bluuebunny/crossref_metadata_2025 huggingface dataset:
Lysosomal SLC46A3 modulates hepatic cytosolic copper homeostasis
Authors: Kim Jung-Hwan , Matsubara Tsutomu , Lee Jaekwon , Fenollar-Ferrer Cristina , Han Kyungreem , Kim Donghwan , Jia Shang , Chang Christopher J. , Yang Heejung , Nagano Tomokazu , Krausz Kristopher W. , Yim Sun-Hee , Gonzalez Frank J.
Published: January 2021

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic toxicity associated with prominent lipid accumulation in humans. Here, the authors report that the lysosomal copper transporter SLC46A3 is induced by TCDD and underlies the hepatic lipid accumulation in mice, potentially via effects on mitochondrial function. SLC46A3 was localized to the lysosome where it modulated intracellular copper levels. Forced expression of hepatic SLC46A3 resulted in decreased mitochondrial membrane potential and abnormal mitochondria morphology consistent with lower copper levels. SLC46A3 expression increased hepatic lipid accumulation similar to the known effects of TCDD exposure in mice and humans. The TCDD-induced hepatic triglyceride accumulation was significantly decreased in Slc46a3−/− mice and was more pronounced when these mice were fed a high-fat diet, as compared to wild-type mice. These data are consistent with a model where lysosomal SLC46A3 induction by TCDD leads to cytosolic copper deficiency resulting in mitochondrial dysfunction leading to lower lipid catabolism, thus linking copper status to mitochondrial function, lipid metabolism and TCDD-induced liver toxicity.
Orthogonal control of mean and variability of endogenous genes in a human cell line
Authors: Bonny Alain R. , Fonseca João Pedro , Park Jesslyn E. , El-Samad Hana
Published: January 2021

Stochastic fluctuations at the transcriptional level contribute to isogenic cell-to-cell heterogeneity in mammalian cell populations. However, we still have no clear understanding of the repercussions of this heterogeneity, given the lack of tools to independently control mean expression and variability of a gene. Here, we engineer a synthetic circuit to modulate mean expression and heterogeneity of transgenes and endogenous human genes. The circuit, a Tunable Noise Rheostat (TuNR), consists of a transcriptional cascade of two inducible transcriptional activators, where the output mean and variance can be modulated by two orthogonal small molecule inputs. In this fashion, different combinations of the inputs can achieve the same mean but with different population variability. With TuNR, we achieve low basal expression, over 1000-fold expression of a transgene product, and up to 7-fold induction of the endogenous gene NGFR. Importantly, for the same mean expression level, we are able to establish varying degrees of heterogeneity in expression within an isogenic population, thereby decoupling gene expression noise from its mean. TuNR is therefore a modular tool that can be used in mammalian cells to enable direct interrogation of the implications of cell-to-cell variability.
Structural basis of malaria parasite phenylalanine tRNA-synthetase inhibition by bicyclic azetidines
Authors: Sharma Manmohan , Malhotra Nipun , Yogavel Manickam , Harlos Karl , Melillo Bruno , Comer Eamon , Gonse Arthur , Parvez Suhel , Mitasev Branko , Fang Francis G. , Schreiber Stuart L. , Sharma Amit
Published: January 2021

The inhibition of Plasmodium cytosolic phenylalanine tRNA-synthetase (cFRS) by a novel series of bicyclic azetidines has shown the potential to prevent malaria transmission, provide prophylaxis, and offer single-dose cure in animal models of malaria. To date, however, the molecular basis of Plasmodium cFRS inhibition by bicyclic azetidines has remained unknown. Here, we present structural and biochemical evidence that bicyclic azetidines are competitive inhibitors of L-Phe, one of three substrates required for the cFRS-catalyzed aminoacylation reaction that underpins protein synthesis in the parasite. Critically, our co-crystal structure of a PvcFRS-BRD1389 complex shows that the bicyclic azetidine ligand binds to two distinct sub-sites within the PvcFRS catalytic site. The ligand occupies the L-Phe site along with an auxiliary cavity and traverses past the ATP binding site. Given that BRD1389 recognition residues are conserved amongst apicomplexan FRSs, this work lays a structural framework for the development of drugs against both Plasmodium and related apicomplexans.
Structures and reactivity of peroxy radicals and dimeric products revealed by online tandem mass spectrometry
Authors: Tomaz Sophie , Wang Dongyu , Zabalegui Nicolás , Li Dandan , Lamkaddam Houssni , Bachmeier Franziska , Vogel Alexander , Monge María Eugenia , Perrier Sébastien , Baltensperger Urs , George Christian , Rissanen Matti , Ehn Mikael , El Haddad Imad , Riva Matthieu
Published: January 2021

