhui , Wang Lifeng , Yu Shuwen , Ding Tao , Xiang Dongmei , Wu Kaifeng
Published: January 2021

Understanding and manipulating hot electron dynamics in semiconductors may enable disruptive energy conversion schemes. Hot electrons in bulk semiconductors usually relax via electron-phonon scattering on a sub-picosecond timescale. Quantum-confined semiconductors such as quantum dots offer a unique platform to prolong hot electron lifetime through their size-tunable electronic structures. Here, we study hot electron relaxation in electron-doped (n-doped) colloidal CdSe quantum dots. For lightly-doped dots we observe a slow 1Pe hot electron relaxation (~10 picosecond) resulting from a Pauli spin blockade of the preoccupying 1Se electron. For heavily-doped dots, a large number of electrons residing in the surface states introduce picosecond Auger recombination which annihilates the valance band hole, allowing us to observe 300-picosecond-long hot electrons as a manifestation of a phonon bottleneck effect. This brings the hot electron energy loss rate to a level of sub-meV per picosecond from a usual level of 1 eV per picosecond. These results offer exciting opportunities of hot electron harvesting by exploiting carrier-carrier, carrier-phonon and spin-spin interactions in doped quantum dots.
Three-dimensional total-internal reflection fluorescence nanoscopy with nanometric axial resolution by photometric localization of single molecules
Authors: Szalai Alan M. , Siarry Bruno , Lukin Jerónimo , Williamson David J. , Unsain Nicolás , Cáceres Alfredo , Pilo-Pais Mauricio , Acuna Guillermo , Refojo Damián , Owen Dylan M. , Simoncelli Sabrina , Stefani Fernando D.
Published: January 2021

Single-molecule localization microscopy enables far-field imaging with lateral resolution in the range of 10 to 20 nanometres, exploiting the fact that the centre position of a single-molecule’s image can be determined with much higher accuracy than the size of that image itself. However, attaining the same level of resolution in the axial (third) dimension remains challenging. Here, we present Supercritical Illumination Microscopy Photometric z-Localization with Enhanced Resolution (SIMPLER), a photometric method to decode the axial position of single molecules in a total internal reflection fluorescence microscope. SIMPLER requires no hardware modification whatsoever to a conventional total internal reflection fluorescence microscope and complements any 2D single-molecule localization microscopy method to deliver 3D images with nearly isotropic nanometric resolution. Performance examples include SIMPLER-direct stochastic optical reconstruction microscopy images of the nuclear pore complex with sub-20 nm axial localization precision and visualization of microtubule cross-sections through SIMPLER-DNA points accumulation for imaging in nanoscale topography with sub-10 nm axial localization precision.
Emr1 regulates the number of foci of the endoplasmic reticulum-mitochondria encounter structure complex
Authors: Rasul Faiz , Zheng Fan , Dong Fenfen , He Jiajia , Liu Ling , Liu Wenyue , Cheema Javairia Yousuf , Wei Wenfan , Fu Chuanhai
Published: January 2021

The endoplasmic reticulum-mitochondria encounter structure (ERMES) complex creates contact sites between the endoplasmic reticulum and mitochondria, playing crucial roles in interorganelle communication, mitochondrial fission, mtDNA inheritance, lipid transfer, and autophagy. The mechanism regulating the number of ERMES foci within the cell remains unclear. Here, we demonstrate that the mitochondrial membrane protein Emr1 contributes to regulating the number of ERMES foci. We show that the absence of Emr1 significantly decreases the number of ERMES foci. Moreover, we find that Emr1 interacts with the ERMES core component Mdm12 and colocalizes with Mdm12 on mitochondria. Similar to ERMES mutant cells, cells lacking Emr1 display defective mitochondrial morphology and impaired mitochondrial segregation, which can be rescued by an artificial tether capable of linking the endoplasmic reticulum and mitochondria. We further demonstrate that the cytoplasmic region of Emr1 is required for regulating the number of ERMES foci. This work thus reveals a crucial regulatory protein necessary for ERMES functions and provides mechanistic insights into understanding the dynamic regulation of endoplasmic reticulum-mitochondria communication.
Deterministic spin-photon entanglement from a trapped ion in a fiber Fabry–Perot cavity
Authors: Kobel Pascal , Breyer Moritz , Köhl Michael
Published: January 2021

