bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic DNA methylation changes in early versus late adulthood suggest nondeterministic effects of childhood adversity: a meta-analysis
Authors: Artigas Rocio , Vega-Tapia Fabián , Hamilton James , Krause Bernardo J.
Published: December 2020

Adverse childhood experiences (ACEs) are associated with a high risk of developing chronic diseases and decreased life expectancy, but no ACE epigenetic biomarkers have been identified until now. The latter may result from the interaction of multiple factors such as age, sex, degree of adversity, and lack of transcriptional effects of DNA methylation changes. We hypothesize that DNA methylation changes are related to childhood adversity levels and current age, and these markers evolve as aging proceeds. Two Gene Expression Omnibus datasets, regarding ACE, were selected (GSE72680 and GSE70603), considering raw- and meta-data availability, including validated ACE index (Childhood Trauma Questionnaire (CTQ) score). For DNA methylation, analyzed probes were restricted to those laying within promoters and first exons, and samples were grouped by CTQ scores terciles, to compare highly (ACE) with non-abused (control) cases. Comparison of control and ACE methylome profile did not retrieve differentially methylated CpG sites (DMCs) after correcting by false discovery rate < 0.05, and this was also observed when samples were separated by sex. In contrast, grouping by decade age ranges (i.e., the 20s, 30s, 40s, and 50s) showed a progressive increase in the number of DMCs and the intensity of changes, mainly related with hypomethylation. Comparison with transcriptome data for ACE subjects in the 40s, and 50s showed a similar age-dependent effect. This study provides evidence that epigenetic markers of ACE are age-dependent, but not defined in the long term. These differences among early, middle, and late adulthood epigenomic profiles suggest a window for interventions aimed to prevent the detrimental effects of ACE.
Multiple Linear Regression Models for Reconstructing and Exploring Processes Controlling the Carbonate System of the Northeast US From Basic Hydrographic Data
Authors: McGarry K. , Siedlecki S. A. , Salisbury J. , Alin S. R.
Published: December 2020

In the coastal ocean, local carbonate system variability is determined by the interaction between ocean acidification and local processes. Sporadic observations indicate that biological metabolism, river input, and water mass mixing are dominant local processes driving carbonate system variability in northeast US shelf waters. These processes are also reflected in the variability of observed temperature (T), salinity (S), oxygen concentration (O2), and nitrate concentration (NO3−). Therefore, regionally specific empirical models can be developed, which relate carbonate system parameters to a combination of basic hydrographic parameters. Here, we develop multiple linear regression models that represent the processes that drive carbonate system variability in the Mid‐Atlantic Bight and Gulf of Maine using observations obtained on three hydrographic surveys in summers between 2007 and 2015. The empirical model equations reveal the observation‐based relationships between carbonate parameters and basic hydrographic variables. Unlike other regions where empirical models have been developed, salinity appears in all models. T is the most important parameter for predicting aragonite saturation state (ΩAR), while S and O2 are most important for predicting pH on total scale (pHT). The basic hydrographic variables explain over 98% of the variability in total alkalinity (TA), dissolved inorganic carbon (DIC), and ΩAR and 89% of the variability in pHT in the calibration data. We recommend applying models that depend on T, S, O2, and NO3− as predictors, which reproduce TA and DIC with R2 > 0.97, ΩAR with R2 > 0.93, and pHT with R2 > 0.77, to reconstruct carbonate system parameters in the region.
China's Interannual Variability of Net Primary Production Is Dominated by the Central China Region
Authors: Peng Jing , Dan Li , Ying Kairan , Yang Shuai , Tang Xiba , Yang Fuqiang
Published: December 2020

It is important to understand regional contributions to interannual and decadal variabilities of vegetation productivity. However, most studies of regional terrestrial carbon cycles focus on the contributions of regional ecosystems to the mean or trend of net primary production (NPP), rather than its interannual variability (IAV). In this study, the IAV of NPP is explored using the simulation of the Australian Community Atmospheric Biosphere Land Exchange model, version 2.1 (CABLE2.1), compared with an eight‐member Trends in Net Land–Atmosphere Carbon Exchanges (TRENDY) ensemble under present conditions (1951–2010). NPP IAV is also analyzed using only CABLE2.1 under future conditions (2041–2100). Under the present conditions, the Central China region (region CC) contributes the largest fraction (CABLE2.1, 28.2%; TRENDY, 33.3% ± 11.5%) of NPP IAV in China. Such an NPP IAV is strongly associated with circulation‐driven variations in precipitation in most of China (∼85%). During the future period, region CC still plays a key role in the national NPP IAV, at ∼24.6%. Although precipitation IAV is still the main driver regulating the NPP IAV for region CC under the future conditions, climate sensitivity of NPP IAV to precipitation IAV may weaken compared with those under the present conditions. Our results highlight the contribution of region CC to the NPP IAV of China as a whole.
Evaluation of the Forecast Performance for Extreme Cold Events in East Asia With Subseasonal‐to‐Seasonal Data Sets From ECMWF
Authors: Dai Guokun , Mu Mu , Li Chunxiang , Han Zhe , Wang Lei
Published: December 2020