Organic peroxy radicals (RO2) play a pivotal role in the degradation of hydrocarbons. The autoxidation of atmospheric RO2 radicals produces highly oxygenated organic molecules (HOMs), including low-volatility ROOR dimers formed by bimolecular RO2 + RO2 reactions. HOMs can initiate and greatly contribute to the formation and growth of atmospheric particles. As a result, HOMs have far-reaching health and climate implications. Nevertheless, the structures and formation mechanism of RO2 radicals and HOMs remain elusive. Here, we present the in-situ characterization of RO2 and dimer structure in the gas-phase, using online tandem mass spectrometry analyses. In this study, we constrain the structures and formation pathway of several HOM-RO2 radicals and dimers produced from monoterpene ozonolysis, a prominent atmospheric oxidation process. In addition to providing insights into atmospheric HOM chemistry, this study debuts online tandem MS analyses as a unique approach for the chemical characterization of reactive compounds, e.g., organic radicals.
Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells
Authors: Muñoz-Rojas Andrés R. , Kelsey Ilana , Pappalardo Jenna L. , Chen Meibin , Miller-Jensen Kathryn
Published: January 2021

Macrophages are innate immune cells that contribute to fighting infections, tissue repair, and maintaining tissue homeostasis. To enable such functional diversity, macrophages resolve potentially conflicting cues in the microenvironment via mechanisms that are unclear. Here, we use single-cell RNA sequencing to explore how individual macrophages respond when co-stimulated with inflammatory stimuli LPS and IFN-γ and the resolving cytokine IL-4. These co-stimulated macrophages display a distinct global transcriptional program. However, variable negative cross-regulation between some LPS + IFN-γ-specific and IL-4-specific genes results in cell-to-cell heterogeneity in transcription. Interestingly, negative cross-regulation leads to mutually exclusive expression of the T-cell-polarizing cytokine genes Il6 and Il12b versus the IL-4-associated factors Arg1 and Chil3 in single co-stimulated macrophages, and single-cell secretion measurements show that these specialized functions are maintained for at least 48 h. This study suggests that increasing functional diversity in the population is one strategy macrophages use to respond to conflicting environmental cues.
Mechanism of SARS-CoV-2 polymerase stalling by remdesivir
Authors: Kokic Goran , Hillen Hauke S. , Tegunov Dimitry , Dienemann Christian , Seitz Florian , Schmitzova Jana , Farnung Lucas , Siewert Aaron , Höbartner Claudia , Cramer Patrick
Published: January 2021

Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryo-electron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling. We show that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3ʹ-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp. In the structure of the remdesivir-stalled state, the 3ʹ-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3ʹ-exonuclease. These mechanistic insights should facilitate the quest for improved antivirals that target coronavirus replication.
Reducing the impact of Auger recombination in quasi-2D perovskite light-emitting diodes
Authors: Jiang Yuanzhi , Cui Minghuan , Li Saisai , Sun Changjiu , Huang Yanmin , Wei Junli , Zhang Li , Lv Mei , Qin Chaochao , Liu Yufang , Yuan Mingjian
Published: January 2021

Rapid Auger recombination represents an important challenge faced by quasi-2D perovskites, which induces resulting perovskite light-emitting diodes’ (PeLEDs) efficiency roll-off. In principle, Auger recombination rate is proportional to materials’ exciton binding energy (Eb). Thus, Auger recombination can be suppressed by reducing the corresponding materials’ Eb. Here, a polar molecule, p-fluorophenethylammonium, is employed to generate quasi-2D perovskites with reduced Eb. Recombination kinetics reveal the Auger recombination rate does decrease to one-order-of magnitude lower compared to its PEA+ analogues. After effective passivation, nonradiative recombination is greatly suppressed, which enables resulting films to exhibit outstanding photoluminescence quantum yields in a broad range of excitation density. We herein demonstrate the very efficient PeLEDs with a peak external quantum efficiency of 20.36%. More importantly, devices exhibit a record luminance of 82,480 cd m−2 due to the suppressed efficiency roll-off, which represent one of the brightest visible PeLEDs yet.
Deep muscle-proteomic analysis of freeze-dried human muscle biopsies reveals fiber type-specific adaptations to exercise training
Authors: Deshmukh A. S. , Steenberg D. E. , Hostrup M. , Birk J. B. , Larsen J. K. , Santos A. , Kjøbsted R. , Hingst J. R. , Schéele C. C. , Murgia M. , Kiens B. , Richter E. A. , Mann M. , Wojtaszewski J. F. P.
Published: January 2021

Skeletal muscle conveys several of the health-promoting effects of exercise; yet the underlying mechanisms are not fully elucidated. Studying skeletal muscle is challenging due to its different fiber types and the presence of non-muscle cells. This can be circumvented by isolation of single muscle fibers. Here, we develop a workflow enabling proteomics analysis of pools of isolated muscle fibers from freeze-dried human muscle biopsies. We identify more than 4000 proteins in slow- and fast-twitch muscle fibers. Exercise training alters expression of 237 and 172 proteins in slow- and fast-twitch muscle fibers, respectively. Interestingly, expression levels of secreted proteins and proteins involved in transcription, mitochondrial metabolism, Ca2+ signaling, and fat and glucose metabolism adapts to training in a fiber type-specific manner. Our data provide a resource to elucidate molecular mechanisms underlying muscle function and health, and our workflow allows fiber type-specific proteomic analyses of snap-frozen non-embedded human muscle biopsies.
A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia
Authors: Flahault Adrien , Girault-Sotias Pierre-Emmanuel , Keck Mathilde , Alvear-Perez Rodrigo , De Mota Nadia , Estéoulle Lucie , Ramanoudjame Sridévi M. , Iturrioz Xavier , Bonnet Dominique , Llorens-Cortes Catherine
Published: January 2021

