bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomic and metatranscriptomic profiling of Lactobacillus casei Zhang in the human gut
Authors: Wang Jicheng , Zhang Jiachao , Liu Wenjun , Zhang Heping , Sun Zhihong
Published: July 2021

Little is known about the replication and dynamic transcription of probiotics during their “passenger” journey in the human GI tract, which has therefore limited the understanding of their probiotic mechanisms. Here, metagenomic and metatranscriptomic sequencing was used to expose the in vivo expression patterns of the probiotic Lactobacillus casei Zhang (LcZ), which was compared with its in vitro growth transcriptomes, as well as the dynamics of the indigenous microbiome response to probiotic consumption. Extraction of the strain-specific reads revealed that replication and transcripts from the ingested LcZ were increased, while those from the resident L. casei strains remained unchanged. Mapping of all sequencing reads to LcZ genome showed that gene expression in vitro and in vivo differed dramatically. Approximately 39% of mRNAs and 45% of sRNAs of LcZ well-expressed were repressed after ingestion into human gut. The expression of ABC transporter genes and amino acid metabolism genes was induced at day 14 of ingestion, and genes for sugar and SCFA metabolism were activated at day 28 of ingestion. Expression of rli28c sRNA with peaked expression during the in vitro stationary phase was also activated in the human gut; this sRNA repressed LcZ growth and lactic acid production in vitro. However, the response of the human gut microbiome to LcZ was limited and heterogeneous. These findings implicate the ingested probiotic has to change its transcription patterns to survive and adapt in the human gut, and the time-dependent activation patterns indicate highly dynamic cross-talk between the probiotic and human gut microbes.
A Bayesian approach to extracting free-energy profiles from cryo-electron microscopy experiments
Authors: Giraldo-Barreto Julian , Ortiz Sebastian , Thiede Erik H. , Palacio-Rodriguez Karen , Carpenter Bob , Barnett Alex H. , Cossio Pilar
Published: July 2021

Cryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature it has the potential to provide information about a biomolecule’s conformational variability and underlying free-energy landscape. However, treating cryo-EM as a single-molecule technique is challenging because of the low signal-to-noise ratio (SNR) in individual particles. In this work, we propose the cryo-BIFE method (cryo-EM Bayesian Inference of Free-Energy profiles), which uses a path collective variable to extract free-energy profiles and their uncertainties from cryo-EM images. We test the framework on several synthetic systems where the imaging parameters and conditions were controlled. We found that for realistic cryo-EM environments and relevant biomolecular systems, it is possible to recover the underlying free energy, with the pose accuracy and SNR as crucial determinants. We then use the method to study the conformational transitions of a calcium-activated channel with real cryo-EM particles. Interestingly, we recover not only the most probable conformation (used to generate a high-resolution reconstruction of the calcium-bound state) but also a metastable state that corresponds to the calcium-unbound conformation. As expected for turnover transitions within the same sample, the activation barriers are on the order of $$k_BT$$

k
B

T

. We expect our tool for extracting free-energy profiles from cryo-EM images to enable more complete characterization of the thermodynamic ensemble of biomolecules.
Surface model of the human red blood cell simulating changes in membrane curvature under strain
Authors: Kuchel Philip W. , Cox Charles D. , Daners Daniel , Shishmarev Dmitry , Galvosas Petrik
Published: July 2021

We present mathematical simulations of shapes of red blood cells (RBCs) and their cytoskeleton when they are subjected to linear strain. The cell surface is described by a previously reported quartic equation in three dimensional (3D) Cartesian space. Using recently available functions in Mathematica to triangularize the surfaces we computed four types of curvature of the membrane. We also mapped changes in mesh-triangle area and curvatures as the RBCs were distorted. The highly deformable red blood cell (erythrocyte; RBC) responds to mechanically imposed shape changes with enhanced glycolytic flux and cation transport. Such morphological changes are produced experimentally by suspending the cells in a gelatin gel, which is then elongated or compressed in a custom apparatus inside an NMR spectrometer. A key observation is the extent to which the maximum and minimum Principal Curvatures are localized symmetrically in patches at the poles or equators and distributed in rings around the main axis of the strained RBC. Changes on the nanometre to micro-meter scale of curvature, suggest activation of only a subset of the intrinsic mechanosensitive cation channels, Piezo1, during experiments carried out with controlled distortions, which persist for many hours. This finding is relevant to a proposal for non-uniform distribution of Piezo1 molecules around the RBC membrane. However, if the curvature that gates Piezo1 is at a very fine length scale, then membrane tension will determine local curvature; so, curvatures as computed here (in contrast to much finer surface irregularities) may not influence Piezo1 activity. Nevertheless, our analytical methods can be extended address these new mechanistic proposals. The geometrical reorganization of the simulated cytoskeleton informs ideas about the mechanism of concerted metabolic and cation-flux responses of the RBC to mechanically imposed shape changes.
Shear-induced chemical segregation in a Fe-based bulk metallic glass at room temperature
Authors: Louzguine-Luzgin D. V. , Trifonov A. S. , Ivanov Yu. P. , Lu A. K. A. , Lubenchenko A. V. , Greer A. L.
Published: July 2021

