bluuebunny/crossref_metadata_2025 huggingface dataset:
The p53-caspase-2 axis in the cell cycle and DNA damage response
Authors: Lim Yoon , Dorstyn Loretta , Kumar Sharad
Published: April 2021

Caspase-2 was discovered almost three decades ago. It was one of the first two mammalian homologs of CED-3, the other being interleukin 1β-converting enzyme (ICE/caspase-1). Despite high similarity with CED-3 and its fly and mammalian counterparts (DRONC and caspase-9, respectively), the function of caspase-2 in apoptosis has remained enigmatic. A number of recent studies suggest that caspase-2 plays an important role in the regulation of p53 in response to cellular stress and DNA damage to prevent the proliferation and accumulation of damaged or aberrant cells. Here, we review these recent observations and their implications in caspase-2-mediated cellular death, senescence, and tumor suppression.
Blood pressure and resting heart rate in 3-17-year-olds in Germany in 2003–2006 and 2014–2017
Authors: Sarganas Giselle , Schienkiewitz Anja , Finger Jonas D. , Neuhauser Hannelore K.
Published: April 2021

To track blood pressure (BP) and resting heart rate (RHR) in children and adolescents is important due to its associations with cardiovascular outcomes in the adulthood. Therefore, the aim of this study was to examine BP and RHR over a decade among children and adolescents living in Germany using national examination data. Cross-sectional data from 3- to 17-year-old national survey participants (KiGGS 2003–06,n = 14,701; KiGGS 2014–17,n = 3509) including standardized oscillometric BP and RHR were used for age- and sex-standardized analysis. Measurement protocols were identical with the exception of the cuff selection rule, which was accounted for in the analyses. Different BP and RHR trends were observed according to age-groups. In 3- to 6-year-olds adjusted mean SBP and DBP were significantly higher in 2014–2017 compared to 2003–2006 (+2.4 and +1.9 mm Hg, respectively), while RHR was statistically significantly lower by −3.8 bpm. No significant changes in BP or in RHR were observed in 7- to 10-year-olds over time. In 11- to 13-year-olds as well as in 14- to 17-year-olds lower BP has been observed (SBP −2.4 and −3.2 mm Hg, respectively, and DBP −1.8 and −1.7 mm Hg), while RHR was significantly higher (+2.7 and +3.7 bpm). BP trends did not parallel RHR trends. The downward BP trend in adolescents seemed to follow decreasing adult BP trends in middle and high-income countries. The increase in BP in younger children needs confirmation from other studies as well as further investigation. In school-aged children and adolescents, the increased RHR trend may indicate decreased physical fitness.
A small molecule binding HMGB1 inhibits caspase-11-mediated lethality in sepsis
Authors: Wang Xiangyu , Li Zhaozheng , Bai Yang , Zhang Rui , Meng Ran , Chen Fangping , Wang Haichao , Billiar Timothy R. , Xiao Xianzhong , Lu Ben , Tang Yiting
Published: April 2021

Caspase-11, a cytosolic lipopolysaccharide (LPS) receptor, mediates lethal immune responses and coagulopathy in sepsis, a leading cause of death worldwide with limited therapeutic options. We previously showed that over-activation of caspase-11 is driven by hepatocyte-released high mobility group box 1 (HMGB1), which delivers extracellular LPS into the cytosol of host cells during sepsis. Using a phenotypic screening strategy with recombinant HMGB1 and peritoneal macrophages, we discovered that FeTPPS, a small molecule selectively inhibits HMGB1-mediated caspase-11 activation. The physical interaction between FeTPPS and HMGB1 disrupts the HMGB1-LPS binding and decreases the capacity of HMGB1 to induce lysosomal rupture, leading to the diminished cytosolic delivery of LPS. Treatment of FeTPPS significantly attenuates HMGB1- and caspase-11-mediated immune responses, organ damage, and lethality in endotoxemia and bacterial sepsis. These findings shed light on the development of HMGB1-targeting therapeutics for lethal immune disorders and might open a new avenue to treat sepsis.
Moving somatic gene editing to the clinic: routes to market access and reimbursement in Europe
Authors: Rigter Tessel , Klein David , Weinreich Stephanie S. , Cornel Martina C.
Published: April 2021

Somatic gene editing (SGE) holds great promise for making genetic therapy possible for many monogenic conditions very soon. Is our current system of European market authorization and reimbursement ready for the expected tsunami of gene therapies? At a recent workshop of the Netherlands ZonMw consortium on ethical, legal, and social implications of personalized medicine, we discussed the current possibilities for bringing new gene therapies to the clinic. In Europe, it is not yet clear whether the route via the European medicines agency as an advanced therapy medicinal product is the most appropriate for evaluation of highly personalized SGE applications, although this may optimally guarantee safety and effectiveness. Compassionate use may ensure faster access than the centralized procedure but does not stimulate the commercial development of products. Prescription to named patients may only provide adequate access for single patients. Temporary authorization of use may allow access to medication half a year before formal market authorization has been granted, but may also have large budget impacts. Magistral compounding under a hospital exemption may be an attractive solution for rare, tailor-made applications at an acceptable price. To approve local experimental use of a therapy on a case-by-case basis may be fast, but does not guarantee optimal safety, effectiveness, and broad implementation. We argue that alternative routes should be considered for products developed for a market of large groups of patients versus unique personalized treatments. A balance between scientific evidence for safety and effectiveness, affordability, and fast access may demand a range of alternative solutions.
Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling
Authors: Huang Hao , Hu Jianyang , Maryam Alishba , Huang Qinghua , Zhang Yuchen , Ramakrishnan Saravanan , Li Jingyu , Ma Haiying , Ma Victor W. S. , Cheuk Wah , So Grace Y. K. , Wang Wei , Cho William C. S. , Zhang Liang , Chan Kui Ming , Wang Xin , Chin Y. Rebecca
Published: April 2021

