bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Cpt1a-Bcl-2 interaction modulates apoptosis resistance and fibrotic remodeling
Authors: Gu Linlin , Surolia Ranu , Larson-Casey Jennifer L. , He Chao , Davis Dana , Kang Jungsoon , Antony Veena B. , Carter A. Brent
Published: August 2021

The mitochondrial calcium uniporter (MCU) regulates metabolic reprogramming in lung macrophages and the progression of pulmonary fibrosis. Fibrosis progression is associated with apoptosis resistance in lung macrophages; however, the mechanism(s) by which apoptosis resistance occurs is poorly understood. Here, we found a marked increase in mitochondrial B-cell lymphoma-2 (Bcl-2) in lung macrophages from subjects with idiopathic pulmonary fibrosis (IPF). Similar findings were seen in bleomycin-injured wild-type (WT) mice, whereas Bcl-2 was markedly decreased in mice expressing a dominant-negative mitochondrial calcium uniporter (DN-MCU). Carnitine palmitoyltransferase 1a (Cpt1a), the rate-limiting enzyme for fatty acid β-oxidation, directly interacted with Bcl-2 by binding to its BH3 domain, which anchored Bcl-2 in the mitochondria to attenuate apoptosis. This interaction was dependent on Cpt1a activity. Lung macrophages from IPF subjects had a direct correlation between CPT1A and Bcl-2, whereas the absence of binding induced apoptosis. The deletion of Bcl-2 in macrophages protected mice from developing pulmonary fibrosis. Moreover, mice had resolution when Bcl-2 was deleted or was inhibited with ABT-199 after fibrosis was established. These observations implicate an interplay between macrophage fatty acid β-oxidation, apoptosis resistance, and dysregulated fibrotic remodeling.
Activation or exhaustion of CD8+ T cells in patients with COVID-19
Authors: Rha Min-Seok , Shin Eui-Cheol
Published: August 2021

In addition to CD4+T cells and neutralizing antibodies, CD8+T cells contribute to protective immune responses against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In patients with COVID-19, CD8+T cells exhibiting activated phenotypes are commonly observed, although the absolute number of CD8+T cells is decreased. In addition, several studies have reported an upregulation of inhibitory immune checkpoint receptors, such as PD-1, and the expression of exhaustion-associated gene signatures in CD8+T cells from patients with COVID-19. However, whether CD8+T cells are truly exhausted during COVID-19 has been a controversial issue. In the present review, we summarize the current understanding of CD8+T-cell exhaustion and describe the available knowledge on the phenotypes and functions of CD8+T cells in the context of activation and exhaustion. We also summarize recent reports regarding phenotypical and functional analyses of SARS-CoV-2-specific CD8+T cells and discuss long-term SARS-CoV-2-specific CD8+T-cell memory.
Myopia prevalence and ocular biometry: a cross-sectional study among minority versus Han schoolchildren in Xinjiang Uygur autonomous region, China
Authors: Shi Yumeng , Wang Yan , Cui Aizhi , Liu Sen , He Xiaolan , Qiu Huijuan , Cui Hanwen , Gao Yunxian , Yang Jin
Published: August 2021

Objectives

To describe and compare the prevalence of refractive error and its associated ocular biometric parameters in a large multi-racial sample of schoolchildren from Xinjiang.

Methods

A total of 67,102 school children of five ethnicity groups aged 6–23 years from 46 schools in Xinjiang participated in this study. The children underwent a comprehensive eye examination for vision screening, including uncorrected visual acuity and standardized refraction. Refractive error was determined by autorefractors and subjective refraction. Refraction was recorded in spherical equivalent (SE). The age- and sex- adjusted prevalence of myopia (SE ≤ −0.5 D), low myopia (−6 D < SE ≤ −0.5 D), high myopia (SE ≤ −6.0 D), astigmatism (cylinder < −0.5 D), and anisometropia (difference in SE between two eyes of 1.0 D) in the five ethnic groups were calculated. Ocular biometric parameters including axial length (AL) and corneal radius of curvature (CR) were measured by AL-scan optical biometer.

Results

The age- and sex- adjusted prevalence of myopia in the Han, Hui, Uyghur, Kyrgyz and Kazakh were 65.8% (95% confidence interval [CI] 65.4, 66.3); 59.1% (95% CI 57.8, 60.4); 30.1% (95% CI 29.2, 30.9); 30.2 (95% CI 28.9, 31.4); and 30.0% (95% CI 27.6, 32.3), respectively. The Han and Hui children also had longer ALs (Han, 23.8; Hui, 23.6, Uyghur, 23.1; Kyrgyz, 23.1; Kazakh, 23.3 mm) and larger AL/CR (Han, 3.04; Hui, 3.00; Uyghur, 2.95; Kyrgyz, 2.96; Kazakh, 2.97) values than the other three minorities (P < 0.01). Overall, girls had shorter ALs, steeper corneas, and smaller AL/CR values than boys (P < 0.01).

