bluuebunny/crossref_metadata_2025 huggingface dataset:
Sizing up DNA nanostructure assembly with native mass spectrometry and ion mobility
Authors: van Dyck Jeroen F. , Burns Jonathan R. , Le Huray Kyle I. P. , Konijnenberg Albert , Howorka Stefan , Sobott Frank
Published: June 2022

Recent interest in biological and synthetic DNA nanostructures has highlighted the need for methods to comprehensively characterize intermediates and end products of multimeric DNA assembly. Here we use native mass spectrometry in combination with ion mobility to determine the mass, charge state and collision cross section of noncovalent DNA assemblies, and thereby elucidate their structural composition, oligomeric state, overall size and shape. We showcase the approach with a prototypical six-subunit DNA nanostructure to reveal how its assembly is governed by the ionic strength of the buffer, as well as how the mass and mobility of heterogeneous species can be well resolved by careful tuning of instrumental parameters. We find that the assembly of the hexameric, barrel-shaped complex is guided by positive cooperativity, while previously undetected higher-order 12- and 18-mer assemblies are assigned to defined larger-diameter geometric structures. Guided by our insight, ion mobility-mass spectrometry is poised to make significant contributions to understanding the formation and structural diversity of natural and synthetic oligonucleotide assemblies relevant in science and technology.
Insights into the mechanism of action of the arbitrium communication system in SPbeta phages
Authors: Gallego del Sol Francisca , Quiles-Puchalt Nuria , Brady Aisling , Penadés José R. , Marina Alberto
Published: June 2022

The arbitrium system is employed by phages of the SPbeta family to communicate with their progeny during infection to decide either to follow the lytic or the lysogenic cycle. The system is controlled by a peptide, AimP, that binds to the regulator AimR, inhibiting its DNA-binding activity and expression of aimX. Although the structure of AimR has been elucidated for phages SPβ and phi3T, there is still controversy regarding the molecular mechanism of AimR function, with two different proposed models for SPβ. In this study, we deepen our understanding of the system by solving the structure of an additional AimR that shows chimerical characteristics with the SPβ receptor. The crystal structures of this AimR (apo, AimP-bound and DNA-bound) together with in vitro and in vivo analyses confirm a mechanism of action by AimP-induced conformational restriction, shedding light on peptide specificity and cross regulation with relevant biological implications.
Cell surface glycan engineering reveals that matriglycan alone can recapitulate dystroglycan binding and function
Authors: Sheikh M. Osman , Capicciotti Chantelle J. , Liu Lin , Praissman Jeremy , Ding Dahai , Mead Daniel G. , Brindley Melinda A. , Willer Tobias , Campbell Kevin P. , Moremen Kelley W. , Wells Lance , Boons Geert-Jan
Published: June 2022

α-Dystroglycan (α-DG) is uniquely modified on O-mannose sites by a repeating disaccharide (-Xylα1,3-GlcAβ1,3-)n termed matriglycan, which is a receptor for laminin-G domain-containing proteins and employed by old-world arenaviruses for infection. Using chemoenzymatically synthesized matriglycans printed as a microarray, we demonstrate length-dependent binding to Laminin, Lassa virus GP1, and the clinically-important antibody IIH6. Utilizing an enzymatic engineering approach, an N-linked glycoprotein was converted into a IIH6-positive Laminin-binding glycoprotein. Engineering of the surface of cells deficient for either α-DG or O-mannosylation with matriglycans of sufficient length recovers infection with a Lassa-pseudovirus. Finally, free matriglycan in a dose and length dependent manner inhibits viral infection of wildtype cells. These results indicate that matriglycan alone is necessary and sufficient for IIH6 staining, Laminin and LASV GP1 binding, and Lassa-pseudovirus infection and support a model in which it is a tunable receptor for which increasing chain length enhances ligand-binding capacity.
Bipolar membrane electrolyzers enable high single-pass CO2 electroreduction to multicarbon products
Authors: Xie Ke , Miao Rui Kai , Ozden Adnan , Liu Shijie , Chen Zhu , Dinh Cao-Thang , Huang Jianan Erick , Xu Qiucheng , Gabardo Christine M. , Lee Geonhui , Edwards Jonathan P. , O’Brien Colin P. , Boettcher Shannon W. , Sinton David , Sargent Edward H.
Published: June 2022

In alkaline and neutral MEA CO2 electrolyzers, CO2 rapidly converts to (bi)carbonate, imposing a significant energy penalty arising from separating CO2 from the anode gas outlets. Here we report a CO2 electrolyzer uses a bipolar membrane (BPM) to convert (bi)carbonate back to CO2, preventing crossover; and that surpasses the single-pass utilization (SPU) limit (25% for multi-carbon products, C2+) suffered by previous neutral-media electrolyzers. We employ a stationary unbuffered catholyte layer between BPM and cathode to promote C2+ products while ensuring that (bi)carbonate is converted back, in situ, to CO2 near the cathode. We develop a model that enables the design of the catholyte layer, finding that limiting the diffusion path length of reverted CO2 to ~10 μm balances the CO2 diffusion flux with the regeneration rate. We report a single-pass CO2 utilization of 78%, which lowers the energy associated with downstream separation of CO2 by 10× compared with past systems.
Construction of a synthetic Saccharomyces cerevisiae pan-genome neo-chromosome
Authors: Kutyna Dariusz R. , Onetto Cristobal A. , Williams Thomas C. , Goold Hugh D. , Paulsen Ian T. , Pretorius Isak S. , Johnson Daniel L. , Borneman Anthony R.
Published: June 2022

