bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum
Authors: Jinendiran Sekar , Teng Weilin , Dahms Hans-Uwe , Liu Wangta , Ponnusamy Vinoth Kumar , Chiu Charles Chien-Chih , Kumar B. S. Dileep , Sivakumar Natesan
Published: August 2020

Colorectal cancer is the most common type of gastrointestinal cancers with poor survival and limited therapeutic options. In this study, four structurally different cyclic dipeptides (or diketopiperazine) were isolated and identified as cyclo (l-Pro-l-Leu), cyclo (l-Pro-l-Val), cyclo (l-Pro-l-Phe) and cyclo (l-Pro-l-Tyr) from the ethyl acetate extract in the cell-free filtrate of Exiguobacterium acetylicum S01. The anticancer potential of identified DKPs on colorectal cancer HT-29 cells in vitro and in vivo zebrafish xenograft model was evaluated. The MTT (3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide)) assay showed that four DKPs exhibited significant inhibition of HT-29 cells viability in a dose-dependent manner whereas there were no cytotoxic effects on normal mouse fibroblast 3T3 cells. Also, we observed that all DKPs induce early and late apoptotic cell death in HT-29 cells. Moreover, the expression levels of apoptotic (cytochrome-c, caspase-3 and Bid) and anti-apoptotic (Bcl-2) markers were up- and down-regulated in HT-29 cells in response to DKPs treatments. Furthermore, these four DKPs remarkably inhibited the tumor progression in a zebrafish xenograft model within a nonlethal dose range. Overall, our findings suggest that cyclic dipeptides derived from E. acetylicum S01 could be promising chemopreventive/ therapeutic candidates against cancer.
Pit lakes from Southern Sweden: natural radioactivity and elementary characterization
Authors: Mantero J. , Thomas R. , Holm E. , Rääf C. , Vioque I. , Ruiz-Canovas C. , García-Tenorio R. , Forssell-Aronsson E. , Isaksson M.
Published: August 2020

Natural radioactivity in the environment is a field gaining more attention in last decades. This work is focused on the study of natural radioactivity complemented with elementary characterization at former non-uraniferous mining areas in Sweden. This aim is addressed through the study of mining lakes, called pit lakes, which are water bodies generated after opencast mining. Environmental matrices (water, sediments and rocks) from 32 Swedish pit lakes, commonly used for recreational purposes were radiometrically characterized via alpha (238U, 234U, 232Th, 230Th, 210Po isotopes) and gamma spectrometry (238U and 232Th series radionuclides). Additionally, ambient dose rate equivalent in the immediate surrounding of each pit lake was quantified. Physico-chemical parameters (pH, specific conductivity, dissolved oxygen, oxidation–reduction potential) and elemental composition (major and trace elements by ICP-MS) were analysed in water samples and elementary composition of sediments/rocks was measured by XRF and SEM–EDX in some specific cases. A non-negligible number of pit lakes (26%) with enhanced U levels in water was found. At some sites, rocks contained up to 4% of U in areas with high degree of interaction with local population. Concerning the elementary perspective, another popular site (due to its turquoise water) was found to have elevated dissolved heavy metal levels. Results obtained in this work prove that measurement of natural radioactivity is another component that should be included in routine analysis of characterization in mining areas, especially if restauration of post-mining sites is intended for human recreational.
Rapid recovery of locomotor performance after leg loss in harvestmen
Authors: Escalante Ignacio , Badger Marc A. , Elias Damian O.
Published: August 2020

Animals have evolved adaptations to deal with environmental challenges. For instance, voluntarily releasing appendages (autotomy) to escape potential predators. Although it may enhance immediate survival, this self-imposed bodily damage may convey long-term consequences. Hence, compensatory strategies for this type of damage might exist. We experimentally induced autotomy in Prionostemma harvestmen. These arachnids are ideal to examine this topic because they show high levels of leg loss in the field but do not regenerate their legs. We video-recorded animals moving on a horizontal track and reconstructed their 3D trajectories with custom software tools to measure locomotor performance. Individuals that lost either three legs total or two legs on the same side of the body showed an immediate and substantial decrease in velocity and acceleration. Surprisingly, harvestmen recovered initial performance after 2 days. This is the quickest locomotor recovery recorded for autotomizing animals. We also found post-autotomy changes in stride and postural kinematics, suggesting a role for kinematic adjustments in recovery. Additionally, following leg loss, some animals changed the gaits used during escape maneuvers, and/or recruited the ‘sensory’ legs for locomotion. Together, these findings suggest that harvestmen are mechanically robust to the bodily damage imposed by leg loss.
Cell death resulted from loss of fumarylacetoacetate hydrolase in Arabidopsis is related to phytohormone jasmonate but not salicylic acid
Authors: Zhou Zhou , Zhi Tiantian , Han Chengyun , Peng Zhihong , Wang Ruozhong , Tong Jianhua , Zhu Qi , Ren Chunmei
Published: August 2020