Breast cancer is a heterogeneous disease, affecting over 3.5 million women worldwide, yet the functional role of cis-regulatory elements including super-enhancers in different breast cancer subtypes remains poorly characterized. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. Here we apply integrated epigenomic and transcriptomic profiling to uncover super-enhancer heterogeneity between breast cancer subtypes, and provide clinically relevant biological insights towards TNBC. Using CRISPR/Cas9-mediated gene editing, we identify genes that are specifically regulated by TNBC-specific super-enhancers, including FOXC1 and MET, thereby unveiling a mechanism for specific overexpression of the key oncogenes in TNBC. We also identify ANLN as a TNBC-specific gene regulated by super-enhancer. Our studies reveal a TNBC-specific epigenomic landscape, contributing to the dysregulated oncogene expression in breast tumorigenesis.
Comprehensive omic characterization of breast cancer in Mexican-Hispanic women
Authors: Romero-Cordoba Sandra L. , Salido-Guadarrama Ivan , Rebollar-Vega Rosa , Bautista-Piña Veronica , Dominguez-Reyes Carlos , Tenorio-Torres Alberto , Villegas-Carlos Felipe , Fernández-López Juan C. , Uribe-Figueroa Laura , Alfaro-Ruiz Luis , Hidalgo-Miranda Alfredo
Published: April 2021

Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1E17K hotspot mutation in 8% of the HM women and identify the AKT1/PIK3CA axis as a potentially druggable target. Also, HM luminal breast tumors present an enhanced immunogenic phenotype compared to Asiatic and Caucasian tumors. This study is an initial effort to include patients from Hispanic populations in the research of breast cancer etiology and biology to further understand breast cancer disparities.
Squeezed light from a nanophotonic molecule
Authors: Zhang Y. , Menotti M. , Tan K. , Vaidya V. D. , Mahler D. H. , Helt L. G. , Zatti L. , Liscidini M. , Morrison B. , Vernon Z.
Published: April 2021

Delicate engineering of integrated nonlinear structures is required for developing scalable sources of non-classical light to be deployed in quantum information processing systems. In this work, we demonstrate a photonic molecule composed of two coupled microring resonators on an integrated nanophotonic chip, designed to generate strongly squeezed light uncontaminated by noise from unwanted parasitic nonlinear processes. By tuning the photonic molecule to selectively couple and thus hybridize only the modes involved in the unwanted processes, suppression of parasitic parametric fluorescence is accomplished. This strategy enables the use of microring resonators for the efficient generation of degenerate squeezed light: without it, simple single-resonator structures cannot avoid contamination from nonlinear noise without significantly compromising pump power efficiency. We use this device to generate 8(1) dB of broadband degenerate squeezed light on-chip, with 1.65(1) dB directly measured.
A systematic approach to generating accurate neural network potentials: the case of carbon
Authors: Shaidu Yusuf , Küçükbenli Emine , Lot Ruggero , Pellegrini Franco , Kaxiras Efthimios , de Gironcoli Stefano
Published: April 2021

Availability of affordable and widely applicable interatomic potentials is the key needed to unlock the riches of modern materials modeling. Artificial neural network-based approaches for generating potentials are promising; however, neural network training requires large amounts of data, sampled adequately from an often unknown potential energy surface. Here we propose a self-consistent approach that is based on crystal structure prediction formalism and is guided by unsupervised data analysis, to construct an accurate, inexpensive, and transferable artificial neural network potential. Using this approach, we construct an interatomic potential for carbon and demonstrate its ability to reproduce first principles results on elastic and vibrational properties for diamond, graphite, and graphene, as well as energy ordering and structural properties of a wide range of crystalline and amorphous phases.
Prediction of high thermoelectric performance in the low-dimensional metal halide Cs3Cu2I5
Authors: Jung Young-Kwang , Han In Taek , Kim Yong Churl , Walsh Aron
Published: April 2021

Metal halides have emerged as a new generation of semiconductors with applications ranging from solar cells to chemical sensors. We assess the thermoelectric potential of Cs3Cu2I5, which has a crystal structure formed of zero-dimensional [Cu2I5]3− anionic clusters that are separated by Cs+ counter cations. We find the compound exhibits the characteristics of a phonon-glass electron-crystal with a large imbalance in the conduction of heat and electrons predicted from first-principles transport theory. Strong anharmonic phonon–phonon scattering results in short-lived acoustic vibrations and an ultra-low lattice thermal conductivity (<0.1 W m−1 K−1). The dispersive conduction band leads to a high electron mobility (>10 cm2 V−1 s−1). For an n-type crystal at 600 K, a thermoelectric figure-of-merit ZT of 2.6 is found to be accessible, which for a cold source of 300 K corresponds to a thermodynamic heat-to-electricity conversion efficiency of 15%.
Delayed orthostatic hypotension in Parkinson’s disease
Authors: Yoo Sang-Won , Kim Joong-Seok , Yoo Ji-Yeon , Yun Eunkyeong , Yoon Uicheul , Shin Na-Young , Lee Kwang-Soo
Published: April 2021