Utilizing the subseasonal‐to‐seasonal (S2S) operational forecasts from the European Centre for Medium‐Range Weather Forecasts, the forecast skill for East Asian extreme cold events during 2015–2019 is evaluated. The results from the ensemble mean surface air temperature anomaly, the extreme forecast index, and the continuous ranked probability score skill reveal that extreme cold events can be captured by numerical models with a lead time of 7 days. It is also found that long‐persistent extreme cold events tend to have a longer skillful forecast lead time, which can exceed 10 days. The long skillful forecast lead time indicates that these events have a high intrinsic predictability, and the remote sea surface temperature anomaly, tropical intra‐seasonal oscillation and stratospheric polar vortex may be possible reasons for this predictability. The results suggest that it may be possible to make S2S and beyond skillful forecasts.
New solution for fast axial scanning in fluorescence microscopy
Authors: Zong Weijian
Published: December 2020

A novel technique based on the remote-focusing concept, using a galvanometer scanner combined with a self-fabricated “step mirror” or “tilted mirror” to transform fast lateral scanning into axial scanning, was reported as a new solution for fast, subcellular, 3D fluorescence imaging.
Viscoelastic microfluidics: progress and challenges
Authors: Zhou Jian , Papautsky Ian
Published: December 2020

The manipulation of cells and particles suspended in viscoelastic fluids in microchannels has drawn increasing attention, in part due to the ability for single-stream three-dimensional focusing in simple channel geometries. Improvement in the understanding of non-Newtonian effects on particle dynamics has led to expanding exploration of focusing and sorting particles and cells using viscoelastic microfluidics. Multiple factors, such as the driving forces arising from fluid elasticity and inertia, the effect of fluid rheology, the physical properties of particles and cells, and channel geometry, actively interact and compete together to govern the intricate migration behavior of particles and cells in microchannels. Here, we review the viscoelastic fluid physics and the hydrodynamic forces in such flows and identify three pairs of competing forces/effects that collectively govern viscoelastic migration. We discuss migration dynamics, focusing positions, numerical simulations, and recent progress in viscoelastic microfluidic applications as well as the remaining challenges. Finally, we hope that an improved understanding of viscoelastic flows in microfluidics can lead to increased sophistication of microfluidic platforms in clinical diagnostics and biomedical research.
Combinatorial nanodot stripe assay to systematically study cell haptotaxis
Authors: Dlamini Mcolisi , Kennedy Timothy E. , Juncker David
Published: December 2020

Haptotaxis is critical to cell guidance and development and has been studied in vitro using either gradients or stripe assays that present a binary choice between full and zero coverage of a protein cue. However, stripes offer only a choice between extremes, while for gradients, cell receptor saturation, migration history, and directional persistence confound the interpretation of cellular responses. Here, we introduce nanodot stripe assays (NSAs) formed by adjacent stripes of nanodot arrays with different surface coverage. Twenty-one pairwise combinations were designed using 0, 1, 3, 10, 30, 44 and 100% stripes and were patterned with 200 × 200, 400 × 400 or 800 × 800 nm2 nanodots. We studied the migration choices of C2C12 myoblasts that express neogenin on NSAs (and three-step gradients) of netrin-1. The reference surface between the nanodots was backfilled with a mixture of polyethylene glycol and poly-d-lysine to minimize nonspecific cell response. Unexpectedly, cell response was independent of nanodot size. Relative to a 0% stripe, cells increasingly chose the high-density stripe with up to ~90% of cells on stripes with 10% coverage and higher. Cell preference for higher vs. lower netrin-1 coverage was observed only for coverage ratios >2.3, with cell preference plateauing at ~80% for ratios ≥4. The combinatorial NSA enables quantitative studies of cell haptotaxis over the full range of surface coverages and ratios and provides a means to elucidate haptotactic mechanisms.
A Phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma
Authors: Shapiro Geoffrey I. , LoRusso Patricia , Dowlati Afshin , T. Do Khanh , Jacobson Caron A. , Vaishampayan Ulka , Weise Amy , Caimi Paolo F. , Eder Joseph Paul , French Christopher A. , Labriola-Tompkins Emily , Boisserie Frédéric , Pierceall William E. , Zhi Jianguo , Passe Sharon , DeMario Mark , Kornacker Martin , Armand Philippe
Published: December 2020

Background

Bromodomain and extra-terminal (BET) proteins are epigenetic readers that can drive carcinogenesis and therapy resistance. RO6870810 is a novel, small-molecule BET inhibitor.

Methods

We conducted a Phase 1 study of RO6870810 administered subcutaneously for 21 or 14 days of 28- or 21-day cycles, respectively, in patients with the nuclear protein of the testis carcinoma (NC), other solid tumours, or diffuse large B-cell lymphoma (DLBCL) with MYC deregulation.

Results

Fatigue (42%), decreased appetite (35%) and injection-site erythema (35%) were the most common treatment-related adverse events. Pharmacokinetic parameters demonstrated linearity over the dose range tested and support once-daily dosing. Pharmacodynamic assessments demonstrated sustained decreases in CD11b levels in peripheral blood mononuclear cells. Objective response rates were 25% (2/8), 2% (1/47) and 11% (2/19) for patients with NC, other solid tumours and DLBCL, respectively. Responding tumours had evidence of deregulated MYC expression.

Conclusions

This trial establishes the safety, favourable pharmacokinetics, evidence of target engagement and preliminary single-agent activity of RO6870810. Responses in patients with NC, other solid tumours and DLBCL provide proof-of-principle for BET inhibition in MYC-driven cancers. The results support further exploration of RO6870810 as monotherapy and in combinations.