Conclusions

Significant ethnic difference in the prevalence of myopia was observed in this study on school-aged children in Xinjiang (Han > Hui > Kyrgyz > Uyghur > Kazakh). This study among different ethnic groups in a multiethnic population is valuable for enriching the ethnical information resources for refractive errors and ocular biometry parameters, as well as facilitating further research on myopia-related diseases and risks.
Quantum theory of the nonlinear Hall effect
Authors: Du Z. Z. , Wang C. M. , Sun Hai-Peng , Lu Hai-Zhou , Xie X. C.
Published: August 2021

The nonlinear Hall effect is an unconventional response, in which a voltage can be driven by two perpendicular currents in the Hall-bar measurement. Unprecedented in the family of the Hall effects, it can survive time-reversal symmetry but is sensitive to the breaking of discrete and crystal symmetries. It is a quantum transport phenomenon that has deep connection with the Berry curvature. However, a full quantum description is still absent. Here we construct a quantum theory of the nonlinear Hall effect by using the diagrammatic technique. Quite different from nonlinear optics, nearly all the diagrams account for the disorder effects, which play decisive role in the electronic transport. After including the disorder contributions in terms of the Feynman diagrams, the total nonlinear Hall conductivity is enhanced but its sign remains unchanged for the 2D tilted Dirac model, compared to the one with only the Berry curvature contribution. We discuss the symmetry of the nonlinear conductivity tensor and predict a pure disorder-induced nonlinear Hall effect for point groups C3, C3h, C3v, D3h, D3 in 2D, and T, Td, C3h, D3h in 3D. This work will be helpful for explorations of the topological physics beyond the linear regime.
Creating synthetic spaces for higher-order topological sound transport
Authors: Chen Hui , Zhang Hongkuan , Wu Qian , Huang Yu , Nguyen Huy , Prodan Emil , Zhou Xiaoming , Huang Guoliang
Published: August 2021

Modern technological advances allow for the study of systems with additional synthetic dimensions. Higher-order topological insulators in topological states of matters have been pursued in lower physical dimensions by exploiting synthetic dimensions with phase transitions. While synthetic dimensions can be rendered in the photonics and cold atomic gases, little to no work has been succeeded in acoustics because acoustic wave-guides cannot be weakly coupled in a continuous fashion. Here, we formulate the theoretical principles and manufacture acoustic crystals composed of arrays of acoustic cavities strongly coupled through modulated channels to evidence one-dimensional (1D) and two-dimensional (2D) dynamic topological pumpings. In particular, the higher-order topological edge-bulk-edge and corner-bulk-corner transport are physically illustrated in finite-sized acoustic structures. We delineate the generated 2D and four-dimensional (4D) quantum Hall effects by calculating first and second Chern numbers and physically demonstrate robustness against the geometrical imperfections. Synthetic dimensions could provide a powerful way for acoustic topological wave steering and open up a platform to explore any continuous orbit in higher-order topological matter in dimensions four and higher.
Integration of FRET and sequencing to engineer kinase biosensors from mammalian cell libraries
Authors: Liu Longwei , Limsakul Praopim , Meng Xianhui , Huang Yan , Harrison Reed E. S. , Huang Tse-Shun , Shi Yiwen , Yu Yiyan , Charupanit Krit , Zhong Sheng , Lu Shaoying , Zhang Jin , Chien Shu , Sun Jie , Wang Yingxiao
Published: August 2021

The limited sensitivity of Förster Resonance Energy Transfer (FRET) biosensors hinders their broader applications. Here, we develop an approach integrating high-throughput FRET sorting and next-generation sequencing (FRET-Seq) to identify sensitive biosensors with varying substrate sequences from large-scale libraries directly in mammalian cells, utilizing the design of self-activating FRET (saFRET) biosensor. The resulting biosensors of Fyn and ZAP70 kinases exhibit enhanced performance and enable the dynamic imaging of T-cell activation mediated by T cell receptor (TCR) or chimeric antigen receptor (CAR), revealing a highly organized ZAP70 subcellular activity pattern upon TCR but not CAR engagement. The ZAP70 biosensor elucidates the role of immunoreceptor tyrosine-based activation motif (ITAM) in affecting ZAP70 activation to regulate CAR functions. A saFRET biosensor-based high-throughput drug screening (saFRET-HTDS) assay further enables the identification of an FDA-approved cancer drug, Sunitinib, that can be repurposed to inhibit ZAP70 activity and autoimmune-disease-related T-cell activation.
A simple pressure-assisted method for MicroED specimen preparation
Authors: Zhao Jingjing , Xu Hongyi , Lebrette Hugo , Carroni Marta , Taberman Helena , Högbom Martin , Zou Xiaodong
Published: August 2021

Micro-crystal electron diffraction (MicroED) has shown great potential for structure determination of macromolecular crystals too small for X-ray diffraction. However, specimen preparation remains a major bottleneck. Here, we report a simple method for preparing MicroED specimens, named Preassis, in which excess liquid is removed through an EM grid with the assistance of pressure. We show the ice thicknesses can be controlled by tuning the pressure in combination with EM grids with appropriate carbon hole sizes. Importantly, Preassis can handle a wide range of protein crystals grown in various buffer conditions including those with high viscosity, as well as samples with low crystal concentrations. Preassis is a simple and universal method for MicroED specimen preparation, and will significantly broaden the applications of MicroED.
Bacterial cellulose spheroids as building blocks for 3D and patterned living materials and for regeneration
Authors: Caro-Astorga Joaquin , Walker Kenneth T. , Herrera Natalia , Lee Koon-Yang , Ellis Tom
Published: August 2021