Orthostatic hypotension (OH) is relatively common in the early stage of Parkinson’s disease (PD). It is divided into delayed OH and classical OH. Classical OH in PD has been investigated widely, however, the clinical implications of delayed OH in PD have seldom been studied. The purpose of this study is to characterize delayed OH in PD. A total of 285 patients with early drug-naïve PD were enrolled and divided into three groups according to orthostatic change: no-OH, delayed OH, and classical OH. The disease severity in terms of motor, non-motor, and cognitive functions was assessed. The cortical thickness of 82 patients was analyzed with brain magnetic resonance imaging. The differences among groups and linear tendency in the order of no-OH, delayed OH, and classical OH were investigated. Seventy-seven patients were re-evaluated. Initial and follow-up evaluations were explored to discern any temporal effects of orthostasis on disease severity. Sixty-four (22.5%) patients were defined as having delayed OH and 117 (41.1%) had classical OH. Between-group comparisons revealed that classical OH had the worst outcomes in motor, non-motor, cognitive, and cortical thickness, compared to the other groups. No-OH and delayed OH did not differ significantly. Linear trends across the pre-ordered OH subtypes found that clinical parameters worsened along with the orthostatic challenge. Clinical scales deteriorated and the linear gradient was maintained during the follow-up period. This study suggests that delayed OH is a mild form of classical OH in PD. PD with delayed OH has milder disease severity and progression.
Detection of exogenous sugars in pineapple juice using compound-specific stable hydrogen isotope analysis
Authors: Kelly Simon D. , Abrahim Aiman , Rinke Peter , Cannavan Andrew
Published: April 2021

An improved procedure for determining 2H/1H isotope ratios, using gas chromatography-isotope ratio mass spectrometry, has been used to detect the addition of exogenous C4-plant-derived sugars to pineapple juice. Isotopic techniques are commonly used to identify the addition of low-cost sugars to fruit juices and are difficult to subvert as it is not economically viable to change the isotopic ratios of the sugars. However, the addition of cane sugar to pineapple juice has presented a significant challenge that is only detected by site-specific 13C analysis of the methyl and methylene positions of ethanol derived from pineapple sugars, measured by nuclear magnetic resonance. This new GC-IRMS-based procedure utilises the trifluoroacetate derivative of sucrose to allow direct measurement of the carbon-bound non-exchangeable hydrogen. This provides advantages over alternative isotopic methods in terms of analysis time and sensitivity. This feasibility study has demonstrated the potential to reliably differentiate between authentic pineapple juices and those adulterated with commercial beet and cane sucrose.
BonZeb: open-source, modular software tools for high-resolution zebrafish tracking and analysis
Authors: Guilbeault Nicholas C. , Guerguiev Jordan , Martin Michael , Tate Isabelle , Thiele Tod R.
Published: April 2021

We present BonZeb—a suite of modular Bonsai packages which allow high-resolution zebrafish tracking with dynamic visual feedback. Bonsai is an increasingly popular software platform that is accelerating the standardization of experimental protocols within the neurosciences due to its speed, flexibility, and minimal programming overhead. BonZeb can be implemented into novel and existing Bonsai workflows for online behavioral tracking and offline tracking with batch processing. We demonstrate that BonZeb can run a variety of experimental configurations used for gaining insights into the neural mechanisms of zebrafish behavior. BonZeb supports head-fixed closed-loop and free-swimming virtual open-loop assays as well as multi-animal tracking, optogenetic stimulation, and calcium imaging during behavior. The combined performance, ease of use and versatility of BonZeb opens new experimental avenues for researchers seeking high-resolution behavioral tracking of larval zebrafish.
Non-invasive characterization of complex coronary lesions
Authors: Vardhan Madhurima , Gounley John , Chen S. James , Chi Eric C. , Kahn Andrew M. , Leopold Jane A. , Randles Amanda
Published: April 2021

Conventional invasive diagnostic imaging techniques do not adequately resolve complex Type B and C coronary lesions, which present unique challenges, require personalized treatment and result in worsened patient outcomes. These lesions are often excluded from large-scale non-invasive clinical trials and there does not exist a validated approach to characterize hemodynamic quantities and guide percutaneous intervention for such lesions. This work identifies key biomarkers that differentiate complex Type B and C lesions from simple Type A lesions by introducing and validating a coronary angiography-based computational fluid dynamic (CFD-CA) framework for intracoronary assessment in complex lesions at ultrahigh resolution. Among 14 patients selected in this study, 7 patients with Type B and C lesions were included in the complex lesion group including ostial, bifurcation, serial lesions and lesion where flow was supplied by collateral bed. Simple lesion group included 7 patients with lesions that were discrete, $$<10\hbox {mm}$$

<
10
mm

long and readily accessible. Intracoronary assessment was performed using CFD-CA framework and validated by comparing to clinically measured pressure-based index, such as FFR. Local pressure, endothelial shear stress (ESS) and velocity profiles were derived for all patients. We validates the accuracy of our CFD-CA framework and report excellent agreement with invasive measurements ($$n=14, R^2 = 0.6, p = 0.0013$$

n
=
14
,

R
2

=
0.6
,
p
=
0.0013

). Ultra-high resolution achieved by the model enable physiological assessment in complex lesions and quantify hemodynamic metrics in all vessels up to 1mm in diameter. Importantly, we demonstrate that in contrast to traditional pressure-based metrics, there is a significant difference in the intracoronary hemodynamic forces, such as ESS, in complex lesions compared to simple lesions at both resting and hyperemic physiological states [n = 14, $$p=0.03$$

p
=
0.03

]. Higher ESS was observed in the complex lesion group ($$7.0\pm 4.7$$

7.0
±
4.7

Pa) than in simple lesion group ($$4.8\pm 3.6$$

4.8
±
3.6

Pa). Complex coronary lesions have higher ESS compared to simple lesions, such differential hemodynamic evaluation can provide much the needed insight into the increase in adverse outcomes for such patients and has incremental prognostic value over traditional pressure-based indices, such as FFR.
Antimonate sequestration from aqueous solution using zirconium, iron and zirconium-iron modified biochars
Authors: Rahman Md. Aminur , Rahman Mohammad Mahmudur , Bahar Md. Mezbaul , Sanderson Peter , Lamb Dane
Published: April 2021

