bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular basis of regio- and stereo-specificity in biosynthesis of bacterial heterodimeric diketopiperazines
Authors: Sun Chenghai , Luo Zhenyao , Zhang Wenlu , Tian Wenya , Peng Haidong , Lin Zhi , Deng Zixin , Kobe Bostjan , Jia Xinying , Qu Xudong
Published: December 2020

Bacterial heterodimeric tryptophan-containing diketopiperazines (HTDKPs) are a growing family of bioactive natural products. They are challenging to prepare by chemical routes due to the polycyclic and densely functionalized backbone. Through functional characterization and investigation, we herein identify a family of three related HTDKP-forming cytochrome P450s (NasbB, NasS1868 and NasF5053) and reveal four critical residues (Qln65, Ala86, Ser284 and Val288) that control their regio- and stereo-selectivity to generate diverse dimeric DKP frameworks. Engineering these residues can alter the specificities of the enzymes to produce diverse frameworks. Determining the crystal structures (1.70–1.47 Å) of NasF5053 (ligand-free and substrate-bound NasF5053 and its Q65I-A86G and S284A-V288A mutants) and molecular dynamics simulation finally elucidate the specificity-conferring mechanism of these residues. Our results provide a clear molecular and mechanistic basis into this family of HTDKP-forming P450s, laying a solid foundation for rapid access to the molecular diversity of HTDKP frameworks through rational engineering of the P450s.
Using antibodies to control DNA-templated chemical reactions
Authors: Baranda Pellejero Lorena , Mahdifar Malihe , Ercolani Gianfranco , Watson Jonathan , Brown Tom , Ricci Francesco
Published: December 2020

DNA-templated synthesis takes advantage of the programmability of DNA-DNA interactions to accelerate chemical reactions under diluted conditions upon sequence-specific hybridization. While this strategy has proven advantageous for a variety of applications, including sensing and drug discovery, it has been so far limited to the use of nucleic acids as templating elements. Here, we report the rational design of DNA templated synthesis controlled by specific IgG antibodies. Our approach is based on the co-localization of reactants induced by the bivalent binding of a specific IgG antibody to two antigen-conjugated DNA templating strands that triggers a chemical reaction that would be otherwise too slow under diluted conditions. This strategy is versatile, orthogonal and adaptable to different IgG antibodies and can be employed to achieve the targeted synthesis of clinically-relevant molecules in the presence of specific IgG biomarker antibodies.
Simultaneous interlayer and intralayer space control in two-dimensional metal−organic frameworks for acetylene/ethylene separation
Authors: Shen Jin , He Xin , Ke Tian , Krishna Rajamani , van Baten Jasper M. , Chen Rundao , Bao Zongbi , Xing Huabin , Dincǎ Mircea , Zhang Zhiguo , Yang Qiwei , Ren Qilong
Published: December 2020

Three-dimensional metal−organic frameworks (MOFs) are cutting-edge materials in the adsorptive removal of trace gases due to the availability of abundant pores with specific chemistry. However, the development of ideal adsorbents combining high adsorption capacity with high selectivity and stability remains challenging. Here we demonstrate a strategy to design adsorbents that utilizes the tunability of interlayer and intralayer space of two-dimensional fluorinated MOFs for capturing acetylene from ethylene. Validated by X-ray diffraction and modeling, a systematic variation of linker atom oxidation state enables fine regulation of layer stacking pattern and linker conformation, which affords a strong interlayer trapping of molecules along with cooperative intralayer binding. The resultant robust materials (ZUL-100 and ZUL-200) exhibit benchmark capacity in the pressure range of 0.001–0.05 bar with high selectivity. Their efficiency in acetylene/ethylene separation is confirmed by breakthrough experiments, giving excellent ethylene productivities (121 mmol/g from 1/99 mixture, 99.9999%), even when cycled under moist conditions.
Imaging fascicular organization of rat sciatic nerves with fast neural electrical impedance tomography
Authors: Ravagli Enrico , Mastitskaya Svetlana , Thompson Nicole , Iacoviello Francesco , Shearing Paul R. , Perkins Justin , Gourine Alexander V. , Aristovich Kirill , Holder David
Published: December 2020

Imaging compound action potentials (CAPs) in peripheral nerves could help avoid side effects in neuromodulation by selective stimulation of identified fascicles. Existing methods have low resolution, limited imaging depth, or are invasive. Fast neural electrical impedance tomography (EIT) allows fascicular CAP imaging with a resolution of <200 µm, <1 ms using a non-penetrating flexible nerve cuff electrode array. Here, we validate EIT imaging in rat sciatic nerve by comparison to micro-computed tomography (microCT) and histology with fluorescent dextran tracers. With EIT, there are reproducible localized changes in tissue impedance in response to stimulation of individual fascicles (tibial, peroneal and sural). The reconstructed EIT images correspond to microCT scans and histology, with significant separation between the fascicles (p < 0.01). The mean fascicle position is identified with an accuracy of 6% of nerve diameter. This suggests fast neural EIT can reliably image the functional fascicular anatomy of the nerves and so aid selective neuromodulation.
Author Correction: Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells
Authors: Huang Deli , Tran Jenny Tuyet , Olson Alex , Vollbrecht Thomas , Tenuta Mary , Guryleva Mariia V. , Fuller Roberta P. , Schiffner Torben , Abadejos Justin R. , Couvrette Lauren , Blane Tanya R. , Saye Karen , Li Wenjuan , Landais Elise , Gonzalez-Martin Alicia , Schief William , Murrell Ben , Burton Dennis R. , Nemazee David , Voss James E.
Published: December 2020

