bluuebunny/crossref_metadata_2025 huggingface dataset:
Shear‐Wave Anisotropy in the Earth's Inner Core
Authors: Wang Sheng , Tkalčić Hrvoje
Published: September 2021

Earth's inner core (IC) anisotropy is widely used to infer the deep Earth's evolution and present dynamics. Many compressional‐wave anisotropy models have been proposed based on seismological observations. In contrast, inner‐core shear‐wave (J‐wave) anisotropy—on a par with the compressional‐wave anisotropy—has been elusive. Here, we present a new class of the J‐wave anisotropy observations utilizing earthquake coda‐correlation wavefield. We establish that the coda‐correlation feature I2‐J, sensitive to J‐wave speed, exhibits time and amplitude changes when sampling the IC differently. J‐waves traversing the IC near its center travel faster for the oblique than equatorial angles relative to the Earth's rotation axis by at least ∼5 s. The simplest explanation is the J‐wave cylindrical anisotropy with a minimum strength of ∼0.8%, formed through the lattice‐preferred‐orientation mechanism of iron. Although we cannot uniquely determine its stable iron phase, the new observations rule out one of the body‐centered‐cubic iron models.
Pacific Northwest Plants Record Multiannual Atmosphere–Ocean Circulation Patterns
Authors: Stein Rebekah A. , Sheldon Nathan D. , Smith Selena Y.
Published: September 2021

Carbon isotope ecology can be used as a measure of plant water stress. Plant water stress is complicated: multiple factors (e.g., evapotranspiration rates, temperature, precipitation, soil texture, and available water) control the magnitude of the isotopic expression. Often, large ocean–atmosphere pressure systems result in the convergence of constructive climate parameters that result in increased plant water stress; for example, El Niño and Pacific Decadal Oscillation (PDO) anomaly phases. We examined the biogeochemistry of three species (Thuja plicata: with a Pacific coastal habitat,Thuja occidentalis: native to the Great Lakes region, andPopulus tremuloides: a cosmopolitan species found throughout North America). Coincident analyses of these species allowed for intercomparison between plants in habitats directly impacted by atmospheric–oceanic controls on water availability and those out of Pacific impact range. There are oscillatory patterns in the carbon isotope discrimination values (Δ13Cleaf) ofThuja plicata, but no clear patterns in Δ13Cleafvalues of the other species. We compare the pattern in isotope discrimination ofT. plicatawith Pacific‐driven multiannual environmental phenomena to determine whether these patterns could be related to the oscillation in Δ13Cleafvalues. The data demonstrate a regular and significant 14‐ to 19‐year periodicity, aligning most closely with PDO climate patterns.Thuja plicatalikely records prolonged stress, like plant available water shortages, which coincide with PDO‐associated shifts in precipitation, humidity, and evapotranspiration. These findings demonstrate that coastal Pacific ecosystems are vulnerable to changes in water availability connected to Pacific teleconnections, providing a new recording tool to examine multiannual climate anomalies.
Biological Nitrogen Fixation in Sediments of a Cyanobacterial Bloom‐Occurring Bay in One Eutrophic Shallow Lake: Occurrence and Related Environmental Factors
Authors: Tian Linqi , Jiang Helong , Bai Leilei , Wang Chunliu , Xu Shengqi
Published: September 2021

Biological nitrogen fixation (BNF) is an important source of bioavailable nitrogen in the aquatic environment that supports primary production. However, little is known about its occurrence and potential in eutrophic freshwater habitats. This study investigated the diazotrophic diversity and seasonal variation of nitrogenase activity (NA) in the sediments of a cyanobacterial bloom‐occurring bay of a freshwater lake. Sequencing analysis of the nifH gene revealed that diazotrophs in Clusters I and III constituted the dominant components of the diazotrophic community in Meiliang Bay. Both nifH and 16S rRNA gene sequencing indicated that the microbes in sediments have different community structures during the winter than during other seasons. The concentrations of dissolved sulfide, sulfate, and nitrate in pore water were significantly correlated with NA in sediments; however, the Mantel test indicated that dissolved sulfide had a more significant effect on the structure of the diazotrophic community than did other environmental factors. Laboratory culture experiments under different redox conditions further confirmed the inhibitory effect of dissolved sulfide on BNF in sediments. This study revealed that the BNF in sediments of Meiliang Bay was closely linked to variations in dissolved sulfide concentration, which has broadened our understanding of BNF in freshwater lakes.
A CRISPR knockout screen reveals new regulators of canonical Wnt signaling
Authors: Evron Tamar , Caspi Michal , Kazelnik Michal , Shor-Nareznoy Yarden , Armoza-Eilat Shir , Kariv Revital , Manber Zohar , Elkon Ran , Sklan Ella H. , Rosin-Arbesfeld Rina
Published: September 2021

The Wnt signaling pathways play fundamental roles during both development and adult homeostasis. Aberrant activation of the canonical Wnt signal transduction pathway is involved in many diseases including cancer, and is especially implicated in the development and progression of colorectal cancer. Although extensively studied, new genes, mechanisms and regulatory modulators involved in Wnt signaling activation or silencing are still being discovered. Here we applied a genome-scale CRISPR-Cas9 knockout (KO) screen based on Wnt signaling induced cell survival to reveal new inhibitors of the oncogenic, canonical Wnt pathway. We have identified several potential Wnt signaling inhibitors and have characterized the effects of the initiation factor DExH-box protein 29 (DHX29) on the Wnt cascade. We show that KO of DHX29 activates the Wnt pathway leading to upregulation of the Wnt target gene cyclin-D1, while overexpression of DHX29 inhibits the pathway. Together, our data indicate that DHX29 may function as a new canonical Wnt signaling tumor suppressor and demonstrates that this screening approach can be used as a strategy for rapid identification of novel Wnt signaling modulators.
Antiatherosclerotic effect of dehydrocorydaline on ApoE−/− mice: inhibition of macrophage inflammation
Authors: Wen Bin , Dang Yuan-ye , Wu Su-hua , Huang Yi-min , Ma Kong-yang , Xu Yi-ming , Zheng Xi-Long , Dai Xiao-yan
Published: September 2021