Shear-induced segregation, by particle size, is known in the flow of colloids and granular media, but is unexpected at the atomic level in the deformation of solid materials, especially at room temperature. In nanoscale wear tests of an Fe-based bulk metallic glass at room temperature, without significant surface heating, we find that intense shear localization under a scanned indenter tip can induce strong segregation of a dilute large-atom solute (Y) to planar regions that then crystallize as a Y-rich solid solution. There is stiffening of the material, and the underlying chemical and structural effects are characterized by transmission electron microscopy. The key influence of the soft Fe–Y interatomic interaction is investigated by ab-initio calculation. The driving force for the induced segregation, and its mechanisms, are considered by comparison with effects in other sheared media.
Ganoderma lucidum promotes sleep through a gut microbiota-dependent and serotonin-involved pathway in mice
Authors: Yao Chunyan , Wang Zhiyuan , Jiang Huiyong , Yan Ren , Huang Qianfei , Wang Yin , Xie Hui , Zou Ying , Yu Ying , Lv Longxian
Published: July 2021

Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative tranquilizing effects. However, the component of G. lucidum that promotes sleep has not been clearly identified. Here, the effect and mechanism of the acidic part of the alcohol extract of G. lucidum mycelia (GLAA) on sleep were studied in mice. Administration of 25, 50 and 100 mg/kg GLAA for 28 days promoted sleep in pentobarbital-treated mice by shortening sleep latency and prolonging sleeping time. GLAA administration increased the levels of the sleep-promoting neurotransmitter 5-hydroxytryptamine and the Tph2, Iptr3 and Gng13 transcripts in the sleep-regulating serotonergic synapse pathway in the hypothalamus during this process. Moreover, GLAA administration reduced lipopolysaccharide and raised peptidoglycan levels in serum. GLAA-enriched gut bacteria and metabolites, including Bifidobacterium, Bifidobacterium animalis, indole-3-carboxylic acid and acetylphosphate were negatively correlated with sleep latency and positively correlated with sleeping time and the hypothalamus 5-hydroxytryptamine concentration. Both the GLAA sleep promotion effect and the altered faecal metabolites correlated with sleep behaviours disappeared after gut microbiota depletion with antibiotics. Our results showed that GLAA promotes sleep through a gut microbiota-dependent and serotonin-associated pathway in mice.
Phylogeography of Prunus armeniaca L. revealed by chloroplast DNA and nuclear ribosomal sequences
Authors: Li Wen-Wen , Liu Li-Qiang , Zhang Qiu-Ping , Zhou Wei-Quan , Fan Guo-Quan , Liao Kang
Published: July 2021

To clarify the phytogeography of Prunus armeniaca L., two chloroplast DNA fragments (trnL-trnF and ycf1) and the nuclear ribosomal DNA internal transcribed spacer (ITS) were employed to assess genetic variation across 12 P. armeniaca populations. The results of cpDNA and ITS sequence data analysis showed a high the level of genetic diversity (cpDNA: HT = 0.499; ITS: HT = 0.876) and a low level of genetic differentiation (cpDNA: FST = 0.1628; ITS: FST = 0.0297) in P. armeniaca. Analysis of molecular variance (AMOVA) revealed that most of the genetic variation in P. armeniaca occurred among individuals within populations. The value of interpopulation differentiation (NST) was significantly higher than the number of substitution types (GST), indicating genealogical structure in P. armeniaca. P. armeniaca shared genotypes with related species and may be associated with them through continuous and extensive gene flow. The haplotypes/genotypes of cultivated apricot populations in Xinjiang, North China, and foreign apricot populations were mixed with large numbers of haplotypes/genotypes of wild apricot populations from the Ili River Valley. The wild apricot populations in the Ili River Valley contained the ancestral haplotypes/genotypes with the highest genetic diversity and were located in an area considered a potential glacial refugium for P. armeniaca. Since population expansion occurred 16.53 kyr ago, the area has provided a suitable climate for the population and protected the genetic diversity of P. armeniaca.
Uncertainty of chemical status in surface waters
Authors: Loga Małgorzata , Przeździecki Karol
Published: July 2021

This article addresses the issue of estimating Pom—the probability of misclassifying the chemical status confidence of a water body status assessment. The main concerns of the authors were chemical quality elements with concentrations in water bodies which are close to or even smaller than the limit of quantification (LOQ). Their values must be set to half of this limit to calculate the mean value. This procedure leads to very low standard deviation values and unrealistic values of Pom for chemical indicators. In turn, this may lead to the false conclusion that not only is the chemical status good but also that this status assessment is perfect. Therefore, for a more reliable calculation of Pom, the authors suggested a modified calculation in which the value of half the LOQ for calculating the mean value was kept, but zero as the concentration value for the standard deviation calculation was adopted. The proposed modification has been applied to the Hierarchical Approach procedure for Pom estimation of the chemical status of Polish rivers and lakes. The crucial finding is that current chemical status assessments may be incorrect in the case of approximately 25% of river water bodies and 30% of lake water bodies categorised as good, and 20% of both types of water bodies classified as below good.
Plasma concentrations of granulocyte colony-stimulating factor (G-CSF) in patients with substance use disorders and comorbid major depressive disorder
Authors: Galván Sandra Torres , Flores-López María , Romero-Sanchiz Pablo , Requena-Ocaña Nerea , Porras-Perales Oscar , Nogueira-Arjona Raquel , Mayoral Fermín , Araos Pedro , Serrano Antonia , Muga Roberto , Pavón Francisco Javier , García-Marchena Nuria , de Fonseca Fernando Rodríguez
Published: July 2021