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20304-y
Strain control of layer-resolved negative capacitance in superlattices
Authors: Walter Raymond , Prosandeev Sergey , Paillard Charles , Bellaiche L.
Published: December 2020

Negative capacitance in BaTiO3/SrTiO3 superlattices is investigated by Monte Carlo simulations in an atomistic effective Hamiltonian model, using fluctuation formulas for responses to the local macroscopic field that incorporates depolarizing fields. We show that epitaxial strain can tune the negative capacitance of the BaTiO3 ferroelectric layer and the overall capacitance of the system. In addition, we predict and explain an original switching of the negative capacitance from the BaTiO3 layer to the SrTiO3 layer at low temperatures for intermediate strains.
Chromosome-scale, haplotype-resolved assembly of human genomes
Authors: Garg Shilpa , Fungtammasan Arkarachai , Carroll Andrew , Chou Mike , Schmitt Anthony , Zhou Xiang , Mac Stephen , Peluso Paul , Hatas Emily , Ghurye Jay , Maguire Jared , Mahmoud Medhat , Cheng Haoyu , Heller David , Zook Justin M. , Moemke Tobias , Marschall Tobias , Sedlazeck Fritz J. , Aach John , Chin Chen-Shan , Church George M. , Li Heng
Published: December 2020

Haplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for single individuals to generate a chromosome-scale phased assembly within 1 day. Applied to four public human genomes, PGP1, HG002, NA12878 and HG00733, DipAsm produced haplotype-resolved assemblies with minimum contig length needed to cover 50% of the known genome (NG50) up to 25 Mb and phased ~99.5% of heterozygous sites at 98–99% accuracy, outperforming other approaches in terms of both contiguity and phasing completeness. We demonstrate the importance of chromosome-scale phased assemblies for the discovery of structural variants (SVs), including thousands of new transposon insertions, and of highly polymorphic and medically important regions such as the human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) regions. DipAsm will facilitate high-quality precision medicine and studies of individual haplotype variation and population diversity.
Frequency selective wave beaming in nonreciprocal acoustic phased arrays
Authors: Adlakha Revant , Moghaddaszadeh Mohammadreza , Attarzadeh Mohammad A. , Aref Amjad , Nouh Mostafa
Published: December 2020

Acoustic phased arrays are capable of steering and focusing a beam of sound via selective coordination of the spatial distribution of phase angles between multiple sound emitters. Constrained by the principle of reciprocity, conventional phased arrays exhibit identical transmission and reception patterns which limit the scope of their operation. This work presents a controllable space–time acoustic phased array which breaks time-reversal symmetry, and enables phononic transition in both momentum and energy spaces. By leveraging a dynamic phase modulation, the proposed linear phased array is no longer bound by the acoustic reciprocity, and supports asymmetric transmission and reception patterns that can be tuned independently at multiple channels. A foundational framework is developed to characterize and interpret the emergent nonreciprocal phenomena and is later validated against benchmark numerical experiments. The new phased array selectively alters the directional and frequency content of the incident signal and imparts a frequency conversion between different wave fields, which is further analyzed as a function of the imposed modulation. The space–time acoustic phased array enables unprecedented control over sound waves in a variety of applications ranging from ultrasonic imaging to non-destructive testing and underwater SONAR telecommunication.
The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity
Authors: Tegler Lotta , Corin Karolina , Pick Horst , Brookes Jennifer , Skuhersky Michael , Vogel Horst , Zhang Shuguang
Published: December 2020

G protein-coupled receptors (GPCRs) are vital for diverse biological functions, including vision, smell, and aging. They are involved in a wide range of diseases, and are among the most important targets of medicinal drugs. Tools that facilitate GPCR studies or GPCR-based technologies or therapies are thus critical to develop. Here we report using our QTY (glutamine, threonine, tyrosine) code to systematically replace 29 membrane-facing leucine, isoleucine, valine, and phenylalanine residues in the transmembrane α-helices of the GPCR CXCR4. This variant, CXCR4QTY29, became more hydrophilic, while retaining the ability to bind its ligand CXCL12. When transfected into HEK293 cells, it inserted into the cell membrane, and initiated cellular signaling. This QTY code has the potential to improve GPCR and membrane protein studies by making it possible to design functional hydrophilic receptors. This tool can be applied to diverse α-helical membrane proteins, and may aid in the development of other applications, including clinical therapies.
Confidence in subjective pain is predicted by reaction time during decision making
Authors: Dildine Troy C. , Necka Elizabeth A. , Atlas Lauren Y.
Published: December 2020