Clinical trials registration

NCT01987362.
Transcriptional factor ATF3 promotes liver fibrosis via activating hepatic stellate cells
Authors: Shi Zhemin , Zhang Kun , Chen Ting , Zhang Yu , Du Xiaoxiao , Zhao Yanmian , Shao Shuai , Zheng Lina , Han Tao , Hong Wei
Published: December 2020

The excessive accumulation of extracellular matrix (ECM) is a key feature of liver fibrosis and the activated hepatic stellate cells (HSCs) are the major producer of ECM proteins. However, the precise mechanisms and target molecules that are involved in liver fibrosis remain unclear. In this study, we reported that activating transcription factor 3 (ATF3) was over-expressed in mice and human fibrotic livers, in activated HSCs and injured hepatocytes (HCs). Both in vivo and in vitro study have revealed that silencing ATF3 reduced the expression of pro-fibrotic genes and inhibited the activation of HSCs, thus alleviating the extent of liver fibrosis, indicating a potential protective role of ATF3 knockdown. However, ATF3 was not involved in either the apoptosis or proliferation of HCs. In addition, our data illustrated that increased nuclear localization of ATF3 promoted the transcription of fibrogenic genes and lnc-SCARNA10, which functioned as a novel positive regulator of TGF-β signaling in liver fibrogenesis by recruiting SMAD3 to the promoter of these genes. Interestingly, further study also demonstrated that lnc-SCARNA10 promoted the expression of ATF3 in a TGF-β/SMAD3-dependent manner, revealing a TGF-β/ATF3/lnc-SCARNA10 axis that contributed to liver fibrosis by activating HSCs. Taken together, our data provide a molecular mechanism implicating induced ATF3 in liver fibrosis, suggesting that ATF3 may represent a useful target in the development of therapeutic strategies for liver fibrosis.
A nuclear-localized cysteine desulfhydrase plays a role in fruit ripening in tomato
Authors: Hu Kang-Di , Zhang Xiao-Yue , Yao Gai-Fang , Rong Yu-Lei , Ding Chen , Tang Jun , Yang Feng , Huang Zhong-Qin , Xu Zi-Mu , Chen Xiao-Yan , Li Yan-Hong , Hu Lan-Ying , Zhang Hua
Published: December 2020

Hydrogen sulfide (H2S) is a gaseous signaling molecule that plays multiple roles in plant development. However, whether endogenous H2S plays a role in fruit ripening in tomato is still unknown. In this study, we show that the H2S-producing enzyme l-cysteine desulfhydrase SlLCD1 localizes to the nucleus. By constructing mutated forms of SlLCD1, we show that the amino acid residue K24 of SlLCD1 is the key amino acid that determines nuclear localization. Silencing of SlLCD1 by TRV-SlLCD1 accelerated fruit ripening and reduced H2S production compared with the control. A SlLCD1 gene-edited mutant obtained through CRISPR/Cas9 modification displayed a slightly dwarfed phenotype and accelerated fruit ripening. This mutant also showed increased cysteine content and produced less H2S, suggesting a role of SlLCD1 in H2S generation. Chlorophyll degradation and carotenoid accumulation were enhanced in the SlLCD1 mutant. Other ripening-related genes that play roles in chlorophyll degradation, carotenoid biosynthesis, cell wall degradation, ethylene biosynthesis, and the ethylene signaling pathway were enhanced at the transcriptional level in the lcd1 mutant. Total RNA was sequenced from unripe tomato fruit treated with exogenous H2S, and transcriptome analysis showed that ripening-related gene expression was suppressed. Based on the results for a SlLCD1 gene-edited mutant and exogenous H2S application, we propose that the nuclear-localized cysteine desulfhydrase SlLCD1 is required for endogenous H2S generation and participates in the regulation of tomato fruit ripening.
A nonlinear magnonic nano-ring resonator
Authors: Wang Qi , Hamadeh Abbass , Verba Roman , Lomakin Vitaliy , Mohseni Morteza , Hillebrands Burkard , Chumak Andrii V. , Pirro Philipp
Published: December 2020

The field of magnonics, which aims at using spin waves as carriers in data-processing devices, has attracted increasing interest in recent years. We present and study micromagnetically a nonlinear nanoscale magnonic ring resonator device for enabling implementations of magnonic logic gates and neuromorphic magnonic circuits. In the linear regime, this device efficiently suppresses spin-wave transmission using the phenomenon of critical resonant coupling, thus exhibiting the behavior of a notch filter. By increasing the spin-wave input power, the resonance frequency is shifted, leading to transmission curves, depending on the frequency, reminiscent of the activation functions of neurons, or showing the characteristics of a power limiter. An analytical theory is developed to describe the transmission curve of magnonic ring resonators in the linear and nonlinear regimes, and is validated by a comprehensive micromagnetic study. The proposed magnonic ring resonator provides a multi-functional nonlinear building block for unconventional magnonic circuits.
Internal dose assessment of 148Gd using isotope ratios of gamma-emitting 146Gd or 153Gd in accidently released spallation target particles
Authors: Rääf C. , Barkauskas V. , Eriksson Stenström K. , Bernhardsson C. , Pettersson H. B. L.
Published: December 2020