Antimony (Sb) is increasingly being recognized as an important contaminant due to its various industrial applications and mining operations. Environmental remediation approaches for Sb are still lacking, as is the understanding of Sb environmental chemistry. In this study, biosolid biochar (BSBC) was produced and utilized to remove antimonate (Sb(V)) from aqueous solution. Zirconium (Zr), Zirconium-iron (Zr–Fe) and Fe–O coated BSBC were synthesized for enhancing Sb(V) sorption capacities of BSBC. The combined results of specific surface area, FTIR, SEM–EDS, TEM–EDS, and XPS confirmed that Zr and/or Zr–Fe were successfully coated onto BSBC. The effects of reaction time, pH, initial Sb(V) concentration, adsorbate doses, ionic strength, temperature, and the influence of major competitive co-existing anions and cations on the adsorption of Sb(V) were investigated. The maximum sorption capacity of Zr–O, Zr–Fe, Zr–FeCl3, Fe–O, and FeCl3 coated BSBC were 66.67, 98.04, 85.47, 39.68, and 31.54 mg/g respectively under acidic conditions. The XPS results revealed redox transformation of Sb(V) species to Sb(III) occurred under oxic conditions, demonstrating the biochar’s ability to behave as an electron shuttle during sorption. The sorption study suggests that Zr–O and Zr–O–Fe coated BSBC could perform as favourable adsorbents for mitigating Sb(V) contaminated waters.
Prevalence of metabolic syndrome and its associated risk factors among staffs in a Malaysian public university
Authors: Manaf Mohd Rizal Abdul , Nawi Azmawati Mohammed , Tauhid Noorlaili Mohd , Othman Hanita , Rahman Mohd Rizam Abdul , Yusoff Hanizah Mohd , Safian Nazaruddin , Ng Pei Yuen , Manaf Zahara Abdul , Kadir Nor Ba’yah Abdul , Yanasegaran Kevina , Basir Siti Munirah Abdul , Ramakrishnappa Sowmya , Ganasegeran Kurubaran
Published: April 2021

Public health systems are concerned with the commensurate rise of metabolic syndrome (MetS) incidence across populations worldwide, due to its tendency to amplify greater risk of diabetes and cardiovascular diseases within communities. This study aimed to determine the prevalence of MetS and its associated risk factors among staffs in a Malaysian public university. A cross-sectional study was conducted among 538 staffs from the Universiti Kebangsaan Malaysia (UKM) between April and June 2019. MetS was defined according to JIS “Harmonized” criteria. A questionnaire that consisted of items on socio-demographics, lifestyle risk behaviors and personal medical history information was administered to participants. Subsequently, a series of physical examination and biochemical assessment was conducted at the hall or foyer of selected faculties in the university. Descriptive and inferential statistics were conducted using SPSS version 22.0. Multivariate models were yielded to determine the risk factors associated with MetS. Statistical significance was set at P < 0.05. The overall prevalence of MetS was 20.6%, with men having greater prevalence than women (24.9% vs. 18.3%). Prevalence of MetS increased with age. Factors contributed to MetS in the overall sample were BMI, hypertension, diabetes and physical activity of moderate intensity. Diabetes and hypertension were significantly associated with MetS in men, whereas BMI, diabetes and hyperlipidemia were significantly associated with MetS in women. Lifestyle behaviors and cardio-metabolic risk factors were associated with MetS for the overall sample, and across genders.
Author Correction: The higher prevalence of extended spectrum beta-lactamases among Escherichia coli ST131 in Southeast Asia is driven by expansion of a single, locally prevalent subclone
Authors: Chen Swaine L. , Ding Ying , Apisarnthanarak Anucha , Kalimuddin Shirin , Archuleta Sophia , Omar Sharifah Faridah Syed , De Partha Pratim , Koh Tse Hsien , Chew Kean Lee , Atiya Nadia , Suwantarat Nuntra , Velayuthan Rukumani Devi , Wong Joshua Guo Xian , Lye David C.
Published: April 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Sex differences in muscle fatigue following isokinetic muscle contractions
Authors: Gomes Miguel , Santos Paulo , Correia Paulo , Pezarat-Correia Pedro , Mendonca Goncalo V.
Published: April 2021