Self-report is the gold standard for measuring pain. However, decisions about pain can vary substantially within and between individuals. We measured whether self-reported pain is accompanied by metacognition and variations in confidence, similar to perceptual decision-making in other modalities. Eighty healthy volunteers underwent acute thermal pain and provided pain ratings followed by confidence judgments on continuous visual analogue scales. We investigated whether eye fixations and reaction time during pain rating might serve as implicit markers of confidence. Confidence varied across trials and increased confidence was associated with faster pain rating reaction times. The association between confidence and fixations varied across individuals as a function of the reliability of individuals’ association between temperature and pain. Taken together, this work indicates that individuals can provide metacognitive judgments of pain and extends research on confidence in perceptual decision-making to pain.
Moderate-to-vigorous physical activity duration is more important than timing for physical function in older adults
Authors: Lai Ting-Fu , Liao Yung , Lin Chien-Yu , Huang Wan-Chi , Hsueh Ming-Chun , Chan Ding-Cheng
Published: December 2020

The positive association between the total duration of physical activity and performances of physical function may vary at different times of the day as circadian rhythm regulates individuals in response to external stimulations. We aimed to examine the association of timing-specific and overall moderate-to-vigorous physical activity (MVPA) with performances of physical function in older adults. A cross-sectional analysis was conducted among 118 older adults (mean age = 70.0 ± 5.0 years). We assessed and identified timing-specific (morning: 06:01–12:00; afternoon: 12:01–18:00; evening: 18:01–24:00) and overall MVPA using a triaxial accelerometer. Different measures of physical function were evaluated including handgrip strength (by grip dynamometer), gait speed (5-m walk test), basic functional mobility (timed up and go test), and lower limb strength (five times sit-to-stand test). Multivariate linear regression models adjusting for covariates were used to investigate the associations. Participants spent 25.0 (± 26.2) minutes in MVPA per day on average, half the time spent during the morning (47.7%), followed by during the afternoon (29.9%) and evening (21.6%). The time spent on overall MVPA was generally associated with better physical function performances. There was statistical evidence for the percentages of MVPA engagement during the morning [B = 0.214, 95% confidence interval (CI) 0.001 to 0.428] and afternoon (B = − 0.273, 95% CI − 0.518 to − 0.027) associated with basic functional mobility but with contrary directions; the percentage of MVPA engagement during the evening was associated with less time spent in gait speed performance (B = − 0.237, 95% CI − 0.468 to − 0.006). Our findings inform implications that the overall MVPA engagement was more important than timing-specific MVPA to older adults’ physical function performances. Strategies for accumulating time of MVPA is more practical and effective than encouraging to engage MVPA in specific timing for the enhancement of functional ability and therefore prevent disability among older adults.
Meta-analysis of viscosity of aqueous deep eutectic solvents and their components
Authors: Gygli Gudrun , Xu Xinmeng , Pleiss Jürgen
Published: December 2020

Deep eutectic solvents (DES) formed by quaternary ammonium salts and hydrogen bond donors are a promising green alternative to organic solvents. Their high viscosity at ambient temperatures can limit biocatalytic applications and therefore requires fine-tuning by adjusting water content and temperature. Here, we performed a meta-analysis of the impact of water content and temperature on the viscosities of four deep eutectic solvents (glyceline, reline, N,N-diethylethanol ammonium chloride-glycerol, N,N-diethylethanol ammonium chloride-ethylene glycol), their components (choline chloride, urea, glycerol, ethylene glycol), methanol, and pure water. We analyzed the viscosity data by an automated workflow, using Arrhenius and Vogel–Fulcher–Tammann–Hesse models. The consistency and completeness of experimental data and metadata was used as an essential criterion of data quality. We found that viscosities were reported for different temperature ranges, half the time without specifying a method of desiccation, and in almost half of the reports without specifying experimental errors. We found that the viscosity of the pure components varied widely, but that all aqueous mixtures (except for reline) have similar excess activation energy of viscous flow $${E}^{excess}_{\eta}$$

E

η

excess

= 3–5 kJ/mol, whereas reline had a negative excess activation energy ($${E}^{excess}_{\eta}$$

E

η

excess

= − 19 kJ/mol). The data and workflows used are accessible at https://doi.org/10.15490/FAIRDOMHUB.1.STUDY.767.1.
Leveraging the effector independent nature of motor imagery when it is paired with physical practice
Authors: Kraeutner Sarah N. , McArthur Jennifer L. , Kraeutner Paul H. , Westwood David A. , Boe Shaun G.
Published: December 2020

While considered analogous to physical practice, the nature of imagery-based skill acquisition—specifically whether or not both effector independent and dependent encoding occurs through motor imagery—is not well understood. Here, motor imagery-based training was applied prior to or after physical practice-based training to probe the nature of imagery-based skill acquisition. Three groups of participants (N = 38) engaged in 10 days of training of a dart throwing task: 5 days of motor imagery prior to physical practice (MIP-PP), motor imagery following physical practice (PP-MIP), or physical practice only (PP-PP). Performance-related outcomes were assessed throughout. Brain activity was measured at three time points using fMRI (pre/mid/post-training; MIP-PP and PP-MIP groups). In contrast with physical practice, motor imagery led to changes in global versus specific aspects of the movement. Following 10 days of training, performance was greater when motor imagery preceded physical practice, although remained inferior to performance resulting from physical practice alone. Greater activation of regions that support effector dependent encoding was observed mid-, but not post-training for the PP-MIP group. Findings indicate that changes driven by motor imagery reflect effector independent encoding, providing new information regarding how motor imagery may be leveraged for skill acquisition.
Higher HbA1c levels associate with lower hippocampal serotonin transporter availability in non-diabetic adults with obesity
Authors: Grundmann Rico , Rullmann Michael , Luthardt Julia , Zientek Franziska , Becker Georg-Alexander , Patt Marianne , Hankir Mohammed K. , Blüher Matthias , Sabri Osama , Hesse Swen
Published: December 2020

