bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation by CNNM2 of ATP5MD expression in the 10q24.32 schizophrenia-associated locus involved in impaired ATP production and neurodevelopment
Authors: Wang Zhongju , Zhu Yongchang , Ye Linyan , Li Qiyang , Guo Bo , Zhao Hao , Bao Xiuqin , Zhuo Qiqi , Yang Tengfei , Li Zhaoqiang , Li Shufen , Hao Bingtao , Zhao Cunyou
Published: May 2021

Genome-wide association studies (GWAS) have accelerated the discovery of numerous genetic variants associated with schizophrenia. However, most risk variants show a small effect size (odds ratio (OR) <1.2), suggesting that more functional risk variants remain to be identified. Here, we employed region-based multi-marker analysis of genomic annotation (MAGMA) to identify additional risk loci containing variants with large OR value from Psychiatry Genomics Consortium (PGC2) schizophrenia GWAS data and then employed summary-data-based mendelian randomization (SMR) to prioritize schizophrenia susceptibility genes. The top-ranked susceptibility gene ATP5MD, encoding an ATP synthase membrane subunit, is observed to be downregulated in schizophrenia by the risk allele of CNNM2-rs1926032 in the schizophrenia-associated 10q24.32 locus. The Atp5md knockout (KO) in mice was associated with abnormal startle reflex and gait, and ATP5MD knockdown (KD) in human induced pluripotent stem cell-derived neurons disrupted the neural development and mitochondrial respiration and ATP production. Moreover, CNNM2-rs1926032 KO could induce downregulation of ATP5MD expression and disruptions of mitochondrial respiration and ATP production. This study constitutes an important mechanistic component that links schizophrenia-associated CNNM2 regions to disruption in energy adenosine system modulation and neuronal function by long-distance chromatin domain downregulation of ATP5MD. This pathogenic mechanism provides therapeutic implications for schizophrenia.
Antibody avidity, persistence, and response to antigen recall: comparison of vaccine adjuvants
Authors: Budroni Sonia , Buricchi Francesca , Cavallone Andrea , Bourguignon Patricia , Caubet Magalie , Dewar Vincent , D’Oro Ugo , Finco Oretta , Garçon Nathalie , El Idrissi Mohamed , Janssens Michel , Leroux-Roels Geert , Marchant Arnaud , Schwarz Tino , Van Damme Pierre , Volpini Gianfranco , van der Most Robbert , Didierlaurent Arnaud M. , Burny Wivine
Published: May 2021

Differences in innate immune ‘imprinting’ between vaccine adjuvants may mediate dissimilar effects on the quantity/quality of persisting adaptive responses. We compared antibody avidity maturation, antibody/memory B cell/CD4+ T cell response durability, and recall responses to non-adjuvanted fractional-dose antigen administered 1-year post-immunization (Day [D]360), between hepatitis B vaccines containing Adjuvant System (AS)01B, AS01E, AS03, AS04, or Alum (NCT00805389). Both the antibody and B cell levels ranked similarly (AS01B/E/AS03 > AS04 > Alum) at peak response, at D360, and following their increases post-antigen recall (D390). Proportions of high-avidity antibodies increased post-dose 2 across all groups and persisted at D360, but avidity maturation appeared to be more strongly promoted by AS vs. Alum. Post-antigen recall, frequencies of subjects with high-avidity antibodies increased only markedly in the AS groups. Among the AS, total antibody responses were lowest for AS04. However, proportions of high-avidity antibodies were similar between groups, suggesting that MPL in AS04 contributes to avidity maturation. Specific combinations of immunoenhancers in the AS, regardless of their individual nature, increase antibody persistence and avidity maturation.
A hydraulic instability drives the cell death decision in the nematode germline
Authors: Chartier Nicolas T. , Mukherjee Arghyadip , Pfanzelter Julia , Fürthauer Sebastian , Larson Ben T. , Fritsch Anatol W. , Amini Rana , Kreysing Moritz , Jülicher Frank , Grill Stephan W.
Published: May 2021

Oocytes are large cells that develop into an embryo upon fertilization1. As interconnected germ cells mature into oocytes, some of them grow—typically at the expense of others that undergo cell death2–4. We present evidence that in the nematode Caenorhabditis elegans, this cell-fate decision is mechanical and related to tissue hydraulics. An analysis of germ cell volumes and material fluxes identifies a hydraulic instability that amplifies volume differences and causes some germ cells to grow and others to shrink, a phenomenon that is related to the two-balloon instability5. Shrinking germ cells are extruded and they die, as we demonstrate by artificially reducing germ cell volumes via thermoviscous pumping6. Our work reveals a hydraulic symmetry-breaking transition central to the decision between life and death in the nematode germline.
Spectroscopic and deep learning-based approaches to identify and quantify cerebral microhemorrhages
Authors: Crouzet Christian , Jeong Gwangjin , Chae Rachel H. , LoPresti Krystal T. , Dunn Cody E. , Xie Danny F. , Agu Chiagoziem , Fang Chuo , Nunes Ane C. F. , Lau Wei Ling , Kim Sehwan , Cribbs David H. , Fisher Mark , Choi Bernard
Published: May 2021