Fumarylacetoacetate hydrolase (FAH) catalyzes the final step in Tyr degradation pathway essential to animals but not well understood in plants. Previously, we found that mutation of SSCD1 encoding Arabidopsis FAH causes cell death under short day, which uncovered an important role of Tyr degradation pathway in plants. Since phytohormones salicylic acid (SA) and jasmonate (JA) are involved in programmed cell death, in this study, we investigated whether sscd1 cell death is related to SA and JA, and found that (1) it is accompanied by up-regulation of JA- and SA-inducible genes as well as accumulation of JA but not SA; (2) it is repressed by breakdown of JA signaling but not SA signaling; (3) the up-regulation of reactive oxygen species marker genes in sscd1 is repressed by breakdown of JA signaling; (4) treatment of wild-type Arabidopsis with succinylacetone, an abnormal metabolite caused by loss of FAH, induces expression of JA-inducible genes whereas treatment with JA induces expression of some Tyr degradation genes with dependence of JA signaling. These results demonstrated that cell death resulted from loss of FAH in Arabidopsis is related to JA but not SA, and suggested that JA signaling positively regulates sscd1 cell death by up-regulating Tyr degradation.
Highly accurate determination of heterogeneously stacked Van-der-Waals materials by optical microspectroscopy
Authors: Hutzler Andreas , Fritsch Birk , Matthus Christian D. , Jank Michael P. M. , Rommel Mathias
Published: August 2020

The composition of Van-der-Waals heterostructures is conclusively determined using a hybrid evaluation scheme of data acquired by optical microspectroscopy. This scheme deploys a parameter set comprising both change in reflectance and wavelength shift of distinct extreme values in reflectance spectra. Furthermore, the method is supported by an accurate analytical model describing reflectance of multilayer systems acquired by optical microspectroscopy. This approach allows uniquely for discrimination of 2D materials like graphene and hexagonal boron nitride (hBN) and, thus, quantitative analysis of Van-der-Waals heterostructures containing structurally very similar materials. The physical model features a transfer-matrix method which allows for flexible, modular description of complex optical systems and may easily be extended to individual setups. It accounts for numerical apertures of applied objective lenses and a glass fiber which guides the light into the spectrometer by two individual weighting functions. The scheme is proven by highly accurate quantification of the number of layers of graphene and hBN in Van-der-Waals heterostructures. In this exemplary case, the fingerprint of graphene involves distinct deviations of reflectance accompanied by additional wavelength shifts of extreme values. In contrast to graphene, the fingerprint of hBN reveals a negligible deviation in absolute reflectance causing this material being only detectable by spectral shifts of extreme values.
Detecting ulcerative colitis from colon samples using efficient feature selection and machine learning
Authors: Khorasani Hanieh Marvi , Usefi Hamid , Peña-Castillo Lourdes
Published: August 2020

Ulcerative colitis (UC) is one of the most common forms of inflammatory bowel disease (IBD) characterized by inflammation of the mucosal layer of the colon. Diagnosis of UC is based on clinical symptoms, and then confirmed based on endoscopic, histologic and laboratory findings. Feature selection and machine learning have been previously used for creating models to facilitate the diagnosis of certain diseases. In this work, we used a recently developed feature selection algorithm (DRPT) combined with a support vector machine (SVM) classifier to generate a model to discriminate between healthy subjects and subjects with UC based on the expression values of 32 genes in colon samples. We validated our model with an independent gene expression dataset of colonic samples from subjects in active and inactive periods of UC. Our model perfectly detected all active cases and had an average precision of 0.62 in the inactive cases. Compared with results reported in previous studies and a model generated by a recently published software for biomarker discovery using machine learning (BioDiscML), our final model for detecting UC shows better performance in terms of average precision.
Land vs. water HIIE effects on muscle oxygenation and physiological parameter responses in postmenopausal women
Authors: Chien Kuei-Yu , Kan Nai-Wen , Liao Yi-Hung , Yang Wen-Ting , Yang Yong
Published: August 2020

Muscle oxygenation (MO) status is the dynamic balance between O2 utilization and O2 delivery. Low-impact high-intensity interval exercise MO responses in the exercise and recovery stage are still unclear. We compared the differences in MO and physiological parameters between high-intensity interval water-based exercise (WHIIE) and high-intensity interval land bike ergonomic exercise (LBEHIIE) in postmenopausal women. Eleven postmenopausal women completed WHIIE or LBEHIIE in counter-balanced order. Eight sets were performed and each exercise set included high intensity with 80% heart rate reserve (HRR) in 30 s and dynamic recovery with 50% HRR in 90 s. Muscle tissue oxygen saturation index (TSI), total hemoglobin (tHb), oxy-hemoglobin (O2Hb), and deoxy-hemoglobin (HHb) were recorded. Blood lactate, heart rate and rating of perceived exertion (RPE) were measured at pre and post-exercise. Under similar exercise intensity, RPE in WHIIE was lower than that in LBEHIIE. The heart rate in WHIIE was lower than that in LBEHIIE at 1 and 2 min post-exercise. During the dynamic recovery, TSI, tHb, and O2Hb in water were higher than on land. A negative correlation was found between the change in TSI and lactate concentration (r = − 0.664). WHIIE produced greater muscle oxygenation during dynamic recovery. Muscle TSI% was inversely related to blood lactate concentration during exercise in water.
The methylation status of the chemerin promoter region located from − 252 to + 258 bp regulates constitutive but not acute-phase cytokine-inducible chemerin expression levels
Authors: Kwiecien Kamila , Brzoza Piotr , Bak Maciej , Majewski Pawel , Skulimowska Izabella , Bednarczyk Kamil , Cichy Joanna , Kwitniewski Mateusz
Published: August 2020