Engineered living materials (ELMs) based on bacterial cellulose (BC) offer a promising avenue for cheap-to-produce materials that can be programmed with genetically encoded functionalities. Here we explore how ELMs can be fabricated in a modular fashion from millimetre-scale biofilm spheroids grown from shaking cultures of Komagataeibacter rhaeticus. Here we define a reproducible protocol to produce BC spheroids with the high yield bacterial cellulose producer K. rhaeticus and demonstrate for the first time their potential for their use as building blocks to grow ELMs in 3D shapes. Using genetically engineered K. rhaeticus, we produce functionalized BC spheroids and use these to make and grow patterned BC-based ELMs that signal within a material and can sense and report on chemical inputs. We also investigate the use of BC spheroids as a method to regenerate damaged BC materials and as a way to fuse together smaller material sections of cellulose and synthetic materials into a larger piece. This work improves our understanding of BC spheroid formation and showcases their great potential for fabricating, patterning and repairing ELMs based on the promising biomaterial of bacterial cellulose.
Predicting carbon nanotube forest attributes and mechanical properties using simulated images and deep learning
Authors: Hajilounezhad Taher , Bao Rina , Palaniappan Kannappan , Bunyak Filiz , Calyam Prasad , Maschmann Matthew R.
Published: August 2021

Understanding and controlling the self-assembly of vertically oriented carbon nanotube (CNT) forests is essential for realizing their potential in myriad applications. The governing process–structure–property mechanisms are poorly understood, and the processing parameter space is far too vast to exhaustively explore experimentally. We overcome these limitations by using a physics-based simulation as a high-throughput virtual laboratory and image-based machine learning to relate CNT forest synthesis attributes to their mechanical performance. Using CNTNet, our image-based deep learning classifier module trained with synthetic imagery, combinations of CNT diameter, density, and population growth rate classes were labeled with an accuracy of >91%. The CNTNet regression module predicted CNT forest stiffness and buckling load properties with a lower root-mean-square error than that of a regression predictor based on CNT physical parameters. These results demonstrate that image-based machine learning trained using only simulated imagery can distinguish subtle CNT forest morphological features to predict physical material properties with high accuracy. CNTNet paves the way to incorporate scanning electron microscope imagery for high-throughput material discovery.
Personalized medicine for reconstruction of critical-size bone defects – a translational approach with customizable vascularized bone tissue
Authors: Kengelbach-Weigand Annika , Thielen Carolina , Bäuerle Tobias , Götzl Rebekka , Gerber Thomas , Körner Carolin , Beier Justus P. , Horch Raymund E. , Boos Anja M.
Published: August 2021

Tissue engineering principles allow the generation of functional tissues for biomedical applications. Reconstruction of large-scale bone defects with tissue-engineered bone has still not entered the clinical routine. In the present study, a bone substitute in combination with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) with or without growth factors BMP-2 and VEGF-A was prevascularized by an arteriovenous (AV) loop and transplanted into a critical-size tibia defect in the sheep model. With 3D imaging and immunohistochemistry, we could show that this approach is a feasible and simple alternative to the current clinical therapeutic option. This study serves as proof of concept for using large-scale transplantable, vascularized, and customizable bone, generated in a living organism for the reconstruction of load-bearing bone defects, individually tailored to the patient’s needs. With this approach in personalized medicine for the reconstruction of critical-size bone defects, regeneration of parts of the human body will become possible in the near future.
Poplar-based thermochromic composites that change colour at 38 °C to 46 °C
Authors: Zou Weihua , Li Zimu , Wang Zhangheng , Sun Delin , Zhang Pingfang
Published: August 2021

The red thermochromic dye (R-TD) is the tetradecanoic acid tetradecyl ester (C28H56O2) and methyl red (C15H15N3O2) mixture that has better permeability enabling its infiltration into wood and better thermochromic properties changing its colour at above 30 °C after about 0.5 min. Thicker poplar-based thermochromic composite specimens (R-PTC, thickness: 5.0 mm) were prepared by filling the R-TD into pre-treated poplar veneer (thickness: 5.0 mm) thus allowing better penetration after pre-treatment. After R-TD infiltration, the R-PTC samples were covered by polypropylene wax for preventing R-TD from overflowing from R-PTC under the action of phase-change temperature. This R-PTC, whose colour can change from light-red to dark-red at 38 °C to 46 °C, can recover to light-red at below 38 °C after about 14 h, and the peak of colour change is at about 42 °C. R-PTC will be suitable for materials used in thermochromic furniture that can indicate the surface temperature to potential users, thus allowing assessment of likely scalded pain when used the furniture.
Cannabis and tobacco use prior to pregnancy and subsequent offspring birth outcomes: a 20-year intergenerational prospective cohort study
Authors: Hines Lindsey A. , Spry Elizabeth A. , Moreno-Betancur Margarita , Mohamad Husin Hanafi , Becker Denise , Middleton Melissa , Craig Jeffrey M. , Doyle Lex W. , Olsson Craig A. , Patton George
Published: August 2021