The development of efficient network nodes is a key element for the realization of quantum networks which promise great capabilities as distributed quantum computing or provable secure communication. We report the realization of a quantum network node using a trapped ion inside a fiber-based Fabry–Perot cavity. We show the generation of deterministic entanglement at a high fidelity of 90.1(17)% between a trapped Yb ion and a photon emitted into the resonator mode. We achieve a success probability for generation and detection of entanglement for a single shot of 2.5 × 10−3 resulting in 62 Hz entanglement rate.
Factors affecting the onset and progression of rotator cuff tears in the general population
Authors: Ichinose Tsuyoshi , Shitara Hitoshi , Tajika Tsuyoshi , Kobayashi Tsutomu , Yamamoto Atsushi , Hamano Noritaka , Sasaki Tsuyoshi , Shimoyama Daisuke , Kamiyama Masataka , Miyamoto Ryosuke , Takagishi Kenji , Chikuda Hirotaka
Published: January 2021

While previous studies have revealed factors affecting the progression of rotator cuff tear (RCT), none have yet described factors affecting its onset. The purpose of this longitudinal observational study was to analyze factors affecting the RCT onset and progression in the general population. The present study included 185 shoulders from 93 participants who completed all the examinations in both 2012 and 2017. Participants received a questionnaire with age, gender, arm dominance, and presence of pain at rest, in motion, and at night. The range of motion (ROM), simple shoulder test (SST) were also examined. Anteroposterior radiograph of the shoulder joint was performed to evaluate the degree of osteoarthritic changes by the Samilson-Prieto (S-P) classification. The degree of RCT was examined by ultrasonography. There were 132 shoulders without RCT and 53 with RCT in 2012. RCT occurred in 21 of 132 shoulders, and the factor affecting the RCT onset was S-P grade 2 osteoarthritic change in 2012 (odds ratio [OR] 10.10). RCT progressed in 22 of 53 shoulders, and the factor affecting RCT progression was the presence of motion pain in 2012 (OR 13.76). These results added new knowledge regarding the natural course of RCT onset and progression.
Septohippocampal transmission from parvalbumin-positive neurons features rapid recovery from synaptic depression
Authors: Yi Feng , Garrett Tavita , Deisseroth Karl , Haario Heikki , Stone Emily , Lawrence J. Josh
Published: January 2021

Parvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca ($$\hbox {PV}_{\text{MS-DBB}}$$

PV
MS-DBB

) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined electrophysiological, optogenetic, and modeling approaches to investigate $$\hbox {PV}_{\text{MS-DBB}}$$

PV
MS-DBB

neuronal properties. $$\hbox {PV}_{\text{MS-DBB}}$$

PV
MS-DBB

neurons had intrinsic membrane properties distinct from acetylcholine- and somatostatin-containing MS-DBB subtypes. Viral expression of the fast-kinetic channelrhodopsin ChETA-YFP elicited action potentials to brief (1–2 ms) 470 nm light pulses. To investigate $$\hbox {PV}_{\text{MS-DBB}}$$

PV
MS-DBB

transmission, light pulses at 5–50 Hz frequencies generated trains of inhibitory postsynaptic currents (IPSCs) in CA1 stratum oriens interneurons. Using a similar approach, optogenetic activation of local hippocampal PV ($$\hbox {PV}_{\text{HC}}$$

PV
HC

) neurons generated trains of $$\hbox {PV}_{\text{HC}}$$

PV
HC

-mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to $$\hbox {PV}_{\text{HC}}$$

PV
HC

synapses, $$\hbox {PV}_{\text{MS-DBB}}$$

PV
MS-DBB

synapses possessed lower initial release probability, transiently resisted STD at gamma (20–50 Hz) frequencies, and recovered more rapidly from synaptic depression. Experimentally-constrained mathematical synapse models explored mechanistic differences. Relative to the $$\hbox {PV}_{\text{HC}}$$

PV
HC

model, the $$\hbox {PV}_{\text{MS-DBB}}$$

PV
MS-DBB

model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of $$\hbox {PV}_{\text{MS-DBB}}$$

PV
MS-DBB

synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.
Far field superlensing inside biological media through a nanorod lens using spatiotemporal information
Authors: Hajiahmadi Mohamad J. , Faraji-Dana Reza , Skrivervik Anja K.
Published: January 2021