Cerebral microhemorrhages (CMHs) are associated with cerebrovascular disease, cognitive impairment, and normal aging. One method to study CMHs is to analyze histological sections (5–40 μm) stained with Prussian blue. Currently, users manually and subjectively identify and quantify Prussian blue-stained regions of interest, which is prone to inter-individual variability and can lead to significant delays in data analysis. To improve this labor-intensive process, we developed and compared three digital pathology approaches to identify and quantify CMHs from Prussian blue-stained brain sections: (1) ratiometric analysis of RGB pixel values, (2) phasor analysis of RGB images, and (3) deep learning using a mask region-based convolutional neural network. We applied these approaches to a preclinical mouse model of inflammation-induced CMHs. One-hundred CMHs were imaged using a 20 × objective and RGB color camera. To determine the ground truth, four users independently annotated Prussian blue-labeled CMHs. The deep learning and ratiometric approaches performed better than the phasor analysis approach compared to the ground truth. The deep learning approach had the most precision of the three methods. The ratiometric approach has the most versatility and maintained accuracy, albeit with less precision. Our data suggest that implementing these methods to analyze CMH images can drastically increase the processing speed while maintaining precision and accuracy.
Glucose and NAADP trigger elementary intracellular β-cell Ca2+ signals
Authors: Heister Paula Maria , Powell Trevor , Galione Antony
Published: May 2021

Pancreatic β-cells release insulin upon a rise in blood glucose. The precise mechanisms of stimulus-secretion coupling, and its failure in Diabetes Mellitus Type 2, remain to be elucidated. The consensus model, as well as a class of currently prescribed anti-diabetic drugs, are based around the observation that glucose-evoked ATP production in β-cells leads to closure of cell membrane ATP-gated potassium (KATP) channels, plasma membrane depolarisation, Ca2+ influx, and finally the exocytosis of insulin granules. However, it has been demonstrated by the inactivation of this pathway using genetic and pharmacological means that closure of the KATP channel alone may not be sufficient to explain all β-cell responses to glucose elevation. We have previously proposed that NAADP-evoked Ca2+ release is an important step in stimulus-secretion coupling in pancreatic β-cells. Here we show using total internal reflection fluorescence (TIRF) microscopy that glucose as well as the Ca2+ mobilising messenger nicotinic acid adenine dinucleotide phosphate (NAADP), known to operate in β-cells, lead to highly localised elementary intracellular Ca2+ signals. These were found to be obscured by measurements of global Ca2+ signals and the action of powerful SERCA-based sequestration mechanisms at the endoplasmic reticulum (ER). Building on our previous work demonstrating that NAADP-evoked Ca2+ release is an important step in stimulus-secretion coupling in pancreatic β-cells, we provide here the first demonstration of elementary Ca2+ signals in response to NAADP, whose occurrence was previously suspected. Optical quantal analysis of these events reveals a unitary event amplitude equivalent to that of known elementary Ca2+ signalling events, inositol trisphosphate (IP3) receptor mediated blips, and ryanodine receptor mediated quarks. We propose that a mechanism based on these highly localised intracellular Ca2+ signalling events mediated by NAADP may initially operate in β-cells when they respond to elevations in blood glucose.
Indications, feasibility and outcome of robotic retroperitoneal lymph node dissection for metastatic testicular germ cell tumours
Authors: Ohlmann Carsten-Henning , Saar Matthias , Pierchalla Laura-Christin , Zangana Miran , Bonaventura Alena , Stöckle Michael , Siemer Stefan , Heinzelbecker Julia
Published: May 2021

Data on robotic retroperitoneal lymph node dissection (R-RPLND) for metastatic testicular germ cell tumours (mTGCTs) are scarce and the use of R-RPLND itself is still under debate. The aim of our study was to evaluate the indications, feasibility and outcomes of R-RPLND, with special emphasis on differences between primary R-RPLND (pR-RPLND) and post-chemotherapeutic R-RPLND (pcR-RPLND) in mTGCTs. We retrospectively analysed the data of patients who underwent R-RPLND for mTGCT between November 2013 and September 2019 in two centres in Germany. Indications, operative technique, intra- and postoperative complications and oncologic outcome were analysed. Twenty-three mTGCT patients underwent R-RPLND (7 pR-RPLND, 16 pcR-RPLND). For pR-RPLND versus pcR-RPLND, median time of surgery was 243 min [interquartile range (IQR) 123–303] versus 359 min (IQR 202–440, p = 0.154) and median blood loss 100 mL (IQR 50–200) versus 275 mL (IQR 100–775, p = 0.018). Intra- and postoperative complications were more frequent in pcR-RPLND (pcR-RPLND: intra/post: 44%/44%; pR-RPLND: intra/post: 0%/29%). However, these were only statistically significant in the case of intraoperative complications (intra: p = 0.036, post: p = 0.579). Intraoperative complications (n = 7), conversions (n = 4) and transfusions (n = 4) occurred in pcR-RPLND patients only. After a median follow-up of 16.3 months (IQR 7.5–35.0) there were no recurrences or deaths. R-RPLND displays a valuable, minimally invasive treatment option in mTGCT. However, R-RPLND is challenging and pcR-RPLND especially bears a considerable risk of complications. This operation should be limited to patients with an easily accessible residual tumour mass and to surgeons experienced in robotic surgery and TGCT treatment.
PapRIV, a BV-2 microglial cell activating quorum sensing peptide
Authors: Janssens Yorick , Debunne Nathan , De Spiegeleer Anton , Wynendaele Evelien , Planas Marta , Feliu Lidia , Quarta Alessandra , Claes Christel , Van Dam Debby , De Deyn Peter Paul , Ponsaerts Peter , Blurton-Jones Matthew , De Spiegeleer Bart
Published: May 2021

Quorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.
Anapole-assisted giant electric field enhancement for surface-enhanced coherent anti-Stokes Raman spectroscopy
Authors: Ghahremani Maryam , Habil Mojtaba Karimi , Zapata-Rodriguez Carlos J.
Published: May 2021

The coherent anti-Stokes Raman spectroscopy (CARS) techniques are recognized for their ability to detect and identify vibrational coherent processes down to the single-molecular levels. Plasmonic oligomers supporting full-range Fano-like line profiles in their scattering spectrum are one of the most promising class of substrates in the context of surface-enhanced (SE) CARS application. In this work, an engineered assembly of metallic disk-shaped nanoparticles providing two Fano-like resonance modes is presented as a highly-efficient design of SECARS substrate. We show that the scattering dips corresponding to the double-Fano spectral line shapes are originated from the mutual interaction of electric and toroidal dipole moments, leading to the so-called non-trivial first- and second-order anapole states. The anapole modes, especially the higher-order ones, can result in huge near-field enhancement due to their light-trapping capability into the so-called “hot spots”. In addition, independent spectral tunability of the second Fano line shape is exhibited by modulating the gap distance of the corner particles. This feature is closely related to the electric current loop associated with the corner particles in the second-order anapole state and provides a simple design procedure of an optimum SECARS substrate, where the electric field hot spots corresponding to three involved wavelengths, i.e., anti-Stokes, pump, and Stokes, are localized at the same spatial position. These findings yield valuable insight into the plasmonic substrate design for SECARS applications as well as for other nonlinear optical processes, such as four-wave mixing and multi-photon surface spectroscopy.
Comparison of cine and real-time cardiac MRI in rhesus macaques
Authors: Moussavi Amir , Mißbach Sophie , Serrano Ferrel Claudia , Ghasemipour Hasti , Kötz Kristin , Drummer Charis , Behr Rüdiger , Zimmermann Wolfram-Hubertus , Boretius Susann
Published: May 2021

Cardiac MRI in rhesus macaques, a species of major relevance for preclinical studies on biological therapies, requires artificial ventilation to realize breath holding. To overcome this limitation of standard cine MRI, the feasibility of Real-Time (RT) cardiac MRI has been tested in a cohort of ten adult rhesus macaques using a clinical MR-system. In spite of lower tissue contrast and sharpness of RT-MRI, cardiac functions were similarly well assessed by RT-MRI compared to cine MRI (similar intra-subject repeatability). However, systematic underestimation of the end-diastolic volume (31 ± 9%), end-systolic volume (20 ± 11%), stroke volume (40 ± 12%) and ejection fraction (13 ± 9%) hamper the comparability of RT-MRI results with those of other cardiac MRI methods. Yet, the underestimations were very consistent (< 5% variability) for repetitive measurements, making RT-MRI an appropriate alternative to cine MRI for longitudinal studies. In addition, RT-MRI enabled the analysis of cardio-respiratory coupling. All functional parameters showed lower values during expiration compared to inspiration, most likely due to the pressure-controlled artificial ventilation. In conclusion, despite systematic underestimation of the functional parameters, RT-MRI allowed the assessment of left ventricular function in macaques with significantly less experimental effort, measurement time, risk and burden for the animals compared to cine MRI.
CoolMomentum: a method for stochastic optimization by Langevin dynamics with simulated annealing
Authors: Borysenko Oleksandr , Byshkin Maksym
Published: May 2021

Deep learning applications require global optimization of non-convex objective functions, which have multiple local minima. The same problem is often found in physical simulations and may be resolved by the methods of Langevin dynamics with Simulated Annealing, which is a well-established approach for minimization of many-particle potentials. This analogy provides useful insights for non-convex stochastic optimization in machine learning. Here we find that integration of the discretized Langevin equation gives a coordinate updating rule equivalent to the famous Momentum optimization algorithm. As a main result, we show that a gradual decrease of the momentum coefficient from the initial value close to unity until zero is equivalent to application of Simulated Annealing or slow cooling, in physical terms. Making use of this novel approach, we propose CoolMomentum—a new stochastic optimization method. Applying Coolmomentum to optimization of Resnet-20 on Cifar-10 dataset and Efficientnet-B0 on Imagenet, we demonstrate that it is able to achieve high accuracies.
Infection with Borrelia afzelii and manipulation of the egg surface microbiota have no effect on the fitness of immature Ixodes ricinus ticks
Authors: Hurry Georgia , Maluenda Elodie , Sarr Anouk , Belli Alessandro , Hamilton Phineas T. , Duron Olivier , Plantard Olivier , Voordouw Maarten J.
Published: May 2021