Despite improvements in cardiovascular disease (CVD) outcomes by cholesterol-lowering statin therapy, the high rate of CVD is still a great concern worldwide. Dehydrocorydaline (DHC) is an alkaloidal compound isolated from the traditional Chinese herbCorydalis yanhusuo. Emerging evidence shows that DHC has anti-inflammatory and antithrombotic benefits, but whether DHC exerts any antiatherosclerotic effects remains unclear. Our study revealed that intraperitoneal (i.p.) injection of DHC in apolipoprotein E-deficient (ApoE−/−) mice not only inhibited atherosclerosis development but also improved aortic compliance and increased plaque stability. In addition, DHC attenuated systemic and vascular inflammation in ApoE−/−mice. As macrophage inflammation plays an essential role in the pathogenesis of atherosclerosis, we next examined the direct effects of DHC on bone marrow-derived macrophages (BMDMs) in vitro. Our RNA-seq data revealed that DHC dramatically decreased the levels of proinflammatory gene clusters. We verified that DHC significantly downregulated proinflammatory interleukin (IL)-1β and IL-18 mRNA levels in a time- and concentration-dependent manner. Furthermore, DHC decreased lipopolysaccharide (LPS)-induced inflammation in BMDMs, as evidenced by the reduced protein levels of CD80, iNOS, NLRP3, IL-1β, and IL-18. Importantly, DHC attenuated LPS-induced activation of p65 and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Thus, we conclude that DHC ameliorates atherosclerosis in ApoE−/−mice by inhibiting inflammation, likely by targeting macrophage p65- and ERK1/2-mediated pathways.
Norcantharidin ameliorates the development of murine lupus via inhibiting the generation of IL-17 producing cells
Authors: Du Li-jun , Feng Yu-xiang , He Zhi-xing , Huang Lin , Wang Qiao , Wen Cheng-ping , Zhang Yun
Published: September 2021

Systemic lupus erythematosus (SLE) is a devastating autoimmune disorder associated with severe organ damage. The abnormality of T cell apoptosis is considered as an important pathogenetic mechanism of SLE. Norcantharidin (NCTD), a derivative of Cantharidin, is an efficacious anti-cancer drug by inhibiting cell proliferation and inducing cell apoptosis. Besides, NCTD has also been proved to protect the function of kidneys, while damaged renal function is the most important predictor of morbidity and mortality in SLE. All these suggest the potential effects of NCTD in SLE treatment. In this study we investigated whether NCTD exerted therapeutic effects in a mouse SLE model. Lupus prone female MRL/lpr mice were treated with NCTD (1, 2 mg·kg−1·d−1, ip) for 8 weeks. We showed that NCTD administration significantly decreased mortality rate, diminished the expression of anti-dsDNA IgG antibody, a diagnostic marker for SLE, as well as restored renal structure and function in MRL/lpr mice. Moreover, NCTD administration dose-dependently inhibited lymphoproliferation and T cell accumulation in the spleens of MRL/lpr mice. We further revealed that NCTD specifically inhibited DN T cell proliferation and Th17 cell differentiation both via blocking activation of signal transducer and activator of transcription 3 (STAT3) signaling pathway. On the other hand, NCTD did not affect T cell apoptosis in MRL/lpr mice. Taken together, our data suggest that NCTD may be as a promising therapeutic drug through targeting T cells for the treatment of SLE.
Long non-coding RNA ZFAS1 promotes pancreatic cancer proliferation and metastasis by sponging miR-497-5p to regulate HMGA2 expression
Authors: Rao Min , Xu Song , Zhang Yong , Liu Yifan , Luan Wenkang , Zhou Junjing
Published: September 2021

The lncRNA ZFAS1 plays a carcinogenic regulatory role in many human tumours, but it is rarely reported in pancreatic cancer. We identify the role and molecular mechanisms of ZFAS1 in pancreatic cancer. The expression of ZFAS1, miR-497-5p and HMGA2 in pancreatic cancer tissues was detected by qRT-PCR. Pancreatic cancer data in The Cancer Genome Atlas were also included in this study. CCK8, EdU, transwell and scratch wound assays were used to investigate the biological effects of ZFAS1 in pancreatic cancer cells. MS2-RIP, RNA pull-down, RNA-ChIP and luciferase reporter assays were used to clarify the molecular biological mechanisms of ZFAS1 in pancreatic cancer. The role of ZFAS1 in vivo was also confirmed via xenograft experiments. ZFAS1 was overexpressed in pancreatic cancer tissues. ZFAS1 promoted the growth and metastasis of pancreatic cancer cells, and miR-497-5p acted as a tumour suppressor gene in pancreatic cancer by targeting HMGA2. We also demonstrated that ZFAS1 exerts its effects by promoting HMGA2 expression through decoying miR-497-5p. We also found that ZFAS1 promoted the progression of pancreatic cancer in vivo by modulating the miR-497-5p/HMGA2 axis. In conclusion, this study revealed a new role for and the molecular mechanisms of ZFAS1 in pancreatic cancer, identifying ZFAS1 as a novel target for the diagnosis and treatment of pancreatic cancer.
Tunable unidirectional nonlinear emission from transition-metal-dichalcogenide metasurfaces
Authors: Nauman Mudassar , Yan Jingshi , de Ceglia Domenico , Rahmani Mohsen , Zangeneh Kamali Khosro , De Angelis Costantino , Miroshnichenko Andrey E. , Lu Yuerui , Neshev Dragomir N.
Published: September 2021