The Synthetic Yeast Genome Project (Sc2.0) represents the first foray into eukaryotic genome engineering and a framework for designing and building the next generation of industrial microbes. However, the laboratory strain S288c used lacks many of the genes that provide phenotypic diversity to industrial and environmental isolates. To address this shortcoming, we have designed and constructed a neo-chromosome that contains many of these diverse pan-genomic elements and which is compatible with the Sc2.0 design and test framework. The presence of this neo-chromosome provides phenotypic plasticity to the Sc2.0 parent strain, including expanding the range of utilizable carbon sources. We also demonstrate that the induction of programmable structural variation (SCRaMbLE) provides genetic diversity on which further adaptive gains could be selected. The presence of this neo-chromosome within the Sc2.0 backbone may therefore provide the means to adapt synthetic strains to a wider variety of environments, a process which will be vital to transitioning Sc2.0 from the laboratory into industrial applications.
A microfluidic optimal experimental design platform for forward design of cell-free genetic networks
Authors: van Sluijs Bob , Maas Roel J. M. , van der Linden Ardjan J. , de Greef Tom F. A. , Huck Wilhelm T. S.
Published: June 2022

Cell-free protein synthesis has been widely used as a “breadboard” for design of synthetic genetic networks. However, due to a severe lack of modularity, forward engineering of genetic networks remains challenging. Here, we demonstrate how a combination of optimal experimental design and microfluidics allows us to devise dynamic cell-free gene expression experiments providing maximum information content for subsequent non-linear model identification. Importantly, we reveal that applying this methodology to a library of genetic circuits, that share common elements, further increases the information content of the data resulting in higher accuracy of model parameters. To show modularity of model parameters, we design a pulse decoder and bistable switch, and predict their behaviour both qualitatively and quantitatively. Finally, we update the parameter database and indicate that network topology affects parameter estimation accuracy. Utilizing our methodology provides us with more accurate model parameters, a necessity for forward engineering of complex genetic networks.
A glycine-rich PE_PGRS protein governs mycobacterial actin-based motility
Authors: Hill Norbert S. , Welch Matthew D.
Published: June 2022

Many key insights into actin regulation have been derived through examining how microbial pathogens intercept the actin cytoskeleton during infection.Mycobacterium marinum, a close relative of the human pathogenMycobacterium tuberculosis, polymerizes host actin at the bacterial surface to drive intracellular movement and cell-to-cell spread during infection. However, the mycobacterial factor that commandeers actin polymerization has remained elusive. Here, we report the identification and characterization of theM. marinumactin-based motility factor designated mycobacterial intracellular rockets A (MirA), which is a member of the glycine-rich PE_PGRS protein family. MirA contains an amphipathic helix to anchor into the mycobacterial outer membrane and, surprisingly, also the surface of host lipid droplet organelles. MirA directly binds to and activates the host protein N-WASP to stimulate actin polymerization through the Arp2/3 complex, directing both bacterial and lipid droplet actin-based motility. MirA is dissimilar to known N-WASP activating ligands and may represent a new class of microbial and host actin regulator. Additionally, the MirA-N-WASP interaction represents a model to understand how the enigmatic PE_PGRS proteins contribute to mycobacterial pathogenesis.
Visible light-controlled living cationic polymerization of methoxystyrene
Authors: Wang Lei , Xu Yupo , Zuo Quan , Dai Haojie , Huang Lei , Zhang Meng , Zheng Yongli , Yu Chunyang , Zhang Shaodong , Zhou Yongfeng
Published: June 2022

Photo-controlled living polymerization has received great attention in recent years. However, despite the great success therein, the report on photo-controlled living cationic polymerization has been greatly limited. We demonstrate here a novel decolorable, metal-free and visible light-controlled living cationic polymerization system by using tris(2,4-dimethoxyphenyl)methylium tetrafluoroborate as the photocatalyst and phosphate as the chain transfer agent (CTA) for polymerization of 4-methoxystyrene. This polymerization reaction under green LED light irradiation shows clear living characteristics including predictable molar mass, low molar-mass dispersity (Đ = 1.25), and sequential polymerization capability. In addition, the photocatalytic system exits excellent “on-off” photo switchability and shows the longest “off period” of 36 h up to now for photo-controlled cationic polymerization. Furthermore, the residual photo-catalyst is easily deactivated and decolored with addition of a base after the polymerization. The present study has extended the photo-controlled living cationic polymerization systems with new organic photocatalysts, phosphate CTA and polymerizable monomer as well as the new properties of excellent photostability and in-situ decolored capacity.
A review on pathology, mechanism, and therapy for cerebellum and tremor in Parkinson’s disease
Authors: Zhong Yuke , Liu Hang , Liu Guohui , Zhao Lili , Dai Chengcheng , Liang Yi , Du Juncong , Zhou Xuan , Mo Lijuan , Tan Changhong , Tan Xinjie , Deng Fen , Liu Xi , Chen Lifen
Published: June 2022