There is increasing evidence that the life-course origins of health and development begin before conception. We examined associations between timing and frequency of preconception cannabis and tobacco use and next generation preterm birth (PTB), low birth weight (LBW) and small for gestational age. 665 participants in a general population cohort were repeatedly assessed on tobacco and cannabis use between ages 14–29 years, before pregnancy. Associations were estimated using logistic regression. Preconception parent (either maternal or paternal) daily cannabis use age 15–17 was associated with sixfold increases in the odds of offspring PTB (aOR 6.65, 95% CI 1.92, 23.09), and offspring LBW (aOR 5.84, 95% CI 1.70–20.08), after adjusting for baseline sociodemographic factors, parent sex, offspring sex, family socioeconomic status, parent mental health at baseline, and concurrent tobacco use. There was little evidence of associations with preconception parental cannabis use at other ages or preconception parental tobacco use. Findings support the hypothesis that the early life origins of growth begin before conception and provide a compelling rationale for prevention of frequent use during adolescence. This is pertinent given liberalisation of cannabis policy.
Quantum tunneling and quantum walks as algorithmic resources to solve hard K-SAT instances
Authors: Campos Ernesto , Venegas-Andraca Salvador E. , Lanzagorta Marco
Published: August 2021

We present a new quantum heuristic algorithm aimed at finding satisfying assignments for hard K-SAT instances using a continuous time quantum walk that explicitly exploits the properties of quantum tunneling. Our algorithm uses a Hamiltonian $$H_A(F)$$

H
A

(
F
)

which is specifically constructed to solve a K-SAT instance F. The heuristic algorithm aims at iteratively reducing the Hamming distance between an evolving state $${|{\psi _j}\rangle }$$

|

ψ
j

⟩

and a state that represents a satisfying assignment for F. Each iteration consists on the evolution of $${|{\psi _j}\rangle }$$

|

ψ
j

⟩

(where j is the iteration number) under $$e^{-iH_At}$$

e

-
i

H
A

t

, a measurement that collapses the superposition, a check to see if the post-measurement state satisfies F and in the case it does not, an update to $$H_A$$

H
A

for the next iteration. Operator $$H_A$$

H
A

describes a continuous time quantum walk over a hypercube graph with potential barriers that makes an evolving state to scatter and mostly follow the shortest tunneling paths with the smaller potentials that lead to a state $${|{s}\rangle }$$

|
s
⟩

that represents a satisfying assignment for F. The potential barriers in the Hamiltonian $$H_A$$

H
A

are constructed through a process that does not require any previous knowledge on the satisfying assignments for the instance F. Due to the topology of $$H_A$$

H
A

each iteration is expected to reduce the Hamming distance between each post measurement state and a state $${|{s}\rangle }$$

|
s
⟩

. If the state $${|{s}\rangle }$$

|
s
⟩

is not measured after n iterations (the number n of logical variables in the instance F being solved), the algorithm is restarted. Periodic measurements and quantum tunneling also give the possibility of getting out of local minima. Our numerical simulations show a success rate of 0.66 on measuring $${|{s}\rangle }$$

|
s
⟩

on the first run of the algorithm (i.e., without restarting after n iterations) on thousands of 3-SAT instances of 4, 6, and 10 variables with unique satisfying assignments.
Thermostable adenosine 5′-monophosphate phosphorylase from Thermococcus kodakarensis forms catalytically active inclusion bodies
Authors: Kamel Sarah , Walczak Miriam C. , Kaspar Felix , Westarp Sarah , Neubauer Peter , Kurreck Anke
Published: August 2021

Catalytically active inclusion bodies (CatIBs) produced in Escherichia coli are an interesting but currently underexplored strategy for enzyme immobilization. They can be purified easily and used directly as stable and reusable heterogenous catalysts. However, very few examples of CatIBs that are naturally formed during heterologous expression have been reported so far. Previous studies have revealed that the adenosine 5′-monophosphate phosphorylase of Thermococcus kodakarensis (TkAMPpase) forms large soluble multimers with high thermal stability. Herein, we show that heat treatment of soluble protein from crude extract induces aggregation of active protein which phosphorolyse all natural 5′-mononucleotides. Additionally, inclusion bodies formed during the expression in E. coli were found to be similarly active with 2–6 folds higher specific activity compared to these heat-induced aggregates. Interestingly, differences in the substrate preference were observed. These results show that the recombinant thermostable TkAMPpase is one of rare examples of naturally formed CatIBs.
Spatial regression and geostatistics discourse with empirical application to precipitation data in Nigeria
Authors: Okunlola Oluyemi A. , Alobid Mohannad , Olubusoye Olusanya E. , Ayinde Kayode , Lukman Adewale F. , Szűcs István
Published: August 2021

In this study, we propose a robust approach to handling geo-referenced data and discuss its statistical analysis. The linear regression model has been found inappropriate in this type of study. This motivates us to redefine its error structure to incorporate the spatial components inherent in the data into the model. Therefore, four spatial models emanated from the re-definition of the error structure. We fitted the spatial and the non-spatial linear model to the precipitation data and compared their results. All the spatial models outperformed the non-spatial model. The Spatial Autoregressive with additional autoregressive error structure (SARAR) model is the most adequate among the spatial models. Furthermore, we identified the hot and cold spot locations of precipitation and their spatial distribution in the study area.
Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients
Authors: Solana Elisabeth , Martinez-Heras Eloy , Montal Victor , Vilaplana Eduard , Lopez-Soley Elisabet , Radua Joaquim , Sola-Valls Nuria , Montejo Carmen , Blanco Yolanda , Pulido-Valdeolivas Irene , Sepúlveda Maria , Andorra Magi , Berenguer Joan , Villoslada Pablo , Martinez-Lapiscina E. H. , Prados Ferran , Saiz Albert , Fortea Juan , Llufriu Sara
Published: August 2021