Granulocyte colony–stimulating factor (G-CSF) has raised much interest because of its role in cocaine addiction in preclinical models. We explored the plasma concentrations of G-CSF in patients diagnosed with substance use disorder (SUD) and highly comorbid psychiatric disorders. In particular, we investigated the association between G-CSF concentrations and comorbid major depressive disorder (MDD) in patients with cocaine and alcohol use disorders (CUD and AUD, respectively). Additionally, patients with MDD but not SUD were included in the study. Three hundred and eleven participants were enrolled in this exploratory study: 136 control subjects, 125 patients with SUD (SUD group) from outpatient treatment programs for cocaine (N = 60, cocaine subgroup) and alcohol (N = 65, alcohol subgroup), and 50 patients with MDD but not SUD (MDD group) from primary-care settings. Participants were assessed based on DSM-IV-TR criteria, and a blood sample was collected to examine the plasma concentrations of G-CSF. G-CSF concentrations were negatively correlated with age in the entire sample (r = − 0.233, p < 0.001) but not in the patients with MDD. G-CSF concentrations were lower in patients with SUD than in controls (p < 0.05), specifically in the cocaine subgroup (p < 0.05). Patients with SUD and comorbid MDD had lower G-CSF concentrations than patients with SUD but not comorbid MDD or controls (p < 0.05). In contrast, patients with MDD but not SUD showed no differences compared with their controls. The negative association between G-CSF concentrations and age in the sample was not observed in patients with MDD. G-CSF concentrations were decreased in patients with SUD and comorbid MDD but not in patients with MDD. Therefore, G-CSF may be useful to improve the stratification of patients with dual diagnosis seeking treatment. Further investigation is needed to explore the impact of sex and type of drug on the expression of G-CSF.
A kinome-centered CRISPR-Cas9 screen identifies activated BRAF to modulate enzalutamide resistance with potential therapeutic implications in BRAF-mutated prostate cancer
Authors: Palit Sander A. L. , van Dorp Jeroen , Vis Daniel , Lieftink Cor , Linder Simon , Beijersbergen Roderick , Bergman Andries M. , Zwart Wilbert , van der Heijden Michiel S.
Published: July 2021

Resistance to drugs targeting the androgen receptor (AR) signaling axis remains an important challenge in the treatment of prostate cancer patients. Activation of alternative growth pathways is one mechanism used by cancer cells to proliferate despite treatment, conferring drug resistance. Through a kinome-centered CRISPR-Cas9 screen in CWR-R1 prostate cancer cells, we identified activated BRAF signaling as a determinant for enzalutamide resistance. Combined pharmaceutical targeting of AR and MAPK signaling resulted in strong synergistic inhibition of cell proliferation. The association between BRAF activation and enzalutamide resistance was confirmed in two metastatic prostate cancer patients harboring activating mutations in the BRAF gene, as both patients were unresponsive to enzalutamide. Our findings suggest that co-targeting of the MAPK and AR pathways may be effective in patients with an activated MAPK pathway, particularly in patients harboring oncogenic BRAF mutations. These results warrant further investigation of the response to AR inhibitors in BRAF-mutated prostate tumors in clinical settings.
Experimental investigation of optically controlled topological transition in bismuth-mica structure
Authors: Zaitsev Anton , Zykov Dmitry , Demchenko Petr , Novoselov Mikhail , Nazarov Ravshanjon , Masyukov Maxim , Makarova Elena , Tukmakova Anastasiia , Asach Aleksei , Novotelnova Anna , Kablukova Natallya , Khodzitsky Mikhail
Published: July 2021

The hyperbolic materials are strongly anisotropic media with a permittivity/permeability tensor having diagonal components of different sign. They combine the properties of dielectric and metal-like media and are described with hyperbolic isofrequency surfaces in wave-vector space. Such media may support unusual effects like negative refraction, near-field radiation enhancement and nanoscale light confinement. They were demonstrated mainly for microwave and infrared frequency ranges on the basis of metamaterials and natural anisotropic materials correspondingly. For the terahertz region, the tunable hyperbolic media were demonstrated only theoretically. This paper is dedicated to the first experimental demonstration of an optically tunable terahertz hyperbolic medium in 0.2–1.0 THz frequency range. The negative phase shift of a THz wave transmitted through the structure consisting of 40 nm (in relation to THz wave transmitted through substrate) to 120 nm bismuth film (in relation to both THz waves transmitted through substrate and air) on 21 µm mica substrate is shown. The optical switching of topological transition between elliptic and hyperbolic isofrequency contours is demonstrated for the effective structure consisting of 40 nm Bi on mica. For the case of 120 nm Bi on mica, the effective permittivity is only hyperbolic in the studied range. It is shown that the in-plane component of the effective permittivity tensor may be positive or negative depending on the frequency of THz radiation and continuous-wave optical pumping power (with a wavelength of 980 nm), while the orthogonal one is always positive. The proposed optically tunable structure may be useful for application in various fields of the modern terahertz photonics.
Determination of k-mer density in a DNA sequence and subsequent cluster formation algorithm based on the application of electronic filter
Authors: Sarkar Bimal Kumar , Sharma Ashish Ranjan , Bhattacharya Manojit , Sharma Garima , Lee Sang-Soo , Chakraborty Chiranjib
Published: July 2021

We describe a novel algorithm for information recovery from DNA sequences by using a digital filter. This work proposes a three-part algorithm to decide the k-mer or q-gram word density. Employing a finite impulse response digital filter, one can calculate the sequence's k-mer or q-gram word density. Further principal component analysis is used on word density distribution to analyze the dissimilarity between sequences. A dissimilarity matrix is thus formed and shows the appearance of cluster formation. This cluster formation is constructed based on the alignment-free sequence method. Furthermore, the clusters are used to build phylogenetic relations. The cluster algorithm is in good agreement with alignment-based algorithms. The present algorithm is simple and requires less time for computation than other currently available algorithms. We tested the algorithm using beta hemoglobin coding sequences (HBB) of 10 different species and 18 primate mitochondria genome (mtDNA) sequences.
Development of a novel micro-bead force spectroscopy approach to measure the ability of a thermo-active polymer to remove bacteria from a corneal model
Authors: Pattem J. , Swift T. , Rimmer S. , Holmes T. , MacNeil S. , Shepherd J.
Published: July 2021