Tremor is one of the core symptoms of Parkinson’s disease (PD), but its mechanism is poorly understood. The cerebellum is a growing focus in PD-related researches and is reported to play an important role in tremor in PD. The cerebellum may participate in the modulation of tremor amplitude via cerebello-thalamo-cortical circuits. The cerebellar excitatory projections to the ventral intermediate nucleus of the thalamus may be enhanced due to PD-related changes, including dopaminergic/non-dopaminergic system abnormality, white matter damage, and deep nuclei impairment, which may contribute to dysregulation and resistance to levodopa of tremor. This review summarized the pathological, structural, and functional changes of the cerebellum in PD and discussed the role of the cerebellum in PD-related tremor, aiming to provide an overview of the cerebellum-related mechanism of tremor in PD.
FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes
Authors: Liang Chi-Qian , Zhou Deng-Cheng , Peng Wen-Tao , Chen Wu-Yun , Wu Hai-Yan , Zhou Yi-Min , Gu Wei-Li , Park Kyu-Sang , Zhao Hui , Pi Long-Quan , Zheng Li , Feng Shan-Shan , Cai Dong-Qing , Qi Xu-Feng
Published: June 2022

Upon injury, the liver is capable of substantial regeneration from the original tissue until an appropriate functional size. The underlying mechanisms controlling the liver regeneration processes are not well elucidated. Previous studies have proposed that the transcription factor FoxO3 is involved in various liver diseases, but its exact role in the regulation of liver regeneration remains largely unclear. To directly test the detailed role of FoxO3 in liver regeneration, both a constitutive Albumin-Cre driver line and adeno-associated virus serotype 8 (AAV8)-Tbg-Cre (AAV-Cre)-injected adult FoxO3fl/fl mice were subjected to 70% partial hepatectomy (PH). Our data demonstrate that FoxO3 deletion accelerates liver regeneration primarily by limiting polyploidization and promoting the proliferation of hepatocytes during liver regeneration. RNA-seq analysis indicates that FoxO3 deficiency greatly alters the expression of gene sets associated with cell proliferation and apoptosis during liver regeneration. Chromatin immunoprecipitation-PCR (ChIP-PCR) and luciferase reporter assays reveal that FoxO3 promotes the expression of Nox4 but suppresses the expression of Nr4a1 in hepatocytes. AAV8 virus-mediated overexpression of Nox4 and knockdown of Nr4a1 significantly suppressed hepatocyte proliferation and liver regeneration in FoxO3-deficient mice. We demonstrate that FoxO3 negatively controls hepatocyte proliferation through Nox4 upregulation and Nr4a1 downregulation, thereby ensuring appropriate functional regeneration of the liver. Our findings provide novel mechanistic insight into the therapeutic mechanisms of FoxO3 in liver damage and repair.
Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration
Authors: Krawetz Roman J. , Abubacker Saleem , Leonard Catherine , Masson Anand O. , Shah Sophia , Narendran Nadia , Tailor Pankaj , Regmi Suresh C. , Labit Elodie , Ninkovic Nicoletta , Corpuz Jessica May , Ito Kenichi , Underhill T. Michael , Salo Paul T. , Schmidt Tannin A. , Biernaskie Jeff A.
Published: June 2022

The wound healing response is one of most primitive and conserved physiological responses in the animal kingdom, as restoring tissue integrity/homeostasis can be the difference between life and death. Wound healing in mammals is mediated by immune cells and inflammatory signaling molecules that regulate tissue resident cells, including local progenitor cells, to mediate closure of the wound through formation of a scar. Proteoglycan 4 (PRG4), a protein found throughout the animal kingdom from fish to elephants, is best known as a glycoprotein that reduces friction between articulating surfaces (e.g. cartilage). Previously, PRG4 was also shown to regulate the inflammatory and fibrotic response. Based on this, we asked whether PRG4 plays a role in the wound healing response. Using an ear wound model, topical application of exogenous recombinant human (rh)PRG4 hastened wound closure and enhanced tissue regeneration. Our results also suggest that rhPRG4 may impact the fibrotic response, angiogenesis/blood flow to the injury site, macrophage inflammatory dynamics, recruitment of immune and increased proliferation of adult mesenchymal progenitor cells (MPCs) and promoting chondrogenic differentiation of MPCs to form the auricular cartilage scaffold of the injured ear. These results suggest that PRG4 has the potential to suppress scar formation while enhancing connective tissue regeneration post-injury by modulating aspects of each wound healing stage (blood clotting, inflammation, tissue generation and tissue remodeling). Therefore, we propose that rhPRG4 may represent a potential therapy to mitigate scar and improve wound healing.
Discrete typing units of Trypanosoma cruzi: Geographical and biological distribution in the Americas
Authors: Velásquez-Ortiz Natalia , Herrera Giovanny , Hernández Carolina , Muñoz Marina , Ramírez Juan David
Published: June 2022

Chagas disease caused by Trypanosoma cruzi is a public health issue in Latin America. This highly diverse parasite is divided into at least seven discrete typing units (DTUs) TcI-TcVI and Tcbat. Some DTUs have been associated with geographical distribution in epidemiological scenarios and clinical manifestations, but these aspects remain poorly understood. Many studies have focused on studying the parasite and its vectors/hosts, using a wide variety of genetic markers and methods. Here, we performed a systematic review of the literature for the last 20 years to present an update of DTUs distribution in the Americas, collecting ecoepidemiological information. We found that the DTUs are widespread across the continent and that there is a whole gamma of genetic markers used for the identification and genotyping of the parasite. The data obtained in this descriptor could improve the molecular epidemiology studies of Chagas disease in endemic regions.
Kolmogorov compression complexity may differentiate different schools of Orthodox iconography
Authors: Peptenatu Daniel , Andronache Ion , Ahammer Helmut , Taylor Richard , Liritzis Ioannis , Radulovic Marko , Ciobanu Bogdan , Burcea Marin , Perc Matjaz , Pham Tuan D. , Tomić Bojan M. , Cîrstea Cosmin Iulian , Lemeni Adrian Nicolae , Gruia Andreea Karina , Grecu Alexandra , Marin Marian , Jelinek Herbert Franz
Published: June 2022