Chemerin is a chemoattractant protein with adipokine properties encoded by the retinoic acid receptor responder 2 (RARRES2) gene. It has gained more attention in the past few years due to its multilevel impact on metabolism and immune responses. However, mechanisms controlling the constitutive and regulated expression of RARRES2 in a variety of cell types remain obscure. To our knowledge, this report is the first to show that DNA methylation plays an important role in the cell-specific expression of RARRES2 in adipocytes, hepatocytes, and B lymphocytes. Using luciferase reporter assays, we determined the proximal fragment of the RARRES2 gene promoter, located from − 252 to + 258 bp, to be a key regulator of transcription. Moreover, we showed that chemerin expression is regulated in murine adipocytes by acute-phase cytokines, interleukin 1β and oncostatin M. In contrast with adipocytes, these cytokines exerted a weak, if any, response in mouse hepatocytes, suggesting that the effects of IL-1β and OSM on chemerin expression is specific to fat tissue. Together, our findings highlight previously uncharacterized mediators and mechanisms that control chemerin expression.
Molecular mapping of QTLs for yield related traits in recombinant inbred line (RIL) population derived from the popular rice hybrid KRH-2 and their validation through SNP genotyping
Authors: Kulkarni Swapnil Ravindra , Balachandran S. M. , Ulaganathan K. , Balakrishnan Divya , Praveen M. , Prasad A. S. Hari , Fiyaz R. A. , Senguttuvel P. , Sinha Pragya , Kale Ravindra R. , Rekha G. , Kousik M. B. V. N. , Harika G. , Anila M. , Punniakoti E. , Dilip T. , Hajira S. K. , Pranathi K. , Das M. Ayyappa , Shaik Mastanbee , Chaitra K. , Rao P. Koteswara , Gangurde Sunil S. , Pandey Manish K. , Sundaram R. M.
Published: August 2020

The study was undertaken to identify the quantitative trait loci (QTLs) governing yield and its related traits using a recombinant inbred line (RIL) population derived from the popular rice hybrid, KRH-2 (IR58025A/KMR3R). A genetic map spanning 294.2 cM was constructed with 126 simple sequence repeats (SSR) loci uniformly distributed across the rice genome. QTL analysis using phenotyping and genotyping information identified a total of 22 QTLs. Of these, five major effect QTLs were identified for the following traits: total grain yield/plant (qYLD3-1), panicle weight (qPW3-1),plant height (qPH12-1),flag leaf width (qFLW4-1)and panicle length (qPL3-1), explaining 20.23–22.76% of the phenotypic variance with LOD scores range of 6.5–10.59. Few genomic regions controlling several traits (QTL hotspot) were identified on chromosome 3 for total grain yield/plant (qYLD3-1)and panicle length (qPL3-1). Significant epistatic interactions were also observed for total grain yield per plant (YLD) and panicle length (PL). While most of these QTLs were observed to be co-localized with the previously reported QTL regions, a novel, major QTL associated with panicle length (qPL3-1) was also identified. SNP genotyping of selected high and low yielding RILs and their QTL mapping with 1,082 SNPs validated most of the QTLs identified through SSR genotyping. This facilitated the identification of novel major effect QTLs with much better resolution and precision. In-silico analysis of novel QTLs revealed the biological functions of the putative candidate gene (s) associated with selected traits. Most of the high-yielding RILs possessing the major yield related QTLs were identified to be complete restorers, indicating their possible utilization in development of superior rice hybrids.
Fano feature induced by a bound state in the continuum via resonant state expansion
Authors: Pankin Pavel S. , Maksimov Dmitrii N. , Chen Kuo-Ping , Timofeev Ivan V.
Published: August 2020

We consider light scattering by an anisotropic defect layer embedded into anisotropic photonic crystal in the spectral vicinity of an optical bound state in the continuum (BIC). Using a resonant state expansion method we derive an analytic solution for reflection and transmission amplitudes. The analytic solution is constructed via a perturbative approach with the BIC as the zeroth order approximation. The solution is found to describe the collapsing Fano feature in the spectral vicinity of the BIC. The findings are confirmed via comparison against direct numerical simulations with the Berreman transfer matrix method.
Quasicrystalline phase-change memory
Authors: Lee Eun-Sung , Yoo Joung E. , Yoon Du S. , Kim Sung D. , Kim Yongjoo , Hwang Soobin , Kim Dasol , Jeong Hyeong-Chai , Kim Won T. , Chang Hye J. , Suh Hoyoung , Ko Dae-Hong , Cho Choonghee , Choi Yongjoon , Kim Do H. , Cho Mann-Ho
Published: August 2020

Phase-change memory utilizing amorphous-to-crystalline phase-change processes for reset-to-set operation as a nonvolatile memory has been recently commercialized as a storage class memory. Unfortunately, designing new phase-change materials (PCMs) with low phase-change energy and sufficient thermal stability is difficult because phase-change energy and thermal stability decrease simultaneously as the amorphous phase destabilizes. This issue arising from the trade-off relationship between stability and energy consumption can be solved by reducing the entropic loss of phase-change energy as apparent in crystalline-to-crystalline phase-change process of a GeTe/Sb2Te3 superlattice structure. A paradigm shift in atomic crystallography has been recently produced using a quasi-crystal, which is a new type of atomic ordering symmetry without any linear translational symmetry. This paper introduces a novel class of PCMs based on a quasicrystalline-to-approximant crystalline phase-change process, whose phase-change energy and thermal stability are simultaneously enhanced compared to those of the GeTe/Sb2Te3 superlattice structure. This report includes a new concept that reduces entropic loss using a quasicrystalline state and takes the first step in the development of new PCMs with significantly low phase-change energy and considerably high thermal stability.
Antibody-protein binding and conformational changes: identifying allosteric signalling pathways to engineer a better effector response
Authors: Al Qaraghuli Mohammed M. , Kubiak-Ossowska Karina , Ferro Valerie A. , Mulheran Paul A.
Published: August 2020