Arthropod vectors carry vector-borne pathogens that cause infectious disease in vertebrate hosts, and arthropod-associated microbiota, which consists of non-pathogenic microorganisms. Vector-borne pathogens and the microbiota can both influence the fitness of their arthropod vectors, and hence the epidemiology of vector-borne diseases. The bacterium Borrelia afzelii, which causes Lyme borreliosis in Europe, is transmitted among vertebrate reservoir hosts by Ixodes ricinus ticks, which also harbour a diverse microbiota of non-pathogenic bacteria. The purpose of this controlled study was to test whether B. afzelii and the tick-associated microbiota influence the fitness of I. ricinus. Eggs obtained from field-collected adult female ticks were surface sterilized (with bleach and ethanol), which reduced the abundance of the bacterial microbiota in the hatched I. ricinus larvae by 28-fold compared to larvae that hatched from control eggs washed with water. The dysbiosed and control larvae were subsequently fed on B. afzelii-infected or uninfected control mice, and the engorged larvae were left to moult into nymphs under laboratory conditions. I. ricinus larvae that fed on B. afzelii-infected mice had a significantly faster larva-to-nymph moulting time compared to larvae that fed on uninfected control mice, but the effect was small (2.4% reduction) and unlikely to be biologically significant. We found no evidence that B. afzelii infection or reduction of the larval microbiota influenced the four other life history traits of the immature I. ricinus ticks, which included engorged larval weight, unfed nymphal weight, larva-to-nymph moulting success, and immature tick survival. A retrospective power analysis found that our sampling effort had sufficient power (> 80%) to detect small effects (differences of 5% to 10%) of our treatments. Under the environmental conditions of this study, we conclude that B. afzelii and the egg surface microbiota had no meaningful effects on tick fitness and hence on the R0 of Lyme borreliosis.
Withaferin A inhibits lymphocyte proliferation, dendritic cell maturation in vitro and prolongs islet allograft survival
Authors: Kumano Kenjiro , Kanak Mazhar A. , Saravanan Prathab Balaji , Blanck J. P. , Liu Yang , Vasu Srividya , Lawrence Michael , Naziruddin Bashoo
Published: May 2021

The immunosuppressive regimen for clinical allogeneic islet transplantation uses beta cell–toxic compounds such as tacrolimus that cause islet graft loss. Previously we reported that the plant-derived steroidal lactone Withaferin A (WA) can protect islet grafts by inhibiting nuclear factor-kappa B (NF-κB). Since the NF-κB signaling pathway is essential for T-cell activation, we hypothesized that long-term WA administration may also provide an immunosuppressive effect. Treatment of BALB/c donor islets and C57BL/6N recipients with WA alone resulted in 80% islet graft long-term survival vs. 40% in low-dose FK506-treated mice. In vitro, WA significantly blocked mouse and human T-cell proliferation by CD3/CD28 bead stimulation and in mixed lymphocyte reaction assay. Treatment of immature dendritic cells with WA prevented their maturation in response to inflammatory stimuli, as seen by decreased expression of CD83 and human leukocyte antigen–DR isotype. Exosomes released by islets treated with WA contained significantly fewer proinflammatory molecules interleukin-6, interleukin-8, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, inducible nitric oxide synthase, and cyclooxygenase-2. In conclusion, WA treatment not only reduced inflammation but also prolonged allograft survival, possibly through suppression of dendritic cell maturation and T-cell proliferation. WA has the potential to inhibit both the innate and adaptive immune response to prolong allograft survival.
Antimicrobial responses of peripheral and central nervous system glia against Staphylococcus aureus
Authors: Choudhury Indra N. , Chacko Anu , Delbaz Ali , Chen Mo , Basu Souptik , St John James A. , Huygens Flavia , Ekberg Jenny A. K.
Published: May 2021

Staphylococcus aureusinfections of the central nervous system are serious and can be fatal.S. aureusis commonly present in the nasal cavity, and after injury to the nasal epithelium it can rapidly invade the brain via the olfactory nerve. The trigeminal nerve constitutes another potential route of brain infection. The glia of these nerves, olfactory ensheathing cells (OECs) and trigeminal nerve Schwann cells (TgSCs), as well as astrocytes populating the glia limitans layer, can phagocytose bacteria. Whilst some glial responses toS. aureushave been studied, the specific responses of different glial types are unknown. Here, we compared how primary mouse OECs, TgSCs, astrocytes and microglia responded toS. aureus. All glial types internalized the bacteria within phagolysosomes, andS. aureus-conjugated BioParticles could be tracked with subtle but significant differences in time-course of phagocytosis between glial types. Live bacteria could be isolated from all glia after 24 h in culture, and microglia, OECs and TgSCs exhibited better protection against intracellularS. aureussurvival than astrocytes. All glial types responded to the bacteria by cytokine secretion. Overall, OECs secreted the lowest level of cytokines, suggesting that these cells, despite showing strong capacity for phagocytosis, have immunomodulatory functions that can be relevant for neural repair.
Author Correction: Macular retinal thickness differs markedly in age-related macular degeneration driven by risk polymorphisms on chromosomes 1 and 10
Authors: Zouache Moussa A. , Bennion Alex , Hageman Jill L. , Pappas Christian , Richards Burt T. , Hageman Gregory S.
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Comparing machine learning algorithms for predicting ICU admission and mortality in COVID-19
Authors: Subudhi Sonu , Verma Ashish , Patel Ankit B. , Hardin C. Corey , Khandekar Melin J. , Lee Hang , McEvoy Dustin , Stylianopoulos Triantafyllos , Munn Lance L. , Dutta Sayon , Jain Rakesh K.
Published: May 2021