Nonlinear light sources are central to a myriad of applications, driving a quest for their miniaturisation down to the nanoscale. In this quest, nonlinear metasurfaces hold a great promise, as they enhance nonlinear effects through their resonant photonic environment and high refractive index, such as in high-index dielectric metasurfaces. However, despite the sub-diffractive operation of dielectric metasurfaces at the fundamental wave, this condition is not fulfilled for the nonlinearly generated harmonic waves, thereby all nonlinear metasurfaces to date emit multiple diffractive beams. Here, we demonstrate the enhanced single-beam second- and third-harmonic generation in a metasurface of crystalline transition-metal-dichalcogenide material, offering the highest refractive index. We show that the interplay between the resonances of the metasurface allows for tuning of the unidirectional second-harmonic radiation in forward or backward direction, not possible in any bulk nonlinear crystal. Our results open new opportunities for metasurface-based nonlinear light-sources, including nonlinear mirrors and entangled-photon generation.
Modelling the persistence and control of Rift Valley fever virus in a spatially heterogeneous landscape
Authors: Tennant Warren S. D. , Cardinale Eric , Cêtre-Sossah Catherine , Moutroifi Youssouf , Le Godais Gilles , Colombi Davide , Spencer Simon E. F. , Tildesley Mike J. , Keeling Matt J. , Charafouddine Onzade , Colizza Vittoria , Edmunds W. John , Métras Raphaëlle
Published: September 2021

The persistence mechanisms of Rift Valley fever (RVF), a zoonotic arboviral haemorrhagic fever, at both local and broader geographical scales have yet to be fully understood and rigorously quantified. We developed a mathematical metapopulation model describing RVF virus transmission in livestock across the four islands of the Comoros archipelago, accounting for island-specific environments and inter-island animal movements. By fitting our model in a Bayesian framework to 2004–2015 surveillance data, we estimated the importance of environmental drivers and animal movements on disease persistence, and tested the impact of different control scenarios on reducing disease burden throughout the archipelago. Here we report that (i) the archipelago network was able to sustain viral transmission in the absence of explicit disease introduction events after early 2007, (ii) repeated outbreaks during 2004–2020 may have gone under-detected by local surveillance, and (iii) co-ordinated within-island control measures are more effective than between-island animal movement restrictions.
Magnetothermal nanoparticle technology alleviates parkinsonian-like symptoms in mice
Authors: Hescham Sarah-Anna , Chiang Po-Han , Gregurec Danijela , Moon Junsang , Christiansen Michael G. , Jahanshahi Ali , Liu Huajie , Rosenfeld Dekel , Pralle Arnd , Anikeeva Polina , Temel Yasin
Published: September 2021

Deep brain stimulation (DBS) has long been used to alleviate symptoms in patients suffering from psychiatric and neurological disorders through stereotactically implanted electrodes that deliver current to subcortical structures via wired pacemakers. The application of DBS to modulate neural circuits is, however, hampered by its mechanical invasiveness and the use of chronically implanted leads, which poses a risk for hardware failure, hemorrhage, and infection. Here, we demonstrate that a wireless magnetothermal approach to DBS (mDBS) can provide similar therapeutic benefits in two mouse models of Parkinson’s disease, the bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and in the unilateral 6-hydroxydopamine (6-OHDA) model. We show magnetothermal neuromodulation in untethered moving mice through the activation of the heat-sensitive capsaicin receptor (transient receptor potential cation channel subfamily V member 1, TRPV1) by synthetic magnetic nanoparticles. When exposed to an alternating magnetic field, the nanoparticles dissipate heat, which triggers reversible firing of TRPV1-expressing neurons. We found that mDBS in the subthalamic nucleus (STN) enables remote modulation of motor behavior in healthy mice. Moreover, mDBS of the STN reversed the motor deficits in a mild and severe parkinsonian model. Consequently, this approach is able to activate deep-brain circuits without the need for permanently implanted hardware and connectors.
Inverse centrifugal effect induced by collective motion of vortices in rotating thermal convection
Authors: Ding Shan-Shan , Chong Kai Leong , Shi Jun-Qiang , Ding Guang-Yu , Lu Hao-Yuan , Xia Ke-Qing , Zhong Jin-Qiang
Published: September 2021

When a fluid system is subject to strong rotation, centrifugal fluid motion is expected, i.e., denser (lighter) fluid moves outward (inward) from (toward) the axis of rotation. Here we demonstrate, both experimentally and numerically, the existence of an unexpected outward motion of warm and lighter vortices in rotating thermal convection. This anomalous vortex motion occurs under rapid rotations when the centrifugal buoyancy is sufficiently strong to induce a symmetry-breaking in the vorticity field, i.e., the vorticity of the cold anticyclones overrides that of the warm cyclones. We show that through hydrodynamic interactions the densely distributed vortices can self-aggregate into coherent clusters and exhibit collective motion in this flow regime. Interestingly, the correlation of the vortex velocity fluctuations within a cluster is scale-free, with the correlation length being proportional ( ≈ 30%) to the cluster length. Such long-range correlation leads to the counterintuitive collective outward motion of warm vortices. Our study brings insights into the vortex dynamics that are widely present in nature.
Targeting the actin nucleation promoting factor WASp provides a therapeutic approach for hematopoietic malignancies
Authors: Biber Guy , Ben-Shmuel Aviad , Noy Elad , Joseph Noah , Puthenveetil Abhishek , Reiss Neria , Levy Omer , Lazar Itay , Feiglin Ariel , Ofran Yanay , Kedmi Meirav , Avigdor Abraham , Fried Sophia , Barda-Saad Mira
Published: September 2021