Far field superlensing of light has generated great attention in optical focusing and imaging applications. The capability of metamaterials to convert evanescent waves to propagative waves has led to numerous proposals in this regard. The common drawback of these approaches is their poor performance inside strongly scattering media like biological samples. Here, we use a metamaterial structure made out of aluminum nanorods in conjunction with time-reversal technique to exploit all temporal and spatial degrees of freedom for superlensing. Using broadband optics, we numerically show that this structure can perform focusing inside biological tissues with a resolution of λ/10. Moreover, for the imaging scheme we propose the entropy criterion for the image reconstruction step to reduce the number of required optical transducers. We propose an imaging scenario to reconstruct the spreading pattern of a diffusive material inside a tissue. In this way super-resolution images are obtained.
Tribo-mechanical properties evaluation of HA/TiO2/CNT nanocomposite
Authors: Zalnezhad Erfan , Musharavati F. , Chen Tianyi , Jaber Fadi , Uzun Kaan , Chowdhury Muhammad E. H. , Khandakar Amith , Liu Junxing , Bae S.
Published: January 2021

In this study, a combination of reverse microemulsion and hydrothermal techniques were used to synthesize HA. A hydrothermal method was used to synthesize HA/TiO2/CNT nanocomposite powders. Cold and hot isostatic pressing techniques were used to fabricate tablet-shaped samples. To investigate the biocompatibility and tribo-mechanical properties of HA/TiO2 and HA/TiO2/CNTs, four samples were prepared with different percentages of CNTs, namely, HA/TiO2 (S0), HA/TiO2/CNT (S1.0), HA/TiO2/CNT (S2.0), and HA/TiO2/CNT (S3.0). The microstructure and morphology of the HA/TiO2/CNTs were characterized by transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction. Hardness test results show that S3.0 displayed the highest surface hardness (285 HV) compared to other samples. The wear rate of HA/TiO2/CNT with the highest CNT content showed a decrease compared with those of the other samples. The results from nanoindentation tests showed that Young’s modulus of the S3.0 sample was 58.1% greater than that of the S0 sample. Furthermore, the human MDA-MB-231 cell line demonstrated good binding to the surface of the samples in the in-vitro biocompatibility evaluation of the HA/TiO2/CNT composites.
Deep learning-based detection of dental prostheses and restorations
Authors: Takahashi Toshihito , Nozaki Kazunori , Gonda Tomoya , Mameno Tomoaki , Ikebe Kazunori
Published: January 2021

The purpose of this study is to develop a method for recognizing dental prostheses and restorations of teeth using a deep learning. A dataset of 1904 oral photographic images of dental arches (maxilla: 1084 images; mandible: 820 images) was used in the study. A deep-learning method to recognize the 11 types of dental prostheses and restorations was developed using TensorFlow and Keras deep learning libraries. After completion of the learning procedure, the average precision of each prosthesis, mean average precision, and mean intersection over union were used to evaluate learning performance. The average precision of each prosthesis varies from 0.59 to 0.93. The mean average precision and mean intersection over union of this system were 0.80 and 0.76, respectively. More than 80% of metallic dental prostheses were detected correctly, but only 60% of tooth-colored prostheses were detected. The results of this study suggest that dental prostheses and restorations that are metallic in color can be recognized and predicted with high accuracy using deep learning; however, those with tooth color are recognized with moderate accuracy.
SHANK2 mutations impair apoptosis, proliferation and neurite outgrowth during early neuronal differentiation in SH-SY5Y cells
Authors: Unsicker Christine , Cristian Flavia-Bianca , von Hahn Manja , Eckstein Volker , Rappold Gudrun A. , Berkel Simone
Published: January 2021