Apelin and arginine-vasopressin (AVP) are conversely regulated by osmotic stimuli. We therefore hypothesized that activating the apelin receptor (apelin-R) with LIT01-196, a metabolically stable apelin-17 analog, may be beneficial for treating the Syndrome of Inappropriate Antidiuresis, in which AVP hypersecretion leads to hyponatremia. We show that LIT01-196, which behaves as a potent full agonist for the apelin-R, has an in vivo half-life of 156 minutes in the bloodstream after subcutaneous administration in control rats. In collecting ducts, LIT01-196 decreases dDAVP-induced cAMP production and apical cell surface expression of phosphorylated aquaporin 2 via AVP type 2 receptors, leading to an increase in aqueous diuresis. In a rat experimental model of AVP-induced hyponatremia, LIT01-196 subcutaneously administered blocks the antidiuretic effect of AVP and the AVP-induced increase in urinary osmolality and induces a progressive improvement of hyponatremia. Our data suggest that apelin-R activation constitutes an original approach for hyponatremia treatment.
Single-layered organic photovoltaics with double cascading charge transport pathways: 18% efficiencies
Authors: Zhang Ming , Zhu Lei , Zhou Guanqing , Hao Tianyu , Qiu Chaoqun , Zhao Zhe , Hu Qin , Larson Bryon W. , Zhu Haiming , Ma Zaifei , Tang Zheng , Feng Wei , Zhang Yongming , Russell Thomas P. , Liu Feng
Published: January 2021

The chemical structure of donors and acceptors limit the power conversion efficiencies achievable with active layers of binary donor-acceptor mixtures. Here, using quaternary blends, double cascading energy level alignment in bulk heterojunction organic photovoltaic active layers are realized, enabling efficient carrier splitting and transport. Numerous avenues to optimize light absorption, carrier transport, and charge-transfer state energy levels are opened by the chemical constitution of the components. Record-breaking PCEs of 18.07% are achieved where, by electronic structure and morphology optimization, simultaneous improvements of the open-circuit voltage, short-circuit current and fill factor occur. The donor and acceptor chemical structures afford control over electronic structure and charge-transfer state energy levels, enabling manipulation of hole-transfer rates, carrier transport, and non-radiative recombination losses.
Integrating single-cobalt-site and electric field of boron nitride in dechlorination electrocatalysts by bioinspired design
Authors: Min Yuan , Zhou Xiao , Chen Jie-Jie , Chen Wenxing , Zhou Fangyao , Wang Zhiyuan , Yang Jia , Xiong Can , Wang Ying , Li Fengting , Yu Han-Qing , Wu Yuen
Published: January 2021

The construction of enzyme-inspired artificial catalysts with enzyme-like active sites and microenvironment remains a great challenge. Herein, we report a single-atomic-site Co catalyst supported by carbon doped boron nitride (BCN) with locally polarized B–N bonds (Co SAs/BCN) to simulate the reductive dehalogenases. Density functional theory analysis suggests that the BCN supports, featured with ionic characteristics, provide additional electric field effect compared with graphitic carbon or N-doped carbon (CN), which could facilitate the adsorption of polarized organochlorides. Consistent with the theoretical results, the Co SAs/BCN catalyst delivers a high activity with nearly complete dechlorination (~98%) at a potential of −0.9 V versus Ag/AgCl for chloramphenicol (CAP), showing that the rate constant (k) contributed by unit mass of metal (k/ratio) is 4 and 19 times more active than those of the Co SAs/CN and state-of-the-art Pd/C catalyst, respectively. We show that Co single atoms coupled with BCN host exhibit high stability and selectivity in CAP dechlorination and suppress the competing hydrogen evolution reaction, endowing the Co SAs/BCN as a candidate for sustainable conversion of organic chloride.
Charge-polarized interfacial superlattices in marginally twisted hexagonal boron nitride
Authors: Woods C. R. , Ares P. , Nevison-Andrews H. , Holwill M. J. , Fabregas R. , Guinea F. , Geim A. K. , Novoselov K. S. , Walet N. R. , Fumagalli L.
Published: January 2021

When two-dimensional crystals are brought into close proximity, their interaction results in reconstruction of electronic spectrum and crystal structure. Such reconstruction strongly depends on the twist angle between the crystals, which has received growing attention due to interesting electronic and optical properties that arise in graphene and transitional metal dichalcogenides. Here we study two insulating crystals of hexagonal boron nitride stacked at small twist angle. Using electrostatic force microscopy, we observe ferroelectric-like domains arranged in triangular superlattices with a large surface potential. The observation is attributed to interfacial elastic deformations that result in out-of-plane dipoles formed by pairs of boron and nitrogen atoms belonging to opposite interfacial surfaces. This creates a bilayer-thick ferroelectric with oppositely polarized (BN and NB) dipoles in neighbouring domains, in agreement with our modeling. These findings open up possibilities for designing van der Waals heterostructures and offer an alternative probe to study moiré-superlattice electrostatic potentials.
Isolation, characterization and prevention of various microbial strains in NIC unit and PIC unit
Authors: Mir M. Amin , Ashraf Muhammad Waqar , Tripathi Vibha , Mir Bilal Ahmad
Published: January 2021