The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5–15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.
Optimizing﻿ ethyl cellulose-ethanol delivery towards enabling ablation of cervical dysplasia
Authors: Mueller Jenna L. , Morhard Robert , DeSoto Michael , Chelales Erika , Yang Jeffrey , Nief Corrine , Crouch Brian , Everitt Jeffrey , Previs Rebecca , Katz David , Ramanujam Nimmi
Published: August 2021

In low-income countries, up to 80% of women diagnosed with cervical dysplasia do not return for follow-up care, primarily due to treatment being inaccessible. Here, we describe development of a low-cost, portable treatment suitable for such settings. It is based on injection of ethyl cellulose (EC)-ethanol to ablate the transformation zone around the os, the site most impacted by dysplasia. EC is a polymer that sequesters the ethanol within a prescribed volume when injected into tissue, and this is modulated by the injected volume and delivery parameters (needle gauge, bevel orientation, insertion rate, depth, and infusion rate). Salient injection-based delivery parameters were varied in excised swine cervices. The resulting injection distribution volume was imaged with a wide-field fluorescence imaging device or computed tomography. A 27G needle and insertion rate of 10 mm/s achieved the desired insertion depth in tissue.Orienting the needle bevel towards the outer edge of the cervix and keeping infusion volumes ≤ 500 µL minimized leakage into off-target tissue. These results guided development of a custom hand-held injector, which was used to locate and ablate the upper quadrant of a swine cervix in vivo with no adverse events or changes in host temperature or heart rate. After 24 h, a distinct region of necrosis was detected that covered a majority (> 75%) of the upper quadrant of the cervix, indicating four injections could effectively cover the full cervix. The work here informs follow up large animal in vivo studies, e.g. in swine, to further assess safety and efficacy of EC-ethanol ablation in the cervix.
Cannabinoid receptor 2 deletion influences social memory and synaptic architecture in the hippocampus
Authors: Komorowska-Müller Joanna Agnieszka , Ravichandran Kishore Aravind , Zimmer Andreas , Schürmann Britta
Published: August 2021

Although the cannabinoid receptor 2 (CB2R) is often thought to play a role mainly outside the brain several publications unequivocally showed the presence of CB2R on hippocampal principal neurons. Activation of CB2R produced a long-lasting membrane potential hyperpolarization, altered the input/output function of CA2/3 principal neurons and produced alterations in gamma oscillations. However, other cellular, molecular and behavioral consequences of hippocampal CB2R signaling have not been studied in detail. Here we demonstrate that the deletion of CB2 leads to a highly significant increase in hippocampal synapsin-I expression levels and particle density, as well as increased vesicular GABA transporter (vGAT) levels. This phenotype was restricted to females and not observed in males. Furthermore, we demonstrate an impairment of social memory in CB2 deficient mice. Our results thus demonstrate that the lack of CB2R leads to changes in the hippocampal synaptic landscape and reveals an important sex-specific difference in endocannabinoid signaling. This study supports a significant role of the CB2R in modulation of different types of memory despite its low expression levels in the brain and provides more insight into a sex-specific role of CB2R in synaptic architecture.
Dioecious hemp (Cannabis sativa L.) plants do not express significant sexually dimorphic morphology in the seedling stage
Authors: Campbell Lesley G. , Peach Kristen , Wizenberg Sydney B.
Published: August 2021

Some economically important crop species are dioecious, producing pollen and ovules on distinct, unisexual, individuals. On-the-spot diagnosis of sex is important to breeders and farmers for crop improvement and maximizing yield, yet diagnostic tools at the seedling stage are understudied and lack a scientific basis. Understanding sexual dimorphism in juvenile plants may provide key ecological, evolutionary and economic insights into dioecious plant species in addition to improving the process of crop cultivation. To address this gap in the literature, we asked: can we reliably differentiate males, females, and co-sexual individuals based on seedling morphology in Cannabis sativa, and do the traits used to distinguish sex at this stage vary between genotypes? To answer these questions, we collected data on phenotypic traits of 112 C. sativa plants (50 female, 52 male, 10 co-sexuals) from two hemp cultivars (CFX-1, CFX-2) during the second week of vegetative growth and used ANOVAs to compare morphology among sexes. We found males grew significantly longer hypocotyls than females by week 2, but this difference depended on the cultivar investigated. Preliminary evidence suggests that co-sexual plants may be distinguished from male and female plants using short hypocotyl length and seedling height, although this relationship requires more study since sample sizes of co-sexual plants were small. In one of the cultivars, two-week old male plants tend to produce longer hypocotyls than other plants, which may help to identify these plants prior to anthesis. We call for increased research effort on co-sexual plants, given their heavy economic cost in industrial contexts and rare mention in the literature. Our preliminary data suggests that short hypocotyl length may be an indicator of co-sexuality. These results are the first steps towards developing diagnostic tools for predicting sex using vegetative morphology in dioecious species and understanding how sexual dimorphism influences phenotype preceding sexual maturity.
Investigation of vibrational manner of carbon nanotubes in the vicinity of ultrasonic argon flow using molecular dynamics simulation
Authors: Karami Iman , Eftekhari S. Ali , Toghraie Davood
Published: August 2021