SHANK2 mutations have been identified in individuals with neurodevelopmental disorders, including intellectual disability and autism spectrum disorders (ASD). Using CRISPR/Cas9 genome editing, we obtained SH-SY5Y cell lines with frameshift mutations on one or both SHANK2 alleles. We investigated the effects of the different SHANK2 mutations on cell morphology, cell proliferation and differentiation potential during early neuronal differentiation. All mutant cell lines showed impaired neuronal differentiation marker expression. Cells with bi-allelic SHANK2 mutations revealed diminished apoptosis and increased proliferation, as well as decreased neurite outgrowth during early neuronal differentiation. Bi-allelic SHANK2 mutations resulted in an increase in p-AKT levels, suggesting that SHANK2 mutations impair downstream signaling of tyrosine kinase receptors. Additionally, cells with bi-allelic SHANK2 mutations had lower amyloid precursor protein (APP) expression compared to controls, suggesting a molecular link between SHANK2 and APP. Together, we can show that frameshift mutations on one or both SHANK2 alleles lead to an alteration of neuronal differentiation in SH-SY5Y cells, characterized by changes in cell growth and pre- and postsynaptic protein expression. We also provide first evidence that downstream signaling of tyrosine kinase receptors and amyloid precursor protein expression are affected.
Perceptual insensitivity to the modulation of interoceptive signals in depression, anxiety, and substance use disorders
Authors: Smith Ryan , Feinstein Justin S. , Kuplicki Rayus , Forthman Katherine L. , Stewart Jennifer L. , Paulus Martin P. ,   Tulsa 1000 Investigators, Aupperle Robin L. , Bodurka Jerzy , Savitz Jonathan B. , Victor Teresa A. , Khalsa Sahib S.
Published: January 2021

This study employed a series of heartbeat perception tasks to assess the hypothesis that cardiac interoceptive processing in individuals with depression/anxiety (N = 221), and substance use disorders (N = 136) is less flexible than that of healthy individuals (N = 53) in the context of physiological perturbation. Cardiac interoception was assessed via heartbeat tapping when: (1) guessing was allowed; (2) guessing was not allowed; and (3) experiencing an interoceptive perturbation (inspiratory breath hold) expected to amplify cardiac sensation. Healthy participants showed performance improvements across the three conditions, whereas those with depression/anxiety and/or substance use disorder showed minimal improvement. Machine learning analyses suggested that individual differences in these improvements were negatively related to anxiety sensitivity, but explained relatively little variance in performance. These results reveal a perceptual insensitivity to the modulation of interoceptive signals that was evident across several common psychiatric disorders, suggesting that interoceptive deficits in the realm of psychopathology manifest most prominently during states of homeostatic perturbation.
Biosynthesis of CuO nanoparticles using aqueous extract of herbal tea (Stachys Lavandulifolia) flowers and evaluation of its catalytic activity
Authors: Veisi Hojat , Karmakar Bikash , Tamoradi Taiebeh , Hemmati Saba , Hekmati Malak , Hamelian Mona
Published: January 2021

Plant derived biogenic synthesis of nanoparticles (NP) has been the recent trend in material science as featured sustainable catalysts. A great deal of the current nanocatalytic research has been oriented on the bio-inspired green catalysts based on their wide applicability. In this context, CuO NPs are synthesized following a green approach using an herbal tea (Stachys Lavandulifolia) flower extract. The phytochemicals contained in it were used asthe internal reductant without applying harsh chemicals or strong heat. The derived nanoparticles also got stabilized by the biomolecular capping. The as-synthesized CuO NPs was characterized over FT-IR, FE-SEM, EDS, TEM, XRD, TGA and UV–Vis spectroscopy. These NPs were exploited as a competent catalyst in the aryl and heteroaryl C–heteroatom (N, O, S) cross coupling reactions affording outstanding yields. The nanocatalyst was isolated and recycled in 8 consecutive runs with reproducible catalytic activity. Rigidity of the CuO/S. Lavandulifolia nanocomposite was further justified by leaching test and heterogeneity test.
Strong texture tuning along different crystalline directions in glass-supported CeO2 thin films by ultrasonic spray pyrolysis
Authors: Zumeta-Dubé Inti , García Rangel José Manuel , Roque Jorge , Romero-Ibarra Issis Claudette , García Sánchez Mario Fidel
Published: January 2021