The current study aimed to investigate whether the in vivo availability of central serotonin reuptake transporters (5-HTT) is associated with plasma levels of glycosylated hemoglobin (HbA1c) in non-diabetic humans with obesity. 5-HTT availability was measured by using positron emission tomography (PET) imaging with the 5-HTT selective radiotracer [11C]DASB in 23 non-diabetic individuals with obesity and 14 healthy, non-obesity controls. Parametric images of binding potential BPND were generated from the PET data and analyzed together with HbA1c levels by using volume of interest analysis for brain areas relevant to appetite control. Voxel-based morphometry (VBM) of individual magnetic resonance imaging data was further performed to correlate grey matter density (GMD) maps with HbA1c. We found significant negative correlations between HbA1c levels and BPND in right and left hippocampus in obesity (r = − 0.717, p < 0.001, and r = − 0.557, p = 0.006, respectively). VBM analyses revealed that higher HbA1c levels were associated with GMD in the right para-hippocampal area. Our results indicate that chronically high blood glucose levels may evoke changes in hippocampal 5-HTT levels that are in part tied to local microstructure.
Observation of magnetic domains in graphene magnetized by controlling temperature, strain and magnetic field
Authors: Alimohammadian Mahsa , Sohrabi Beheshteh
Published: December 2020

Since the production of ferromagnetic graphene as an extremely important matter in spintronics has made a revolution in future technology, a great deal of efforts has recently been done to reach a simple and cost-effective method. Up to now, controlling the magnetic properties at extremely low temperature have been investigated only by adding and removing atoms in graphene lattice. In this regard, the effect of strain on the magnetic and electronic properties of graphene has been probed. Here, the ferromagnetic properties are what have been created by strain, magnetic field, and temperature along with observation of the parallel magnetic domains in ferromagnetic graphene for the first time as a great achievement. In this way, we have represented the following: First, introducing three novel methods based on temperature, magnetic field, and strain for producing ferromagnetic graphene; Second, obtaining ferromagnetic graphene at room temperature by significant magnetization saturation in mass-scale; Third, probing the electronic systems and vibrational modes by Raman and IR spectroscopy; Fourth, introducing stacking and aggregation as two types of gathering process for graphene sheets; Fifth, comparing the results with leidenfrost effect-based method which the temperature, magnetic fields, and strain are simultaneously applied to graphene flakes (our previous work).
Detailed evaluation of the upper airway in the Dp(16)1Yey mouse model of Down syndrome
Authors: Takahashi Tatsunori , Sakai Noriaki , Iwasaki Tomonori , Doyle Timothy C. , Mobley William C. , Nishino Seiji
Published: December 2020

A high prevalence of obstructive sleep apnea (OSA) has been reported in Down syndrome (DS) owing to the coexistence of multiple predisposing factors related to its genetic abnormality, posing a challenge for the management of OSA. We hypothesized that DS mice recapitulate craniofacial abnormalities and upper airway obstruction of human DS and can serve as an experimental platform for OSA research. This study, thus, aimed to quantitatively characterize the upper airway as well as craniofacial abnormalities in Dp(16)1Yey (Dp16) mice. Dp16 mice demonstrated craniofacial hypoplasia, especially in the ventral part of the skull and the mandible, and rostrally positioned hyoid. These changes were accompanied with a shorter length and smaller cross-sectional area of the upper airway, resulting in a significantly reduced upper airway volume in Dp16 mice. Our non-invasive approach, a combination of computational fluid dynamics and high-resolution micro-CT imaging, revealed a higher negative pressure inside the airway of Dp16 mice compared to wild-type littermates, showing the potential risk of upper airway collapse. Our study indicated that Dp16 mice can be a useful model to examine the pathophysiology of increased upper airway collapsibility of DS and to evaluate the efficacy of therapeutic interventions for breathing and sleep anomalies.
Atherogenic index of plasma and coronary artery calcification progression beyond traditional risk factors according to baseline coronary artery calcium score
Authors: Won Ki-Bum , Han Donghee , Lee Ji Hyun , Choi Su-Yeon , Chun Eun Ju , Park Sung Hak , Han Hae-Won , Sung Jidong , Jung Hae Ok , Chang Hyuk-Jae
Published: December 2020

This study aimed to evaluate the association between the atherogenic index of plasma (AIP), which has been suggested as a novel marker for atherosclerosis, and coronary artery calcification (CAC) progression according to the baseline coronary artery calcium score (CACS). We included 12,326 asymptomatic Korean adults who underwent at least two CAC evaluations from December 2012 to August 2016. Participants were stratified into four groups according to AIP quartiles, which were determined by the log of (triglyceride/high-density lipoprotein cholesterol). Baseline CACSs were divided into three groups: 0, 1 − 100, and > 100. CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up CACSs (Δ√transformed CACS). Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period. During a mean 3.3-year follow-up period, the overall incidence of CAC progression was 30.6%. The incidences of CAC progression and annualized Δ√transformed CACS were markedly elevated with increasing AIP quartile in participants with baseline CACSs of 0 and 1 − 100, but not in those with a baseline CACS > 100. The AIP level was associated with the annualized Δ√transformed CACS in participants with baseline CACSs of 0 (β = 0.016; P < 0.001) and 1 − 100 (β = 0.035; P < 0.001), but not in those with baseline CACS > 100 (β = 0.032; P = 0.385). After adjusting for traditional risk factors, the AIP was significantly associated with CAC progression in those with baseline CACS ≤ 100. The AIP has value for predicting CAC progression in asymptomatic adults without heavy baseline CAC.
Elucidating the constitutive relationship of calcium–silicate–hydrate gel using high throughput reactive molecular simulations and machine learning
Authors: Lyngdoh Gideon A. , Li Hewenxuan , Zaki Mohd , Krishnan N. M. Anoop , Das Sumanta
Published: December 2020