The health of the hospital associated persons, particularly those dealing directly with insertion of devices, are serious cause of concern for hospitals. In this study, the most prevalent organism on the surface of medical devices in PICU wereCoNS(16.66%) andStaphylococcus aureus(16.66%), while in NICU the most prevalent organism wasKlebsiellaspp. (11.25%) amongEntero-bacteriaceaegroup followed byAcinetobacter baumannii(10%),Escherichia coli(2.5%),CoNS(6.25%),S. aureus(6.25%) andEnterococcus faecalis(6.25%). The most common species identified from blood specimen of clinical samples shows the maximum presence ofCandidasp. (60/135) followed byA. baumannii(21/135),Klebsiella Pneumoniae(20/135),Enterococci(12/135), Burkholderiacepacia complex(8/135),S. aureus(6/135),E. coli(5/135),Pseudomonas aeruginosa(3/135). Different antibiotics have been used against these micro-organisms; but Cotrimoxazole, Vancomycin have been found more effective againstCoNS bacteria, Clindamycin, Tetracycline forS. aureus, Nitofurantoin for Acinetobacter, and forE. faecalis,A. baumanii, andKlebsiella, erythromycin, Colistin, and Ceftriaxone have been found more effective respectively.
A retrospective cross-sectional study for predicting 72-h mortality in patients with serum aspartate aminotransferase levels ≥ 3000 U/L
Authors: Saito Kai , Sugawara Hitoshi , Watanabe Tamami , Ishii Akira , Fukuchi Takahiko
Published: January 2021

Risk factors associated with 72-h mortality in patients with extremely high serum aspartate aminotransferase levels (AST; ≥ 3000 U/L) are unknown. This single-centre, retrospective, case-controlled, cross-sectional study obtained data from medical records of adult patients treated at Saitama Medical Center, Japan, from 2005 to 2019. We conducted a multivariate logistic after adjusting for age, sex, height, weight, body mass index, Brinkman Index, vital signs, biochemical values, updated Charlson Comorbidity Index (CCI) score, CCI components, and underlying causes. A logistic regression model with selected validity risks and higher C-statistic for predicting 72-h mortality was established. During the 15-year period, 428 patients (133 non-survivors and 295 survivors [cases and controls by survival < 72 and ≥ 72 h, respectively]) with AST levels ≥ 3000 U/L were identified. The 72-h mortality rate was 133/428 (31.1%). The model used for predicting 72-h mortality through the assessment of alkaline phosphatase, creatine kinase, serum sodium, potassium, and phosphorus levels had a C-statistic value of 0.852 (sensitivity and specificity, 76.6%). The main independent risk factors associated with 72-h mortality among patients with AST levels ≥ 3000 U/L included higher serum values of alkaline phosphatase, creatine kinase, serum sodium, potassium, and phosphorus.
Dynamical magnetic behavior of anisotropic spinel-structured ferrite for GHz technologies
Authors: Yasukawa Yukiko , Nozawa Kouhei , Tiittanen Taneli , Karppinen Maarit , Lindén Johan , Shirsath Sagar E. , Yabukami Shin
Published: January 2021

We have fabricated a high quality magnetic Ni0.5Zn0.5Fe2O4 ferrite powder/polymer composite sheet consisting of common and environmentally friendly elements only. The sheet was then tested for its dynamic permeability by irradiating with electromagnetic waves with frequencies up to 50 GHz. Two different originally developed methods were used for the high-frequency permeability measurements, a short-circuited microstrip line method and a microstrip line-probe method. It is challenging to measure the dynamic permeability of magnetic thin films/sheets beyond 10 GHz because of the low response signal from these materials. However, the two methods produced essentially equivalent results. In the frequency dependent permeability profile, the maximum position of the profile, $$\mu ^{\prime \prime }_{max}$$

μ

max

″

, shifted towards higher frequencies upon increasing an applied (strong) static external magnetic field, $$H_{dc}$$

H

dc

. A linear relationship between $$\mu^ {\prime \prime }_{max}$$

μ

max

″

and $$H_{dc}$$

H

dc

for the entire range of $$H_{dc}$$

H

dc

was observed even at small $$H_{dc}$$

H

dc

. In general, the spinel-structured Ni-based ferrites exhibit low magnetic anisotropy, but the present sample showed a uniaxial-anisotropic behavior in the parallel direction of the sheet. Our Ni0.5Zn0.5Fe2O4 powder/polymer composite sheet thus exhibits high performance at GHz frequencies, and should be applicable e.g. as an anisotropic electromagnetic wave-interference material.
Autophagy is deregulated in cancer-associated fibroblasts from oral cancer and is stimulated during the induction of fibroblast senescence by TGF-β1
Authors: Tan May Leng , Parkinson E. Kenneth , Yap Lee Fah , Paterson Ian C.
Published: January 2021