The complexity in the styles of 1200 Byzantine icons painted between 13th and 16th from Greece, Russia and Romania was investigated through the Kolmogorov algorithmic information theory. The aim was to identify specific quantitative patterns which define the key characteristics of the three different painting schools. Our novel approach using the artificial surface images generated with Inverse FFT and the Midpoint Displacement (MD) algorithms, was validated by comparison of results with eight fractal and non-fractal indices. From the analyzes performed, normalized Kolmogorov compression complexity (KC) proved to be the best solution because it had the best complexity pattern differentiations, is not sensitive to the image size and the least affected by noise. We conclude that normalized KC methodology does offer capability to differentiate the icons within a School and amongst the three Schools.
African mitochondrial haplogroup L7: a 100,000-year-old maternal human lineage discovered through reassessment and new sequencing
Authors: Maier Paul A. , Runfeldt Göran , Estes Roberta J. , Vilar Miguel G.
Published: June 2022

Archaeological and genomic evidence suggest that modernHomo sapienshave roamed the planet for some 300–500 thousand years. In contrast, global human mitochondrial (mtDNA) diversity coalesces to one African female ancestor (“Mitochondrial Eve”) some 145 thousand years ago, owing to the ¼ gene pool size of our matrilineally inherited haploid genome. Therefore, most of human prehistory was spent in Africa where early ancestors of Southern African Khoisan and Central African rainforest hunter-gatherers (RFHGs) segregated into smaller groups. Their subdivisions followed climatic oscillations, new modes of subsistence, local adaptations, and cultural-linguistic differences, all prior to their exodus out of Africa. Seven African mtDNA haplogroups (L0–L6) traditionally captured this ancient structure—these L haplogroups have formed the backbone of the mtDNA tree for nearly two decades. Here we describe L7, an eighth haplogroup that we estimate to be ~ 100 thousand years old and which has been previously misclassified in the literature. In addition, L7 has a phylogenetic sublineage L7a*, the oldest singleton branch in the human mtDNA tree (~ 80 thousand years). We found that L7 and its sister group L5 are both low-frequency relics centered around East Africa, but in different populations (L7: Sandawe; L5: Mbuti). Although three small subclades of African foragers hint at the population origins of L5'7, the majority of subclades are divided into Afro-Asiatic and eastern Bantu groups, indicative of more recent admixture. A regular re-estimation of the entire mtDNA haplotype tree is needed to ensure correct cladistic placement of new samples in the future.
Fabrication of stainless-steel microfibers with amorphous-nanosized microstructure with enhanced mechanical properties
Authors: Sharifikolouei Elham , Sarac Baran , Zheng Yonghui , Bala Piotr , Eckert Jürgen
Published: June 2022

Metallic glasses (MG) have attracted much attention due to their superior hardness and good corrosion resistance. However, designing new MG compositions is still a big challenge, and their integration into different systems is limited when they are in the shape of bulk materials. Here, we present a new method for the fabrication of MG in the form of microfibers which could greatly help them to be integrated within different systems. The newly proposed technique has the ability to form MG structure from commercially available alloy compositions thanks to its significantly improved quenching rate(~ 108 K.s−1). In this technique, individual melt droplets are ejected on a rotating wheel forming a thin film which are ruptured upon solidification leading to the formation of MG microfibers. In this regard, we have fabricated microfibers from a commercial DIN 1.4401 stainless-steel which could form a completely amorphous structure confirmed by DSC, XRD, and HRTEM. The fabricated MG microfibers show an increased hardness for more than two-fold from 3.5 ± 0.17 GPa for the as-received stainless-steel to 7.77 ± 0.60 GPa for the amorphous microfibers. Subsequent heat-treatment of the microfibers resulted in a nanocrystalline structure with the presence of amorphous regions when the hardness increases even further to 13.5 ± 2.0 GPa. We propose that confinement of both shear transformation zones and dislocations in the heat-treated MG microfibers plays a major role in enhancing strength.
A pupillometric study of developmental and individual differences in cognitive effort in visual word recognition
Authors: Shechter Adi , Hershman Ronen , Share David L.
Published: June 2022

Throughout the history of modern psychology, the neural basis of cognitive performance, and particularly its efficiency, has been assumed to be an essential determinant of developmental and individual differences in a wide range of human behaviors. Here, we examine one aspect of cognitive efficiency—cognitive effort, using pupillometry to examine differences in word reading among adults (N = 34) and children (N = 34). The developmental analyses confirmed that children invested more effort in reading than adults, as indicated by larger and sustained pupillary responses. The within-age (individual difference) analyses comparing faster (N = 10) and slower (N = 10) performers revealed that in both age groups, the faster readers demonstrated accelerated pupillary responses compared to slower readers, although both groups invested a similar overall degree of cognitive effort. These findings have the potential to open up new avenues of research in the study of skill growth in word recognition and many other domains of skill learning.
Random walk diffusion simulations in semi-permeable layered media with varying diffusivity
Authors: Alemany Ignasi , Rose Jan N. , Garnier-Brun Jérôme , Scott Andrew D. , Doorly Denis J.
Published: June 2022