Among various types of nanostructures, carbon nanotube (CNT) is one of the most important nanostructures. These nanostructures have been considered due to their mechanical, thermal, and vibrational properties. In this research, this nanostructure’s vibrational behavior in the vicinity of argon flow in the vicinity of ultrasonic velocity was investigated. The effect of factors such as the stability of atomic structures, the atomic manner of carbon nanotubes in the presence of ultrasonic fluid, the influence of carbon nanotubes’ length, and the chirality of carbon nanotubes on vibrational behavior was studied by molecular dynamics simulation. The MD simulations display an enhance in amplitude and a decrease in the oscillation frequency. Physically, these simulations’ results indicated the appropriate mechanical strength of carbon nanotubes in the presence of argon fluid. Numerically, the simulated carbon nanotubes’ minimum oscillation amplitude and frequency were equal to 2.02 nm and 10.14 ps−1. On the other hand, the maximum physical quantities were expressed as 4.03 nm and 13.01 ps−1.
Quantifying the value of on-farm measurements to inform the selection of key performance indicators for livestock production systems
Authors: Jones Andy , Takahashi Taro , Fleming Hannah , Griffith Bruce , Harris Paul , Lee Michael
Published: August 2021

The use of key performance indicators (KPIs) to assist on-farm decision making has long been seen as a promising strategy to improve operational efficiency of agriculture. The potential benefit of KPIs, however, is heavily dependent on the economic relevance of the metrics used, and an overabundance of ambiguously defined KPIs in the livestock industry has disincentivised many farmers to collect information beyond a minimum requirement. Using high-resolution sheep production data from the North Wyke Farm Platform, a system-scale grazing trial in southwest United Kingdom, this paper proposes a novel framework to quantify the information values of industry recommended KPIs, with the ultimate aim of compiling a list of variables to measure and not to measure. The results demonstrated a substantial financial benefit associated with a careful selection of metrics, with top-ranked variables exhibiting up to 3.5 times the information value of those randomly chosen. When individual metrics were used in isolation, ewe weight at lambing had the greatest ability to predict the subsequent lamb value at slaughter, surpassing all mid-season measures representing the lamb’s own performance. When information from multiple metrics was combined to inform on-farm decisions, the peak benefit was observed under four metrics, with inclusion of variables beyond this point shown to be detrimental to farm profitability regardless of the combination selected. The framework developed herein is readily extendable to other livestock species, and with minimal modifications to arable and mixed agriculture as well.
Application of the improved simple bedside method for emergency temporary pacemaker implantation suitable for primary hospitals
Authors: Zhong Changqing , Mao Shanjun , Guang Jieli , Zhang Yi
Published: August 2021

The purpose of the research was to evaluate the safety and effectiveness of the X-ray-free improved simple bedside method for emergency temporary pacemaker implantation as well as the practicability of the method in primary hospitals. Patients [including those suffering from sick sinus syndrome and third-degree and advanced atrioventricular blockage (AVB)] who needed emergency temporary pacemaker implantation from July 2017 to August 2020 in Hunan Provincial People’s Hospital were selected. They were stochastically divided into a research group (95 cases) treated with the improved simple bedside method and a control group (95 cases) with X-ray guidance. The ordinary bipolar electrodes were used in both groups. On this condition, the operation duration, the first-attempt success rate of electrodes, pacing threshold, success rate of the operation, the rate of electrode displacement, and complications in the two groups were separately calculated. The comparison results of the research group with the control group are shown as follows: operation time [(18 ± 5.91) min vs. (43 ± 2.99) min, P < 0.05], the first-attempt success rate of the electrode (97% vs. 98%, P > 0.05), pacing threshold [(0.97 ± 0.35) vs. (0.97 ± 0.32) V, P > 0.05], success rate of the operation (98.9% vs. 100%, P > 0.05), the rate of electrode displacement (8.4% vs. 7.3%, P > 0.05) and complications (3.2% vs. 2.1%, P > 0.05). The emergency temporary pacemaker implantation based on the improved simple bedside method is as safe and effective as the surgical method under X-ray guidance, and the operation is simpler and easier to learn and requires a shorter operating time, therefore, it is more suitable for use in emergency and primary hospitals.
Tandem domain structure determination based on a systematic enumeration of conformations
Authors: Malliavin Thérèse E.
Published: August 2021

Protein structure determination is undergoing a change of perspective due to the larger importance taken in biology by the disordered regions of biomolecules. In such cases, the convergence criterion is more difficult to set up and the size of the conformational space is a obstacle to exhaustive exploration. A pipeline is proposed here to exhaustively sample protein conformations using backbone angle limits obtained by nuclear magnetic resonance (NMR), and then to determine the populations of conformations. The pipeline is applied to a tandem domain of the protein whirlin. An original approach, derived from a reformulation of the Distance Geometry Problem is used to enumerate the conformations of the linker connecting the two domains. Specifically designed procedure then permit to assemble the domains to the linker conformations and to optimize the tandem domain conformations with respect to two sets of NMR measurements: residual dipolar couplings and paramagnetic resonance enhancements. The relative populations of optimized conformations are finally determined by fitting small angle X-ray scattering (SAXS) data. The most populated conformation of the tandem domain is a semi-closed one, fully closed and more extended conformations being in minority, in agreement with previous observations. The SAXS and NMR data show different influences on the determination of populations.
Macroscopic detection of demyelinated lesions in mouse PNS with neutral red dye
Authors: Yamazaki Reiji , Osanai Yasuyuki , Kouki Tom , Shinohara Yoshiaki , Huang Jeffrey K. , Ohno Nobuhiko
Published: August 2021