Prediction of material behavior using machine learning (ML) requires consistent, accurate, and, representative large data for training. However, such consistent and reliable experimental datasets are not always available for materials. To address this challenge, we synergistically integrate ML with high-throughput reactive molecular dynamics (MD) simulations to elucidate the constitutive relationship of calcium–silicate–hydrate (C–S–H) gel—the primary binding phase in concrete formed via the hydration of ordinary portland cement. Specifically, a highly consistent dataset on the nine elastic constants of more than 300 compositions of C–S–H gel is developed using high-throughput reactive simulations. From a comparative analysis of various ML algorithms including neural networks (NN) and Gaussian process (GP), we observe that NN provides excellent predictions. To interpret the predicted results from NN, we employ SHapley Additive exPlanations (SHAP), which reveals that the influence of silicate network on all the elastic constants of C–S–H is significantly higher than that of water and CaO content. Additionally, the water content is found to have a more prominent influence on the shear components than the normal components along the direction of the interlayer spaces within C–S–H. This result suggests that the in-plane elastic response is controlled by water molecules whereas the transverse response is mainly governed by the silicate network. Overall, by seamlessly integrating MD simulations with ML, this paper can be used as a starting point toward accelerated optimization of C–S–H nanostructures to design efficient cementitious binders with targeted properties.
Temporal trend of cancer mortality in a Brazilian state with a medium Human Development Index (1980–2018)
Authors: Lima Marcela Sampaio , Siqueira Hianga Fayssa Fernandes , Moura Alex Rodrigues , Hora Evânia Curvelo , Brito Hugo Leite de Farias , Marques Adriane Dórea , Brito Érika de Abreu Costa , Cipolotti Rosana , Lima Carlos Anselmo
Published: December 2020

Emerging economy countries in epidemiological transition have been especially challenged in the fight against cancer. This was an ecological study that aimed to describe the temporal trend of cancer mortality in a Brazilian northeastern state with a medium Human Development Index using official Brazilian mortality data from 1980 to 2018. We calculated the mortality crude rate (CR) and age-standardized rate (ASR) based on official population counts and estimates. The Joinpoint Regression Program, National Cancer Institute, USA, was used to calculate time trends of cancer mortality. There were 34,214 deaths from cancer, excluding nonmelanoma skin cancer, in Sergipe. The overall cancer mortality ASR was 70.1 and 57.9 per 100,000 men and women, respectively. For the last five years, the leading causes of cancer deaths were prostate (21.3), trachea, bronchus and lung (11.7), stomach (6.5), oral cavity (5.4) and liver and intrahepatic bile ducts (5.1) in males and breast (13.8), trachea, bronchus and lung (6.6), cervix (6.4), colon/rectum (5.8) and central nervous system (3.6) in females. In addition, there was a significant reduction in deaths from ill-defined causes in the series. Our results show that although there has been an increase in cancer mortality rates associated with Western lifestyles, such as prostate, breast and colon/rectum, high rates of cancer related to poverty and infections, such as stomach and cervix, still persist in Sergipe.
An automated instrument for intrauterine insemination sperm preparation
Authors: Jafek Alex , Feng Haidong , Brady Hayden , Petersen Kevin , Chaharlang Marzieh , Aston Kenneth , Gale Bruce , Jenkins Timothy , Samuel Raheel
Published: December 2020

Sperm preparation is critical to achieving a successful intrauterine insemination and requires the processing of a semen sample to remove white blood cells, wash away seminal plasma, and reduce sample volume. We present an automated instrument capable of performing a sperm preparation starting with a diluted semen sample. We compare our device against a density gradient centrifugation by processing 0.5 mL portions of patient samples through each treatment. In 5 min of operating time, the instrument recovers an average of 86% of all sperm and 82% of progressively motile sperm from the original sample while removing white blood cells, replacing the seminal plasma, and reducing the volume of the sample to the clinically required level. In 25 min of operating time, density gradient centrifugation recovers an average of 33% of all sperm and 41% of progressively motile sperm. The automated instrument could improve access to IUI as a treatment option by allowing satellite doctor’s offices to offer intrauterine insemination as an option for patients without the clinical support required by existing methods.
Baculovirus-free insect cell expression system for high yield antibody and antigen production
Authors: Korn Janin , Schäckermann Dorina , Kirmann Toni , Bertoglio Federico , Steinke Stephan , Heisig Janyn , Ruschig Maximilian , Rojas Gertrudis , Langreder Nora , Wenzel Esther Veronika , Roth Kristian Daniel Ralph , Becker Marlies , Meier Doris , van den Heuvel Joop , Hust Michael , Dübel Stefan , Schubert Maren
Published: December 2020