Cancer cells depend on actin cytoskeleton rearrangement to carry out hallmark malignant functions including activation, proliferation, migration and invasiveness. Wiskott–Aldrich Syndrome protein (WASp) is an actin nucleation-promoting factor and is a key regulator of actin polymerization in hematopoietic cells. The involvement of WASp in malignancies is incompletely understood. Since WASp is exclusively expressed in hematopoietic cells, we performedin silicoscreening to identify small molecule compounds (SMCs) that bind WASp and promote its degradation. We describe here one such identified molecule; this WASp-targeting SMC inhibits key WASp-dependent actin processes in several types of hematopoietic malignancies in vitro and in vivo without affecting naïve healthy cells. This small molecule demonstrates limited toxicity and immunogenic effects, and thus, might serve as an effective strategy to treat specific hematopoietic malignancies in a safe and precisely targeted manner.
Coevolutionary methods enable robust design of modular repressors by reestablishing intra-protein interactions
Authors: Jiang Xian-Li , Dimas Rey P. , Chan Clement T. Y. , Morcos Faruck
Published: September 2021

Genetic sensors with unique combinations of DNA recognition and allosteric response can be created by hybridizing DNA-binding modules (DBMs) and ligand-binding modules (LBMs) from distinct transcriptional repressors. This module swapping approach is limited by incompatibility between DBMs and LBMs from different proteins, due to the loss of critical module-module interactions after hybridization. We determine a design strategy for restoring key interactions between DBMs and LBMs by using a computational model informed by coevolutionary traits in the LacI family. This model predicts the influence of proposed mutations on protein structure and function, quantifying the feasibility of each mutation for rescuing hybrid repressors. We accurately predict which hybrid repressors can be rescued by mutating residues to reinstall relevant module-module interactions. Experimental results confirm that dynamic ranges of gene expression induction were improved significantly in these mutants. This approach enhances the molecular and mechanistic understanding of LacI family proteins, and advances the ability to design modular genetic parts.
Intracavity incoherent supercontinuum dynamics and rogue waves in a broadband dissipative soliton laser
Authors: Meng Fanchao , Lapre Coraline , Billet Cyril , Sylvestre Thibaut , Merolla Jean-Marc , Finot Christophe , Turitsyn Sergei K. , Genty Goëry , Dudley John M.
Published: September 2021

Understanding dynamical complexity is one of the most important challenges in science. Significant progress has recently been made in optics through the study of dissipative soliton laser systems, where dynamics are governed by a complex balance between nonlinearity, dispersion, and energy exchange. A particularly complex regime of such systems is associated with noise-like pulse multiscale instabilities, where sub-picosecond pulses with random characteristics evolve chaotically underneath a much longer envelope. However, although observed for decades in experiments, the physics of this regime remains poorly understood, especially for highly-nonlinear cavities generating broadband spectra. Here, we address this question directly with a combined numerical and experimental study that reveals the physical origin of instability as nonlinear soliton dynamics and supercontinuum turbulence. Real-time characterisation reveals intracavity extreme events satisfying statistical rogue wave criteria, and both real-time and time-averaged measurements are in quantitative agreement with modelling.
Identification of lead vacancy defects in lead halide perovskites
Authors: Keeble David J. , Wiktor Julia , Pathak Sandeep K. , Phillips Laurie J. , Dickmann Marcel , Durose Ken , Snaith Henry J. , Egger Werner
Published: September 2021

Perovskite photovoltaics advance rapidly, but questions remain regarding point defects: while experiments have detected the presence of electrically active defects no experimentally confirmed microscopic identifications have been reported. Here we identify lead monovacancy (VPb) defects in MAPbI3 (MA = CH3NH3+) using positron annihilation lifetime spectroscopy with the aid of density functional theory. Experiments on thin film and single crystal samples all exhibited dominant positron trapping to lead vacancy defects, and a minimum defect density of ~3 × 1015 cm−3 was determined. There was also evidence of trapping at the vacancy complex $$({{{{{\rm{V}}}}}}_{{{{{\rm{Pb}}}}}}{{{{{\rm{V}}}}}}_{{{{{\rm{I}}}}}})^{-}$$

(

V

Pb

V

I

)

−

in a minority of samples, but no trapping to MA-ion vacancies was observed. Our experimental results support the predictions of other first-principles studies that deep level, hole trapping, $${{{{{{\rm{V}}}}}}}_{{{{{{\rm{Pb}}}}}}}^{2-}$$

V

Pb

2
−

, point defects are one of the most stable defects in MAPbI3. This direct detection and identification of a deep level native defect in a halide perovskite, at technologically relevant concentrations, will enable further investigation of defect driven mechanisms.
Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid
Authors: Peters Kristian , Herman Stephanie , Khoonsari Payam Emami , Burman Joachim , Neumann Steffen , Kultima Kim
Published: September 2021