Lysophosphatidylcholine (LPC)-induced demyelination is a versatile animal model that is frequently used to identify and examine molecular pathways of demyelination and remyelination in the central (CNS) and peripheral nervous system (PNS). However, identification of focally demyelinated lesion had been difficult and usually required tissue fixation, sectioning and histological analysis. Recently, a method for labeling and identification of demyelinated lesions in the CNS by intraperitoneal injection of neutral red (NR) dye was developed. However, it remained unknown whether NR can be used to label demyelinated lesions in PNS. In this study, we generated LPC-induced demyelination in sciatic nerve of mice, and demonstrated that the demyelinated lesions at the site of LPC injection were readily detectable at 7 days postlesion (dpl) by macroscopic observation of NR labeling. Moreover, NR staining gradually decreased from 7 to 21 dpl over the course of remyelination. Electron microscopy analysis of NR-labeled sciatic nerves at 7 dpl confirmed demyelination and myelin debris in lesions. Furthermore, fluorescence microscopy showed NR co-labeling with activated macrophages and Schwann cells in the PNS lesions. Together, NR labeling is a straightforward method that allows the macroscopic detection of demyelinated lesions in sciatic nerves after LPC injection.
Rational design of heterodimeric receptors capable of activating target signaling molecules
Authors: Kongkrongtong Tatphon , Zhang Ruolan , Kawahara Masahiro
Published: August 2021

Intracellular signal transduction is regulated by a variety of transmembrane receptors. Many researchers have aimed to arbitrarily regulate the intracellular signaling and subsequent cell fate with artificial receptors, of which the ligand recognition and signaling properties could be artificially designed. Although several architectures of homodimeric artificial receptors have been reported, engineering of heterodimeric receptors, which are abundant among natural receptors, have yet to be thoroughly investigated. In this study, we rationally design artificial heterodimeric receptors for activating target signaling molecules. We locate a tyrosine motif on an engineered tyrosine kinase domain, which is further connected to a small molecule-responsive heterodimeric module, attaining a pair of heterodimeric receptors with different tyrosine motifs within the pair. The resultant heterodimeric receptors successfully activate target signaling molecules and even control cell proliferation levels according to the properties of tyrosine motifs connected. Thus, our heterodimeric receptors may open a new era of tailor-made designer receptors, which could be useful for cell therapy against intractable diseases.
The selective adsorption performance and mechanism of multiwall magnetic carbon nanotubes for heavy metals in wastewater
Authors: Wang Zhongbing , Xu Wenbin , Jie Fanghui , Zhao Zongwen , Zhou Kai , Liu Hui
Published: August 2021

The safe treatment of heavy metals in wastewater is directly related to human health and social development. In this paper, a new type of recyclable adsorbent is synthesized through the oxidation of enhancer and modification with magnetic nanoparticles. The new adsorbent not only inherits the advantages of multiwall carbon nanotubes (6O-MWCNTs), but also exhibits a new magnetic property and further improved adsorption capacity, which is conducive to the magnetic separation and recovery of heavy metals. The adsorption results indicate that multiwall magnetic carbon nanotubes (6O-MWCNTs@Fe3O4) have a good performance for Pb(II) selective adsorption, with a maximum adsorption capacity of 215.05 mg/g, much higher than the existing adsorption capacity of the same type of adsorbents. Under the action of an external magnetic field, 6O-MWCNTs@Fe3O4 that adsorbed metal ions can quickly achieve good separation from the solution. The joint characterization results of FTIR and XPS show that under the action of both coordination and electrostatic attraction, the C=O bond in the –COOH group is induced to open by the metal ions and transforms into an ionic bond, and the metal ions are stably adsorbed on the surface of 6O-MWCNTs@Fe3O4. Pb(II) has a stronger attraction than Cu(II) and Cd(II) to the lone pair of electrons in oxygen atoms to form complexes, due to the covalent index of Pb (6.41) is more larger than that of Cu (2.98) and Cd (2.71).These data provide a new type of recyclable adsorbent for the efficient treatment of heavy metal ions in wastewater and enrich relevant theoretical knowledge.
A novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration
Authors: Tateiwa Daisuke , Nakagawa Shinichi , Tsukazaki Hiroyuki , Okada Rintaro , Kodama Joe , Kushioka Junichi , Bal Zeynep , Ukon Yuichiro , Hirai Hiromasa , Kaito Takashi
Published: August 2021