Muscle fatigue is a limiting factor of human performance. It is unclear whether sex-based differences in fatigability exist during dynamic exercise of varying velocities of contraction. We aimed at exploring sex differences in muscle fatigue elicited by maximal isokinetic muscle contractions performed at different angular velocities. Twenty-six healthy participants (13 men: 23.2 ± 1.5; 13 women: 21.9 ± 3.0 years) were tested for concentric knee-extension at slow, moderate and fast angular isokinetic velocity (60, 180 and 300º.s−1, respectively), on non-consecutive days. The impact of sex on fatigue resistance and consecutive recovery for each isokinetic condition was explored by calculating the percent change in maximal voluntary isometric contraction (MVIC) and in rate of torque development (RTD), from pre- to post-isokinetic exercise (30 repetitions). The isokinetic fatigue index was also determined. No sex differences were obtained in response to isokinetic contractions completed at 60º.s−1. After performing muscle contractions at 300º.s−1, women had a significantly greater loss in MVIC than men (− 18.4 ± 5.5 vs. − 12.9 ± 3.8%; p = 0.009) and larger decreases in work output during isokinetic exercise (− 34.2 ± 8.9 vs − 27.5 ± 10.6%; p = 0.017). Recovery of initial MVIC strength was greater for women post-exercise at 180º.s−1 (15.6 ± 4.1% vs. 6.7 ± 9.5; p = 0.003). No differences were found between sexes in any condition for RTD from pre- to post-fatigue. These results suggest the presence of a sexually dimorphic fatigability in response to dynamic (isokinetic) contractions favouring men at higher absolute velocities of contraction.
Spatial segregation of mixed-sized counterions in dendritic polyelectrolytes
Authors: Kłos J. S. , Paturej J.
Published: April 2021

Langevin dynamics simulations are utilized to study the structure of a dendritic polyelectrolyte embedded in two component mixtures comprised of conventional (small) and bulky counterions. We vary two parameters that trigger conformational properties of the dendrimer: the reduced Bjerrum length, $$\lambda _B^*$$

λ
B
∗

, which controls the strength of electrostatic interactions and the number fraction of the bulky counterions, $$f_b$$

f
b

, which impacts on their steric repulsion. We find that the interplay between the electrostatic and the counterion excluded volume interactions affects the swelling behavior of the molecule. As compared to its neutral counterpart, for weak electrostatic couplings the charged dendrimer exists in swollen conformations whose size remains unaffected by $$f_b$$

f
b

. For intermediate couplings, the absorption of counterions into the pervaded volume of the dendrimer starts to influence its conformation. Here, the swelling factor exhibits a maximum which can be shifted by increasing $$f_b$$

f
b

. For strong electrostatic couplings the dendrimer deswells correspondingly to $$f_b$$

f
b

. In this regime a spatial separation of the counterions into core–shell microstructures is observed. The core of the dendrimer cage is preferentially occupied by the conventional ions, whereas its periphery contains the bulky counterions.
Characteristics of PCDD/Fs in PM2.5 from emission stacks and the nearby ambient air in Taiwan
Authors: Pan Shih Yu , Liou Yi Ting , Chang Moo Been , Chou Charles C.-K. , Ngo Tuan Hung , Chi Kai Hsien
Published: April 2021

This study aimed to find the characteristics of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in fine particulate matter from different stationary emission sources (coal-fired boiler, CFB; municipal waste incinerator, MWI; electric arc furnace, EAF) in Taiwan and the relationship between PM2.5 and PM2.5-bound PCDD/Fs with Taiwanese mortality risk. PM2.5 was quantified using gravimetry and corresponding chemical analyses were done for PM2.5-bound chemicals. Mortality risks of PM2.5 exposure and PCDD/Fs exposure were calculated using Poisson regression. The highest concentration of PM2.5 (0.53 ± 0.39 mg/Nm3) and PCDD/Fs (0.206 ± 0.107 ng I-TEQ/Nm3) was found in CFB and EAF, respectively. Higher proportions of PCDDs over PCDFs were observed in the flue gases of CFB and MWI whereas it was reversed in EAF. For ambient air, PCDD/F congeners around the stationary sources were dominated by PCDFs in vapor phase. Positive matrix factorization (PMF) analysis found that the sources of atmosphere PCDD/Fs were 14.6% from EAF (r = 0.81), 52.6% from CFB (r = 0.74), 18.0% from traffic (r = 0.85) and 14.8% from MWI (r = 0.76). For the dioxin congener distribution, PCDDs were dominant in flue gases of CFB and MWI, PCDFs were dominant in EAF. It may be attributed to the different formation mechanisms among wastes incineration, steel-making, and coal-burning processes.
Susceptibility of Drosophila suzukii larvae to the combined administration of the entomopathogens Bacillus thuringiensis and Steinernema carpocapsae
Authors: Mastore Maristella , Quadroni Silvia , Brivio Maurizio F.
Published: April 2021

Non-native pests are often responsible for serious crop damage. Since Drosophila suzukii has invaded North America and Europe, the global production of soft, thin-skinned fruits has suffered severe losses. The control of this dipteran by pesticides, although commonly used, is not recommended because of the negative impact on the environment and human health. A possible alternative is the use of bio-insecticides, including Bacillus thuringiensis and entomopathogenic nematodes, such as Steinernema carpocapsae. These biological control agents have a fair effectiveness when used individually on D. suzukii, but both have limits related to different environmental, methodological, and physiological factors. In this work, we tested various concentrations of B. thuringiensis and S. carpocapsae to evaluate their efficacy on D. suzukii larvae, when administered individually or in combination by using agar traps. In the combined trials, we added the nematodes after 16 h or concurrently to the bacteria, and assessed larvae lethality from 16 to 48 h. The assays demonstrated a higher efficacy of the combined administration, both time-shifted and concurrent; the obtained data also showed a relevant decrease of the time needed to kill the larvae. Particularly, the maximum mortality rate, corresponding to 79% already at 16 h, was observed with the highest concentrations (0.564 µg/mL of B. thuringiensis and 8 × 102 IJs of S. carpocapsae) in the concurrent trials. This study, conducted by laboratory tests under controlled conditions, is a good starting point to develop a further application step through field studies for the control of D. suzukii.
Dynamically induced friction reduction in micro-structured interfaces
Authors: Menga N. , Bottiglione F. , Carbone G.
Published: April 2021