Numerous monoclonal antibodies have been developed successfully for the treatment of various diseases. Nevertheless, the development of biotherapeutic antibodies is complex, expensive, and time-consuming, and to facilitate this process, careful structural analysis beyond the antibody binding site is required to develop a more efficacious antibody. In this work, we focused on protein antigens, since they induce the largest antibody changes, and provide interesting cases to compare and contrast. The structures of 15 anti-protein antibodies were analysed to compare the antigen-bound/unbound forms. Surprisingly, three different classes of binding-induced changes were identified. In class (B1), the antigen binding fragment distorted significantly, and we found changes in the loop region of the heavy chain’s constant domain; this corresponds well with expected allosteric movements. In class (B2), we found changes in the same loop region without the overall distortion. In class (B3), these changes did not present, and only local changes at the complementarity determining regions were found. Consequently, structural analysis of antibodies is crucial for therapeutic development. Careful evaluation of allosteric movements must be undertaken to develop better effector responses, especially during the transformation of these antibodies from small fragments at the discovery stage to full antibodies at the subsequent development stages.
Changes in the core endophytic mycobiome of carrot taproots in response to crop management and genotype
Authors: Abdelrazek Sahar , Choudhari Sulbha , Thimmapuram Jyothi , Simon Philipp , Colley Micaela , Mengiste Tesfaye , Hoagland Lori
Published: August 2020

Fungal endophytes can influence production and post-harvest challenges in carrot, though the identity of these microbes as well as factors affecting their composition have not yet been determined, which prevents growers from managing these organisms to improve crop performance. Consequently, we characterized the endophytic mycobiome in the taproots of three carrot genotypes that vary in resistance to two pathogens grown in a trial comparing organic and conventional crop management using Illumina sequencing of the internal transcribed spacer (ITS) gene. A total of 1,480 individual operational taxonomic units (OTUs) were identified. Most were consistent across samples, indicating that they are part of a core mycobiome, though crop management influenced richness and diversity, likely in response to differences in soil properties. There were also differences in individual OTUs among genotypes and the nematode resistant genotype was most responsive to management system indicating that it has greater control over its endophytic mycobiome, which could potentially play a role in resistance. Members of the Ascomycota were most dominant, though the exact function of most taxa remains unclear. Future studies aimed at overcoming difficulties associated with isolating fungal endophytes are needed to identify these microbes at the species level and elucidate their specific functional roles.
Advanced MRI features in relapsing multiple sclerosis patients with and without CSF oligoclonal IgG bands
Authors: Zhao Lin , Abrigo Jill , Chen Qianyun , Au Cheryl , Ng Angel , Fan Ping , Mok Vincent , Qiu Wei , Kermode Allan G. , Lau Alexander Y.
Published: August 2020

Oligoclonal IgG bands (OCB) in cerebrospinal fluid (CSF) are important in diagnosis of multiple sclerosis (MS). We evaluated the MRI features of clinically definite MS subjects with and without CSF-OCB. Relapsing MS subjects were recruited from a prospective registry in a university center. CSF-OCB were detected using isoelectric focusing and lgG-specific immunofixation. MRI metrics including brain volumes, lesion volumes and microstructural measures, were analyzed by FMRIB Software Library (FSL) and Statistical Parametric Mapping (SPM). Seventy-five subjects with relapsing MS were analyzed. Forty-four (59%) subjects had an interval MRI at around 1 year. CSF-OCB were detected in 46 (61%) subjects. The OCB-positive group had a higher proportion of cerebellar lesions than the OCB-negative group (23.9% vs. 3.4%, p = 0.057). Except for amygdala volumes which were lower in the OCB-positive group (p = 0.034), other regional brain volumes including the subcortical deep gray matter and corpus callosum were similar. The two groups also showed comparable brain atrophy rate. For DTI, the OCB-positive group showed significantly higher mean diffusivity (MD) value in perilesional normal-appearing white matter (p = 0.043). Relapsing MS patients with and without CSF-OCB shared similar MRI features regarding volumetric analyses and DTI microstructural integrity.
Responses of active soil microorganisms facing to a soil biostimulant input compared to plant legacy effects
Authors: Hellequin Eve , Monard Cécile , Chorin Marion , Le bris Nathalie , Daburon Virginie , Klarzynski Olivier , Binet Françoise
Published: August 2020

Agriculture is changing to rely on agroecological practices that take into account biodiversity, and the ecological processes occurring in soils. The use of agricultural biostimulants has emerged as a valid alternative to chemicals to indirectly sustain plant growth and productivity. Certain BS have been shown to select and stimulate plant beneficial soil microorganisms. However, there is a lack of knowledge on the effects and way of action of the biostimulants operating on soil functioning as well as on the extent and dynamic of these effects. In this study we aimed to decipher the way of action of a seaweed and amino-acids based biostimulant intended to be applied on soil crop residues to increase their microbial mineralization and the further release of nutrients. By setting-up a two-phase experiment (soil plant-growing and soil incubation), our objectives were to (1) determine the effects of the soil biostimulant over time on the active soil bacteria and fungi and the consequences on the organic carbon mineralization in bare soils, and (2) assess the biostimulant effects on soil microorganisms relatively to plant legacy effects in planted soils. We demonstrated that the soil biostimulant had a delayed effect on the active soil microorganisms and activated both plant growth promoting bacteria and saprophytes microorganisms at the medium-term of 49 days. However, the changes in the abundances of active microbial decomposers were not associated to a higher mineralization rate of organic carbon derived from soil and/or litter. The present study assessed the biostimulant beneficial effect on active soil microbial communities as similar as or even higher than the legacy effects of eitherA. thalianaorT. aestivumplants. We specifically showed that the biostimulant increased the active fungal richness to a higher extent than observed in soils that previously grew the two plants tested.
Equilibrium properties of assembly of interacting superparamagnetic nanoparticles
Authors: Usov N. A. , Serebryakova O. N.
Published: August 2020