Many of the characteristics ascribed to cancer-associated fibroblasts (CAFs) are shared by activated, autophagic and senescent fibroblasts. Whilst most oral squamous cell carcinomas (OSCCs) are genetically unstable (GU-OSCC), genetically stable variants (GS-OSCC) have been described and, notably, CAF activation (myofibroblast differentiation) and senescence are characteristics particularly associated with GU-OSCCs. However, it is not known whether autophagy is disrupted in these cells or whether autophagy regulates the development of the myofibroblast and senescent phenotypes. In this study, we show that senescent CAFs from GU-OSCCs contained more autophagosomes than normal human oral fibroblasts (NHOFs) and CAFs from GS-OSCCs possibly due to autophagic impairment. Further, we show that deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-β1, induced fibroblast activation and senescence: In response to TGF-β1, autophagy was induced prior to the development of the activated and senescent phenotypes. Lastly, we show that both SAR405- and TGF-β1-treated NHOFs enhance OSCC cell migration but only TGF-β1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-β1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.
Couette flow of viscoelastic dusty fluid in a rotating frame along with the heat transfer
Authors: Bilal Muhammad , Khan Salaha , Ali Farhad , Arif Muhammad , Khan Ilyas , Nisar Kottakkaran Sooppy
Published: January 2021

Viscoelastic fluid is an advanced fluid which exhibits both elastic and viscous properties. Whereas rotation of viscoelastic fluid is a very complex phenomenon and has an immense amount of applications in engineering and product making industries. Due to various applications in real life researchers are working to understand the rheology of viscoelastic fluids. Viscoelastic dusty fluids are used in gas cooling systems. In nuclear reactors, dusty fluids are used to lower the temperature of the system. Such fluids are also used in centrifugal separators, which separate solid particles from the liquid state, etc. Therefore, in the present study, viscoelastic dusty fluid is analyzed. More precisely free convective Couette flow under the influence of the transversely applied uniform magnetic field in a rotating frame is considered. The subject fluid is driven by the sine oscillations of the upper plate along with the effect of free convection. Due to rotation, the fluid and dust particles have complex velocities which is the sum of primary velocity and secondary velocity. The flow regime is modeled in terms of partial differential equations. To non-dimensionalize the system of governing equations, dimensionless variables have been derived through Buckingham-Pi theorem. The system of partial differential equations is solved through assumed periodic solutions (Poincare-Light Hill Technique). The expressions for skin friction (shear stresses at $$y = 0$$

y
=
0

) and Nusselt number (the rate of heat transfer) are also calculated. Moreover, parametric influence on Nusselt number, and velocity profile of the fluid and the dust particles, is discussed. It is observed that increase in rotation parameter η causes retardation in the velocity of dust particles and the fluid. This is due to the fact that the increase in η enhances the Coriolis forces that are in fact inertial forces, causing a retardation in the velocity of the fluid phase and the dust phase.
Electron-ion coincidence measurements of molecular dynamics with intense X-ray pulses
Authors: Li Xiang , Inhester Ludger , Osipov Timur , Boll Rebecca , Coffee Ryan , Cryan James , Gatton Ave , Gorkhover Tais , Hartman Gregor , Ilchen Markus , Knie André , Lin Ming-Fu , Minitti Michael P. , Weninger Clemens , Wolf Thomas J. A. , Son Sang-Kil , Santra Robin , Rolles Daniel , Rudenko Artem , Walter Peter
Published: January 2021

Molecules can sequentially absorb multiple photons when irradiated by an intense X-ray pulse from a free-electron laser. If the time delay between two photoabsorption events can be determined, this enables pump-probe experiments with a single X-ray pulse, where the absorption of the first photon induces electronic and nuclear dynamics that are probed by the absorption of the second photon. Here we show a realization of such a single-pulse X-ray pump-probe scheme on N$$_2$$

2

molecules, using the X-ray induced dissociation process as an internal clock that is read out via coincident detection of photoelectrons and fragment ions. By coincidence analysis of the kinetic energies of the ionic fragments and photoelectrons, the transition from a bound molecular dication to two isolated atomic ions is observed through the energy shift of the inner-shell electrons. Via ab-initio simulations, we are able to map characteristic features in the kinetic energy release and photoelectron spectrum to specific delay times between photoabsorptions. In contrast to previous studies where nuclear motions were typically revealed by measuring ion kinetics, our work shows that inner-shell photoelectron energies can also be sensitive probes of nuclear dynamics, which adds one more dimension to the study of light-matter interactions with X-ray pulses.
Concentration-dependent oscillation of specific loss power in magnetic nanofluid hyperthermia
Authors: Kim Ji-wook , Wang Jie , Kim Hyungsub , Bae Seongtae
Published: January 2021