As predicting the trajectory of COVID-19 is challenging, machine learning models could assist physicians in identifying high-risk individuals. This study compares the performance of 18 machine learning algorithms for predicting ICU admission and mortality among COVID-19 patients. Using COVID-19 patient data from the Mass General Brigham (MGB) Healthcare database, we developed and internally validated models using patients presenting to the Emergency Department (ED) between March-April 2020 (n = 3597) and further validated them using temporally distinct individuals who presented to the ED between May-August 2020 (n = 1711). We show that ensemble-based models perform better than other model types at predicting both 5-day ICU admission and 28-day mortality from COVID-19. CRP, LDH, and O2 saturation were important for ICU admission models whereas eGFR <60 ml/min/1.73 m2, and neutrophil and lymphocyte percentages were the most important variables for predicting mortality. Implementing such models could help in clinical decision-making for future infectious disease outbreaks including COVID-19.
Cryptic developmental events determine medulloblastoma radiosensitivity and cellular heterogeneity without altering transcriptomic profile
Authors: Malawsky Daniel Shiloh , Weir Seth J. , Ocasio Jennifer Karin , Babcock Benjamin , Dismuke Taylor , Cleveland Abigail H. , Donson Andrew M. , Vibhakar Rajeev , Wilhelmsen Kirk , Gershon Timothy R.
Published: May 2021

It is unclear why medulloblastoma patients receiving similar treatments experience different outcomes. Transcriptomic profiling identified subgroups with different prognoses, but in each subgroup, individuals remain at risk of incurable recurrence. To investigate why similar-appearing tumors produce variable outcomes, we analyzed medulloblastomas triggered in transgenic mice by a common driver mutation expressed at different points in brain development. We genetically engineered mice to express oncogenic SmoM2, starting in multipotent glio-neuronal stem cells, or committed neural progenitors. Both groups developed medulloblastomas with similar transcriptomic profiles. We compared medulloblastoma progression, radiosensitivity, and cellular heterogeneity, determined by single-cell transcriptomic analysis (scRNA-seq). Stem cell-triggered medulloblastomas progressed faster, contained more OLIG2-expressing stem-like cells, and consistently showed radioresistance. In contrast, progenitor-triggered MBs progressed slower, down-regulated stem-like cells and were curable with radiation. Progenitor-triggered medulloblastomas also contained more diverse stromal populations, with more Ccr2+ macrophages and fewer Igf1+ microglia, indicating that developmental events affected the subsequent tumor microenvironment. Reduced mTORC1 activity in M-Smo tumors suggests that differential Igf1 contributed to differences in phenotype. Developmental events in tumorigenesis that were obscure in transcriptomic profiles thus remained cryptic determinants of tumor composition and outcome. Precise understanding of medulloblastoma pathogenesis and prognosis requires supplementing transcriptomic/methylomic studies with analyses that resolve cellular heterogeneity.
Super-resolution imaging reveals α-synuclein seeded aggregation in SH-SY5Y cells
Authors: Sang Jason C. , Hidari Eric , Meisl Georg , Ranasinghe Rohan T. , Spillantini Maria Grazia , Klenerman David
Published: May 2021

Aggregation of α-synuclein (α-syn) is closely linked to Parkinson’s disease (PD) and the related synucleinopathies. Aggregates spread through the brain during the progression of PD, but the mechanism by which this occurs is still not known. One possibility is a self-propagating, templated-seeding mechanism, but this cannot be established without quantitative information about the efficiencies and rates of the key steps in the cellular process. To address this issue, we imaged the uptake and seeding of unlabeled exogenous α-syn fibrils by SH-SY5Y cells and the resulting secreted aggregates, using super-resolution microscopy. Externally-applied fibrils very inefficiently induced self-assembly of endogenous α-syn in a process accelerated by the proteasome. Seeding resulted in the increased secretion of nanoscopic aggregates (mean 35 nm diameter), of both α-syn and Aβ. Our results suggest that cells respond to seed-induced disruption of protein homeostasis predominantly by secreting nanoscopic aggregates; this mechanism may therefore be an important protective response by cells to protein aggregation.
Effect of different monomer precursors with identical functionality on the properties of the polymer network
Authors: Torres-Knoop Ariana , Schamboeck Verena , Govindarajan Nitish , Iedema Pieter D. , Kryven Ivan
Published: May 2021

The association between thermo-mechanical properties in polymers and functionality of monomer precursors is frequently exploited in the materials science. However, it is not known if there are more variables beyond monomer functionality that have a similar link. Here, by using simulations to generate spatial networks from chemically different monomers with identical functionality we show that such networks have universal graph-theoretical properties as well as a near-universal elastic modulus. The vitrification temperature was found to be universal only up to a certain network density, as measured by the bond conversion. The latter observation is explained by the fact that monomer’s tendency to coil enhances formation of topological holes, which, when accumulated, amount to a percolating cell complex restricting network’s mobility. This higher-order percolation occurs late after gelation and is shown to coincide with the onset of brittleness, as indicated by a sudden increase in the glass transition temperature.
Automated analysis of genomic sequences facilitates high-throughput and comprehensive description of bacteria
Authors: Hitch Thomas C A , Riedel Thomas , Oren Aharon , Overmann Jörg , Lawley Trevor D , Clavel Thomas
Published: May 2021

The study of microbial communities is hampered by the large fraction of still unknown bacteria. However, many of these species have been isolated, yet lack a validly published name or description. The validation of names for novel bacteria requires that the uniqueness of those taxa is demonstrated and their properties are described. The accepted format for this is the protologue, which can be time-consuming to create. Hence, many research fields in microbiology and biotechnology will greatly benefit from new approaches that reduce the workload and harmonise the generation of protologues.