The pure alpha emitter 148Gd may have a significant radiological impact in terms of internal dose to exposed humans in case of accidental releases from a spallation source using a tungsten target, such as the one to be used in the European Spallation Source (ESS). In this work we aim to present an approach to indirectly estimate the whole-body burden of 148Gd and the associated committed effective dose in exposed humans, by means of high-resolution gamma spectrometry of the gamma-emitting radiogadolinium isotopes 146Gd and 153Gd that are accompanied by 148Gd generated from the operation of the tungsten target. Theoretical minimum detectable whole-body activity (MDA) and associated internal doses from 148Gd are calculated using a combination of existing biokinetic models and recent computer simulation studies on the generated isotope ratios of 146Gd/148Gd and 153Gd/148Gd in the ESS target. Of the two gamma-emitting gadolinium isotopes, 146Gd is initially the most sensitive indicator of the presence of 148Gd if whole-body counting is performed within a month after the release, using the twin photo peaks of 146Gd centered at 115.4 keV (MDA < 1 Bq for ingested 148Gd, and < 25 Bq for inhaled 148Gd). The corresponding minimum detectable committed effective doses will be less than 1 µSv for ingested 148Gd, but substantially higher for inhaled 148Gd (up to 0.3 mSv), depending on operation time of the target prior to the release. However, a few months after an atmospheric release, 153Gd becomes a much more sensitive indicator of body burdens of 148Gd, with a minimum detectable committed effective doses ranging from 18 to 77 µSv for chronic ingestion and between 0.65 to 2.7 mSv for acute inhalation in connection to the release. The main issue with this indirect method for 148Gd internal dose estimation, is whether the primary photon peaks from 146 and 153Gd can be detected undisturbed. Preliminary simulations show that nuclides such as 182Ta may potentially create perturbations that could impair this evaluation method, and which impact needs to be further studied in future safety assessments of accidental target releases.
Elucidating the regulatory mechanism of Swi1 prion in global transcription and stress responses
Authors: Du Zhiqiang , Regan Jeniece , Bartom Elizabeth , Wu Wei-Sheng , Zhang Li , Goncharoff Dustin Kenneth , Li Liming
Published: December 2020

Transcriptional regulators are prevalent among identified prions in Saccharomyces cerevisiae, however, it is unclear how prions affect genome-wide transcription. We show here that the prion ([SWI+]) and mutant (swi1∆) forms of Swi1, a subunit of the SWI/SNF chromatin-remodeling complex, confer dramatically distinct transcriptomic profiles. In [SWI+] cells, genes encoding for 34 transcription factors (TFs) and 24 Swi1-interacting proteins can undergo transcriptional modifications. Several TFs show enhanced aggregation in [SWI+] cells. Further analyses suggest that such alterations are key factors in specifying the transcriptomic signatures of [SWI+] cells. Interestingly, swi1∆ and [SWI+] impose distinct and oftentimes opposite effects on cellular functions. Translation-associated activities, in particular, are significantly reduced in swi1∆ cells. Although both swi1∆ and [SWI+] cells are similarly sensitive to thermal, osmotic and drought stresses, harmful, neutral or beneficial effects were observed for a panel of tested chemical stressors. Further analyses suggest that the environmental stress response (ESR) is mechanistically different between swi1∆ and [SWI+] cells—stress-inducible ESR (iESR) are repressed by [SWI+] but unchanged by swi1∆ while stress-repressible ESR (rESR) are induced by [SWI+] but repressed by swi1∆. Our work thus demonstrates primarily gain-of-function outcomes through transcriptomic modifications by [SWI+] and highlights a prion-mediated regulation of transcription and phenotypes in yeast.
Chain architectures of various cellulose-based antiscalants on the inhibition of calcium carbonate scale
Authors: Yu Wei , Yang Hu
Published: December 2020

Two series of cellulose-based antiscalants with different chain architectures, i.e., linear carboxymethyl cellulose (CMC) and branch-shaped carboxymethyl cellulose-graft-poly(acrylic acid) (CMC-g-PAA), were synthesized. The carboxyl groups were distributed on CMC backbone but mainly on the grafted chains of CMC-g-PAA. The addition of CMC and CMC-g-PAA can both increase the surface energy of CaCO3 scale and decrease its crystal nucleation rate, thereby inhibiting CaCO3 scale formation. The structural effects of these cellulose-based antiscalants, especially the chain architectures, on the scale inhibition were investigated in detail. High degree of carboxymethyl substitution caused better inhibition effect of linear CMC. However, CMC-g-PAA with an appropriate content of carboxyl groups but high average number of PAA grafted chains can achieve high inhibition performance. Besides, with similar contents of carboxyl groups, CMC-g-PAA showed much better inhibition performance than CMC due to the distinct multi-dimensional spatial structure of graft copolymer in solution, causing the enhanced chelation and dispersion effects. Characterization of CaCO3 crystal by scanning electron microscopy and X-ray diffraction confirmed that crystal distortion effect obviously existed in CMC but quite minor in CMC-g-PAA. The differences between the scale-inhibition performance of CMC and CMC-g-PAA should be attributed to the different scale-inhibition mechanisms originated in their distinct chain architectures.
The role of microRNA-3085 in chondrocyte function
Authors: Le Linh , Niu Lingzi , Barter Matthew J. , Young David A. , Dalmay Tamas , Clark Ian M. , Swingler Tracey E.
Published: December 2020