Antibodies are essential tools for therapy and diagnostics. Yet, production remains expensive as it is mostly done in mammalian expression systems. As most therapeutic IgG require mammalian glycosylation to interact with the human immune system, other expression systems are rarely used for production. However, for neutralizing antibodies that are not required to activate the human immune system as well as antibodies used in diagnostics, a cheaper production system would be advantageous. In our study, we show cost-efficient, easy and high yield production of antibodies as well as various secreted antigens including Interleukins and SARS-CoV-2 related proteins in a baculovirus-free insect cell expression system. To improve yields, we optimized the expression vector, media and feeding strategies. In addition, we showed the feasibility of lyophilization of the insect cell produced antibodies. Furthermore, stability and activity of the antibodies was compared to antibodies produced by Expi293F cells revealing a lower aggregation of antibodies originating from High Five cell production. Finally, the newly established High Five expression system was compared to the Expi293F mammalian expression system in regard of yield and costs. Most interestingly, all tested proteins were producible in our High Five cell expression system what was not the case in the Expi293F system, hinting that the High Five cell system is especially suited to produce difficult-to-express target proteins.
Assembly properties of bacterial tubulin homolog FtsZ regulated by the positive regulator protein ZipA and ZapA from Pseudomonas aeruginosa
Authors: Rahman Mujeeb ur , Li Zhe , Zhang Tingting , Du Shuheng , Ma Xueqin , Wang Ping , Chen Yaodong
Published: December 2020

Bacterial tubulin homolog FtsZ self-assembles into dynamic protofilaments, which forms the scaffold for the contractile ring (Z-ring) to achieve bacterial cell division. Here, we study the biochemical properties of FtsZ from Pseudomonas aeruginosa (PaFtsZ) and the effects of its two positive regulator proteins, ZipA and ZapA. Similar to Escherichia coli FtsZ, PaFtsZ had a strong GTPase activity, ~ 7.8 GTP min-1 FtsZ-1 at pH 7.5, and assembled into mainly short single filaments in vitro. However, PaFtsZ protofilaments were mixtures of straight and “intermediate-curved” (100–300 nm diameter) in pH 7.5 solution and formed some bundles in pH 6.5 solution. The effects of ZipA on PaFtsZ assembly varied with pH. In pH 6.5 buffer ZipA induced PaFtsZ to form large bundles. In pH 7.5 buffer PaFtsZ-ZipA protofilaments were not bundled, but ZipA enhanced PaFtsZ assembly and promoted more curved filaments. Comparable to ZapA from other bacterial species, ZapA from P. aeruginosa induced PaFtsZ protofilaments to associate into long straight loose bundles and/or sheets at both pH 6.5 and pH 7.5, which had little effect on the GTPase activity of PaFtsZ. These results provide us further information that ZipA functions as an enhancer of FtsZ curved filaments, while ZapA works as a stabilizer of FtsZ straight filaments.
Characterising particulate matter source contributions in the pollution control zone of mining and related industries using bivariate statistical techniques
Authors: Sooktawee Sirapong , Kanabkaew Thongchai , Boonyapitak Suteera , Patpai Aduldech , Piemyai Nirun
Published: December 2020

Na Phra Lan Subdistrict is a pollution control zone with the highest PM10 level in Thailand. Major mobile and industrial sources in the area are related to stone crushing, quarrying and mining. This study used statistical techniques to investigate the potential sources influencing high PM10 levels in Na Phra Lan. Hourly PM10 data and related parameters (PM2.5, PMcoarse and NOx) from 2014–2017 were analysed using time series, bivariate polar plot and conditional bivariate probability function (CBPF). Results of diurnal variation revealed two peaks of PM10 levels from 06:00–10:00 and 19:00–23:00 every month. For seasonal variation, high PM10 concentrations were found from October to February associated with the cool and dry weather during these months. The bivariate polar plot and CBPF confirmed two potential sources, i.e., resuspended dust from mobile sources close to the air quality monitoring station (receptor) and industrial sources of mining, quarrying and stone crushing far from the station on the northeast side. While the industrial source areas played a role in background PM10 concentrations, the influence of mobile sources increased the concentrations resulting in two PM10 peaks daily. From the study results, we proposed that countermeasure activities should focus on potential source areas, resuspended road dust from vehicles and the industrial sources related to quarrying and mining, rather than distributing equal attention to all sources.
Quantum control using quantum memory
Authors: Roget Mathieu , Herzog Basile , Di Molfetta Giuseppe
Published: December 2020

We propose a new quantum numerical scheme to control the dynamics of a quantum walker in a two dimensional space–time grid. More specifically, we show how, introducing a quantum memory for each of the spatial grid, this result can be achieved simply by acting on the initial state of the whole system, and therefore can be exactly controlled once for all. As example we prove analytically how to encode in the initial state any arbitrary walker’s mean trajectory and variance. This brings significantly closer the possibility of implementing dynamically interesting physics models on medium term quantum devices, and introduces a new direction in simulating aspects of quantum field theories (QFTs), notably on curved manifold.
Novel plasma biomarkers improve discrimination of metabolic health independent of weight
Authors: Ellison Stephen , Abdulrahim Jawan W. , Kwee Lydia Coulter , Bihlmeyer Nathan A. , Pagidipati Neha , McGarrah Robert , Bain James R. , Kraus William E. , Shah Svati H.
Published: December 2020