The strong facet-dependent performance of glass-supported CeO2 thin films in different applications (catalysis, smart windows, etc.) has been the target of diverse fundamental and technological approaches. However, the design of accurate, cost-effective and scalable methods with the potential for large-area coverage that produce highly textured glass-supported CeO2 thin films remains a technological challenge. In the present work, it is demonstrated that under proper tuning conditions, the ultrasonic spray pyrolysis technique enables one to obtain glass-supported polycrystalline CeO2 films with noticeable texture along both the (100) and (111) directions, as well as with randomly oriented crystallites (no texture). The influence of flow rates, solution molarity, and substrate temperature on the texture and morphological characteristics, as well as optical absorption and Raman response of the deposited films, is evaluated. The obtained results are discussed on the basis of the combined dependence of the CeO2-exposed surfaces on the thermodynamic stability of the corresponding facets and the reaction kinetics, which modulate the crystallite growth direction.
Mild synthesis of isoxazoline derivatives via an efficient [4 + 1] annulation reaction of transient nitrosoalkenes and sulfur ylides
Authors: Hua Ting-Bi , Liu Cheng-Xiong , Hu Wei-Min , Wang Long , Yang Qing-Qing
Published: January 2021

An efficient [4 + 1] annulation between α-bromooximes and sulfur ylides via in situ generation of nitrosoalkenes under mild basic reaction conditions has been developed, providing an expeditious and scalable approach to synthesize biologically interesting isoxazoline derivatives with good to excellent yields.
Chemoprotective antimalarials identified through quantitative high-throughput screening of Plasmodium blood and liver stage parasites
Authors: Dorjsuren Dorjbal , Eastman Richard T. , Wicht Kathryn J. , Jansen Daniel , Talley Daniel C. , Sigmon Benjamin A. , Zakharov Alexey V. , Roncal Norma , Girvin Andrew T. , Antonova-Koch Yevgeniya , Will Paul M. , Shah Pranav , Sun Hongmao , Klumpp-Thomas Carleen , Mok Sachel , Yeo Tomas , Meister Stephan , Marugan Juan Jose , Ross Leila S. , Xu Xin , Maloney David J. , Jadhav Ajit , Mott Bryan T. , Sciotti Richard J. , Winzeler Elizabeth A. , Waters Norman C. , Campbell Robert F. , Huang Wenwei , Simeonov Anton , Fidock David A.
Published: January 2021

The spread of Plasmodium falciparum parasites resistant to most first-line antimalarials creates an imperative to enrich the drug discovery pipeline, preferably with curative compounds that can also act prophylactically. We report a phenotypic quantitative high-throughput screen (qHTS), based on concentration–response curves, which was designed to identify compounds active against Plasmodium liver and asexual blood stage parasites. Our qHTS screened over 450,000 compounds, tested across a range of 5 to 11 concentrations, for activity against Plasmodium falciparum asexual blood stages. Active compounds were then filtered for unique structures and drug-like properties and subsequently screened in a P. berghei liver stage assay to identify novel dual-active antiplasmodial chemotypes. Hits from thiadiazine and pyrimidine azepine chemotypes were subsequently prioritized for resistance selection studies, yielding distinct mutations in P. falciparum cytochrome b, a validated antimalarial drug target. The thiadiazine chemotype was subjected to an initial medicinal chemistry campaign, yielding a metabolically stable analog with sub-micromolar potency. Our qHTS methodology and resulting dataset provides a large-scale resource to investigate Plasmodium liver and asexual blood stage parasite biology and inform further research to develop novel chemotypes as causal prophylactic antimalarials.
Anatomical and ontogenetic influences on muscle density
Authors: Leonard Kaitlyn C. , Worden Nikole , Boettcher Marissa L. , Dickinson Edwin , Omstead Kailey M. , Burrows Anne M. , Hartstone-Rose Adam
Published: January 2021