In this paper we present random walk based solutions to diffusion in semi-permeable layered media with varying diffusivity. We propose a novel transit model for solving the interaction of random walkers with a membrane. This hybrid model is based on treating the membrane permeability and the step change in diffusion coefficient as two interactions separated by an infinitesimally small layer. By conducting an extensive analytical flux analysis, the performance of our hybrid model is compared with a commonly used membrane transit model (reference model). Numerical simulations demonstrate the limitations of the reference model in dealing with step changes in diffusivity and show the capability of the hybrid model to overcome this limitation and to offer substantial gains in computational efficiency. The suitability of both random walk transit models for the application to simulations of diffusion tensor cardiovascular magnetic resonance (DT-CMR) imaging is assessed in a histology-based domain relevant to DT-CMR. In order to demonstrate the usefulness of the new hybrid model for other possible applications, we also consider a larger range of permeabilities beyond those commonly found in biological tissues.
LXR agonist modifies neuronal lipid homeostasis and decreases PGD2 in the dorsal root ganglia in western diet-fed mice
Authors: Elshareif Nadia , Gavini Chaitanya K. , Mansuy-Aubert Virginie
Published: June 2022

The prevalence of peripheral neuropathy is high in diabetic and overweight populations. Chronic neuropathic pain, a symptom of peripheral neuropathy, is a major disabling symptom that leads to a poor quality of life. Glucose management for diabetic and prediabetic individuals often fail to reduce or improve pain symptoms, therefore, exploring other mechanisms is necessary to identify effective treatments. A large body of evidence suggest that lipid signaling may be a viable target for management of peripheral neuropathy in obese individuals. The nuclear transcription factors, Liver X Receptors (LXR), are known regulators of lipid homeostasis, phospholipid remodeling, and inflammation. Notably, the activation of LXR using the synthetic agonist GW3965, delayed western diet (WD)-induced allodynia in rodents. To further understand the neurobiology underlying the effect of LXR, we used translating ribosome affinity purification and evaluated translatomic changes in the sensory neurons of WD-fed mice treated with the LXR agonist GW3965. We also observed that GW3965 decreased prostaglandin levels and decreased free fatty acid content, while increasing lysophosphatidylcholine, phosphatidylcholine, and cholesterol ester species in the sensory neurons of the dorsal root ganglia (DRG). These data suggest novel downstream interplaying mechanisms that modifies DRG neuronal lipid following GW3965 treatment.
Mechanistic insights into photochromic 3H-naphthopyran showing strong photocoloration
Authors: Gierczyk Błażej , Rode Michał F. , Burdzinski Gotard
Published: June 2022

3,3-Diphenylbenzo[f]chromene (1) represents an important architectural platform for photochromic systems. Since the practical utility of such chromophores is largely dependent upon the kinetics of coloration and decoloration, elucidating the mechanistic details of these processes is of great value. Toward this end, we studied the photochromic reaction of (3-(2-methoxyphenyl)-3-phenyl-3H-benzo[f]chromene (2) by both time-resolved UV–vis and mid-IR spectroscopies. We found that irradiation of 2 at 365 nm generates long-lived colored transoid-cis isomers with lifetimes of 17.1 s and 17.5 min (at 21 °C) and even longer-lived transoid-trans isomers with a lifetime of 16 h. These experimental results were supplemented with ab initio ground-state and excited-state calculations, and the resulting theoretical interpretation may be useful for the design of new photochromic systems with optimized photofunctionality.
Critical contributions of pre-S1 shoulder and distal TRP box in DAG-activated TRPC6 channel by PIP2 regulation
Authors: Mori Masayuki X. , Okada Ryo , Sakaguchi Reiko , Hase Hideharu , Imai Yuko , Polat Onur K. , Itoh Satoru G. , Okumura Hisashi , Mori Yasuo , Okamura Yasushi , Inoue Ryuji
Published: June 2022

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 or PIP2) regulates the activities of numerous membrane proteins, including diacylglycerol(DAG)-activated TRPC3/6/7 channels. Although PIP2 binding is known to support DAG-activated TRP channel activity, its binding site remains unknown. We screened for PIP2 binding sites within TRPC6 channels through extensive mutagenesis. Using voltage-sensitive phosphatase (DrVSP), we found that Arg437 and Lys442, located in the channel’s pre-S1 domain/shoulder, are crucial for interaction with PIP2. To gain structural insights, we conducted computer protein–ligand docking simulations with the pre-S1 domain/shoulder of TRPC6 channels. Further, the functional significance of PIP2 binding to the pre-S1 shoulder was assessed for receptor-operated channel functions, cross-reactivity to DAG activation, and the kinetic model simulation. These results revealed that basic residues in the pre-S1 domain/shoulder play a central role in the regulation of PIP2-dependent gating. In addition, neutralizing mutation of K771 in the distal TRP box reversed the effect of PIP2 depletion from inhibiting to potentiating channel activity. A similar effect was seen in TRPV1 channels, which suggests that TRPC6 possesses a common but robust polarity switch mediating the PIP2-dependent effect. Overall, these mutagenesis studies reveal functional and structural insights for how basic residues and channel segments in TRP channels are controlled through phosphoinositides recognition.
Porous defective carbon ferrite for adsorption and photocatalysis toward nitrogen compounds in pre-treated biogas slurry
Authors: Li Jie
Published: June 2022