Chronic diseases affecting the central nervous system (CNS) like Alzheimer’s or Parkinson’s disease typically develop with advanced chronological age. Yet, aging at the metabolic level has been explored only sporadically in humans using biofluids in close proximity to the CNS such as the cerebrospinal fluid (CSF). We have used an untargeted liquid chromatography high-resolution mass spectrometry (LC-HRMS) based metabolomics approach to measure the levels of metabolites in the CSF of non-neurological control subjects in the age of 20 up to 74. Using a random forest-based feature selection strategy, we extracted 69 features that were strongly related to age (page < 0.001, rage = 0.762, R2Boruta age = 0.764). Combining an in-house library of known substances with in silico chemical classification and functional semantic annotation we successfully assigned putative annotations to 59 out of the 69 CSF metabolites. We found alterations in metabolites related to the Cytochrome P450 system, perturbations in the tryptophan and kynurenine pathways, metabolites associated with cellular energy (NAD+, ADP), mitochondrial and ribosomal metabolisms, neurological dysfunction, and an increase of adverse microbial metabolites. Taken together our results point at a key role for metabolites found in CSF related to the Cytochrome P450 system as most often associated with metabolic aging.
Author Correction: New species and records of Trichoderma isolated as mycoparasites and endophytes from cultivated and wild coffee in Africa
Authors: del Carmen H. Rodríguez María , Evans Harry C. , de Abreu Lucas M. , de Macedo Davi M. , Ndacnou Miraine K. , Bekele Kifle B. , Barreto Robert W.
Published: September 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Robust neuronal differentiation of human iPSC-derived neural progenitor cells cultured on densely-spaced spiky silicon nanowire arrays
Authors: Harberts Jann , Siegmund Malte , Schnelle Matteo , Zhang Ting , Lei Yakui , Yu Linwei , Zierold Robert , Blick Robert H.
Published: September 2021

Nanostructured cell culture substrates featuring nanowire (NW) arrays have been applied to a variety of basic cell lines and rodent neurons to investigate cellular behavior or to stimulate cell responses. However, patient-derived human neurons—a prerequisite for studying e.g. neurodegenerative diseases efficiently—are rarely employed due to sensitive cell culture protocols and usually long culturing periods. Here, we present human patient induced pluripotent stem cell-derived neurons cultured on densely-spaced spiky silicon NW arrays (600 NWs/ 100 µm$$^2$$

2

with NW lengths of 1 µm) which show mature electrophysiological characteristics after only 20 days of culturing. Exemplary neuronal growth and network formation on the NW arrays are demonstrated using scanning electron microscopy and immunofluorescence microscopy. The cells and neurites rest in a fakir-like settling state on the NWs only in contact with the very NW tips shown by cross-sectional imaging of the cell/NW interface using focused ion beam milling and confocal laser scanning microscopy. Furthermore, the NW arrays promote the cell culture by slightly increasing the share of differentiated neurons determined by the quantification of immunofluorescence microscopy images. The electrophysiological functionality of the neurons is confirmed with patch-clamp recordings showing the excellent capability to fire action potentials. We believe that the short culturing time to obtain functional human neurons generated from patient-derived neural progenitor cells and the robustness of this differentiation protocol to produce these neurons on densely-spaced spiky nanowire arrays open up new pathways for stem cell characterization and neurodegenerative disease studies.
Deep mutational scanning of the plasminogen activator inhibitor-1 functional landscape
Authors: Huttinger Zachary M. , Haynes Laura M. , Yee Andrew , Kretz Colin A. , Holding Matthew L. , Siemieniak David R. , Lawrence Daniel A. , Ginsburg David
Published: September 2021

The serine protease inhibitor (SERPIN) plasminogen activator inhibitor-1 (PAI-1) is a key regulator of the fibrinolytic system, inhibiting the serine proteases tissue- and urokinase-type plasminogen activator (tPA and uPA, respectively). Missense variants render PAI-1 non-functional through misfolding, leading to its turnover as a protease substrate, or to a more rapid transition to the latent/inactive state. Deep mutational scanning was performed to evaluate the impact of amino acid sequence variation on PAI-1 inhibition of uPA using an M13 filamentous phage display system. Error prone PCR was used to construct a mutagenized PAI-1 library encompassing ~ 70% of potential single amino acid substitutions. The relative effects of 27% of all possible missense variants on PAI-1 inhibition of uPA were determined using high-throughput DNA sequencing. 826 missense variants demonstrated conserved inhibitory activity while 1137 resulted in loss of PAI-1 inhibitory function. The least evolutionarily conserved regions of PAI-1 were also identified as being the most tolerant of missense mutations. The results of this screen confirm previous low-throughput mutational studies, including those of the reactive center loop. These data provide a powerful resource for explaining structure–function relationships for PAI-1 and for the interpretation of human genomic sequence variants.
Temporal lobe activation during episodic memory encoding following traumatic brain injury
Authors: Taing Abbie S. , Mundy Matthew E. , Ponsford Jennie L. , Spitz Gershon
Published: September 2021