Magnetic dipole coupling between the colloidal superparamagnetic nanoparticles (SPNPs) depending on the concentration has been paid significant attention due to its critical role in characterizing the Specific Loss Power (SLP) in magnetic nanofluid hyperthermia (MNFH). However, despite immense efforts, the physical mechanism of concentration-dependent SLP change behavior is still poorly understood and some contradictory results have been recently reported. Here, we first report that the SLP of SPNP MNFH agent shows strong concentration-dependent oscillation behavior. According to the experimentally and theoretically analyzed results, the energy competition among the magnetic dipole interaction energy, magnetic potential energy, and exchange energy, was revealed as the main physical reason for the oscillation behavior. Empirically demonstrated new finding and physically established model on the concentration-dependent SLP oscillation behavior is expected to provide biomedically crucial information in determining the critical dose of an agent for clinically safe and highly efficient MNFH in cancer clinics.
FMRI-based identity classification accuracy in left temporal and frontal regions predicts speaker recognition performance
Authors: Aglieri Virginia , Cagna Bastien , Velly Lionel , Takerkart Sylvain , Belin Pascal
Published: January 2021

Speaker recognition is characterized by considerable inter-individual variability with poorly understood neural bases. This study was aimed at (1) clarifying the cerebral correlates of speaker recognition in humans, in particular the involvement of prefrontal areas, using multi voxel pattern analysis (MVPA) applied to fMRI data from a relatively large group of participants, and (2) at investigating the relationship across participants between fMRI-based classification and the group’s variable behavioural performance at the speaker recognition task. A cohort of subjects (N = 40, 28 females) selected to present a wide distribution of voice recognition abilities underwent an fMRI speaker identification task during which they were asked to recognize three previously learned speakers with finger button presses. The results showed that speaker identity could be significantly decoded based on fMRI patterns in voice-sensitive regions including bilateral temporal voice areas (TVAs) along the superior temporal sulcus/gyrus but also in bilateral parietal and left inferior frontal regions. Furthermore, fMRI-based classification accuracy showed a significant correlation with individual behavioural performance in left anterior STG/STS and left inferior frontal gyrus. These results highlight the role of both temporal and extra-temporal regions in performing a speaker identity recognition task with motor responses.
A model-based quantification of startle reflex habituation in larval zebrafish
Authors: Beppi Carolina , Straumann Dominik , Bögli Stefan Yu
Published: January 2021

Zebrafish is an established animal model for the reproduction and study of neurobiological pathogenesis of human neurological conditions. The ‘startle reflex’ in zebrafish larvae is an evolutionarily preserved defence response, manifesting as a quick body-bend in reaction to sudden sensory stimuli. Changes in startle reflex habituation characterise several neuropsychiatric disorders and hence represent an informative index of neurophysiological health. This study aimed at establishing a simple and reliable experimental protocol for the quantification of startle reflex response and habituation. The fish were stimulated with 20 repeated pulses of specific vibratory frequency, acoustic intensity/power, light-intensity and interstimulus-interval, in three separate studies. The cumulative distance travelled, namely the sum of the distance travelled (mm) during all 20 stimuli, was computed as a group-level description for all the experimental conditions in each study. Additionally, by the use of bootstrapping, the data was fitted to a model of habituation with a first-order exponential representing the decay of locomotor distance travelled over repeated stimulation. Our results suggest that startle habituation is a stereotypic first-order process with a decay constant ranging from 1 to 2 stimuli. Habituation memory lasts no more than 5 min, as manifested by the locomotor activity recovering to baseline levels. We further observed significant effects of vibratory frequency, acoustic intensity/power and interstimulus-interval on the amplitude, offset, decay constant and cumulative distance travelled. Instead, the intensity of the flashed light did not contribute to significant behavioural variations. The findings provide novel insights as to the influence of different stimuli parameters on the startle reflex habituation and constitute a helpful reference framework for further investigation.
Win-stay/lose-switch, prospecting-based settlement strategy may not be adaptive under rapid environmental change
Authors: Kloskowski Janusz
Published: January 2021

Understanding animal responses to environmental change is crucial for management of ecological traps. Between-year habitat selection was investigated in red‐necked grebes (Podiceps grisegena) breeding on semi-natural fish ponds, where differential stocking of fish created contrasting yet poorly predictable brood-stage food availabilities. Grebes lured to low-quality ponds were more likely to shift territories than birds nesting on high-quality ponds, and tended to move to ponds whose habitat quality had been high in the previous year, irrespective of the current quality of the new and old territories. The territory switchers typically visited their future breeding ponds during or immediately after the brood-rearing period. However, owing to rotation of fish stocks, the habitat quality of many ponds changed in the following year, and then switchers from low-quality ponds and stayers on previously high-quality ponds were ecologically trapped. Thus, although breeders were making an informed choice, their settlement decisions, based on the win–stay/lose–switch rule and prospecting a year in advance, were inappropriate in conditions of year-to-year habitat fluctuations. Effective adaptation to rapid environmental change may necessitate both learning to correctly evaluate uncertain environmental cues and abandonment of previously adaptive decision-making algorithms (here prioritizing past-year information and assuming temporal autocorrelation of habitat quality).
Estimating mouse and rat use in American laboratories by extrapolation from Animal Welfare Act-regulated species
Authors: Carbone Larry
Published: January 2021