Carbon ferrite (C-Fe3O4) with hydrophilic functional groups and lattice defects was synthesized in anhydrous molten alkali system by fern leaves and ferric chloride as raw materials. Structural characterization results showed that carbon ferrite obtained oxygen-containing groups on the carbon surface. And structural pores and lattice defects resulted from spontaneous accumulation and “directive-connection” of ferrite (Fe3O4) nanoparticles. Carbon ferrite displayed an adsorption efficiency of 29.0% and excellent photocatalytic degradation of 80.8% toward nitrogen compounds (initial concentration of 430 mg/L) in pre-treated biogas slurry. The micromechanism for nitrogen compounds removal was discussed at the molecular/atomic level by exploring carbon ferrite “structure-activity”, which provides a design idea from microscopic perspective for the preparation of environmental materials with reactive sites.
Integrating variant functional annotation scores have varied abilities to improve power of genome-wide association studies
Authors: Gao Jianhui , Espin-Garcia Osvaldo , Paterson Andrew D. , Sun Lei
Published: June 2022

Functional annotations have the potential to increase power of genome-wide association studies (GWAS) by prioritizing variants according to their biological function, but this potential has not been well studied. We comprehensively evaluated all 1132 traits in the UK Biobank whose SNP-heritability estimates were given “medium” or “high” labels by Neale’s lab. For each trait, we integrated GWAS summary statistics of close to 8 million common variants (minor allele frequency$$>1\%$$>1%) with either their 75 individual functional scores or their meta-scores, using three different data-integration methods. Overall, the number of new genome-wide significant findings after data-integration increases as a trait SNP-heritability estimate increases. However, there is a trade-off between new findings and loss of baseline GWAS findings, resulting in similar total numbers of significant findings between using GWAS alone and integrating GWAS with functional scores, across all 1132 traits analyzed and all three data-integration methods considered. Our findings suggest that, even with the current biobank-level sample size, more informative functional scores and/or new data-integration methods are needed to further improve the power of GWAS of common variants. For example, studying variants in coding sequence and obtaining cell-type-specific scores are potential future directions.
Seasonal variations in the occurrence of preeclampsia and potential implication of upper respiratory infections in South Korea
Authors: Kim Eui Hyeok , Lee Sang Ah , Min Seunggi , Jung Yong Wook
Published: June 2022

The aim of this study was to examine the effect of seasonal changes on the incidence of preeclampsia (PE) in South Korea and East Asian populations, and to evaluate the relationship between upper respiratory infection (URI) during pregnancy and the development of PE. This cohort study included women who had singleton births between 2012 and 2018 in South Korea. A total of 548,080 first singleton births were analyzed, and 9311 patients (1.70%) were diagnosed with PE. Multivariate analysis showed that older age (≥ 30 years old), low income, residing in the southern part of South Korea, history of cigarette smoking, heavy drinking, higher body mass index, hypertension, or diabetes mellitus were risk factors for PE. Univariate analysis showed that URI was associated with the incidence of PE (P = 0.0294). However, this association was not statistically significant in the multivariate analysis (aOR 1.01; 95% CI 0.95–1.07). After adjusting for confounding variables, the occurrence of PE was the highest in December (aOR 1.21; 95% CI 1.10–1.34) and lowest in July and August. This study demonstrated that there are seasonal variations in the occurrence of PE in South Korea. Moreover, URI may be associated with the development of PE.
Acceleration and deceleration of quantum dynamics based on inter-trajectory travel with fast-forward scaling theory
Authors: Masuda Shumpei , Koenig Jacob , Steele Gary A.
Published: June 2022

Quantum information processing requires fast manipulations of quantum systems in order to overcome dissipative effects. We propose a method to accelerate quantum dynamics and obtain a target state in a shorter time relative to unmodified dynamics, and apply the theory to a system consisting of two linearly coupled qubits. We extend the technique to accelerate quantum adiabatic evolution in order to rapidly generate a desired target state, thereby realizing a shortcut to adiabaticity. Further, we address experimental limitations to the rate of change of control parameters for quantum devices which often limit one’s ability to generate a desired target state with high fidelity. We show that an initial state following decelerated dynamics can reach a target state while varying control parameters more slowly, enabling more experimentally feasible driving schemes.
Unusual free oligosaccharides in human bovine and caprine milk
Authors: Weng Wei-Chien , Liao Hung-En , Huang Shih-Pei , Tsai Shang-Ting , Hsu Hsu-Chen , Liew Chia Yen , Gannedi Veeranjaneyulu , Hung Shang-Cheng , Ni Chi-Kung
Published: June 2022