The stochastic Landau–Lifshitz equation is used to investigate the relaxation process and equilibrium magnetization of interacting assembly of superparamagnetic nanoparticles (SPMNPs) uniformly distributed in a nonmagnetic matrix. For weakly interacting assembly, the equilibrium magnetization is shown to deviate significantly from the Langevin law at moderate and large magnetic fields under the influence of their magnetic anisotropies. For dense assemblies with noticeable influence of the magneto-dipole interaction, a significant dependence of the initial susceptibility on the assembly density is revealed. The difference between the initial susceptibility and the corresponding Langevin susceptibility can serve as an indication of appreciable influence of the magneto-dipole interaction on the assembly properties. A new self-consistent approach is developed to explain the effect of mutual magneto-dipole interaction on the behavior of dense assembly of SPMNPs. The probability densities of the components of random magnetic field acting on magnetic NPs are calculated at thermodynamic equilibrium. The self-consistent probability densities of these components are found to be close to Gaussian distribution. A decreasing equilibrium assembly magnetization as a function of its density can be explained as a disorienting effect of the random magnetic field on the NPs magnetic moments.
A novel nomogram model for differentiating Kawasaki disease from sepsis
Authors: Liu Xiao-Ping , Huang Yi-Shuang , Kuo Ho-Chang , Xia Han-Bing , Yi-Sun  , Huang Wei-Dong , Lang Xin-Ling , Liu Chun-Yi , Liu Xi
Published: August 2020

Kawasaki disease (KD) is a form of systemic vasculitis that occurs in children under the age of 5 years old. Due to prolonged fever and elevated inflammatory markers that are found in both KD and sepsis, the treatment approach differs for each. We enrolled a total of 420 children (227 KD and 193 sepsis) in this study. Logistic regression and a nomogram model were used to analyze the laboratory markers. We randomly selected 247 children as the training modeling group and 173 as the validation group. After completing a logistic regression analysis, white blood cell (WBC), anemia, procalcitonin (PCT), C-reactive protein (CRP), albumin, and alanine transaminase (ALT) demonstrated a significant difference in differentiating KD from sepsis. The patients were scored according to the nomogram, and patients with scores greater than 175 were placed in the high-risk KD group. The area under the curve of the receiver operating characteristic curve (ROC curve) of the modeling group was 0.873, sensitivity was 0.893, and specificity was 0.746, and the ROC curve in the validation group was 0.831, sensitivity was 0.709, and specificity was 0.795. A novel nomogram prediction model may help clinicians differentiate KD from sepsis with high accuracy.
Radio frequency emissions from dark-matter-candidate magnetized quark nuggets interacting with matter
Authors: VanDevender J. Pace , Buchenauer C. Jerald , Cai Chunpei , VanDevender Aaron P. , Ulmen Benjamin A.
Published: August 2020

Quark nuggets are theoretical objects composed of approximately equal numbers of up, down, and strange quarks. They are also called strangelets, nuclearites, AQNs, slets, Macros, and MQNs. Quark nuggets are a candidate for dark matter, which has been a mystery for decades despite constituting ~ 85% of the universe’s mass. Most previous models of quark nuggets have assumed no intrinsic magnetic field; however, Tatsumi found that quark nuggets may exist in magnetars as a ferromagnetic liquid with a magnetic field BS = 1012±1 T. We apply that result to quark nuggets, a dark-matter candidate consistent with the Standard Model, and report results of analytic calculations and simulations that show they spin up and emit electromagnetic radiation at ~ 104 to ~ 109 Hz after passage through planetary environments. The results depend strongly on the value of Bo, which is a parameter to guide and interpret observations. A proposed sensor system with three satellites at 51,000 km altitude illustrates the feasibility of using radio-frequency emissions to detect 0.003 to 1,600 MQNs, depending on Bo, during a 5 year mission.
Active and social life is associated with lower non-social fearfulness in pet dogs
Authors: Hakanen Emma , Mikkola Salla , Salonen Milla , Puurunen Jenni , Sulkama Sini , Araujo César , Lohi Hannes
Published: August 2020

Behavioural problems are leading welfare issues in domestic dogs. In particular, anxiety-related behavioural problems, such as fearfulness and noise sensitivity are highly prevalent conditions that cause distress to fearful dogs. To better understand the environmental factors associated with non-social fear, including noise sensitivity, fear of novel situations, and fear of surfaces and heights, a large online survey including data on 13,700 Finnish pet dogs was performed by the dog owners. After fulfilling inclusion criteria, this data consisted of 9,613 dogs with fear of fireworks, 9,513 dogs with fear of thunder, 6,945 dogs with fear of novel situations, and 2,932 dogs with fear of surfaces and heights. Logistic regression analyses revealed that dogs with frequent non-social fear had experienced less socialisation during puppyhood, were more often neutered, had inexperienced owners, lived without conspecifics, participated less frequently in activities or training, and lived in more urban environments. In addition, we identified several breed differences, and a tendency of more common non-social fear in small dog breeds, which suggests a genetic background. Non-social fearfulness has a negative effect on well-being of the dogs. Our findings suggest that the socialisation and the living environment and the value of other dogs’ company and owner interaction via activities and training may improve the well-being of the dogs.
Parental psychological distress in the postnatal period in Japan: a population-based analysis of a national cross-sectional survey
Authors: Takehara Kenji , Suto Maiko , Kato Tsuguhiko
Published: August 2020