We sought to determine if novel plasma biomarkers improve traditionally defined metabolic health (MH) in predicting risk of cardiovascular disease (CVD) events irrespective of weight. Poor MH was defined in CATHGEN biorepository participants (n > 9300), a follow-up cohort (> 5600 days) comprising participants undergoing evaluation for possible ischemic heart disease. Lipoprotein subparticles, lipoprotein-insulin resistance (LP-IR), and GlycA were measured using NMR spectroscopy (n = 8385), while acylcarnitines and amino acids were measured using flow-injection, tandem mass spectrometry (n = 3592). Multivariable Cox proportional hazards models determined association of poor MH and plasma biomarkers with time-to-all-cause mortality or incident myocardial infarction. Low-density lipoprotein particle size and high-density lipoprotein, small and medium particle size (HMSP), GlycA, LP-IR, short-chain dicarboxylacylcarnitines (SCDA), and branched-chain amino acid plasma biomarkers were independently associated with CVD events after adjustment for traditionally defined MH in the overall cohort (p = 3.3 × 10−4–3.6 × 10−123), as well as within most of the individual BMI categories (p = 8.1 × 10−3–1.4 × 10−49). LP-IR, GlycA, HMSP, and SCDA improved metrics of model fit analyses beyond that of traditionally defined MH. We found that LP-IR, GlycA, HMSP, and SCDA improve traditionally defined MH models in prediction of adverse CVD events irrespective of BMI.
New insights into the autofluorescence properties of cellulose/nanocellulose
Authors: Ding Qijun , Han Wenjia , Li Xia , Jiang Yifei , Zhao Chuanshan
Published: December 2020

This work explored the fluorescence properties of nano/cellulose isolated from bleached softwood kraft pulp by TEMPO oxidation. Fluorescence spectra showed that all samples exhibited a typical emission peak at 574 nm due to the probabilistic formation of unsaturated bonds by glycosidic bonds independent of lignin. Increasing the excitation wavelengths (510–530 nm) caused red shift of fluorescence emission peaks (570–585 nm) with unchanged fluorescence intensity. Conversely, changing acid/alkaline conditions led to an increase of fluorescence intensity with no shifting of fluorescence emission peak. This can be attributed to an increase in the polarity of the solution environment but does not cause interaction of functional groups within the system identified by generalized two-dimensional correlation fluorescence spectroscopy. This study provides new insight in applying nano/cellulose with special luminous characteristics in biomedicine area such as multi-color biological imaging and chemical sensing.
The role of IgE specific for galactose-α-1,3-galactose in predicting cetuximab induced hypersensitivity reaction: a systematic review and a diagnostic meta-analysis
Authors: Lungulescu Cristian Virgil , Ungureanu Bogdan Silviu , Turcu-Stiolica Adina , Ghimpau Valentina , Artene Stefan Alexandru , Cazacu Irina Mihaela , Grecu Alexandru Florian , Dinescu Venera Cristina , Croitoru Adina , Volovat Simona Ruxandra
Published: December 2020

Recombinant monoclonal antibodies are used for treating various diseases, from asthma, rheumatoid arthritis, and inflammatory bowel disease to cancer. Although monoclonal antibodies are known to have fewer toxic reactions compared with the conventional cytotoxic antineoplastic drugs, the cases of severe systemic hypersensitivity reaction (HSR) should be acknowledged. Our aim was to assess the diagnostic accuracy of the anti-IgE for galactose-α-1,3-galactose in patients with HSRs to cetuximab. We searched in PubMed, Cochrane Library, Scopus, and World of Science databases to July 1st, 2020. We included a total of 6 studies, with 1074 patients. Meta-analysis was performed using bivariate analysis and the random-effect model. The pooled sensitivity was 73% (95% CI 62–81%) and the pooled specificity was 88% (95% CI 79–94%). We had not found significant heterogeneity and, despite some discrepancies in the nature of data available in the analysed studies, we draw the conclusion that the presence of cetuximab specific IgE (anti cetuximab antibody) and/or galactose-α-1,3-galactose shows moderate to high sensitivity and specificity of developing an HSR. More studies are needed to establish a protocol necessary for the proper prediction and avoidance of HSR related to cetuximab.
Telocytes contribute to aging-related modifications in the prostate
Authors: Sanches Bruno Domingos Azevedo , Tamarindo Guilherme Henrique , dos Santos Maldarine Juliana , da Silva Alana Della Torre , dos Santos Vitória Alário , Lima Maria Letícia Duarte , Rahal Paula , Góes Rejane Maira , Taboga Sebastião Roberto , Felisbino Sérgio Luis , Carvalho Hernandes F.
Published: December 2020