MicroRNAs have been shown to play a role in cartilage development, homeostasis and breakdown during osteoarthritis. We previously identified miR-3085 in humans as a chondrocyte-selective microRNA, however it could not be detected by Northern blot. The aim of the current study was to prove that miR-3085 is a microRNA and to investigate the function of miR-3085 in signaling pathways relevant to cartilage homeostasis and osteoarthritis. Here, we confirm that miR-3085 is a microRNA and not another class of small RNA using (1) a pre-miR hairpin maturation assay, (2) expression levels in a Dicer null cell line, and (3) Ago2 pulldown. MicroRNA-3085-3p is expressed more highly in micromass than monolayer cultured chondrocytes. Transfection of miR-3085-3p into chondrocytes decreases expression of COL2A1 and ACAN, both of which are validated as direct targets of miR-3085-3p. Interleukin-1 induces the expression of miR-3085-3p, at least in part via NFκB. In a feed-forward mechanism, miR-3085-3p then potentiates NFκB signaling. However, at early time points after transfection, its action appears to be inhibitory. MyD88 has been shown to be a direct target of miR-3085-3p and may be responsible for the early inhibition of NFκB signaling. However, at later time points, MyD88 knockdown remains inhibitory and so other functions of miR-3085-3p are clearly dominant. TGFβ1 also induces the expression of miR-3085-3p, but in this instance, it exerts a feedback inhibition on signaling with SMAD3 and SMAD4 shown to be direct targets. This in vitro analysis shows that miR-3085-3p functions in chondrocytes to induce IL-1-signaling, reduce TGFβ1 signaling, and inhibit expression of matrix genes. These data suggest that miR-3085-3p has a role in chondrocyte function and could contribute to the process of osteoarthritis.
Activation of NLRP3 by uropathogenic Escherichia coli is associated with IL-1β release and regulation of antimicrobial properties in human neutrophils
Authors: Demirel Isak , Persson Alexander , Brauner Annelie , Särndahl Eva , Kruse Robert , Persson Katarina
Published: December 2020

The NLRP3 inflammasome and IL-1β have recently been linked to the severity of uropathogenic Escherichia coli (UPEC)-mediated urinary tract infection (UTI). However, not much is known about the contribution of NLRP3 to the antimicrobial properties of neutrophils and the release of IL-1β during UPEC infection. The purpose of this study was to elucidate the mechanisms behind UPEC-induced IL-1β release from human neutrophils, and to investigate the contribution of the NLRP3 inflammasome in neutrophil-mediated inhibition of UPEC growth. We found that the UPEC strain CFT073 increased the expression of NLRP3 and increased caspase-1 activation and IL-1β release from human neutrophils. The IL-1β release was mediated by the NLRP3 inflammasome and by serine proteases in an NF-κB-and cathepsin B-dependent manner. The UPEC virulence factors α-hemolysin, type-1 fimbriae and p-fimbriae were all shown to contribute to UPEC mediated IL-1β release from neutrophils. Furthermore, inhibition of caspase-1 and NLRP3 activation increased neutrophil ROS-production, phagocytosis and the ability of neutrophils to suppress UPEC growth. In conclusion, this study demonstrates that UPEC can induce NLRP3 and serine protease-dependent release of IL-1β from human neutrophils and that NLRP3 and caspase-1 can regulate the antimicrobial activity of human neutrophils against UPEC.
Strip-width determines competitive strengths and grain yields of intercrop species in relay intercropping system
Authors: Raza Muhammad Ali , Cui Liang , Qin Ruijun , Yang Feng , Yang Wenyu
Published: December 2020

Maize/soybean relay intercropping system (MSR) is a popular cultivation method to obtain high yields of both crops with reduced inputs. However, in MSR, the effects of different strip widths on competitive strengths and grain yields of intercrop species are still unclear. Therefore, in a two-year field experiment, soybean was relay-intercropped with maize in three different strip-width arrangements (narrow-strips, 180 cm; medium-strips, 200 cm; and wide-strips, 220 cm), and all intercropping results were compared with sole maize (SM) and sole soybean (SS). Results showed that the optimum strip-width for obtaining high grain yields of maize and soybean was 200 cm (medium-strips), which improved the competitive-ability of soybean by maintaining the competitive-ability of maize in MSR. On average, maize and soybean produced 98% and 77% of SM and SS yield, respectively, in medium-strips. The improved grain yields of intercrop species in medium-strips increased the total grain yield of MSR by 15% and land equivalent ratio by 22%, which enhanced the net-income of medium-strips (by 99%, from 620 US $ ha−1 in wide-strips to 1233 US $ ha−1 in medium-strips). Overall, these findings imply that following the optimum strip-width in MSR, i. e., strip-width of 200 cm, grain yields, and competitive interactions of intercrop species can be improved.
Genetic variation, phylogenetic relationship and spatial distribution of ‘Candidatus Phytoplasma ulmi’ strains in Germany
Authors: Schneider B. , Hüttel B. , Zübert C. , Kube M.
Published: December 2020

A recent survey in Germany revealed the wide presence of ‘Candidatus Phytoplasma ulmi’ in native elm stands. Accessions were studied for their genetic variability and phylogenetic relationship based on the conserved groEL and the variable imp gene. While the groEL sequences revealed a high intraspecific homology of more than 99%, the homology of the imp gene dropped to 71% between distantly related sequences. Twenty-nine groEL and 74 imp genotypes were distinguished based on polymorphic sites. Phylogenetic analysis of the groEL gene clustered all ‘Ca. P. ulmi’ strains and separated them from related phytoplasmas of the 16SrV group. The inferred phylogeny of the imp gene resulted in a different tree topology and separated the ‘Ca. P. ulmi’ genotypes into two clusters, one closely related to the flavescence dorée phytoplasma strain FD-D (16SrV-D), the other affiliated with the flavescence dorée phytoplasma strains FD-C and FD70 and the alder yellows phytoplasma (16SrV-C). In both phylograms, ‘Ca. P. ulmi’ genotypes from Scots elm trees formed a coherent cluster, while genotypes from European white elms and field elms grouped less strictly. The regional distribution pattern was congruent for some of the groEL and imp genotypes, but a strict linkage for all genotypes was not apparent.
Tuning domain wall dynamics by shaping nanowires cross-sections
Authors: Altbir Dora , Fonseca Jakson M. , Chubykalo-Fesenko Oksana , Corona Rosa M. , Moreno Roberto , Carvalho-Santos Vagson L. , Ivanov Yurii P.
Published: December 2020