Mental health assessments of both members of a couple are important when considering the child-rearing environment. The prevalence and factors associated with both parents’ psychological distress have not been fully investigated. A nationally representative sample from the 2016 Comprehensive Survey of Living Conditions in Japan was used to examine the prevalence of moderate and severe psychological distress in parents in the first year after childbirth. In total, 3,514 two-parent households raising children under one year old met the study criteria. The Japanese version of Kessler 6 was used to assess moderate and severe psychological distress. The prevalence of either or both parents experiencing psychological distress in the first year after birth were 15.1% and 3.4%, respectively. A multivariate logistic regression analysis showed factors of fathers who worked ≥ 55 h a week, reduced duration of sleep in mothers, age in months of the youngest child, and high household expenditures were significantly associated with both parents simultaneously having moderate or severe psychological distress. This study implied the importance of prevention and early detection of parental psychological distress in both parents. Assessing parents’ psychological distress and work-style reform in the childcare period is an urgent issue to improve their mental health conditions.
Collagen VIα2 chain deficiency causes trabecular bone loss by potentially promoting osteoclast differentiation through enhanced TNFα signaling
Authors: Pham Hai T. , Kram Vardit , Dar Qurratul-Ain , Komori Taishi , Ji Youngmi , Mohassel Payam , Rooney Jachinta , Li Li , Kilts Tina M. , Bonnemann Carsten , Lamande Shireen , Young Marian F.
Published: August 2020

Type VI collagen is well known for its role in muscular disorders, however its function in bone is still not well understood. To examine its role in bone we analyzed femoral and vertebral bone mass by micro-computed tomography analysis, which showed lower bone volume/total volume and trabecular number in Col6α2-KO mice compared with WT. Dynamic histomorphometry showed no differences in trabecular bone formation between WT and Col6α2-KO mice based on the mineral appositional rate, bone formation rate, and mineralizing perimeter. Femoral sections were assessed for the abundance of Tartrate Resistant Acid Phosphatase-positive osteoclasts, which revealed that mutant mice had more osteoclasts compared with WT mice, indicating that the primary effect of Col6a2 deficiency is on osteoclastogenesis. When bone marrow stromal cells (BMSCs) from WT and Col6α2-KO mice were treated with rmTNFα protein, the Col6α2-KO cells expressed higher levels of TNFα mRNA compared with WT cells. This was accompanied by higher levels of p-p65, a down-stream target of TNFα, suggesting that BMSCs from Col6α2-KO mice are highly sensitive to TNFα signaling. Taken together, our data imply that Col6a2 deficiency causes trabecular bone loss by enhancing osteoclast differentiation through enhanced TNFα signaling.
Abdominal aorta diameter as a novel marker of diabetes incidence risk in elderly women
Authors: Dereziński Tadeusz , Zozulińska-Ziółkiewicz Dorota , Uruska Aleksandra , Dąbrowski Mariusz
Published: August 2020

The prevalence of diabetes mellitus is increasing worldwide, including the nation of Poland. The aim of this prospective and observational study was to determine risk factors and the predictors of diabetes incidence in elderly women, and to calculate the diabetes incidence ratio in this population. Two-hundred women, aged 65–74, who were non-diabetic at baseline in 2012 were followed for 6.5 years. All women were checked for incident diabetes. In non-diabetic subjects, diagnostic procedures for diabetes were performed according to Poland’s Diabetes recommendations. Between April 2012 and September 2018, 25 women developed diabetes and the next 11 cases were diagnosed based on FPG or oral glucose tolerance test. Women with incident diabetes had significantly higher baseline FPG, triglycerides (TG), TG/HDL cholesterol ratio and visceral adiposity index (VAI) score, and lower abdominal aorta diameter (AAD), HDL cholesterol and eGFR. In the Cox proportional hazard regression analysis, only AAD < 18 mm and VAI score ≥ 3.8 were independently associated with diabetes risk, hazard ratio (HR) 2.47 (95% confidence interval 1.21–5.02), P = 0.013 and HR 2.83 (1.35–5.94), P = 0.006 respectively. In the backward stepwise regression analysis including all variables, diabetes incidence could be predicted from a linear combination of the independent variables: AAD < 18 mm (P = 0.002), VAI score ≥ 3.8 (P < 0.001) and FPG ≥ 5.6 mmol/L (P = 0.011). The calculated incidence of diabetes was 2769.2 new cases/100,000 persons per year. AAD below 18 mm seem to be a novel, independent marker of diabetes risk in elderly women, and AAD assessment during routine abdomen ultrasound may be helpful in identifying females at early elderliness with high risk of diabetes incidence.
Six to 12-year outcomes of magnetic sphincter augmentation for gastroesophageal reflux disease
Authors: Ferrari Davide , Asti Emanuele , Lazzari Veronica , Siboni Stefano , Bernardi Daniele , Bonavina Luigi
Published: August 2020