Alone among Western nations, the United States has a two-tier system for welfare protections for vertebrate animals in research. Because its Animal Welfare Act (AWA) excludes laboratory rats and mice (RM), government veterinarians do not inspect RM laboratories and RM numbers are only partially reported to government agencies1. Without transparent statistics, it is impossible to track efforts to reduce or replace these sentient animals’ use or to project government resources needed if AWA coverage were expanded to include them. I obtained annual RM usage data from 16 large American institutions and compared RM numbers to institutions’ legally-required reports of their AWA-covered mammals. RM comprised approximately 99.3% of mammals at these representative institutions. Extrapolating from 780,070 AWA-covered mammals in 2017–18, I estimate that 111.5 million rats and mice were used per year in this period. If the same proportion of RM undergo painful procedures as are publicly reported for AWA-covered animals, then some 44.5 million mice and rats underwent potentially painful experiments. These data inform the questions of whether the AWA needs an update to cover RM, or whether the NIH should increase transparency of funded animal research. These figures can benchmark progress in reducing animal numbers in general and more specifically, in painful experiments. This estimate is higher than any others available, reflecting the challenges of obtaining statistics without consistent and transparent institutional reports.
The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals
Authors: Strawbridge Rona J. , Johnston Keira J. A. , Bailey Mark E. S. , Baldassarre Damiano , Cullen Breda , Eriksson Per , deFaire Ulf , Ferguson Amy , Gigante Bruna , Giral Philippe , Graham Nicholas , Hamsten Anders , Humphries Steve E. , Kurl Sudhir , Lyall Donald M. , Lyall Laura M. , Pell Jill P. , Pirro Matteo , Savonen Kai , Smit Andries J. , Tremoli Elena , Tomainen Tomi-Pekka , Veglia Fabrizio , Ward Joey , Sennblad Bengt , Smith Daniel J.
Published: January 2021

Understanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely to apply to more genetically diverse populations. Overall, this study provides proof of concept that common biology underlying mental and physical illness may help to stratify subsets of individuals with different cardiometabolic profiles.
Modelling adaptation strategies to reduce adverse impacts of climate change on maize cropping system in Northeast China
Authors: Jiang Rong , He Wentian , He Liang , Yang J. Y. , Qian B. , Zhou Wei , He Ping
Published: January 2021

Maize (Zea mays L.) production in Northeast China is vulnerable to climate change. Thus, exploring future adaptation measures for maize is crucial to developing sustainable agriculture to ensure food security. The current study was undertaken to evaluate the impacts of climate change on maize yield and partial factor productivity of nitrogen (PFPN) and explore potential adaptation strategies in Northeast China. The Decision Support System for Agrotechnology Transfer (DSSAT) model was calibrated and validated using the measurements from nine maize experiments. DSSAT performed well in simulating maize yield, biomass and N uptake for both calibration and validation periods (normalized root mean square error (nRMSE) < 10%, −5% < normalized average relative error (nARE) < 5% and index of agreement (d) > 0.8). Compared to the baseline (1980–2010), the average maize yields and PFPN would decrease by 7.6–32.1% and 3.6–14.0 kg N kg−1 respectively under future climate scenarios (2041–2070 and 2071–2100) without adaptation. Optimizing N application rate and timing, establishing rotation system with legumes, adjusting planting dates and breeding long-season cultivars could be effective adaptation strategies to climate change. This study demonstrated that optimizing agronomic crop management practices would assist to make policy development on mitigating the negative impacts of future climate change on maize production.
Double transition metal MXene (TixTa4−xC3) 2D materials as anodes for Li-ion batteries
Authors: Syamsai Ravuri , Rodriguez Jassiel R. , Pol Vilas G. , Van Le Quyet , Batoo Khalid Mujasam , Adil Syed Farooq , Pandiaraj Saravanan , Muthumareeswaran M. R. , Raslan Emad H. , Grace Andrews Nirmala
Published: January 2021

A bi-metallic titanium–tantalum carbide MXene, TixTa(4−x)C3 is successfully prepared via etching of Al atoms from parent TixTa(4−x)AlC3 MAX phase for the first time. X-ray diffractometer and Raman spectroscopic analysis proved the crystalline phase evolution from the MAX phase to the lamellar MXene arrangements. Also, the X-ray photoelectron spectroscopy (XPS) study confirmed that the synthesized MXene is free from Al after hydro fluoric acid (HF) etching process as well as partial oxidation of Ti and Ta. Moreover, the FE-SEM and TEM characterizations demonstrate the exfoliation process tailored by the TixTa(4−x)C3 MXene after the Al atoms from its corresponding MAX TixTa(4−x)AlC3 phase, promoting its structural delamination with an expanded interlayer d-spacing, which can allow an effective reversible Li-ion storage. The lamellar TixTa(4−x)C3 MXene demonstrated a reversible specific discharge capacity of 459 mAhg−1 at an applied C-rate of 0.5 °C with a capacity retention of 97% over 200 cycles. An excellent electrochemical redox performance is attributed to the formation of a stable, promising bi-metallic MXene material, which stores Li-ions on the surface of its layers. Furthermore, the TixTa(4−x)C3 MXene anode demonstrate a high rate capability as a result of its good electron and Li-ion transport, suggesting that it is a promising candidate as Li-ion anode material.
The effectiveness of Bacopa monnieri (Linn.) Wettst. as a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data
Authors: Brimson James M. , Brimson Sirikalaya , Prasanth Mani Iyer , Thitilertdecha Premrutai , Malar Dicson Sheeja , Tencomnao Tewin
Published: January 2021