We have developed Protologger, a bioinformatic tool that automatically generates all the necessary readouts for writing a detailed protologue. By producing multiple taxonomic outputs, functional features and ecological analysis using the 16S rRNA gene and genome sequences from a single species, the time needed to gather the information for describing novel taxa is substantially reduced. The usefulness of Protologger was demonstrated by using three published isolate collections to describe 34 novel taxa, encompassing 17 novel species and 17 novel genera, including the automatic generation of ecologically and functionally relevant names. We also highlight the need to utilise multiple taxonomic delineation methods, as while inconsistencies between each method occur, a combined approach provides robust placement. Protologger is open source; all scripts and datasets are available, along with a webserver at www.protologger.de
Seasonal change is a major driver of soil resistomes at a watershed scale
Authors: Xiang Qian , Qiao Min , Zhu Dong , Giles Madeline , Neilson Roy , Yang Xiao-Ru , Zhu Yong-Guan , Chen Qing-Lin
Published: May 2021

Soils harbor the most diverse naturally evolved antibiotic resistomes on Earth that threaten human health, ecosystem processes, and food security. Yet the importance of spatial and temporal variability in shaping the distribution of soil resistomes is not well explored. Here, a total of 319 topsoil samples were collected at a watershed scale during four seasons (spring to winter) and high-throughput quantitative PCR (HT-qPCR) was used to characterize the profiles of soil antibiotic resistance genes (ARGs). A significant and negative correlation was observed between soil ARG profiles and seasonal dissimilarity, which along with seasonally dependent distance-decay relationships highlight the importance of seasonal variability in shaping soil antibiotic resistomes. Significant, though weak, distance-decay relationships were identified in spring, summer and winter, for ARG similarities with geographic distances. There were also strong interactions between specific soil ARGs and Actinobacteria, Firmicutes and Proteobacteria. Moreover, we found that the relative abundance of soil Actinobacteria, Firmicutes and Proteobacteria correlated significantly with annual mean temperature and annual mean precipitation at a watershed scale. A random forest model showed that seasonal change rather than spatial variation was the most important predictor of the composition of soil ARGs. Together, these results constitute an advance in our understanding of the relative importance of spatial and temporal variability in shaping soil ARG profiles, which will provide novel insights allowing us to forecast their distribution under a changing environment.
Comment on “FeS colloids – formation and mobilization pathways in natural waters” by Noël et al., Environ. Sci. Nano, 2020, 7, 2102–2116
Authors: Peiffer Stefan
Published: May 2021

Unraveling the products of sulfidation of ferric (oxyhydr)oxides is of paramount importance for the understanding of key biogeochemical processes such as cryptic sulfur cycling or rapid formation of pyrite.
Germinated millet flour (Pennisetum glaucum(L.) R. BR.) improves adipogenesis and glucose metabolism and maintains thyroid functionin vivo
Authors: Theodoro Jaqueline Maciel Vieira , Martinez Oscar David Medina , Grancieri Mariana , Toledo Renata Celi Lopes , Binoti Mirella Lima , Martins Amanda M. Dias , Carvalho Carlos Wanderlei Piler , Lisboa Patrícia Cristina , Martino Hércia Stampini Duarte
Published: May 2021

The germinated millet flour reduced the gluconeogenesis, hyperinsulinemia, and adiposity, without interfering with the thyroid hormones, in rats fed with a high-fructose diet.
Evaluating the effect of ionic strength on PNA:DNA duplex formation kinetics
Authors: Swenson Colin S. , Lackey Hershel H. , Reece Eric J. , Harris Joel M. , Heemstra Jennifer M. , Peterson Eric M.
Published: May 2021

Single-molecule fluorescence imaging detects distinct hybridization events to determine rates of association and dissociation.
A new method for detecting intramolecular H-bonds of aromatic amides based on the de-shielding effect of carbonyl groups on β-protons
Authors: Min Jing , Wang Chunyu , Wang Liyan
Published: May 2021

We develop a Δ(δβH) method to detect intramolecular hydrogen bonds in aromatic amide compounds, which is based on the fact that the de-shielding effect of carbonyl groups on β-hydrogen is enhanced due to the restricted intramolecular rotation.
Exploiting oxidative coupling of methane performed over La2(Ce1−xMgx)2O7−δ catalysts with disordered defective cubic fluorite structure
Authors: Petrolini Davi D. , Marcos Francielle F. C. , Lucrédio Alessandra F. , Mastelaro Valmor R. , Assaf José M. , Assaf Elisabete M.
Published: May 2021

The oxidative coupling of methane reaction to produce C2 compounds was studied using La2(Ce1−xMgx)2O7−δ catalysts with disordered defective cubic fluorite structures, varying the Mg content (0.0 ≤ x ≤ 1.0), CH4/O2 ratio, temperature, and WHSV.
Electronic and magnetic states of Fe ions in Co2FeBO5
Authors: Knyazev Yurii V. , Kazak Natalia V. , Zhandun Vyacheslav S. , Bartolomé Juan , Arauzo Ana , Belskaya Nadejda A. , Bayukov Oleg A. , Bezmaternykh Leonard N. , Ovchinnikov Sergey G.
Published: May 2021

The ferrimagnet Co2FeBO5 has been studied experimentally using 57Fe Mössbauer spectroscopy and theoretically using DFT + GGA calculations.
Dual sensing of methionine and aspartic acid in aqueous medium by a quinoline-based fluorescent probe
Authors: Elamathi C. , Butcher R. J. , Mohankumar A. , Sundararaj P. , Elango K. P. , Kalaivani P. , Prabhakaran R.
Published: May 2021