Free oligosaccharides are abundant macronutrients in milk and involved in prebiotic functions and antiadhesive binding of viruses and pathogenic bacteria to colonocytes. Despite the importance of these oligosaccharides, structural determination of oligosaccharides is challenging, and milk oligosaccharide biosynthetic pathways remain unclear. Oligosaccharide structures are conventionally determined using a combination of chemical reactions, exoglycosidase digestion, nuclear magnetic resonance spectroscopy, and mass spectrometry. Most reported free oligosaccharides are highly abundant and have lactose at the reducing end, and current oligosaccharide biosynthetic pathways in human milk are proposed based on these oligosaccharides. In this study, a new mass spectrometry technique, which can identify linkages, anomericities, and stereoisomers, was applied to determine the structures of free oligosaccharides in human, bovine, and caprine milk. Oligosaccharides that do not follow the current biosynthetic pathways and are not synthesized by any discovered enzymes were found, indicating the existence of undiscovered biosynthetic pathways and enzymes.
Deficiency of exopolysaccharides and O-antigen makes Halomonas bluephagenesis self-flocculating and amenable to electrotransformation
Authors: Xu Tong , Chen Junyu , Mitra Ruchira , Lin Lin , Xie Zhengwei , Chen Guo-Qiang , Xiang Hua , Han Jing
Published: June 2022

Halomonas bluephagenesis, a haloalkaliphilic bacterium and native polyhydroxybutyrate (PHB) producer, is a non-traditional bioproduction chassis for the next generation industrial biotechnology (NGIB). A single-sgRNA CRISPR/Cas9 genome editing tool is optimized using dual-sgRNA strategy to delete large DNA genomic fragments (>50 kb) with efficiency of 12.5% forH. bluephagenesis. The non-essential or redundant gene clusters ofH. bluephagenesis, including those encoding flagella, exopolysaccharides (EPSs) and O-antigen, are sequentially deleted using this improved genome editing strategy. Totally, ~3% of the genome is reduced with its rapid growth and high PHB-production ability unaffected. The deletion of EPSs and O-antigen gene clusters shows two excellent properties from industrial perspective. Firstly, the EPSs and O-antigen deleted mutant rapidly self-flocculates and precipitates within 20 min without centrifugation. Secondly, DNA transformation into the mutant using electroporation becomes feasible compared to the wild-typeH. bluephagenesis. The genome-reducedH. bluephagenesismutant reduces energy and carbon source requirement to synthesize PHB comparable to its wild type. TheH. bluephagenesischassis with a reduced genome serves as an improved version of a NGIB chassis for productions of polyhydroxyalkanoates (PHA) or other chemicals.
The influence of HLA genotype on the development of metal hypersensitivity following joint replacement
Authors: Langton David J. , Bhalekar Rohan M. , Joyce Thomas J. , Rushton Stephen P. , Wainwright Benjamin J. , Nargol Matthew E. , Shyam Nish , Lie Benedicte A. , Pabbruwe Moreica B. , Stewart Alan J. , Waller Susan , Natu Shonali , Ren Renee , Hornick Rachelle , Darlay Rebecca , Su Edwin P. , Nargol Antoni V. F.
Published: June 2022

Background

Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed-type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established.

Methods

At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype, and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time-dependent receiver operator curves.

Results

Using next-generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure, and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1% for pre-operative and post-operative models respectively.

Conclusions

The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient’s genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient-specific responses to different biomaterials.
General Aspects – Current and Future Perspectives
Authors: Liwszyc Guillermo Eli , Larramendy Marcelo L.
Published: June 2022

Environmental risk assessment is a scientific practice that identifies and evaluates the likelihood of an activity or substance to threaten the environment in general, and/or living organisms, natural habitats and ecosystems, in particular. It is a term used to describe the overall process or method allowing (a) the identification of hazards and risk factors that have the potential to cause harm and (b) the analysis and evaluation of the risk associated with that particular hazard. It also suggests all the appropriate ways to eliminate or minimize the hazard, or control the risk when the hazard cannot be eliminated. This book covers many non-traditional marsupial and placental mammalian species employed to analyse the jeopardising effects of environmental pollutants, as well as examples of applications of models in integrated assessment solutions. We hope that this book will provide answers or at least provide some clues to the inherent potential risk of the presence of these xenobiotics in our environment. This book aims to shed some light on the matter, whilst offering relevant tools for evaluating risk and providing a framework of practical discussions. These will foster decisions and actions required to reduce environmental health risks against environmental factors. This book presents some real-life examples, extending concepts (of hazardous factors) to living species that may stimulate new research ideas and trends in the relevant fields.
Didelphis virginiana (Marsupialia, Didelphimorphia): A Proposal for its Use as a Biomonitor of Environmental Pollution
Authors: Ruiz-Piña Hugo Antonio , Osten Jaime Rendón-von , Flores-Serrano Rosa María
Published: June 2022

There is a lack of scientific research in the literature on the ecotoxicology of marsupials, more specifically on opossums of the genus Didelphis. So far, little is known about how marsupials have responded to disturbances caused by strong anthropogenic antecedents, both present and past. Currently, there are very few studies related to the presence of contaminants in opossums and even fewer regarding the evaluation of the possible effects that these contaminants may exert on these organisms. Studies on the presence of organochlorine pesticide residues in tissue and blood samples, and polycyclic aromatic hydrocarbons in muscle and other tissues of the Virginia opossum, Didelphis virginiana, have confirmed this suspicion. Likewise, there is evidence of the presence of metals in the hair and livers of opossums. The wide distribution of D. virginiana in rural and urban environments of the American continent and its feeding habits allow us to use the opossum as a good bioindicator of human environmental contamination in any region where it is found, as well as a receptor species in ecological risk assessments.
Marine Mammals as Indicators of Environmental Pollution and Potential Health Effects
Authors: Desforges J.-P. W. , Siebert U. , Routti H. , Levin M. , Dietz R. , Basu N. , Letcher R. J. , Jenssen B. M. , Sonne C.
Published: June 2022