The magnetic sphincter augmentation (MSA) device has been proven safe and effective in controlling typical reflux symptoms and esophageal acid exposure for up to 6-year follow-up. Longer term outcomes have not been reported yet. A prospectively maintained database was reviewed to assess long-term safety and efficacy of the laparoscopic MSA procedure at a single referral center. Gastro-Esophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL), use of proton-pump inhibitors (PPI), and esophageal acid exposure were compared to baseline. Favorable outcomes were defined as ≥ 50% improvement of GERD-HRQL total score and PPI discontinuation. Between March 2007 and March 2020, 335 patients met the study inclusion criteria, and 124 of them were followed from 6 to 12 years after surgery (median 9 years, IQR 2). Mean total GERD-HRQL score significantly improved from 19.9 to 4.01 (p < 0.001), and PPI were discontinued by 79% of patients. The mean total percent time with pH < 4 decreased from 9.6% at baseline to 4.1% (p < 0.001), with 89% of patients achieving pH normalization. Independent predictors of a favorable outcome were age at intervention < 40 years (OR 4.17) and GERD-HRQL score > 15 (OR 4.09). We confirm long-term safety and efficacy of MSA in terms of symptom improvement, decreased drug dependency, and reduced esophageal acid exposure.
Autologous transplantation of adipose-derived stromal cells combined with sevoflurane ameliorates acute lung injury induced by cecal ligation and puncture in rats
Authors: Liang Zuodi , Zhou Heng , Tang Rurong , Zhang Shuo , Chen Xiaohuan , Pei Ling
Published: August 2020

Adipose-derived stromal cells (ADSCs) have excellent capacities for regeneration and tissue protection, while sevoflurane, as a requisite component of surgical procedures, has shown therapeutic benefit in animal models of sepsis. This study therefore determined if the combination of sevoflurane and ADSCs exerted additional protective effects against acute lung injury (ALI) induced by cecal ligation and puncture (CLP) in rats. The animals were randomized into five groups: (sham operation (group I), CLP followed by mechanical ventilation (group II), CLP plus sevoflurane at 0.5 minimum alveolar concentration (group III), CLP plus intravenous autologous 5 × 106 ADSCs (group IV), and CLP plus sevoflurane and ADSCs (group V). Levels of the pro-inflammatory cytokines tumor necrosis factor-α, transforming growth factor-β1, interleukin-1β and interleukin-6 were significantly increased in CLP rats. Moreover, epithelial sodium channel expression levels and activities of Na/K-ATPase and alveolar fluid clearance were significantly reduced in CLP-induced ALI rats. ADSCs improved all these parameters, and these effects were further enhanced by the addition of sevoflurane. In conclusion, combined treatment with ADSCs and sevoflurane is superior to either ADSCs or sevoflurane therapy alone for preventing ALI. This beneficial effect may be partly due to improved alveolar fluid clearance by the paracrine or systemic production of keratinocyte growth factor and via anti-inflammatory properties.
Aberrant pregnancy-associated plasma protein-A expression in breast cancers prognosticates clinical outcomes
Authors: Prithviraj Prashanth , Anaka Matthew , Thompson Erik W. , Sharma Revati , Walkiewicz Marzena , Tutuka Candani S. A. , Behren Andreas , Kannourakis George , Jayachandran Aparna
Published: August 2020

Elevated levels of pregnancy-associated plasma protein-A (PAPP-A) have been implicated in the pathogenesis of various malignancies, including breast cancers. Breast cancer is one of the most frequent carcinomas and is the second most common cancer type detected in women of child-bearing age. Throughout pregnancy PAPP-A is produced and secreted by the placental syncytiotrophoblast cells; co-incidentally pregnancy-associated breast cancers often have an aggressive clinical course. The components of the PAPP-A/IGF axis was assessed in a panel of breast cancer cell lines. Using neutralising antibodies the impact of PAPP-A/IGF axis on cell motility was evaluated. PAPP-A was expressed in four of the twelve breast cancer cell lines tested. Blocking PAPP-A and IGFBP4 with neutralising antibodies significantly decreased motiliy of MDA-MB-231 cells. Upregulation of PAPP-A expression in breast tumours resulted in a trend towards worse overall survival. Notably, PAPP-A expression also positively correlated with epithelial-to-mesenchymal transition markers. In conclusion, these results indicate that PAPP-A plays an important role in breast cancer progression and it may be a promising therapeutic target in breast cancer.
Real time monitoring of oxygen uptake of hepatocytes in a microreactor using optical microsensors
Authors: Gehre Christian , Flechner Marie , Kammerer Sarah , Küpper Jan-Heiner , Coleman Charles Dominic , Püschel Gerhard Paul , Uhlig Katja , Duschl Claus
Published: August 2020

Most in vitro test systems for the assessment of toxicity are based on endpoint measurements and cannot contribute much to the establishment of mechanistic models, which are crucially important for further progress in this field. Hence, in recent years, much effort has been put into the development of methods that generate kinetic data. Real time measurements of the metabolic activity of cells based on the use of oxygen sensitive microsensor beads have been shown to provide access to the mode of action of compounds in hepatocytes. However, for fully exploiting this approach a detailed knowledge of the microenvironment of the cells is required. In this work, we investigate the cellular behaviour of three types of hepatocytes, HepG2 cells, HepG2-3A4 cells and primary mouse hepatocytes, towards their exposure to acetaminophen when the availability of oxygen for the cell is systematically varied. We show that the relative emergence of two modes of action, one NAPQI dependent and the other one transient and NAPQI independent, scale with expression level of CYP3A4. The transient cellular response associated to mitochondrial respiration is used to characterise the influence of the initial oxygen concentration in the wells before exposure to acetaminophen on the cell behaviour. A simple model is presented to describe the behaviour of the cells in this scenario. It demonstrates the level of control over the role of oxygen supply in these experiments. This is crucial for establishing this approach into a reliable and powerful method for the assessment of toxicity.
Rapid three-dimensional multiparametric MRI with quantitative transient-state imaging
Authors: Gómez Pedro A. , Cencini Matteo , Golbabaee Mohammad , Schulte Rolf F. , Pirkl Carolin , Horvath Izabela , Fallo Giada , Peretti Luca , Tosetti Michela , Menze Bjoern H. , Buonincontri Guido
Published: August 2020