A quinoline-based Schiff base sensor (6MPS) has been developed for the selective sensing of methionine and aspartic acid in aqueous medium in both in vitro and in vivo live cells through “on–off–on” type selective detection of copper ion.
Distribution of engineered Ag nanoparticles in the aquatic-terrestrial transition zone: a long-term indoor floodplain mesocosm study
Authors: Metreveli George , Kurtz Sandra , Rosenfeldt Ricki R. , Seitz Frank , Kumahor Samuel K. , Grün Alexandra , Klitzke Sondra , Vogel Hans-Jörg , Bundschuh Mirco , Baumann Thomas , Schulz Ralf , Manz Werner , Lang Friederike , Schaumann Gabriele E.
Published: May 2021

The major mechanisms controlling the fate of citrate-coated silver nanoparticles in the aquatic-terrestrial transition zone determined in a mesocosm study are aggregation, sedimentation, and enrichment in/on biota.
Effects of cranberry beverages on oxidative stress and gut microbiota in subjects with Helicobacter pylori infection: a randomized, double-blind, placebo-controlled trial
Authors: Gao Tao , Hou Meiling , Zhang Bo , Pan Xin , Liu Chengxia , Sun Chongxiu , Jia Mengru , Lin Song , Xiong Ke , Ma Aiguo
Published: May 2021

The current randomized double-blind placebo-controlled trial showed that cranberry beverages significantly improved the antioxidant status in Helicobacter pylori positive subjects, which may be related to the reshaping of the gut microbiota.
Amelioration of high-fat diet-induced obesity and its associated complications by a myricetin derivative-rich fraction from Syzygium malaccense in C57BL/6J mice
Authors: Nallappan Devi , Chua Kek Heng , Ong Kien Chai , Chong Chun Wie , Teh Cindy Shuan Ju , Palanisamy Uma Devi , Kuppusamy Umah Rani
Published: May 2021

S. malaccense myricetin derivatives reverse high-fat diet-induced obesity-associated metabolic complications by upregulating UCP-1 and increasing the abundance of gut Akkermansia.
Nanoprobe-mediated precise imaging and therapy of glioma
Authors: Tang Tao , Chang Baisong , Zhang Mingxi , Sun Taolei
Published: May 2021

After rational component regulation and surface modification, functional nanoprobes could efficiently cross the blood–brain barrier and target gliomas to realize precise imaging, drug delivery or therapy for gliomas.
Constructing cationic covalent organic frameworks by a post-function process for an exceptional iodine capture via electrostatic interactions
Authors: Zhai Lipeng , Sun Shuzhuan , Chen Pengjing , Zhang Yuwei , Sun Qikun , Xu Qing , Wu Yujie , Nie Riming , Li Zhongping , Mi Liwei
Published: May 2021

Cationic covalent organic frameworks are obtained via post-functionalization and compared to the neutral COFs, the I2 uptake capacities are improved by 1.3 times due to the electrostatic interactions between COFs’ networks and I2 molecules.
Touch-sensitive yellow organic mechanophosphorescence and a versatile strategy for white organic mechanoluminescence
Authors: Yue Lingtai , Wang Yaguang , Ma Jie , Yuan Shou , Xue Shanfeng , Sun Qikun , Yang Wenjun
Published: May 2021

Touch-sensitive bright yellow mechanophosphorescent organic crystal is obtained, which enables tunable dual emitting and even white mechanoluminescence by co-crystallization with blue mechanofluorescent crystals.
Synthesis and biological evaluation of novel artemisone–piperazine–tetronamide hybrids
Authors: Wei Meng-Xue , Yu Jia-Ying , Liu Xin-Xin , Li Xue-Qiang , Yang Jin-Hui , Zhang Meng-Wei , Yang Pei-Wen , Zhang Si-Si , He Yu
Published: May 2021

Six novel artemisone–piperazine–tetronamide hybrids were efficiently synthesised and investigated for their cytotoxicity against some human cancer cells.
Magnetic-gold theranostic nanoagent used for targeting quad modalities T1 & T2-MRI/CT/PA imaging and photothermal therapy of tumours
Authors: Liu Jinlei , Wang Dan , Wang Guannan
Published: May 2021

The schematic diagram of the biofunctionalized magneto-gold nanoparticles as theranostic nanoagents for T1 & T2-MRI/CT/PAI quad modalities imaging and PTT therapy of tumours.
Folding and fluorescence enhancement with strong odd–even effect for a series of merocyanine dye oligomers
Authors: Hu Xiaobo , Schulz Alexander , Lindner Joachim O. , Grüne Matthias , Bialas David , Würthner Frank
Published: May 2021

A series of merocyanine (MC) oligomers with a varying number of chromophores from two to six has been synthesizedviaa peptide synthesis strategy.
Understanding multi-scale battery degradation with a macro-to-nano zoom through its hierarchy
Authors: Zan Guibin , Zhang Jin , Monaco Federico , Gul Sheraz , Qian Guannan , Li Jizhou , Vine David J. , Cloetens Peter , Yun Wenbing , Pianetta Piero , Liu Yijin
Published: May 2021

Lithium-ion batteries (LIBs) feature structural and chemical complexities across a broad range of length scales.
Synthetic gamma-ray light curves of Kerr black hole magnetospheric activity from particle-in-cell simulations
Authors: Crinquand B. , Cerutti B. , Dubus G. , Parfrey K. , Philippov A.
Published: May 2021

Context. The origin of ultra-rapid flares of very high-energy radiation from active galactic nuclei remains elusive. Magnetospheric processes, occurring in the close vicinity of the central black hole, could account for these flares.