Microbial keratitis occurs from the infection of the cornea by fungi and or bacteria. It remains one of the most common global causes of irreversible blindness accounting for 3.5% (36 million) of blind people as of 2015. This paper looks at the use of a bacteria binding polymer designed to bind Staphylococcus aureus and remove it from the corneal surface. Mechanical unbinding measurements were used to probe the interactions of a thermo-active bacteria-binding polymer, highly-branched poly(N-isopropyl acrylamide), functionalised with modified vancomycin end groups (HB-PNIPAM-Van) to bacteria placed on rabbit corneal surfaces studied ex-vivo. This was conducted during sequential temperature phase transitions of HB-PNIPAM-Van-S. aureus below, above and below the lower critical solution temperature (LCST) in 3 stages, in-vitro, using a novel micro-bead force spectroscopy (MBFS) approach via atomic force microscopy (AFM). The effect of temperature on the functionality of HB-PNIPAM-Van-S. aureus showed that the polymer-bacteria complex reduced the work done in removing bacterial aggregates at T > LCST (p < 0.05), exhibiting reversibility at T < LCST (p < 0.05). At T < LCST, the breaking force, number of unbinding events, percentage fitted segments in the short and long range, and the percentage of unbinding events occurring in the long range (> 2.5 µm) increased (p < 0.05). Furthermore, the LCST phase transition temperature showed 100 × more unbinding events in the long-range z-length (> 2.5 µm) compared to S. aureus aggregates only. Here, we present the first study using AFM to assess the reversible mechanical impact of a thermo-active polymer-binding bacteria on a natural corneal surface.
Mooring observed intraseasonal oscillations in the central South China Sea during summer monsoon season
Authors: Jan Sen , Chang Ming-Huei , Yang Yiing Jang , Sui Chung-Hsiung , Cheng Yu-Hsin , Yeh Yu-Yu , Lee Chung-Wei
Published: July 2021

The South China Sea (SCS) is a high biodiversity region in the world ocean, supports abundant marine resources to the peripheral nations, and affects weather/climate in southeast Asia. A better understanding of its circulation is important to better prediction and management of the SCS. Here we reveal sizable intraseasonal oscillations at period ~ 50 days between May and November 2017 in the acoustic Doppler current profiler observed velocity in the central SCS. Satellite observed wind and sea level data together with a process-oriented numerical experiment suggest that the oscillations were caused by locally-generated and remotely-penetrated westward-propagating Rossby waves. The summer southwesterly monsoon strengthening/weakening and the resultant Ekman pumping velocity and shoreward Ekman transport increase/decrease and consequent coastal sea level rise/fall off the west coast of Palawan create westward-propagating Rossby waves causing velocity oscillations in the central SCS. Besides the local generation, Rossby waves with sea level anomaly > 0.2 m propagating from the Pacific through the Sulu Sea into the SCS could contribute to the intraseasonal velocity oscillations in the central SCS.
Results from a large cross-sectional study assessing Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma hominis urogenital infections in patients with primary infertility
Authors: Paira Daniela Andrea , Molina Guillermo , Tissera Andrea Daniela , Olivera Carolina , Molina Rosa Isabel , Motrich Ruben Dario
Published: July 2021

Female and male infertility have been associated to Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma hominis urogenital infections. However, evidence from large studies assessing their prevalence and putative associations in patients with infertility is still scarce. The study design was a cross-sectional study including 5464 patients with a recent diagnosis of couple’s primary infertility and 404 healthy control individuals from Cordoba, Argentina. Overall, the prevalence of C. trachomatis, Ureaplasma spp. and M. hominis urogenital infection was significantly higher in patients than in control individuals (5.3%, 22.8% and 7.4% vs. 2.0%, 17.8% and 1.7%, respectively). C. trachomatis and M. hominis infections were significantly more prevalent in male patients whereas Ureaplasma spp. and M. hominis infections were more prevalent in female patients. Of clinical importance, C. trachomatis and Ureaplasma spp. infections were significantly higher in patients younger than 25 years. Moreover, Ureaplasma spp. and M. hominis infections were associated to each other in either female or male patients being reciprocal risk factors of their co-infection. Our data revealed that C. trachomatis, Ureaplasma spp. and M. hominis are prevalent uropathogens in patients with couple’s primary infertility. These results highlight the importance of including the screening of urogenital infections in the diagnostic workup of infertility.
Ice microphysical processes exert a strong control on the simulated radiative energy budget in the tropics
Authors: Sullivan Sylvia C. , Voigt Aiko
Published: July 2021