Physiological cross-sectional area (PCSA), an important biomechanical variable, is an estimate of a muscle’s contractile force potential and is derived from dividing muscle mass by the product of a muscle’s average fascicle length and a theoretical constant representing the density of mammalian skeletal muscle. This density constant is usually taken from experimental studies of small samples of several model taxa using tissues collected predominantly from the lower limbs of adult animals. The generalized application of this constant to broader analyses of mammalian myology assumes that muscle density (1) is consistent across anatomical regions and (2) is unaffected by the aging process. To investigate the validity of these assumptions, we studied muscles of rabbits (Oryctolagus cuniculus) in the largest sample heretofore investigated explicitly for these variables, and we did so from numerous anatomical regions and from three different age-cohorts. Differences in muscle density and histology as a consequence of age and anatomical region were evaluated using Tukey’s HSD tests. Overall, we observed that older individuals tend to have denser muscles than younger individuals. Our findings also demonstrated significant differences in muscle density between anatomic regions within the older cohorts, though none in the youngest cohort. Approximately 50% of the variation in muscle density can be explained histologically by the average muscle fiber area and the average percent fiber area. That is, muscles with larger average fiber areas and a higher proportion of fiber area tend to be denser. Importantly, using the age and region dependent measurements of muscle density that we provide may increase the accuracy of PCSA estimations. Although we found statistically significant differences related to ontogeny and anatomical region, if density cannot be measured directly, the specific values presented herein should be used to improve accuracy. If a single muscle density constant that has been better validated than the ones presented in the previous literature is preferred, then 1.0558 and 1.0502 g/cm3 would be reasonable constants to use across all adult and juvenile muscles respectively.
Post-conception heat exposure increases clinically unobserved pregnancy losses
Authors: Hajdu Tamás , Hajdu Gábor
Published: January 2021

Evidence of the relationship between temperature during pregnancy and human embryo mortality is limited. Most importantly, the literature lacks causal estimations and studies on early pregnancy losses. Here, we estimate the impact of early pregnancy temperature exposure on the clinically unobserved pregnancy loss rate. We use administrative data of clinically observed pregnancies from more than three decades for Hungary. We apply an empirical approach that allows us to infer the impact of temperature on the clinically unobserved pregnancy loss rate from the estimated effects on the clinically observed conception rate. The results show that exposure to hot temperatures during the first few weeks after the conception week increases the clinically unobserved pregnancy loss rate, whereas exposure to colder temperatures seems to decrease it. Importantly, the temperature-induced changes represent changes in the total number of pregnancy losses rather than a compositional change between clinically observed and clinically unobserved pregnancy losses.
Headache and musculoskeletal pain in school children are associated with uncorrected vision problems and need for glasses: a case–control study
Authors: Thorud Hanne-Mari Schiøtz , Aurjord Rakel , Falkenberg Helle K.
Published: January 2021

Musculoskeletal pain and headache are leading causes of years lived with disability, and an escalating problem in school children. Children spend increasingly more time reading and using digital screens, and increased near tasks intensify the workload on the precise coordination of the visual and head-stabilizing systems. Even minor vision problems can provoke headache and neck- and shoulder (pericranial) pain. This study investigated the association between headaches, pericranial tenderness, vision problems, and the need for glasses in children. An eye and physical examination was performed in twenty 10–15 year old children presenting to the school health nurse with headache and pericranial pain (pain group), and twenty age-and-gender matched classmates (control group). The results showed that twice as many children in the pain group had uncorrected vision and needed glasses. Most children were hyperopic, and glasses were recommended mainly for near work. Headache and pericranial tenderness were significantly correlated to reduced binocular vision, reduced distance vision, and the need for new glasses. That uncorrected vision problems are related to upper body musculoskeletal symptoms and headache, indicate that all children with these symptoms should have a full eye examination to promote health and academic performance.
Effects of open-label placebos on test performance and psychological well-being in healthy medical students: a randomized controlled trial
Authors: Kleine-Borgmann Julian , Schmidt Katharina , Billinger Marieke , Forkmann Katarina , Wiech Katja , Bingel Ulrike
Published: January 2021

Psychological distress is prevalent in students and can predispose to psychiatric disorders. Recent findings indicate that distress might be linked to impaired cognitive performance in students. Experimental findings in healthy participants suggest that placebo interventions can improve cognition. However, whether non-deceptive (i.e., open-label, OLP) placebos can enhance cognitive function and emotional well-being is unclear. Using a randomized-controlled design we demonstrate a positive impact of OLP on subjective well-being (i.e., stress, fatigue, and confusion) after a 21-day OLP application in healthy students during midterm exams. OLP did not improve test performance, but, within the OLP group, test performance was positively correlated with measures of general belief in the benefit of medication. These results show that OLP can counteract negative effects of acute stress on psychological well-being and might improve cognitive performance if supported by positive treatment expectations. Additionally, our findings in healthy volunteers warrant further investigation in exploring the potential of OLP in reducing stress-related psychological effects in patients. The trial was preregistered at the German Clinical Trials Register on December 20, 2017 (DRKS00013557).