Telocytes are interstitial cells present in the stroma of several organs, including the prostate. There is evidence that these cells are present during prostate alveologenesis, in which these cells play a relevant role, but there is no information about the presence of and possible changes in telocytes during prostate aging. Throughout aging, the prostate undergoes several spontaneous changes in the stroma that are pro-pathogenic. Our study used histochemistry, 3D reconstructions, ultrastructure and immunofluorescence to compare the adult prostate with the senile prostate of the Mongolian gerbil, in order to investigate possible changes in telocytes with senescence and a possible role for these cells in the age-associated alterations. It was found that the layers of perialveolar smooth muscle become thinner as the prostatic alveoli become more dilated during aging, and that telocytes form a network that involves smooth muscle cells, which could possibly indicate a role for telocytes in maintaining the integrity of perialveolar smooth muscles. On the other hand, with senescence, VEGF+ telocytes are seen in stroma possibly contributing to angiogenesis, together with TNFR1+ telocytes, which are associated with a pro-inflammatory microenvironment in the prostate. Together, these data indicate that telocytes are important both in understanding the aging-related changes that are seen in the prostate and also in the search for new therapeutic targets for pathologies whose frequency increases with age.
TMEM150B is dispensable for oocyte maturation and female fertility in mouse
Authors: Liu Ran , Ke Hanni , Shao Tong , Qin Yingying , Zhao Shidou
Published: December 2020

Premature ovarian insufficiency (POI) refers to severe decline of ovary function in females which usually leads to infertility. It has been reported that the TMEM150B gene is mostly associated with age at natural menopause, early menopause and POI, but its role in female reproduction remains unknown. In this study, we found Tmem150b was highly expressed in mouse oocytes, but its deletion had no obvious effect on meiotic maturation of oocytes indicated by first polar body emission and spindle morphology. There were also no obvious differences in follicle development and corpus luteum formation between knockout and wild type mice. Finally, knockout of Tmem150b did not affect female fertility and sexual hormone levels. In summary, our results suggest that TMEM150B is not essential for female fertility in mice.
Differential effects of socio-demographic factors on maternal haemoglobin concentration in three sub-Saharan African Countries
Authors: Amugsi Dickson A. , Dimbuene Zacharie T. , Kyobutungi Catherine
Published: December 2020

Low Haemoglobin concentration (Hb) among women of reproductive age is a severe public health problem in sub-Saharan Africa. This study investigated the effects of putative socio-demographic factors on maternal Hb at different points of the conditional distribution of Hb concentration. We utilised quantile regression to analyse the Demographic and Health Surveys data from Ghana, Democratic Republic of the Congo (DRC) and Mozambique. In Ghana, maternal schooling had a positive effect on Hb of mothers in the 5th and 10th quantiles. A one-year increase in education was associated with an increase in Hb across all quantiles in Mozambique. Conversely, a year increase in schooling was associated with a decrease in Hb of mothers in the three upper quantiles in DRC. A unit change in body mass index had a positive effect on Hb of mothers in the 5th, 10th, 50th and 90th, and 5th to 50th quantiles in Ghana and Mozambique, respectively. We observed differential effects of breastfeeding on maternal Hb across all quantiles in the three countries. The effects of socio-demographic factors on maternal Hb vary at the various points of its distribution. Interventions to address maternal anaemia should take these variations into account to identify the most vulnerable groups.
On the curious case of the recent decade, mid-spring precipitation deficit in central Europe
Authors: Ionita M. , Nagavciuc V. , Kumar R. , Rakovec O.
Published: December 2020

Central Europe has experienced a severe drought almost every April for the last 14 years consecutively, driven by record high temperatures, low flows, high evapotranspiration, and high soil moisture deficit. The dynamic of this recent and recurrent mid-spring dryness is not yet understood. Here we show that the period 2007–2020 was characterized by a reduction of ~50% of the usual April rainfall amount over large areas in central Europe. The precipitation deficit and the record high temperatures were triggered by a multiyear recurrent high-pressure system centered over the North Sea and northern Germany and a decline in the temperature gradient between the Arctic region and the mid-latitudes, which diverted the Atlantic storm tracks northward. From a long-term perspective, the precipitation, temperature, and soil moisture anomalies observed over the last 14 years have reached the highest amplitudes over the observational record. Our study provides an in-depth analysis of the hydroclimate extremes in central Europe over the last 140 years and their atmospheric drivers, enabling us to increase our dynamical understating of long-term dry periods, which is vital to enhance forecasting and mitigation of such events.
Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression
Authors: Di Domenico Annunziata , Pipinikas Christodoulos P. , Maire Renaud S. , Bräutigam Konstantin , Simillion Cedric , Dettmer Matthias S. , Vassella Erik , Thirlwell Chrissie , Perren Aurel , Marinoni Ilaria
Published: December 2020

Recent data suggest that Pancreatic Neuroendocrine Tumours (PanNETs) originate from α- or β-cells of the islets of Langerhans. The majority of PanNETs are non-functional and do not express cell-type specific hormones. In the current study we examine whether tumour DNA methylation (DNAme) profiling combined with genomic data is able to identify cell of origin and to reveal pathways involved in PanNET progression. We analyse genome-wide DNAme data of 125 PanNETs and sorted α- and β-cells. To confirm cell identity, we investigate ARX and PDX1 expression. Based on epigenetic similarities, PanNETs cluster in α-like, β-like and intermediate tumours. The epigenetic similarity to α-cells progressively decreases in the intermediate tumours, which present unclear differentiation. Specific transcription factor methylation and expression vary in the respective α/β-tumour groups. Depending on DNAme similarity to α/β-cells, PanNETs have different mutational spectra, stage of the disease and prognosis, indicating potential means of PanNET progression.