Simulations of the global climate system at storm-resolving resolutions of 2 km are now becoming feasible and show promising realism in clouds and precipitation. However, shortcomings in their representation of microscale processes, like the interaction of cloud droplets and ice crystals with radiation, can still restrict their utility. Here, we illustrate how changes to the ice microphysics scheme dramatically alter both the vertical profile of cloud-radiative heating and top-of-atmosphere outgoing longwave radiation (terrestrial infrared cooling) in storm-resolving simulations over the Asian monsoon region. Poorly-constrained parameters in the ice nucleation scheme, overactive conversion of ice to snow, and inconsistent treatment of ice crystal effective radius between microphysics and radiation alter cloud-radiative heating by a factor of four and domain-mean infrared cooling by 30 W m−2. Vertical resolution, on the other hand, has a very limited impact. Even in state-of-the-art models then, uncertainties in microscale cloud properties exert a strong control on the radiative budget that propagates to both atmospheric circulation and regional climate. These uncertainties need to be reduced to realize the full potential of storm-resolving models.
Characterization of the impact of mixing and droplet volumes on the behavior of microfluidic ion-selective droptodes
Authors: Wetzler-Quevedo Shannon P. , Meyerhoff Mark E. , Bailey Ryan C.
Published: July 2021

Droplet microfluidic optodes, or “droptodes”, allow for rapid detection of small ions in complex matrices. Droptodes' sensitivity can be manipulated by varying microfluidic channel geometry and droplet size.
Pre-shear bioprinting of highly oriented porous hydrogel microfibers to construct anisotropic tissues
Authors: Shao Lei , Hou Ruixia , Zhu Yabin , Yao Yudong
Published: July 2021

A pre-shear bioprinting strategy of oriented porous cell-laden hydrogel microfiber to construct anisotropic tissues is first proposed. Different cells encapsulated in the oriented microfibers exhibit oriented growth behaviors similar to that in vivo.
Dihydro-Si-rhodamine for live-cell localization microscopy
Authors: Zhang Xiaodong , Zhang Mengmeng , Yan Yu , Wang Mingkang , Li Jin , Yu Yang , Xiao Yi , Luo Xiao , Qian Xuhong , Yang Youjun
Published: July 2021

Fluorophores with photo-modulatory fluorescence properties are valuable for cutting-edge localization microscopy.
A double bilayer to study the nonequilibrium environmental response of GIRK2 in complex states
Authors: Weng Junben , Wang Anhui , Zhang Dinglin , Liao Chenyi , Li Guohui
Published: July 2021

In a nonequilibrium environment, global functional rocking motion of GIRK2 complex were identified. The antiparallel alignment double bilayer provides a strategy to investigate factors in an asymmetric environment.
Thermoelectrics in ice slabs: charge dynamics and thermovoltages
Authors: Zhang Hongwei , De Poorter John , Mukherjee Ranit , Boreyko Jonathan B. , Qiao Rui
Published: July 2021

The thermoelectrification of an ice slab involves a fast initial stage and a subsequent slow stage, and the sign and magnitude of the steady-state thermovoltage depend strongly on ice slab’s thickness.
Hybrid dual-function thermal energy harvesting and storage technologies: towards self-chargeable flexible/wearable devices
Authors: Teixeira Joana S. , Costa Rui S. , Pires Ana L. , Pereira André M. , Pereira Clara
Published: July 2021

This review focuses on the advances in thermally-chargeable supercapacitors for flexible/wearable applications, starting from an overview of thermoelectric generators and supercapacitors up to the rational design of all-in-one hybrid technologies.
Isonitrile ruthenium and iron PNP complexes: synthesis, characterization and catalytic assessment for base-free dehydrogenative coupling of alcohols
Authors: Nguyen Duc Hanh , Merel Delphine , Merle Nicolas , Trivelli Xavier , Capet Frédéric , Gauvin Régis M.
Published: July 2021

Ruthenium and iron PNP pincer complexes bearing isocyanides ancillary ligands have been prepared, and assessed for alcohol acceptorless dehydrogenative coupling.
Design and synthesis of Ba3SiSe5 with suitable birefringence modulated via MIV atoms in the Ba–MIV–Q (MIV = Si, Ge; Q = S, Se) system
Authors: Cheng Huanhuan , Tudi Abudukadi , Wang Peng , Zhang Kewang , Yang Zhihua , Pan Shilie
Published: July 2021

A new ternary Ba-based selenide, Ba3SiSe5, featuring isolated SiSe4 tetrahedra and exhibiting moderate birefringence, has been synthesized and characterized for the first time.
Marginal energy intensity of water supply
Authors: Liu Yang , Mauter Meagan S.
Published: July 2021

Marginal energy intensity (MEI) rigorously disaggregates energy consumption across a complex water supply system to the resolution of individual consumers. MEI is a robust metric for optimizing water utility energy management and retrofit strategies.
Coulombically-stabilized oxygen hole polarons enable fully reversible oxygen redox
Authors: Abate Iwnetim I. , Pemmaraju C. Das , Kim Se Young , Hsu Kuan H. , Sainio Sami , Moritz Brian , Vinson John , Toney Michael F. , Yang Wanli , Gent William E. , Devereaux Thomas P. , Nazar Linda F. , Chueh William C.
Published: July 2021

Coulombic stabilization and large kinetic barrier in concert stabilize oxygen holes and mitigate voltage hysteresis during oxygen redox of positive electrodes in batteries.
Catalyst-free, scalable heterocyclic flow photocyclopropanation
Authors: Klöpfer Viktor , Eckl Robert , Floß Johannes , Roth Philippe M. C. , Reiser Oliver , Barham Joshua P.
Published: July 2021

Visible light continuous flow photocyclopropanation of heterocyclic compounds is reported in a non-chlorinated biodegradable solvent. Design of Experiments optimization was used to arrive at optimal conditions that are safe, sustainable and scalable.
Inertial focusing and zeta potential measurements of single-nanoparticles using octet-nanochannels
Authors: Kishimoto Shohei , Tsutsui Makusu , Yokota Kazumichi , Taniguchi Masateru
Published: July 2021