Novel methods for quantitative, transient-state multiparametric imaging are increasingly being demonstrated for assessment of disease and treatment efficacy. Here, we build on these by assessing the most common Non-Cartesian readout trajectories (2D/3D radials and spirals), demonstrating efficient anti-aliasing with a k-space view-sharing technique, and proposing novel methods for parameter inference with neural networks that incorporate the estimation of proton density. Our results show good agreement with gold standard and phantom references for all readout trajectories at 1.5 T and 3 T. Parameters inferred with the neural network were within 6.58% difference from the parameters inferred with a high-resolution dictionary. Concordance correlation coefficients were above 0.92 and the normalized root mean squared error ranged between 4.2 and 12.7% with respect to gold-standard phantom references for T1 and T2. In vivo acquisitions demonstrate sub-millimetric isotropic resolution in under five minutes with reconstruction and inference times < 7 min. Our 3D quantitative transient-state imaging approach could enable high-resolution multiparametric tissue quantification within clinically acceptable acquisition and reconstruction times.
A novel approach to genetic engineering of T-cell subsets by hematopoietic stem cell infection with a bicistronic lentivirus
Authors: Bogert N. V. , Furkel J. , Din S. , Braren I. , Eckstein V. , Müller J. A. , Uhlmann L. , Katus H. A. , Konstandin M. H.
Published: August 2020

Lentiviral modification of hematopoietic stem cells (HSCs) paved the way for in vivo experimentation and therapeutic approaches in patients with genetic disease. A disadvantage of this method is the use of a ubiquitous promoter leads not only to genetic modification of the leukocyte subset of interest e.g. T-cells, but also all other subsequent leukocyte progeny of the parent HSCs. To overcome this limitation we tested a bicistronic lentivirus, enabling subset specific modifications. Designed novel lentiviral constructs harbor a global promoter (mPGK) regulating mCherry for HSCs selection and a T-cell specific promoter upstream of eGFP. Two T-cell specific promoters were assessed: the distal Lck—(dLck) and the CD3δ-promoter. Transduced HSCs were FACS sorted by mCherry expression and transferred into sublethally irradiated C57/BL6 mice. Successful transplantation and T-cell specific expression of eGFP was monitored by peripheral blood assessment. Furthermore, recruitment response of lentiviral engineered leukocytes to the site of inflammation was tested in a peritonitis model without functional impairment. Our constructed lentivirus enables fast generation of subset specific leukocyte transgenesis as shown in T-cells in vivo and opens new opportunities to modify other HSCs derived subsets in the future.
A fluorescent probe for monitoring PTP-PEST enzymatic activity
Authors: Casey Garrett R. , Stains Cliff I.
Published: August 2020

Design and optimization of a direct activity assay for PTP-PEST.
Evaluation of swabs from 15 commercially available oral fluid sample collection devices for the analysis of commonly abused substances: doping agents and drugs of abuse
Authors: Sobczak Łukasz , Goryński Krzysztof
Published: August 2020

Selection of a device for oral fluid sample collection has great impact on analysis results.
Metabolic profiling of rats poisoned with paraquat and treated with Xuebijing using a UPLC-QTOF-MS/MS metabolomics approach
Authors: Liu Wen , Li Sha , Wu Yang Ke , Yan Xiao , Zhu Yi Ming , Jiang Fei Ya , Jiang Yu , Zou Liang Hong , Wang Tong Tong
Published: August 2020

In this study, we used an UPLC-QTOF-MS/MS metabolomics approach combined with pattern recognition, cluster analysis, and metabolic pathway analyses to investigate changes in metabolite levels in SD rats poisoned with PQ and subsequently treated with XBJ or left untreated.
Boosting electrocatalytic reduction of nitrogen to ammonia under ambient conditions by alloy engineering
Authors: Jin Yu , Ding Xin , Zhang Linlin , Cong Meiyu , Xu Fanfan , Wei Yu , Hao Shengjie , Gao Yan
Published: August 2020

Alloying engineering supplied a second catalytic site for achieving both effective adsorptive activation of chemical insertion of N2 and intermediate desorption from the catalyst surface, which boosted NRR performance.
Accelerated lithium-ion conduction in covalent organic frameworks
Authors: Sheng Li , Wang Li , Wang Jianlong , Xu Hong , He Xiangming
Published: August 2020

We design a porous separator that consists of a covalent organic framework (COF), the ionic conductivity of which is 8 times higher than that of the most well-established separator of lithium-ion batteries.
A biomass-derived super-flexible hierarchically porous carbon film electrode prepared via environment-friendly ice-microcrystal pore-forming for supercapacitors
Authors: Ying Zongrong , Zhang Yongzheng , Lin Xuemei , Hui Shengjie , Wang Yuxuan , Yang Yibei , Li Yuchun
Published: August 2020

An efficient environmentally friendly ice-microcrystal pore-forming strategy utilizing N-methylmorpholine-N-oxide was developed to prepare a biomass-based super-flexible carbon film electrode.