The temporal lobes are critical for encoding and retrieving episodic memories. The temporal lobes are preferentially disrupted following a traumatic brain injury (TBI), likely contributing to the difficulties observed in episodic memory. However, the underlying neural changes that precipitate or maintain these difficulties in individuals with TBI remains poorly understood. Here, we use functional magnetic resonance imaging (fMRI) to interrogate the relationship between temporal lobe activation and encoding of episodic stimuli. Participants encoded face, scene, and animal stimuli during an fMRI run. In an out-of-scanner task, participants were required to correctly identify previously displayed stimuli over two presentation runs (each in-scanner stimuli presented twice). Forty-three patients with moderate-severe TBI were recruited and compared with 38 demographically similar healthy controls. The pattern of behavioural performance between groups depended on the stimuli presentation run. The TBI group demonstrated poorer episodic memory for faces and scenes during the first presentation, but not the second presentation. When episodic memory was analysed across all presentation runs, behavioural deficits were only apparent for faces. Interestingly, processing of faces emerged as the only between group-difference on fMRI, whereby TBI participants had an increased signal in the middle temporal gyrus extending to the superior temporal sulcus. These findings provide evidence to suggest that following TBI: (a) episodic memory is preferentially impaired for complex stimuli such as faces, and (b) robust behavioural inefficiencies are reflected in increased activation in specific temporal lobe structures during encoding.
A comparative biomechanical study of the Distal Tibia Nail against compression plating for the osteosynthesis of supramalleolar corrective osteotomies
Authors: Greenfield Julia , Appelmann Philipp , Lafon Yoann , Bruyère-Garnier Karine , Rommens Pol Maria , Kuhn Sebastian
Published: September 2021

The Distal Tibia Nail (DTN; Mizuho, Japan) has demonstrated higher biomechanical stiffness to locking plates in previous research for A3 distal tibia fractures. It is here investigated as a fixation option for supramalleolar corrective osteotomies (SMOT). Sixteen Sawbones tibiae were implanted with either a DTN (n = 8) or Medial Distal Tibia Plate (MDTP; n = 8) and a SMOT simulated. Two surgical outcome scenarios were envisaged: “best-case” representing an intact lateral cortex, and “worst-case” representing a fractured lateral cortex. All samples were subjected to compressive (350 N, 700 N) and torsional (± 4 Nm, ± 8 Nm) testing. Samples were evaluated using calculated construct stiffness from force–displacement data, interfragmentary movement and Von Mises’ strain distribution. The DTN demonstrated a greater compressive stiffness for the best-case surgical scenario, whereas the MDTP showed higher stiffness (p < 0.05) for the worst-case surgical scenario. In torsional testing, the DTN proved more resistant to torsion in the worst-case surgical setup (p < 0.05) for both ± 4 Nm and ± 8 Nm. The equivalent stiffness of the DTN against the MDTP supports the use of this implant for SMOT fixation and should be considered as a treatment option particularly in patients presenting vascularisation problems where the MDTP is an inappropriate choice.
Application of water based drilling clay-nanoparticles in heat transfer of fractional Maxwell fluid over an infinite flat surface
Authors: Asjad Muhammad Imran , Ali Rizwan , Iqbal Azhar , Muhammad Taseer , Chu Yu-Ming
Published: September 2021

In the present paper, unsteady free convection flow of Maxwell fluid containing clay-nanoparticles is investigated. These particles are hanging in water, engine oil and kerosene. The values for nanofluids based on the Maxwell-Garnett and Brinkman models for effective thermal conductivity and viscosity are calculated numerically. The integer order governing equations are being extended to the novel non-integer order fractional derivative. Analytical solutions of temperature and velocity for Maxwell fluid are build using Laplace transform technique and expressed in such a way that they clearly satisfied the boundary conditions. To see the impact of different flow parameters on the velocity, we have drawn some graphs. As a result, we have seen that the fractional model is superior in narrate the decay property of field variables. Some limiting solutions are obtained and compared with the latest existing literature. Moreover, significant results can be observed for clay nanoparticles with different base fluids.
Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model
Authors: Joo Nam Soo , Cho Hyung-Ju , Shinbashi Meagan , Choi Jae Young , Milla Carlos E. , Engelhardt John F. , Wine Jeffrey J.
Published: September 2021

Mucus clearance, a primary innate defense mechanism of airways, is defective in patients with cystic fibrosis (CF) and CF animals. In previous work, the combination of a low dose of the cholinergic agonist, carbachol with forskolin or a β adrenergic agonist, isoproterenol synergistically increased mucociliary clearance velocity (MCCV) in ferret tracheas. Importantly, the present study shows that synergistic MCCV can also be produced in CF ferrets, with increases ~ 55% of WT. Synergistic MCCV was also produced in pigs. The combined agonists increased MCCV by increasing surface fluid via multiple mechanisms: increased fluid secretion from submucosal glands, increased anion secretion across surface epithelia and decreased Na+absorption. To avoid bronchoconstriction, the cAMP agonist was applied 30 min before carbachol. This approach to increasing mucus clearance warrants testing for safety and efficacy in humans as a potential therapeutic for muco-obstructive diseases.
Sustainable intensification of maize and wheat cropping system through pulse intercropping
Authors: Tripathi S. C. , Venkatesh Karnam , Meena Raj Pal , Chander Subhash , Singh G. P.
Published: September 2021

The intercropping of legumes with cereals help to achieve sustainable intensification by their mutual complementarity at efficiently using radiation, nutrients, etc. Several studies indicated such beneficial effects on the other component crop however, little research has been conducted to quantify their effects on the subsequent crop in a cropping system. In this study, the effect of the legume intercropping on the entire cropping system, particularly the maize + legume-wheat system was studied. Four legumes intercropped to maize followed by wheat crop were studied for intensification measures such as wheat equivalent yield (WEY), land equivalent ratio (LER), sustainable value index (SVI), and economic returns. N saving effect of legumes on the subsequent wheat crop was quantified with two N levels. Maize + cowpea-wheat combination was the most productive and economic intercrop combination (LER = 1.71, SVI = 0.96) with an increase in net economic return (43.63%) with a B:C ratio of 1.94. An additional 25% N (37.5 kg ha−1) was saved in the wheat crop when the legume intercropping was undertaken with maize. The results suggest that intercropping is the key to diversification and reduces the risk of crop failures by enhancing land-use efficiency, soil fertility, and economic returns under weather vagaries. This will be beneficial to small and marginal farmers of many countries.
Relative density of United States forests has shifted to higher levels over last two decades with important implications for future dynamics
Authors: Woodall C. W. , Weiskittel A. R.
Published: September 2021