Electrokinetics in octet nanochannels was demonstrated to enable particle focusing via inertial effects to accurate single-nanoparticle zeta-potential measurements.
Dielectrophoretic medium exchange around droplets for on-chip fabrication of layer-by-layer microcapsules
Authors: Sun Haizhen , Ren Yukun , Jiang Tianyi , Tao Ye , Jiang Hongyuan
Published: July 2021

We introduce a unique medium exchange approach, namely, tilted-angle dielectrophoresis, to accomplish layer-by-layer (LbL) coating on droplets in a wide microchannel.
Determination of the surface temperature of magnetically heated nanoparticles using a catalytic approach
Authors: Díaz-Puerto Zarick Juliana , Raya-Barón Álvaro , van Leeuwen Piet W. N. M. , Asensio Juan M. , Chaudret Bruno
Published: July 2021

The surface temperature on catalytically active magnetic nanoparticles (Fe2.2C@Ru) was estimated from their catalytic performances under magnetic induction. In different solvents, surface temperatures well-above the boiling point were determined.
Topological defect-containing Fe/N co-doped mesoporous carbon nanosheets as novel electrocatalysts for the oxygen reduction reaction and Zn–air batteries
Authors: Ding Junjie , Wu Dongchuang , Huang Senhe , Lu Chenbao , Chen Yu , Zhang Jichao , Zhang Longhai , Li Jin , Ke Changchun , Tranca Diana , Kymakis Emmanuel , Zhuang Xiaodong
Published: July 2021

Topological defect-containing carbons (or high-entropy carbons), which are synthesized from an azulene-enriched precursor, show strong relationship between topological defects and Fe sites for oxygen reduction.
Enantioselectivity switch in asymmetric Michael addition reactions using phosphonium salts
Authors: Fang Guosheng , Wang Hongyu , Zheng Changwu , Pan Lu , Zhao Gang
Published: July 2021

A catalyst-controlled enantioselectivity switch for asymmetric Michael reactions has been successfully realized by fine tuning chiral organophosphonium salts.
Innovative route for the preparation of high-performance polyolefin materials based on unique dendrimeric silica particles
Authors: Cecílio Duarte M. , Fernandes Auguste , Lourenço João Paulo , McKenna Timothy F. L. , Ribeiro M. Rosário
Published: July 2021

An innovative methodology for the preparation of high-performance polyolefin-based materials combining a unique dendrimeric silica carrier, a straightforward in situ supporting procedure and in situ ethylene polymerization technique was developed.
Highly 2,3-selective polymerization of phenylallene and its derivatives by vanadium complexes
Authors: Gao Xiang , Nie Jinxin , Chen Xiaojian , Zhou Li , Hou Xiaohua , Zou Hui
Published: July 2021

Allene polymerizations by vanadium complexes using various Al co-catalysts were carried out. All the vanadium complexes show moderate activity for phenylallene and high 2,3-selectivity (>99%).
The transition to first year chemistry: student, secondary and tertiary educator's perceptions of student preparedness
Authors: Leong Elizabeth , Mercer Agnes , Danczak Stephen M. , Kyne Sara H. , Thompson Christopher D.
Published: July 2021

Student preparedness is an essential component of transition to university influenced by a broad suite of attributes including academic aptitude, prior knowledge, self-efficacy, self-confidence and a complex assortment of study and life skills. In the case of chemistry education, students' self-perceptions of preparedness are intrinsically linked to prior learning of both theory and hands on laboratory experiences, and interwoven with intricacies such as science identity, gender, and secondary school background. Accordingly, this study sought to establish a deeper understanding of learners' and educators' perceptions of student preparedness upon commencing tertiary studies in chemistry. The research used a mixed methods approach including questionnaires, focus groups, and interviews to capture the breadth and depth of these perceptions. 924 students from the first year chemistry cohort completed either one or two surveys designed to capture their prospective and retrospective self-perceptions of how well prepared they were for the course. Nine of these students also participated in focus groups. Secondary educator's views were captured via a qualitative online survey to conveniently enable a broad cohort to be sampled, while tertiary educators from the institution where this study was conducted were interviewed in person. Key findings from students include: a strong correlation between self-perception of preparedness and academic performance, those with negative perceptions of preparedness are genuinely an at-risk category, an overall positive shift for perceptions of preparedness for students as they get to the end of the semester (which is more pronounced for students who attended private secondary schools), and a significant disparity between genders at the start of the semester that was no longer present by the end. Additional key findings include the disparity between secondary and tertiary educator's perspectives of how well prepared students are for the transition to tertiary level chemistry studies. While the former have a favourable view, the latter consider many students to be quite poorly prepared, with each cohort ultimately focusing on different attributes. We suggest the implications for these findings include the importance of emphasising expectations of students as they commence their courses, and that work still needs to be done to align the perspectives of educators at all levels when it comes to preparing and supporting students as they transition to higher education.
Development of a machine learning-based tool to evaluate correct Lewis acid–base model use in written responses to open-ended formative assessment items
Authors: Yik Brandon J. , Dood Amber J. , Cruz-Ramírez de Arellano Daniel , Fields Kimberly B. , Raker Jeffrey R.
Published: July 2021