The understanding of the domain wall (DW) dynamics along magnetic nanowires is crucial for spintronic applications. In this work, we perform a detailed analysis of the transverse DW motion along nanowires with polygonal cross-sections. If the DW displaces under a magnetic field above the Walker limit, the oscillatory motion of the DW is observed. The amplitude, the frequency of oscillations, and the DW velocity depend on the number of sides of the nanowire cross-section, being the DW velocity in a wire with a triangular cross-section one order of magnitude larger than that in a circular nanowire. The decrease in the nanowire cross-section area yields a DW behavior similar to the one presented in a cylindrical nanowire, which is explained using an analytical model based on the general kinetic momentum theorem. Micromagnetic simulations reveal that the oscillatory behavior of the DW comes from energy changes due to deformations of the DW shape during the rotation around the nanowire.
Optoelectronic synapse using monolayer MoS2 field effect transistors
Authors: Islam Molla Manjurul , Dev Durjoy , Krishnaprasad Adithi , Tetard Laurene , Roy Tania
Published: December 2020

Optical data sensing, processing and visual memory are fundamental requirements for artificial intelligence and robotics with autonomous navigation. Traditionally, imaging has been kept separate from the pattern recognition circuitry. Optoelectronic synapses hold the special potential of integrating these two fields into a single layer, where a single device can record optical data, convert it into a conductance state and store it for learning and pattern recognition, similar to the optic nerve in human eye. In this work, the trapping and de-trapping of photogenerated carriers in the MoS2/SiO2 interface of a n-channel MoS2 transistor was employed to emulate the optoelectronic synapse characteristics. The monolayer MoS2 field effect transistor (FET) exhibits photo-induced short-term and long-term potentiation, electrically driven long-term depression, paired pulse facilitation (PPF), spike time dependent plasticity, which are necessary synaptic characteristics. Moreover, the device’s ability to retain its conductance state can be modulated by the gate voltage, making the device behave as a photodetector for positive gate voltages and an optoelectronic synapse at negative gate voltages.
Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC
Authors: Li Hongzhen , Chaitankar Vijender , Zhu Jianqiong , Chin Kyung , Liu Wenli , Pirooznia Mehdi , Rodgers Griffin P.
Published: December 2020

Olfactomedin 4 (OLFM4) is expressed in normal prostate epithelial cells and immortalized normal human prostate epithelial cells (RWPE1), but the identity of OLFM4-expressing cells within these populations and OLFM4’s physiological functions in these cells have not been elucidated. Using single-cell RNA sequencing analysis, we found here that OLFM4 was expressed in multiple stem/progenitor-like cell populations in both the normal prostate epithelium and RWPE1 cells and was frequently co-expressed with KRT13 and LY6D in RWPE1 cells. Functionally, OLFM4-knockout RWPE1 cells exhibited enhanced proliferation of the stem/progenitor-like cell population, shifts stem/progenitor-like cell division to favor symmetric division and differentiated into higher levels PSA expression cells in organoid assays compared with OLFM4-wild RWPE1 cells. Bulk-cell RNA sequencing analysis pinpointed that cMYC expression were enhanced in the OLFM4-knockout RWPE1 cells compared with OLFM4-wild cells. Molecular and signaling pathway studies revealed an increase in the WNT/APC/MYC signaling pathway gene signature, as well as that of MYC target genes that regulate multiple biological processes, in OLFM4-knockout RWPE1 cells. These findings indicated that OLFM4 is co-expressed with multiple stem/progenitor cell marker genes in prostate epithelial cells and acts as a novel mediator in prostate stem/progenitor cell proliferation and differentiation.
Variation of the human mu-opioid receptor (OPRM1) gene predicts vulnerability to frustration
Authors: Daniel Alan M. , Rushing Brenda G. , Tapia Menchaca Karla Y.
Published: December 2020

Understanding the emotional reaction to loss, or frustration, is a critical problem for the field of mental health. Animal models of loss have pointed to the opioid system as a nexus of frustration, physical pain, and substance abuse. However, few attempts have been made to connect the results of animal models of loss to human behavior. Allelic differences in the human mu opioid receptor gene, notably the A118G single nucleotide polymorphism, have been linked to individual differences in pain sensitivity, depressive symptoms, and reward processing. The present study explored the relationship between A118G and behavior in two frustrating tasks in humans. Results showed that carriers of the mutant G-allele were slower to recover behavior following a reward downshift and abandoned a frustrating task earlier than those without the mutation. Additionally, G-carriers were more sensitive to physical pain. These results highlight the overlap between frustration and pain, and suggest that genetic variation in opioid tone may contribute to individual differences in vulnerability and resilience following emotional disturbances.
Inflammatory marker changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women
Authors: Masala G. , Bendinelli B. , Della Bella C. , Assedi M. , Tapinassi S. , Ermini I. , Occhini D. , Castaldo M. , Saieva C. , Caini S. , D’Elios M. M. , Palli D.
Published: December 2020