Aims. Our aim is to bridge the gap between simulations and observations by synthesizing gamma-ray light curves in order to characterize the activity of a black hole magnetosphere, using kinetic simulations.

Methods. We performed global axisymmetric 2D general-relativistic particle-in-cell simulations of a Kerr black hole magnetosphere. We included a self-consistent treatment of radiative processes and plasma supply, as well as a realistic magnetic configuration, with a large-scale equatorial current sheet. We coupled our particle-in-cell code with a ray-tracing algorithm in order to produce synthetic light curves.

Results. These simulations show a highly dynamic magnetosphere, as well as very efficient dissipation of the magnetic energy. An external supply of magnetic flux is found to maintain the magnetosphere in a dynamic state, otherwise the magnetosphere settles in a quasi-steady Wald-like configuration. The dissipated energy is mostly converted to gamma-ray photons. The light curves at low viewing angle (face-on) mainly trace the spark gap activity and exhibit high variability. On the other hand, no significant variability is found at high viewing angle (edge-on), where the main contribution comes from the reconnecting current sheet.

Conclusions. We observe that black hole magnetospheres with a current sheet are characterized by a very high radiative efficiency. The typical amplitude of the flares in our simulations is lower than is detected in active galactic nuclei. These flares could result from the variation in parameters external to the black hole.
Comparison of active region upflow and core properties using simultaneous spectroscopic observations from IRIS and Hinode
Authors: Barczynski Krzysztof , Harra Louise , Kleint Lucia , Panos Brandon , Brooks David H.
Published: May 2021

Context. The origin of the slow solar wind is still an open issue. It has been suggested that upflows at the edge of active regions are a possible source of the plasma outflow and therefore contribute to the slow solar wind.

Aims. We investigate the origin and morphology of the upflow regions and compare the upflow region and the active region core properties.

Methods. We studied how the plasma properties of flux, Doppler velocity, and non-thermal velocity change throughout the solar atmosphere, from the chromosphere via the transition region to the corona in the upflow region and the core of an active region. We studied limb-to-limb observations of the active region (NOAA 12687) obtained from 14 to 25 November 2017. We analysed spectroscopic data simultaneously obtained from IRIS and Hinode/EIS in the six emission lines Mg II 2796.4Å, C II 1335.71Å, Si IV 1393.76Å, Fe XII 195.12Å, Fe XIII 202.04Å, and Fe XIV 270.52Å and 274.20Å. We studied the mutual relationships between the plasma properties for each emission line, and we compared the plasma properties between the neighbouring formation temperature lines. To find the most characteristic spectra, we classified the spectra in each wavelength using the machine learning technique k-means.

Results. We find that in the upflow region the Doppler velocities of the coronal lines are strongly correlated, but the transition region and coronal lines show no correlation. However, their fluxes are strongly correlated. The upflow region has a lower density and lower temperature than the active region core. In the upflow region, the Doppler velocity and non-thermal velocity show a strong correlation in the coronal lines, but the correlation is not seen in the active region core. At the boundary between the upflow region and the active region core, the upflow region shows an increase in the coronal non-thermal velocity, the emission obtained from the DEM, and the domination of the redshifted regions in the chromosphere.

Conclusions. The obtained results suggest that at least three parallel mechanisms generate the plasma upflow: (1) The reconnection between closed loops and open magnetic field lines in the lower corona or upper chromosphere; (2) the reconnection between the chromospheric small-scale loops and open magnetic field; and (3) the expansion of the magnetic field lines that allows the chromospheric plasma to escape to the solar corona.
Biological activity of benzoxazolinone and benzoxazolinthione derivatives
Authors: Giyasov K , Turaeva G. S. , Turaeva H T
Published: May 2021

The article presents the herbicidal, defoliating, fungicidal properties of the synthesized derivatives of benzoxazolinones and benzoxazolinethions. It was shown that 3-alkylbenzoxazolinones, 3-alkyl-6-halobenzoxazolinones and 2-alkylthiobenzoxazoles exhibit herbicidal action during the growing season of plants, and they also cause cotton leaves to drop up to 70%. It was found that 3-alkylbenzoxazolinones and 2-alkylthiobenzoxazoles exhibited fungicidal activity against the pathogen, Fugarium oxyporum and Verticillum dahlia. Among them, 2-methylthiobenzoxazole inhibited spores of the fungi Verticillum dahlia by 96.4% and benzoxazolyl-2-carbamic acid butyl ester by 65%. These compounds exhibit fungicidal action against the pathogens of powdery mildew on cucumbers - Erysiphe cichoraceorum and powdery mildew on wheat - Erysiphe graminis, approaching the control Karatan. Apparently, these compounds are chemicals of contact action.
Types and quantities of weeds found in corn fields and the effect of herbicides on grain yield
Authors: Turdiyeva Nilufar , Umarova Zulaykho , Sayfullaeva Nazokat , Togaeva Dilnura , Bahodirova Shakrizoda
Published: May 2021

Agrotechnical measures and crop rotation also do not ensure complete eradication of weeds. Therefore, it is necessary to use herbicides. Mapping by type and quantity of weeds grown among agricultural crops should be carried out in all crop rotation fields and herbicides should be applied on this basis, i.e. it is important to choose one or another herbicide based on the study of the composition and amount of weeds grown in fields. In the cultivation of corn in Uzbekistan, first of all, it should be aimed at obtaining high yields from its grain. To do this, it is necessary to use all available agro-technical measures. In modern intensive farming, weed control, which is common among agricultural crops, is a key measure.