Tree size-density dynamics can inform key trends in forest productivity along with opportunities to increase ecosystem resiliency. Here, we employ a novel approach to estimate the relative density (RD, range 0–1) of any given forest based on its current size-density relationship compared to a hypothetical maximum using the coterminous US national forest inventory between 1999 and 2020. The analysis suggests a static forest land area in the US with less tree abundance but greatly increased timber volume and tree biomass. Coupled with these resource trends, an increase in RD was identified with 90% of US forest land now reaching a biologically-relevant threshold of canopy closure and/or self-thinning induced mortality (RD > 0.3), particularly in areas prone to future drought conditions (e.g., West Coast). Notably, the area of high RD stands (RD > 0.6) has quintupled over the past 20 years while the least stocked stands (RD < 0.3) have decreased 3%. The evidence from the coterminous US forest RD distribution suggest opportunities to increase live tree stocking in understocked stands, while using density management to address tree mortality and resilience to disturbances in increasingly dense forests.
Computing molecular excited states on a D-Wave quantum annealer
Authors: Teplukhin Alexander , Kendrick Brian K. , Mniszewski Susan M. , Zhang Yu , Kumar Ashutosh , Negre Christian F. A. , Anisimov Petr M. , Tretiak Sergei , Dub Pavel A.
Published: September 2021

The possibility of using quantum computers for electronic structure calculations has opened up a promising avenue for computational chemistry. Towards this direction, numerous algorithmic advances have been made in the last five years. The potential of quantum annealers, which are the prototypes of adiabatic quantum computers, is yet to be fully explored. In this work, we demonstrate the use of a D-Wave quantum annealer for the calculation of excited electronic states of molecular systems. These simulations play an important role in a number of areas, such as photovoltaics, semiconductor technology and nanoscience. The excited states are treated using two methods, time-dependent Hartree–Fock (TDHF) and time-dependent density-functional theory (TDDFT), both within a commonly used Tamm–Dancoff approximation (TDA). The resulting TDA eigenvalue equations are solved on a D-Wave quantum annealer using the Quantum Annealer Eigensolver (QAE), developed previously. The method is shown to reproduce a typical basis set convergence on the example $$\hbox {H}_2$$

H
2

molecule and is also applied to several other molecular species. Characteristic properties such as transition dipole moments and oscillator strengths are computed as well. Three potential energy profiles for excited states are computed for $$\hbox {NH}_3$$

NH
3

as a function of the molecular geometry. Similar to previous studies, the accuracy of the method is dependent on the accuracy of the intermediate meta-heuristic software called qbsolv.
Management of the “building-base system” action, using a life cycle model
Authors: Sobczak-Piąstka Justyna , Kichaeva Oksana , Firsov Pavlo , Zolotov Sergey , Famulyak Yuriy
Published: September 2021

This research aims to highlight the problem of creating various models that reflect the life cycle of the “building-base” system, and link the reliability of this system with its technical condition. Based on the proposed model of the life cycle “reconstructed building-base”, it is possible to regulate the condition of the building towards its restoration, changing the category of technical condition to higher and obtain new, adequate to the current state, reliability indicators. During the operation of this model, it is possible to control the system management on the basis of the obtained quantitative values of reliability. The result of the reliability calculation is the determination of such a technical solution of strengthening the “building-base” system, which will provide a given level of reliability. The research provides an example of the calculation of an operable monumental building before and after its restoration.
Evaluation of fish feeder manufactured from local raw materials
Authors: Khater El-Sayed , Bahnasawy Adel , Morsy Osama
Published: September 2021

An automatic feeder for fish feeding was manufactured and evaluated successively. Feed pellet size, air flow rate and feeder screw speed were the most important factors affecting the performance and efficiency of the automatic feeder. It was tested at 3 sizes of pellets (1, 2 and 3 mm), 3 air flow rates (10, 15 and 20 m3 min−1) and 5 screw speeds (180, 360, 540, 720 and 900 rpm). The automatic feeder productivity, efficiency, specific energy consumption and costs were determined. The obtained results indicated that the automatic feeder productivity increases with increasing feed pellets size, air flow rate and rotational speed of screw treatments under study, the automatic feeder efficiency increased with increasing rotational speed of screw until it reached the highest value at 540 rpm and then remain constant at 720–900 rpm and after that decreased with increasing speed. Meanwhile, the specific energy consumption of automatic feeder decreased with increasing feed pellets size, air flow rate and rotational speed of screw treatments under study. The total cost of using automatic feeder ranged from 0.09 to 0.16 EGP kg−1 ($ = 15.63 EGP) for all treatments under study. This feeder will save time, effort and cost for fish industry.
Empirical assessment of seismic design hazard’s exceedance area
Authors: Iervolino Iunio , Vitale Antonio , Cito Pasquale
Published: September 2021