The study and protection of environmental and human health is complex given the variety of anthropogenic and natural stressors threatening the well-being of exposed organisms. Researchers have turned to wild animals as sentinel species to study the critical questions relating to environmental chemical contamination and potential adverse health effects of contaminant exposure. Marine mammals are one group of animals that are particularly suited as indicators of environmental health because of their long lifespan, high trophic level, spatial distribution at various scales, and propensity to accumulate and respond to environmental contaminants. This chapter discusses how marine mammals are used to monitor and identify chemical pollutants of concern and determine potential health effects on practically all vertebrate physiological systems and across biological scales, from the molecular to the population level. We highlight the diversity of study designs, pollutant classes, methodological tools, and unique insights gained on source, transport, fate, and health effects of contaminants from studies of marine mammal toxicology to showcase the usefulness of these sentinel species as indicators in ecotoxicology.
Transition metal-catalysed carbene- and nitrene transfer to carbon monoxide and isocyanides
Authors: Roose T. R. , Verdoorn D. S. , Mampuys P. , Ruijter E. , Maes B. U. W. , Orru R. V. A.
Published: June 2022

In this review the transition metal-catalysed carbene- and nitrene transfer to carbon monoxide and isocyanides will be disclosed. The resulting heteroallene allows for in situ transformation towards numerous functional groups and organic compounds.
Understanding and modelling the magnitude of the change in current of nanopore sensors
Authors: Tang Wenxian , Fried Jasper P. , Tilley Richard D. , Gooding J. Justin
Published: June 2022

This paper reviews various theoretical models used for understanding the magnitude of the current responses of nanopore sensors.
Comparative performance and ecotoxicity assessment of Y2(CO3)3, ZnO/TiO2, and Fe3O4 nanoparticles for arsenic removal from water
Authors: Salazar H. , Martins P. M. , Batista Daniela , Shejale K. P. , Sharma R. K. , R. Krishnapriya , Ferdov S. , Botelho G. , Fidalgo-Marijuan A. , Cássio Fernanda , Lanceros-Mendez S.
Published: June 2022

This systematic study includes physical–chemical characterisation of nanomaterials, arsenic adsorption assays, adsorption mechanism proposal, and acute toxicity assays with Daphnia magna.
RNA-seq-based transcriptome analysis of the anti-inflammatory effect of artesunate in the early treatment of the mouse cerebral malaria model
Authors: Wang Qi , Tang Yexiao , Pan Ziyi , Yuan Yueming , Zou Yuanyuan , Zhang Hongying , Guo Xueying , Guo Wenfeng , Huang Xinan , Wu Zhibin , Li Changqing , Xu Qin , Song Jianping , Deng Changsheng
Published: June 2022

The present study provides new insights into the molecular mechanisms by which artesunate improves prognosis in cerebral malaria, in particular inhibition of host cytokine storm.
Simple ultrasensitive electrochemical detection of the DBP plasticizer for the risk assessment of South Korean river waters
Authors: Gurudatt N. G. , Lee Kyungyeon , Heo Woong , Jung Hyo-Il
Published: June 2022

We present a simple electrochemical strategy for the ultrasensitive quantitative analysis of DBP plasticizer in water. The proposed aptasensor is comparable to GC-MS in sensitivity and it was applied to monitor the river waters contamination.
In situ forming injectable γ-poly(glutamic acid)/PEG adhesive hydrogels for hemorrhage control
Authors: Ye Huijun , Xian Yiwen , Li Shurong , Zhang Chong , Wu Decheng
Published: June 2022

An injectable adhesive hydrogel based on N-hydroxysuccinimide γ-poly(glutamic acid) and 4-armed poly(ethylene glycol) amine showed rapid gelation time, strong mechanical strength, satisfactory burst pressure and excellent hemostatic performance.
A novel photoelectrochemical sensor based on SiNWs@PDA for efficient detection of myocardial infarction
Authors: Li Hui-Jun , Zhi Shibo , Zhang Shen , Guo Xiaoyu , Huang Yueyi , Xu Ling , Wang Xianying , Wang Ding , Zhu Minfang , He Bin
Published: June 2022

A simple-structured photoelectrochemical immunosensor was constructed from polydopamine and silicon nanowire arrays. This type of sensor facilitates rapid detection of troponin I.
Medical applications of biopolymer nanofibers
Authors: Jeevanandam Jaison , Pan Sharadwata , Rodrigues João , Elkodous M. Abd , Danquah Michael K.
Published: June 2022

This review is an overview of various biopolymer nanofibers and their distinct synthesis approaches. Further, the medical applications of biopolymer nanofibers, including drug delivery systems and biosensor fabrication, are also discussed.
Highly dispersed silica-supported iridium and iridium–aluminium catalysts for methane activation prepared via surface organometallic chemistry
Authors: Escomel Léon , Abbott Daniel F. , Mougel Victor , Veyre Laurent , Thieuleux Chloé , Camp Clément
Published: June 2022

The grafting of an iridium-aluminium precursor onto silica followed by thermal treatment under H2 yields small (<2 nm), narrowly distributed nanoparticles used as catalysts for methane H/D exchange.