We investigate the dynamic behavior of a regular array of in-plane elastic supports interposed between a sliding rigid body and a rigid substrate. Each support is modelled as a mass connected to a fixed pivot by means of radial and tangential elastic elements. Frictional interactions are considered at the interface between the supports and the sliding body. Depending on the specific elastic properties of the supports, different dynamic regimes can be achieved, which, in turn, affect the system frictional behavior. Specifically, due to transverse microscopic vibration of the supports, a lower friction force opposing the macroscopic motion of the rigid body can be achieved compared to the case where no supports are present and rubbing occurs with the substrate. Furthermore, we found that the supports static orientation plays a key role in determining the frictional interactions, thus offering the chance to specifically design the array aiming at controlling the resulting interfacial friction force.
Vestibular attenuation to random-waveform galvanic vestibular stimulation during standing and treadmill walking
Authors: Hannan Kelci B. , Todd Makina K. , Pearson Nicole J. , Forbes Patrick A. , Dakin Christopher J.
Published: April 2021

The ability to move and maintain posture is critically dependent on motion and orientation information provided by the vestibular system. When this system delivers noisy or erred information it can, in some cases, be attenuated through habituation. Here we investigate whether multiple mechanisms of attenuation act to decrease vestibular gain due to noise added using supra-threshold random-waveform galvanic vestibular stimulation (GVS). Forty-five participants completed one of three conditions. Each condition consisted of two 4-min standing periods with stimulation surrounding a 1-h period of either walking with stimulation, walking without stimulation, or sitting quietly. An instrumented treadmill recorded horizontal forces at the feet during standing and walking. We quantified response attenuation to GVS by comparing vestibular stimulus-horizontal force gain between conditions. First stimulus exposure caused an 18% decrease in gain during the first 40 s of standing. Attenuation recommenced only when subjects walked with stimulation, resulting in a 38% decrease in gain over 60 min that did not transfer to standing following walking. The disparity in attenuation dynamics and absent carry over between standing and walking suggests that two mechanisms of attenuation, one associated with first exposure to the stimulus and another that is task specific, may act to decrease vestibulomotor gain.
Genomic characterization of a polyvalent hydrocarbonoclastic bacterium Pseudomonas sp. strain BUN14
Authors: Mahjoubi Mouna , Aliyu Habibu , Neifar Mohamed , Cappello Simone , Chouchane Habib , Souissi Yasmine , Masmoudi Ahmed Salaheddine , Cowan Don A. , Cherif Ameur
Published: April 2021

Bioremediation offers a viable alternative for the reduction of contaminants from the environment, particularly petroleum and its recalcitrant derivatives. In this study, the ability of a strain ofPseudomonasBUN14 to degrade crude oil, pristane and dioxin compounds, and to produce biosurfactants, was investigated. BUN14 is a halotolerant strain isolated from polluted sediment recovered from the refinery harbor on the Bizerte coast, north Tunisia and capable of producing surfactants. The strain BUN14 was assembled into 22 contigs of 4,898,053 bp with a mean GC content of 62.4%. Whole genome phylogeny and comparative genome analyses showed that strain BUN14 could be affiliated with two validly describedPseudomonasType Strains,P. kunmingensisDSM 25974TandP. chloritidismutansAW-1T. The current study, however, revealed that the two Type Strains are probably conspecific and, given the priority of the latter, we proposed thatP. kunmingensisDSM 25974 is a heteronym ofP. chloritidismutansAW-1T. Using GC-FID analysis, we determined that BUN14 was able to use a range of hydrocarbons (crude oil, pristane, dibenzofuran, dibenzothiophene, naphthalene) as a sole carbon source. Genome analysis of BUN14 revealed the presence of a large repertoire of proteins (154) related to xenobiotic biodegradation and metabolism. Thus, 44 proteins were linked to the pathways for complete degradation of benzoate and naphthalene. The annotation of conserved functional domains led to the detection of putative genes encoding enzymes of the rhamnolipid biosynthesis pathway. Overall, the polyvalent hydrocarbon degradation capacity of BUN14 makes it a promising candidate for application in the bioremediation of polluted saline environments.
No association between pyrite content and lung cell responses to coal particles
Authors: Zosky Graeme R. , Bennett Ellen J. , Pavez Macarena , Beamish B. Basil
Published: April 2021

There has been an increase in the identification of cases of coal workers’ pneumoconiosis (CWP) in recent years around the world. While there are a range of possible explanations for this, studies have implicated the pyrite content of coal as a key determinant of CWP risk. However, experimental studies to support this link are limited. The aim of this study was to assess the association between the pyrite content, and subsequent release of bioavailable iron, in coal particles and the response of lung cells involved in the pathogenesis of CWP (epithelial cells, macrophages and fibroblasts). Using real-world Australian coal samples, we found no evidence of an association between the pyrite content of the coal and the magnitude of the detrimental cell response. We did find evidence of an increase in IL-8 production by epithelial cells with increasing bioavailable iron (p = 0.01), however, this was not linked to the pyrite content of the coal (p = 0.75) and we did not see any evidence of a positive association in the other cell types. Given the lack of association between the pyrite content of real-world coal particles and lung cell cytotoxicity (epithelial cells and macrophages), inflammatory cytokine production (epithelial cells, macrophages and fibroblasts), and cell proliferation (fibroblasts) our data do not support the use of coal pyrite content as a predictor of CWP risk.
Repositioning metformin and propranolol for colorectal and triple negative breast cancers treatment
Authors: Anselmino L. E. , Baglioni M. V. , Malizia F. , Laluce N. Cesatti , Etichetti C. Borini , Marignac V. L. Martínez , Rozados V. , Scharovsky O. G. , Girardini J. , Rico M. J. , Menacho Márquez M.
Published: April 2021