Acid–base chemistry is a key reaction motif taught in postsecondary organic chemistry courses. More specifically, concepts from the Lewis acid–base model are broadly applicable to understanding mechanistic ideas such as electron density, nucleophilicity, and electrophilicity; thus, the Lewis model is fundamental to explaining an array of reaction mechanisms taught in organic chemistry. Herein, we report the development of a generalized predictive model using machine learning techniques to assess students’ written responses for the correct use of the Lewis acid–base model for a variety (N= 26) of open-ended formative assessment items. These items follow a general framework of prompts that ask: why a compound can act as (i) an acid, (ii) a base, or (iii) both an acid and a base (i.e., amphoteric)? Or, what is happening and why for aqueous proton-transfer reactions and reactions that can only be explained using the Lewis model. Our predictive scoring model was constructed from a large collection of responses (N= 8520) using a machine learning technique,i.e., support vector machine, and subsequently evaluated using a variety of validation procedures resulting in overall 84.5–88.9% accuracies. The predictive model underwent further scrutiny with a set of responses (N= 2162) from different prompts not used in model construction along with a new prompt type: non-aqueous proton-transfer reactions. Model validation with these data achieved 92.7% accuracy. Our results suggest that machine learning techniques can be used to construct generalized predictive models for the evaluation of acid–base reaction mechanisms and their properties. Links to open-access files are provided that allow instructors to conduct their own analyses on written, open-ended formative assessment items to evaluate correct Lewis model use.
A unified strategy to prostaglandins: chemoenzymatic total synthesis of cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost guided by biocatalytic retrosynthesis
Authors: Zhu Kejie , Jiang Meifen , Ye Baijun , Zhang Guo-Tai , Li Weijian , Tang Pei , Huang Zedu , Chen Fener
Published: July 2021

We report a unified chemoenzymatic asymmetric synthesis of five prostaglandins, featuring two enzymatic redox transformations and a copper(ii)-catalyzed regioselective p-phenylbenzoylation.
Hydrophobized metallic meshes can ease water droplet rolling
Authors: Abubakar Abba Abdulhamid , Yilbas Bekir Sami , Al-Qahtani Hussain , Mohammed Anwaruddin Siddiqui
Published: July 2021

Rolling liquid droplets are of great interest for various applications including self-cleaning of surfaces.
Morphological changes of silica aged under environmental conditions by three-dimensional nanoscale quantifications
Authors: Chal Bruno , Roiban Lucian , Baeza Guilhem P. , Masenelli-Varlot Karine , Jestin Jacques , Yrieix Bernard , Foray Genevieve
Published: July 2021

Combining techniques, we follow surfaces, particles, and pores within aggregates and their evolution. A reliable ageing chronology was achieved on several length scales for an ultraporous nanostructured silica via 3D quantification.
The Dion–Jacobson perovskite CsSbCl4: a promising Pb-free solar-cell absorber with optimal bandgap ∼1.4 eV, strong optical absorption ∼105cm−1, and large power-conversion efficiency above 20%
Authors: Guo Wen-hui , Zhu Yao-hui , Zhang Min , Du Juan , Cen Yu-lang , Liu Shi-ming , He Yong , Zhong Hong-xia , Wang Xinqiang , Shi Jun-jie
Published: July 2021

A novel Pb-free perovskite CsSbCl4is found with a direct bandgap 1.41 eV, strong optical absorption 105 cm−1, high hole mobility 104 cm2V−1s−1, and large PCE > 20%.
Molecule-specific vibration-based chiral differentiation of Raman spectra using cysteine modified gold nanoparticles: the cases of tyrosine and phenylalanine
Authors: Sun Xueping , Wang Ning , He Yanxiu , Kong Huanjun , Yang Haifeng , Liu Xinling
Published: July 2021

The chirality of amino acids plays a key role in many biochemical processes, with the development of spectroscopic analysis methods for the chiral differentiation of amino acids being significant.
Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp12/7/8 RNA-dependent RNA polymerase
Authors: Bertolin Agustina P. , Weissmann Florian , Zeng Jingkun , Posse Viktor , Milligan Jennifer C. , Canal Berta , Ulferts Rachel , Wu Mary , Drury Lucy S. , Howell Michael , Beale Rupert , Diffley John F.X.
Published: July 2021

The coronavirus disease 2019 (COVID-19) global pandemic has turned into the largest public health and economic crisis in recent history impacting virtually all sectors of society. There is a need for effective therapeutics to battle the ongoing pandemic. Repurposing existing drugs with known pharmacological safety profiles is a fast and cost-effective approach to identify novel treatments. The COVID-19 etiologic agent is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded positive-sense RNA virus. Coronaviruses rely on the enzymatic activity of the replication–transcription complex (RTC) to multiply inside host cells. The RTC core catalytic component is the RNA-dependent RNA polymerase (RdRp) holoenzyme. The RdRp is one of the key druggable targets for CoVs due to its essential role in viral replication, high degree of sequence and structural conservation and the lack of homologues in human cells. Here, we have expressed, purified and biochemically characterised active SARS-CoV-2 RdRp complexes. We developed a novel fluorescence resonance energy transfer-based strand displacement assay for monitoring SARS-CoV-2 RdRp activity suitable for a high-throughput format. As part of a larger research project to identify inhibitors for all the enzymatic activities encoded by SARS-CoV-2, we used this assay to screen a custom chemical library of over 5000 approved and investigational compounds for novel SARS-CoV-2 RdRp inhibitors. We identified three novel compounds (GSK-650394, C646 and BH3I-1) and confirmed suramin and suramin-like compounds as in vitro SARS-CoV-2 RdRp activity inhibitors. We also characterised the antiviral efficacy of these drugs in cell-based assays that we developed to monitor SARS-CoV-2 growth.
An all-out assault on SARS-CoV-2 replication
Authors: Hay Ronald T.
Published: July 2021