Chronic low-grade inflammation plays a role in the pathogenesis of several chronic diseases including cancer. Physical activity (PA) and diet have been supposed to modulate inflammatory markers. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of pro-inflammatory cytokines, a secondary analysis in the DAMA factorial trial. The 234 study participants (healthy postmenopausal women with high breast density, 50–69 years, non smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Interleukins (IL)-1α, -1β, -6, tumor necrosis factor-α and C-reactive protein were measured at baseline and at the end of the intervention. Intention-to-treat-analyses were carried out using Tobit regression. Although all cytokines tended to increase over time, after 24 months women in the PA intervention (arms 2 + 3) showed lower levels of IL-1α (exp(β) = 0.66; p = 0.04) and IL-6 (exp(β) = 0.70; p = 0.01) in comparison with women in the control group (arms 1 + 4). No effects of the dietary intervention emerged. In healthy postmenopausal women with high breast density a moderate-intensity PA appears to slow the age-related increase of pro-inflammatory cytokines.
Fluorescent ligands for dopamine D2/D3 receptors
Authors: Allikalt Anni , Purkayastha Nirupam , Flad Khajidmaa , Schmidt Maximilian F. , Tabor Alina , Gmeiner Peter , Hübner Harald , Weikert Dorothee
Published: December 2020

Fluorescent ligands are versatile tools for the study of G protein-coupled receptors. Depending on the fluorophore, they can be used for a range of different applications, including fluorescence microscopy and bioluminescence or fluorescence resonance energy transfer (BRET or FRET) assays. Starting from phenylpiperazines and indanylamines, privileged scaffolds for dopamine D2-like receptors, we developed dansyl-labeled fluorescent ligands that are well accommodated in the binding pockets of D2and D3receptors. These receptors are the target proteins for the therapy for several neurologic and psychiatric disorders, including Parkinson’s disease and schizophrenia. The dansyl-labeled ligands exhibit binding affinities up to 0.44 nM and 0.29 nM at D2R and D3R, respectively. When the dansyl label was exchanged for sterically more demanding xanthene or cyanine dyes, fluorescent ligands 10a-c retained excellent binding properties and, as expected from their indanylamine pharmacophore, acted as agonists at D2R. While the Cy3B-labeled ligand 10b was used to visualize D2R and D3R on the surface of living cells by total internal reflection microscopy, ligand 10a comprising a rhodamine label showed excellent properties in a NanoBRET binding assay at D3R.
Radiologic imaging shows variable accuracy in diagnosing orbital inflammatory disease and assessing its activity
Authors: Lee Min Joung , Hamilton Bronwyn E. , Pettersson David , Ogle Kimberly , Murdock Jennifer , Dailey Roger A. , Ng John D. , Steele Eric A. , Verma Rohan , Planck Stephen R. , Martin Tammy M. , Choi Dongseok , Rosenbaum James T.
Published: December 2020

Radiologic orbital imaging provides important information in the diagnosis and management of orbital inflammation. However, the diagnostic value of orbital imaging is not well elucidated. This study aimed to investigate the diagnostic accuracy of orbital imaging to diagnose orbital inflammatory diseases and its ability to detect active inflammation. We collected 75 scans of 52 patients (49 computed tomography (CT) scans; 26 magnetic resonance (MR) imaging scans). Clinical diagnoses included thyroid eye disease (TED) (41 scans, 31 patients), non-specific orbital inflammation (NSOI) (22 scans, 14 patients), sarcoidosis (4 scans, 3 patients), IgG4-related ophthalmic disease (IgG4-ROD) (5 scans, 3 patients), and granulomatosis with polyangiitis (GPA) (3 scans, 1 patient). Two experienced neuroradiologists interpreted the scans, offered a most likely diagnosis, and assessed the activity of inflammation, blinded to clinical findings. The accuracy rate of radiological diagnosis compared to each clinical diagnosis was evaluated. Sensitivity and specificity in detecting active inflammation were analyzed for TED and NSOI. The accuracy rate of radiologic diagnosis was 80.0% for IgG4-ROD, 77.3% for NSOI, and 73.2% for TED. Orbital imaging could not diagnose sarcoidosis. Orbital CT had a sensitivity of 50.0% and a specificity of 75.0% to predict active TED using clinical assessment as the gold standard. The sensitivity/specificity of orbital MR was 83.3/16.7% for the detection of active NSOI. In conclusion, orbital imaging is accurate for the diagnosis of IgG4, NSOI, and TED. Further studies with a large number of cases are needed to confirm this finding, especially with regard to uncommon diseases. Orbital CT showed moderate sensitivity and good specificity for identifying active TED.
Gravettian cranial morphology and human group affinities during the European Upper Palaeolithic
Authors: Mounier Aurélien , Heuzé Yann , Samsel Mathilde , Vasilyev Sergey , Klaric Laurent , Villotte Sébastien
Published: December 2020

Archaeologically defined Upper Palaeolithic (UP, 45,000–10,000 years ago) “cultures” are often used as proxies to designate fossil populations. While recent genomic studies have partly clarified the complex relationship between European UP “cultures” and past population dynamics, they leave open numerous questions regarding the biological characterization of these human groups, especially regarding the Mid-UP period (MUP, 33,000–24,000 years ago), which encompasses a pan-European cultural mosaic (Gravettian) with several regional facies. Here, we analyse a large database of well-dated and well-preserved UP crania, including MUP specimens from South-West France (SWF) and Moravia, using 3D geometric morphometrics to test for human group affinities. Our results show that the Gravettian makers from these two regions form a remarkably phenetically homogeneous sample which is different from, and more homogeneous than, the Late UP sample. Those results are congruent with genomic studies indicating a genetic continuity within the Gravettian manufacturers and a discontinuity marked by the Last Glacial Maximum (LGM). Moreover, our study expands the geographical range of the MUP phenetic continuity to SWF, for which aDNA data are scarce, and clarifies the post-LGM European population structure in SWF, with a possible dual ancestry stemming from different LGM refugia.
Two-color in-resin CLEM of Epon-embedded cells using osmium resistant green and red fluorescent proteins
Authors: Tanida Isei , Furuta Yoko , Yamaguchi Junji , Kakuta Soichiro , Oliva Trejo Juan Alejandro , Uchiyama Yasuo
Published: December 2020