Although bone morphogenetic protein (BMP) has potent osteoinductivity, the potential adverse events attributed to its burst release prevent its widespread clinical application. Therefore, there is a strong need for BMP delivery systems that maximize osteoinductivity while preventing adverse effects. We evaluated the bone-regenerating potential of NOVOSIS putty (NP), a novel composite combining hydroxyapatite, beta-tricalcium phosphate microsphere/poloxamer 407-based hydrogel, and recombinant human (rh) BMP-2. In vitro assessment of release kinetics by enzyme-linked immunosorbent assay demonstrated sustained release of rhBMP-2 from NP and burst release from collagen sponge (CS), and in vivo assessment of release kinetics by longitudinal tracking of fluorescently labeled rhBMP-2 showed a longer biological half-life of rhBMP-2 with NP than with CS. Furthermore, osteogenic gene expression in MC3T3-E1 cells was significantly higher after co-culture with NP than after co-culture with CS, suggesting that the sustained release of rhBMP-2 from NP effectively contributed to the differentiation of osteoblasts. In a rat spinal fusion model, the volume and quality of newly formed bone was higher in the NP group than in the CS group. Use of NP results in efficient bone regeneration through sustained release of rhBMP-2 and improves the quality of BMP-induced bone.
Molecular diversity of Uzbekistan’s fishes assessed with DNA barcoding
Authors: Sheraliev Bakhtiyor , Peng Zuogang
Published: August 2021

Uzbekistan is one of two doubly landlocked countries in the world, where all rivers are endorheic basins. Although fish diversity is relatively poor in Uzbekistan, the fish fauna of the region has not yet been fully studied. The aim of this study was to establish a reliable barcoding reference database for fish in Uzbekistan. A total of 666 specimens, belonging to 59 species within 39 genera, 17 families, and 9 orders, were subjected to polymerase chain reaction amplification in the barcode region and sequenced. The length of the 666 barcodes was 682 bp. The average K2P distances within species, genera, and families were 0.22%, 6.33%, and 16.46%, respectively. The average interspecific distance was approximately 28.8 times higher than the mean intraspecific distance. The Barcode Index Number (BIN) discordance report showed that 666 specimens represented 55 BINs, of which five were singletons, 45 were taxonomically concordant, and five were taxonomically discordant. The barcode gap analysis demonstrated that 89.3% of the fish species examined could be discriminated by DNA barcoding. These results provide new insights into fish diversity in the inland waters of Uzbekistan and can provide a basis for the development of further studies on fish fauna.
Molybdenum impregnated g-C3N4 nanotubes as potentially active photocatalyst for renewable energy applications
Authors: Iqbal Naseer , Afzal Adeel , Khan Ibrahim , Khan Muhammad Shahzeb , Qurashi Ahsanulhaq
Published: August 2021

Molybdenum (Mo) impregnated g-C3N4 (Mo-CN) nanotubes are fabricated via a thermal/hydrothermal process to augment photoelectrochemical properties during solar-driven water-splitting (SDWS) reactions. Graphitic-C3N4 is an attractive material for photocatalysis because of its suitable band energy, high thermal and chemical stability. The FE-SEM and HR-TEM comprehend the nanotube-like morphology of Mo-CN. The spectroscopic characterization revealed bandgap energy of 2.63 eV with high visible-light activity. The x-ray diffraction of pristine g-C3N4 and Mo-CN nanotubes discloses the formation of triazine-based nanocrystalline g-C3N4, which remains stable during hydrothermal impregnation of Mo. Furthermore, Mo-CN nanotubes possess high sp2-hybridized nitrogen content, and metallic/oxidized Mo nanoparticles (in a ratio of 1:2) are impregnated into g-C3N4. The XPS analysis confirms C, N, and Mo for known atomic and oxidation states in Mo-CN. Furthermore, high photocurrent efficiency (~ 5.5 mA/cm2) is observed from 5%-Mo-CN nanotubes. That displays efficient SDWS by 5%-Mo-CN nanotubes than other counterparts. Impedance spectroscopy illustrated the lowest charge transfer resistance (Rct) of 5%-Mo-CN nanotubes, which further confirms the fast electron transfer kinetics and efficient charge separation resulting in high photocurrent generation. Hence, 5%Mo-CN composite nanotubes can serve as a potential photocatalytic material for viable solar-driven water splitting.
Oral microflora and pregnancy: a systematic review and meta-analysis
Authors: Jang Hoonji , Patoine Alexa , Wu Tong Tong , Castillo Daniel A. , Xiao Jin
Published: August 2021

Understanding changes in oral flora during pregnancy, its association to maternal health, and its implications to birth outcomes is essential. We searched PubMed, Embase, Web of Science, and Cochrane Library in May 2020 (updated search in April and June 2021), and conducted a systematic review and meta-analyses to assess the followings: (1) oral microflora changes throughout pregnancy, (2) association between oral microorganisms during pregnancy and maternal oral/systemic conditions, and (3) implications of oral microorganisms during pregnancy on birth outcomes. From 3983 records, 78 studies were included for qualitative assessment, and 13 studies were included in meta-analysis. The oral microflora remains relatively stable during pregnancy; however, pregnancy was associated with distinct composition/abundance of oral microorganisms when compared to postpartum/non-pregnant status. Oral microflora during pregnancy appears to be influenced by oral and systemic conditions (e.g. gestational diabetes mellitus, pre-eclampsia, etc.). Prenatal dental care reduced the carriage of oral pathogens (e.g. Streptococcus mutans). The Porphyromonas gingivalis in subgingival plaque was more abundant in women with preterm birth. Given the results from meta-analyses were inconclusive since limited studies reported outcomes on the same measuring scale, more future studies are needed to elucidate the association between pregnancy oral microbiota and maternal oral/systemic health and birth outcomes.