Design ground motion intensities determine the actions for which structures are checked, in the conventional approach of seismic codes, not to fail the target performances. On the other hand, due to inherent characteristics of probabilistic seismic hazard analysis (PSHA), it is expected that site-specific design intensity based on PSHA is exceeded in the epicentral area of moderate-to-high magnitude earthquakes. In the context of regional seismic loss assessment and of the evolution of seismic codes from the regulator perspective, it is useful to gather insights about the extent of the zone around the earthquake source where code-conforming structures are expected to be systematically exposed to seismic actions larger than those accounted for in design. To assess such areal extent based on empirical evidence is the scope of the study presented in the paper. To this aim, peak ground acceleration ShakeMap data for Italian earthquakes from 2008 to 2020 were compared to the current design intensities in the same areas for which the maps are available. This allowed, first, to develop simple semi-empirical models of the exceedance area versus the magnitude of the earthquakes. Second, it allowed to model the probability that an earthquake of given magnitude causes exceedance of the design intensity via logistic regressions. Coupling the first and second class of models provides an approximation of the expected exceedance (logarithmic) area upon occurrence of an earthquake of given magnitude. Such an area can be of several thousand square kilometers for earthquakes occurring relatively frequently in countries such as Italy.
Structure and stability of the designer protein WRAP-T and its permutants
Authors: Mylemans Bram , Lee Xiao Yin , Laier Ina , Helsen Christine , Voet Arnout R. D.
Published: September 2021

$$\beta $$
β
-Propeller proteins are common natural disc-like pseudo-symmetric proteins that contain multiple repeats (‘blades’) each consisting of a 4-stranded anti-parallel $$\beta $$
β
-sheet. So far, 4- to 12-bladed $$\beta $$
β
-propellers have been discovered in nature showing large functional and sequential variation. Using computational design approaches, we created perfectly symmetric $$\beta $$
β
-propellers out of natural pseudo-symmetric templates. These proteins are useful tools to study protein evolution of this very diverse fold. While the 7-bladed architecture is the most common, no symmetric 7-bladed monomer has been created and characterized so far. Here we describe such a engineered protein, based on a highly symmetric natural template, and test the effects of circular permutation on its stability. Geometrical analysis of this protein and other artificial symmetrical proteins reveals no systematic constraint that could be used to help in engineering of this fold, and suggests sequence constraints unique to each $$\beta $$
β
-propeller sub-family.
Pan-cancer proteogenomic investigations identify post-transcriptional kinase targets
Authors: Elmas Abdulkadir , Tharakan Serena , Jaladanki Suraj , Galsky Matthew D. , Liu Tao , Huang Kuan-lin
Published: September 2021

Identifying genomic alterations of cancer proteins has guided the development of targeted therapies, but proteomic analyses are required to validate and reveal new treatment opportunities. Herein, we develop a new algorithm, OPPTI, to discover overexpressed kinase proteins across 10 cancer types using global mass spectrometry proteomics data of 1,071 cases. OPPTI outperforms existing methods by leveraging multiple co-expressed markers to identify targets overexpressed in a subset of tumors. OPPTI-identified overexpression of ERBB2 and EGFR proteins correlates with genomic amplifications, while CDK4/6, PDK1, and MET protein overexpression frequently occur without corresponding DNA- and RNA-level alterations. Analyzing CRISPR screen data, we confirm expression-driven dependencies of multiple currently-druggable and new target kinases whose expressions are validated by immunochemistry. Identified kinases are further associated with up-regulated phosphorylation levels of corresponding signaling pathways. Collectively, our results reveal protein-level aberrations—sometimes not observed by genomics—represent cancer vulnerabilities that may be targeted in precision oncology.
Chemical shielding of H2O and HF encapsulated inside a C60 cage
Authors: Jarvis Samuel P. , Sang Hongqian , Junqueira Filipe , Gordon Oliver , Hodgkinson Jo E. A. , Saywell Alex , Rahe Philipp , Mamone Salvatore , Taylor Simon , Sweetman Adam , Leaf Jeremy , Duncan David A. , Lee Tien-Lin , Thakur Pardeep K. , Hoffman Gabriella , Whitby Richard J. , Levitt Malcolm H. , Held Georg , Kantorovich Lev , Moriarty Philip , Jones Robert G.
Published: September 2021

Molecular surgery provides the opportunity to study relatively large molecules encapsulated within a fullerene cage. Here we determine the location of an H2O molecule isolated within an adsorbed buckminsterfullerene cage, and compare this to the intrafullerene position of HF. Using normal incidence X-ray standing wave (NIXSW) analysis, coupled with density functional theory and molecular dynamics simulations, we show that both H2O and HF are located at an off-centre position within the fullerene cage, caused by substantial intra-cage electrostatic fields generated by surface adsorption of the fullerene. The atomistic and electronic structure simulations also reveal significant internal rotational motion consistent with the NIXSW data. Despite this substantial intra-cage interaction, we find that neither HF or H2O contribute to the endofullerene frontier orbitals, confirming the chemical isolation of the encapsulated molecules. We also show that our experimental NIXSW measurements and theoretical data are best described by a mixed adsorption site model.
Application of new N- and S-doped amorphous carbon in D-μSPE and its combination with deep eutectic solvent-based DLLME for the extraction of some mycotoxins from soymilk
Authors: Rezaeefar Anahid , Farajzadeh Mir Ali , Nemati Mahboob , Afshar Mogaddam Mohammad Reza , Lotfipour Farzaneh
Published: September 2021

A new amorphous carbon-based dispersive micro solid-phase extraction method was developed for the extraction and preconcentration of several mycotoxins from soymilk samples.