Drug repositioning refers to new uses for existing drugs outside the scope of the original medical indications. This approach fastens the process of drug development allowing finding effective drugs with reduced side effects and lower costs. Colorectal cancer (CRC) is often diagnosed at advanced stages, when the probability of chemotherapy resistance is higher. Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, highly metastatic and difficult to treat. For both tumor types, available treatments are generally associated to severe side effects. In our work, we explored the effect of combining metformin and propranolol, two repositioned drugs, in both tumor types. We demonstrate that treatment affects viability, epithelial-mesenchymal transition and migratory potential of CRC cells as we described before for TNBC. We show that combined treatment affects different steps leading to metastasis in TNBC. Moreover, combined treatment is also effective preventing the development of 5-FU resistant CRC. Our data suggest that combination of metformin and propranolol could be useful as a putative adjuvant treatment for both TNBC and CRC and an alternative for chemo-resistant CRC, providing a low-cost alternative therapy without associated toxicity.
Self-reported and cotinine-verified smoking and increased risk of incident hearing loss
Authors: Lee Woncheol , Chang Yoosoo , Shin Hocheol , Ryu Seungho
Published: April 2021

We examined the associations of smoking status and urinary cotinine levels, an objective measure of smoking, with the development of new-onset HL. This cohort study was performed in 293,991 Korean adults free of HL who underwent a comprehensive screening examination and were followed for up to 8.8 years. HL was defined as a pure-tone average of thresholds at 0.5, 1.0, and 2.0 kHz ≥ 25 dB in both ears. During a median follow-up of 4.9 years, 2286 participants developed new-onset bilateral HL. Self-reported smoking status was associated with an increased risk of new-onset bilateral HL. Multivariable-adjusted HRs (95% CIs) for incident HL comparing former smokers and current smokers to never-smokers were 1.14 (1.004–1.30) and 1.40 (1.21–1.61), respectively. Number of cigarettes, pack-years, and urinary cotinine levels were consistently associated with incident HL. These associations were similarly observed when introducing changes in smoking status, urinary cotinine, and other confounders during follow-up as time-varying covariates. In this large cohort of young and middle-aged men and women, smoking status based on both self-report and urinary cotinine level were independently associated with an increased incidence of bilateral HL. Our findings indicate smoking is an independent risk factor for HL.
TMS-EEG signatures of glutamatergic neurotransmission in human cortex
Authors: Belardinelli Paolo , König Franca , Liang Chen , Premoli Isabella , Desideri Debora , Müller-Dahlhaus Florian , Gordon Pedro Caldana , Zipser Carl , Zrenner Christoph , Ziemann Ulf
Published: April 2021

Neuronal activity in the brain reflects an excitation–inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (dextromethorphan, an NMDA receptor antagonist; perampanel, an AMPA receptor antagonist) and an L-type voltage-gated calcium channel blocker (nimodipine) on transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) potentials (TEPs) and TMS-induced oscillations (TIOs) in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled crossover design. Single-pulse TMS was delivered to the hand area of left primary motor cortex. Dextromethorphan increased the amplitude of the N45 TEP, while it had no effect on TIOs. Perampanel reduced the amplitude of the P60 TEP in the non-stimulated hemisphere, and increased TIOs in the beta-frequency band in the stimulated sensorimotor cortex, and in the alpha-frequency band in midline parietal channels. Nimodipine and placebo had no effect on TEPs and TIOs. The TEP results extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA receptor-mediated glutamatergic excitation. In contrast, AMPA receptor-mediated glutamatergic neurotransmission contributes to propagated activity reflected in the P60 potential and midline parietal induced oscillations. This pharmacological characterization of TMS-EEG responses will be informative for interpreting TMS-EEG abnormalities in neuropsychiatric disorders with pathological excitation–inhibition balance.
The application of ozonated water rearranges the Vitis vinifera L. leaf and berry transcriptomes eliciting defence and antioxidant responses
Authors: Campayo Ana , Savoi Stefania , Romieu Charles , López-Jiménez Alberto José , Serrano de la Hoz Kortes , Salinas M. Rosario , Torregrosa Laurent , Alonso Gonzalo L.
Published: April 2021

Ozonated water has become an innovative, environmentally friendly tool for controlling the development of fungal diseases in the vineyard or during grape postharvest conservation. However, little information is currently available on the effects of ozonated water sprayings on the grapevine physiology and metabolism. Using the microvine model, we studied the transcriptomic response of leaf and fruit organs to this treatment. The response to ozone was observed to be organ and developmental stage-dependent, with a decrease of the number of DEGs (differentially expressed genes) in the fruit from the onset of ripening to later stages. The most highly up-regulated gene families were heat-shock proteins and chaperones. Other up-regulated genes were involved in oxidative stress homeostasis such as those of the ascorbate–glutathione cycle and glutathione S-transferases. In contrast, genes related to cell wall development and secondary metabolites (carotenoids, terpenoids, phenylpropanoids / flavonoids) were generally down-regulated after ozone treatment, mainly in the early stage of fruit ripening. This down-regulation may indicate a possible carbon competition favouring the re-establishment and maintenance of the redox homeostasis rather than the synthesis of secondary metabolites at the beginning of ripening, the most ozone responsive developmental stage.
Clinical evaluation of direct anterior approach total hip arthroplasty for severe developmental dysplasia of the hip
Authors: Liu Zaiyang , Bell Courtney D. , Ong Alvin C. , Zhang Jun , Li Jie , Zhang Yuan
Published: April 2021