The coronavirus pandemic has had a huge impact on public health with over 165 million people infected, 3.4 million deaths and a hugely deleterious effect on most economies. While vaccination effectively protects against the disease it is likely that viruses will evolve that can replicate in hosts immunised with the present vaccines. Thus, there is a great unmet need for effective antivirals that can block the development of serious disease in infected patients. The seven papers published in this issue of the Biochemical Journal address this need by expressing and purifying components required for viral replication, developing biochemical assays for these components and using the assays to screen a library of pre-existing pharmaceuticals for drugs that inhibited the target in vitro and inhibited viral replication in cell culture. The candidate drugs obtained are potential antivirals that may protect against SARS-CoV-2 infection. While not all the antiviral candidates will make it through to the clinic, they will be useful tool compounds and can act as the starting point for further drug discovery programmes.
Mapping the interaction surface of scorpion β-toxins with an insect sodium channel
Authors: Zhorov Boris S. , Du Yuzhe , Song Weizhong , Luo Ningguang , Gordon Dalia , Gurevitz Michael , Dong Ke
Published: July 2021

The interaction of insect-selective scorpion depressant β-toxins (LqhIT2 and Lqh-dprIT3 from Leiurus quinquestriatus hebraeus) with the Blattella germanica sodium channel, BgNav1-1a, was investigated using site-directed mutagenesis, electrophysiological analyses, and structural modeling. Focusing on the pharmacologically defined binding site-4 of scorpion β-toxins at the voltage-sensing domain II (VSD-II), we found that charge neutralization of D802 in VSD-II greatly enhanced the channel sensitivity to Lqh-dprIT3. This was consistent with the high sensitivity of the splice variant BgNav2-1, bearing G802, to Lqh-dprIT3, and low sensitivity of BgNav2-1 mutant, G802D, to the toxin. Further mutational and electrophysiological analyses revealed that the sensitivity of the WT = D802E < D802G < D802A < D802K channel mutants to Lqh-dprIT3 correlated with the depolarizing shifts of activation in toxin-free channels. However, the sensitivity of single mutants involving IIS4 basic residues (K4E = WT << R1E < R2E < R3E) or double mutants (D802K = K4E/D802K = R3E/D802K > R2E/D802K > R1E/D802K > WT) did not correlate with the activation shifts. Using the cryo-EM structure of the Periplaneta americana channel, NavPaS, as a template and the crystal structure of LqhIT2, we constructed structural models of LqhIT2 and Lqh-dprIT3-c in complex with BgNav1-1a. These models along with the mutational analysis suggest that depressant toxins approach the salt-bridge between R1 and D802 at VSD-II to form contacts with linkers IIS1–S2, IIS3–S4, IIIP5–P1 and IIIP2–S6. Elimination of this salt-bridge enables deeper penetration of the toxin into a VSD-II gorge to form new contacts with the channel, leading to increased channel sensitivity to Lqh-dprIT3.
Metabolic determinants of B-cell selection
Authors: Chan Lai N. , Aghania Eamon , Leveille Etienne , Müschen Markus
Published: July 2021

B-cells are antibody-producing cells of the adaptive immune system. Approximately 75% of all newly generated B-cells in the bone marrow are autoreactive and express potentially harmful autoantibodies. To prevent autoimmune disease, the immune system has evolved a powerful mechanism to eliminate autoreactive B-cells, termed negative B-cell selection. While designed to remove autoreactive clones during early B-cell development, our laboratory recently discovered that transformed B-cells in leukemia and lymphoma are also subject to negative selection. Indeed, besides the risk of developing autoimmune disease, B-cells are inherently prone to malignant transformation: to produce high-affinity antibodies, B-cells undergo multiple rounds of somatic immunoglobulin gene recombination and hypermutation. Reflecting high frequencies of DNA-breaks, adaptive immune protection by B-cells comes with a dramatically increased risk of development of leukemia and lymphoma. Of note, B-cells exist under conditions of chronic restriction of energy metabolism. Here we discuss how these metabolic gatekeeper functions during B-cell development provide a common mechanism for the removal of autoreactive and premalignant B-cells to safeguard against both autoimmune diseases and B-cell malignancies.
The future of immune checkpoint combinations with tumor-targeted small molecule drugs
Authors: Sceneay Jaclyn , Sinclair Charles
Published: July 2021

Immune-checkpoint blockade (ICB) has transformed the landscape of cancer treatment. However, there is much to understand around refractory or acquired resistance in patients in order to utilize ICB therapy to its full potential. In this perspective article, we discuss the opportunities and challenges that are emerging as our understanding of immuno-oncology resistance matures. Firstly, there has been remarkable progress made to understand the exquisite overlap between oncogenic and immune signaling pathways. Several cancer-signaling pathways are constitutively active in oncogenic settings and also play physiological roles in immune cell function. A growing number of precision oncology tumor-targeted drugs show remarkable immunogenic properties that might be harnessed with rational combination strategies. Secondly, we now understand that the immune system confers a strong selective pressure on tumors. Whilst this pressure can lead to novel tumor evolution and immune escape, there is a growing recognition of tumor-intrinsic dependencies that arise in immune pressured environments. Such dependencies provide a roadmap for novel tumor-intrinsic drug targets to alleviate ICB resistance. We anticipate that rational combinations with existing oncology drugs and a next wave of tumor-intrinsic drugs that specifically target immunological resistance will represent the next frontier of therapeutic opportunity.