Bacopamonnieri (Linn.) Wettst. has been used in traditional medicine as a drug to enhance and improve memory. In this regard, this study aims to provide B. monnieri's efficacy as a neuroprotective drug and as a nootropic against various neurological diseases. Literatures were collected, following Prisma guidelines, from databases, including Scopus, PubMed, Google Scholar, and Science Direct and were scrutinized using a quality scoring system. Means, standard deviations and ‘n’ numbers were extracted from the metrics and analyzed. Jamovi computer software for Mac was used to carry out the meta-analysis. The selected studies suggested that the plant extracts were able to show some improvements in healthy subjects which were determined in Auditory Verbal Learning Task, digit span-reverse test, inspection time task and working memory, even though it was not significant, as no two studies found statistically significant changes in the same two tests. B. monnieri was able to express modest improvements in subjects with memory loss, wherein only a few of the neuropsychological tests showed statistical significance. B. monnieri in a cocktail with other plant extracts were able to significantly reduce the effects of Alzheimer’s disease, and depression which cannot be solely credited as the effect of B. monnieri. Although in one study B. monnieri was able to potentiate the beneficial effects of citalopram; on the whole, currently, there are only limited studies to establish the memory-enhancing and neuroprotective effects of B. monnieri. More studies have to be done in the future by comparing the effect with standard drugs, in order to establish these effects clinically in the plant and corroborate the preclinical data.
Hybrid quantum-classical approach to enhanced quantum metrology
Authors: Yang Xiaodong , Chen Xi , Li Jun , Peng Xinhua , Laflamme Raymond
Published: January 2021

Quantum metrology plays a fundamental role in many scientific areas. However, the complexity of engineering entangled probes and the external noise raise technological barriers for realizing the expected precision of the to-be-estimated parameter with given resources. Here, we address this problem by introducing adjustable controls into the encoding process and then utilizing a hybrid quantum-classical approach to automatically optimize the controls online. Our scheme does not require any complex or intractable off-line design, and it can inherently correct certain unitary errors during the learning procedure. We also report the first experimental demonstration of this promising scheme for the task of finding optimal probes for frequency estimation on a nuclear magnetic resonance (NMR) processor. The proposed scheme paves the way to experimentally auto-search optimal protocol for improving the metrology precision.
Kinetics and thermodynamics evaluation of carbon dioxide enhanced oil shale pyrolysis
Authors: Zhao Shuai , Sun Youhong , Lü Xiaoshu , Li Qiang
Published: January 2021

The pyrolysis process of oil shale is significantly affected by atmospheric conditions. In this paper, the pyrolysis experiments of oil shale under non-isothermal conditions are carried out using nitrogen and carbon dioxide as heat-carrying fluids. The results show that the activation energy of the second stage of oil shale pyrolysis under carbon dioxide is less than that under nitrogen. The thermodynamic analysis of the second stage of oil shale pyrolysis shows that Gibbs free energy, activation enthalpy and activation entropy are higher under carbon dioxide than those under nitrogen, which obeys the law of carbon dioxide promoting oil shale pyrolysis. In addition, the volatile release characteristics of oil shale in the second stage of pyrolysis were analyzed, which proves that the volatile release characteristics of oil shale under carbon dioxide are higher than that under nitrogen. Therefore, carbon dioxide is helpful to promote the pyrolysis of oil shale and increases the release of volatile substances during pyrolysis.
Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis
Authors: Islam Md Imtiazul , Seo Hoonhee , Kim Sukyung , Sadu Venkata S. , Lee Kee-In , Song Ho-Yeon
Published: January 2021

The emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis creates the urgency for new anti-tuberculosis drugs to improve the efficiency of current tuberculosis treatment. In the search for a new potential tuberculosis drug, we synthesized an isoindole based chemical library and screened a potential candidate with significant anti-tuberculosis activity. The compound named 2-hydroxy-4-(4-nitro-1,3-dioxoisoindolin-2-yl) benzoic acid (IDD-B40) showed strong activity against all the tested drug-susceptible and drug-resistant strains of M. tuberculosis, with the 50% minimum inhibitory concentrations (MIC50) of 0.39 μg/ml both in culture broth and inside Raw 264.7 cells. Also, IDD-B40, in combination with rifampicin, exhibited a direct synergistic effect against both XDR and H37Rv M. tuberculosis. Besides, IDD-B40 showed a better post-antibiotic effect (PAE) than did some first-line drugs and showed no significant cytotoxicity to any cell line tested, with a selectivity index of ≥ 128. Although IDD-B40 showed a result similar to isoniazid in the preliminary mycolic acid inhibition assay, it did not exhibit any effect against other mycolic acid-producing nontuberculous mycobacterial strains (NTM), and different non-mycobacterial pathogenic strains, so further studies are required to confirm the mode of action of IDD-B40. Considering its results against M. tuberculosis, IDD-B40 is a potential anti-tuberculosis drug candidate. However, further studies are required to evaluate its potential in vivo effect and therapeutic potential.