It is challenging to treat developmental dysplasia of the hip (DDH) classified Crowe III-IV using direct anterior approach (DAA) total hip arthroplasty (THA), and very little is known on its outcome. This study aimed to investigate the clinical result in this defined disorder with DAA versus posterolateral approach. Twenty-three consecutive hips with Crowe III-IV DDH who underwent DAA were retrospectively evaluated from 2016 through 2018. Outcomes were primarily assessed by HHS, WOMAC, and SF-12 physical scales. The second evaluations included leg length discrepancy, hip muscle strength, radiographic review, complications, and limp recovery. Results were compared to a control cohort of 50 hips underwent posterolateral THA concurrently within the observational period. At last follow-up (DAA 28.5 months; PLA 39.0 months), the mean increase of the HHS for DAA was 48.2 and 30.3 for PLA (p = 0.003). The improvement in WOMAC score in DAA cohort was 15.89 higher that of the PLA cohort after adjusting preoperative difference [R2 = 0.532, P = 0.000, 95% CI (10.037, 21.735)]. DAA had more rapid recovery of hip abductor strength at 1-month (p = 0.03) and hip flexor strength at 3 months (p = 0.007) compared to PLA. No significant differences were found in the radiographic analysis with the exception of increased acetabular anteversion in the DAA cohort (p = 0.036). Satisfactory improvement in limp, indicated by the percentage of limp graded as none and mild to the total, was much higher in DAA cohort (97.6%), compared to that of PLA cohort (90.0%, p = 0.032). DAA for high-dislocated dysplasia demonstrate a significant improvement in clinical result comparable to posterolateral approach. Improved clinical outcome in terms of increased HHS and WOMAC scores, rapid recovery of hip abductor and flexor strength, and enhanced limp recovery without an increased risk in complications, could be acquired when the surgeons were specialized in this approach.
RETRACTED ARTICLE: Carvacrol and PPARγ agonist, pioglitazone, affects inhaled paraquat-induced lung injury in rats
Authors: Amin Fatemeh , Memarzia Arghavan , Rad Hamideh Kazemi , Kazerani Hamid Reza , Boskabady Mohammad Hossein
Published: April 2021

Exposed rats to normal saline and paraquat (PQ) aerosol as control and PQ group, rats exposed to PQ and treated with 20 and 80 mg/kg/day carvacrol, 5 and 10 mg/kg/day pioglitazone, low dose of pioglitazone + carvacrol and 0.03 mg/kg/day dexamethasone (Dexa) for 16 days after the end of PQ exposure were studied (n = 6 in each group). Lung pathological changes, tracheal responsiveness to methacholine and ovalbumin (OVA) as well as transforming growth factor beta (TGF-β) and interleukin (IL)-6 level in the lung tissue homogenize as well as TGF-β, IL-6, oxidant and antioxidant levels oxidant and antioxidants were increased in PQ group (p < 0.01 to p < 0.001). Lung pathological changes, tracheal responsiveness to methacholine and OVA as well as TGF-β, IL-6 oxidant and antioxidant levels were improved in all treated groups except lung pathological changes in treated group with low dose of pioglitazone (p < 0.05 to p < 0.001). The effects of low dose of pioglitazone and carvacrol alone were significantly lower than in the combination group of low dose of pioglitazone + carvacrol (p < 0.05 to p < 0.001). Carvacrol treatment improved inhaled PQ-induced lug injury similar to the effects of dexamethasone. The synergic effect of carvacrol and pioglitazone suggests PPAR-γ receptor mediated effects of carvacrol on inhaled PQ-induced lung injury.
3D cell sheet structure augments mesenchymal stem cell cytokine production
Authors: Bou-Ghannam Sophia , Kim Kyungsook , Grainger David W. , Okano Teruo
Published: April 2021

Mesenchymal stem cells (MSCs) secrete paracrine factors that play crucial roles during tissue regeneration. An increasing body of evidence suggests that this paracrine function is enhanced by MSC cultivation in three-dimensional (3D) tissue-like microenvironments. Toward this end, this study explored scaffold-free cell sheet technology as a new 3D platform. MSCs cultivated on temperature-responsive culture dishes to a confluent 2D monolayer were harvested by temperature reduction from 37 to 20 °C that induces a surface wettability transition from hydrophobic to hydrophilic. Release of culture-adherent tension induced spontaneous cell sheet contraction, reducing the diameter 2.4-fold, and increasing the thickness 8.0-fold to render a 3D tissue-like construct with a 36% increase in tissue volume. This 2D-to-3D transition reorganized MSC actin cytoskeleton from aligned to multidirectional, corresponding to a cell morphological change from elongated in 2D monolayers to rounded in 3D cell sheets. 3D culture increased MSC gene expression of cell interaction proteins, β-catenin, integrin β1, and connexin 43, and of pro-tissue regenerative cytokines, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and interleukin-10 (IL-10), and increased VEGF secretion per MSC 2.1-fold relative to 2D cultures. Together, these findings demonstrate that MSC therapeutic potency can be enhanced by 3D cell sheet tissue structure.