In-resin CLEM of Epon embedded samples can greatly simplify the correlation of fluorescent images with electron micrographs. The usefulness of this technique is limited at present by the low number of fluorescent proteins that resist CLEM processing. Additionally, no study has reported the possibility of two-color in-resin CLEM of Epon embedded cells. In this study, we screened for monomeric green and red fluorescent proteins that resist CLEM processing. We identified mWasabi, CoGFP variant 0, and mCherry2; two green and one red fluorescent proteins as alternatives for in-resin CLEM. We expressed mitochondria-localized mCherry2 and histone H2B tagged with CoGFP variant 0 in cells. Green and red fluorescence was detected in 100 nm-thin sections of the Epon-embedded cells. In the same thin sections, we correlated the fluorescent signals to mitochondria and the nucleus using a scanning electron microscope. Similar results were obtained when endoplasmic reticulum-localized mCherry2 and histone H2B tagged with CoGFP variant 0 were expressed in the cells. Two-color in-resin CLEM of two cytoplasmic organelles, mitochondria and endoplasmic reticulum, was also achieved using mitochondria-localized mCherry2 and endoplasmic reticulum-localized mWasabi. In summary, we report three new fluorescent protein-alternatives suitable for in-resin CLEM of Epon-embedded samples, and achieved Epon-based two-color in-resin CLEM.
Structural insights and evaluation of the potential impact of missense variants on the interactions of SLIT2 with ROBO1/4 in cancer progression
Authors: Sengupta Debmalya , Bhattacharya Gairika , Ganguli Sayak , Sengupta Mainak
Published: December 2020

The cognate interaction of ROBO1/4 with its ligand SLIT2 is known to be involved in lung cancer progression. However, the precise role of genetic variants, disrupting the molecular interactions is less understood. All cancer-associated missense variants of ROBO1/4 and SLIT2 from COSMIC were screened for their pathogenicity. Homology modelling was done in Modeller 9.17, followed by molecular simulation in GROMACS. Rigid docking was performed for the cognate partners in PatchDock with refinement in HADDOCK server. Post-docking alterations in conformational, stoichiometric, as well as structural parameters, were assessed. The disruptive variants were ranked using a weighted scoring scheme. In silico prioritisation of 825 variants revealed 379 to be potentially pathogenic out of which, about 12% of the variants, i.e. ROBO1 (14), ROBO4 (8), and SLIT2 (23) altered the cognate docking. Six variants of ROBO1 and 5 variants of ROBO4 were identified as "high disruptors" of interactions with SLIT2 wild type. Likewise, 17 and 13 variants of SLIT2 were found to be "high disruptors" of its interaction with ROBO1 and ROBO4, respectively. Our study is the first report on the impact of cancer-associated missense variants on ROBO1/4 and SLIT2 interactions that might be the drivers of lung cancer progression.
A highly sensitive method for the detection of recombinant PERV-A/C env RNA using next generation sequencing technologies
Authors: Kono Ken , Kataoka Kiyoko , Yuan Yuzhe , Yusa Keisuke , Uchida Kazuhisa , Sato Yoji
Published: December 2020

Several xenogenic cell-based therapeutic products are currently under development around the world for the treatment of human diseases. Porcine islet cell products for treating human diabetes are a typical example. Since porcine cells possess endogenous retrovirus (PERV), which can replicate in human cells in vitro, the potential transmission of PERV has raised concerns in the development of these products. Four subgroups of infectious PERV have been identified, namely PERV-A, -B, -C, and recombinant PERV-A/C. Among them, PERV-A/C shows a high titre and there was a paper reported that an incidence of PERV-A/C viremia was increased in diseased pigs; thus, it would be important to monitor the emergence of PERV-A/C after transplantation of porcine products. In this study, we developed a highly sensitive method for the detection of PERV-A/C using next generation sequencing (NGS) technologies. A model PERV-C spiked with various doses of PERV-A/C were amplified by RT-PCR and the amplicons were analysed by NGS. We found that the NGS analysis allowed the detection of PERV-A/C at the abundance ratios of 1% and 0.1% with true positive rates of 100% and 57%, respectively, indicating that it would be useful for the rapid detection of PERV-A/C emergence after transplantation of porcine products.
Cisplatin induced neurotoxicity is mediated by Sarm1 and calpain activation
Authors: Cetinkaya-Fisgin Aysel , Luan Xinghua , Reed Nicole , Jeong Ye Eun , Oh Byoung Chol , Hoke Ahmet
Published: December 2020

Cisplatin is a commonly used chemotherapy agent with significant dose-limiting neurotoxicity resulting in peripheral neuropathy. Although it is postulated that formation of DNA-platinum adducts is responsible for both its cytotoxicity in cancer cells and side effects in neurons, downstream mechanisms that lead to distal axonal degeneration are unknown. Here we show that activation of calpains is required for both neurotoxicity and formation of DNA-platinum adduct formation in neurons but not in cancer cells. Furthermore, we show that neurotoxicity of cisplatin requires activation of Sarm1, a key regulator of Wallerian degeneration, as mice lacking the Sarm1 gene do not develop peripheral neuropathy as evaluated by both behavioral or pathological measures. These findings indicate that Sarm1 and/or specific calpain inhibitors could be developed to prevent cisplatin induced peripheral neuropathy.