bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and dynamic mechanisms of CBF3-guided centromeric nucleosome formation
Authors: Guan Ruifang , Lian Tengfei , Zhou Bing-Rui , He Emily , Wu Carl , Singleton Martin , Bai Yawen
Published: March 2021

Accurate chromosome segregation relies on the specific centromeric nucleosome–kinetochore interface. In budding yeast, the centromere CBF3 complex guides the deposition of CENP-A, an H3 variant, to form the centromeric nucleosome in a DNA sequence-dependent manner. Here, we determine the structures of the centromeric nucleosome containing the native CEN3 DNA and the CBF3core bound to the canonical nucleosome containing an engineered CEN3 DNA. The centromeric nucleosome core structure contains 115 base pair DNA including a CCG motif. The CBF3core specifically recognizes the nucleosomal CCG motif through the Gal4 domain while allosterically altering the DNA conformation. Cryo-EM, modeling, and mutational studies reveal that the CBF3core forms dynamic interactions with core histones H2B and CENP-A in the CEN3 nucleosome. Our results provide insights into the structure of the budding yeast centromeric nucleosome and the mechanism of its assembly, which have implications for analogous processes of human centromeric nucleosome formation.
Local electronic structure rearrangements and strong anharmonicity in YH3 under pressures up to 180 GPa
Authors: Purans J. , Menushenkov A. P. , Besedin S. P. , Ivanov A. A. , Minkov V. S. , Pudza I. , Kuzmin A. , Klementiev K. V. , Pascarelli S. , Mathon O. , Rosa A. D. , Irifune T. , Eremets M. I.
Published: March 2021

The discovery of superconductivity above 250 K at high pressure in LaH10 and the prediction of overcoming the room temperature threshold for superconductivity in YH10 urge for a better understanding of hydrogen interaction mechanisms with the heavy atom sublattice in metal hydrides under high pressure at the atomic scale. Here we use locally sensitive X-ray absorption fine structure spectroscopy (XAFS) to get insight into the nature of phase transitions and the rearrangements of local electronic and crystal structure in archetypal metal hydride YH3 under pressure up to 180 GPa. The combination of the experimental methods allowed us to implement a multiscale length study of YH3: XAFS (short-range), Raman scattering (medium-range) and XRD (long-range). XANES data evidence a strong effect of hydrogen on the density of 4d yttrium states that increases with pressure and EXAFS data evidence a strong anharmonicity, manifested as yttrium atom vibrations in a double-well potential.
The essential role of PRAK in tumor metastasis and its therapeutic potential
Authors: Wang Yuqing , Wang Wei , Wu Haoming , Zhou Yu , Qin Xiaodan , Wang Yan , Wu Jia , Sun Xiu-Yuan , Yang Yan , Xu Hui , Qian Xiaoping , Pang Xuewen , Li Yan , Zhang Zhiqian , Han Jiahuai , Zhang Yu
Published: March 2021

Metastasis is the leading cause of cancer-related death. Despite the recent advancements in cancer treatment, there is currently no approved therapy for metastasis. The present study reveals a potent and selective activity of PRAK in the regulation of tumor metastasis. While showing no apparent effect on the growth of primary breast cancers or subcutaneously inoculated tumor lines, Prak deficiency abrogates lung metastases in PyMT mice or mice receiving intravenous injection of tumor cells. Consistently, PRAK expression is closely associated with metastatic risk in human cancers. Further analysis indicates that loss of function of PRAK leads to a pronounced inhibition of HIF-1α protein synthesis, possibly due to reduced mTORC1 activities. Notably, pharmacological inactivation of PRAK with a clinically relevant inhibitor recapitulates the anti-metastatic effect of Prak depletion, highlighting the therapeutic potential of targeting PRAK in the control of metastasis.
Harnessing the central dogma for stringent multi-level control of gene expression
Authors: Greco F. Veronica , Pandi Amir , Erb Tobias J. , Grierson Claire S. , Gorochowski Thomas E.
Published: March 2021

Strictly controlled inducible gene expression is crucial when engineering biological systems where even tiny amounts of a protein have a large impact on function or host cell viability. In these cases, leaky protein production must be avoided, but without affecting the achievable range of expression. Here, we demonstrate how the central dogma offers a simple solution to this challenge. By simultaneously regulating transcription and translation, we show how basal expression of an inducible system can be reduced, with little impact on the maximum expression rate. Using this approach, we create several stringent expression systems displaying >1000-fold change in their output after induction and show how multi-level regulation can suppress transcriptional noise and create digital-like switches between ‘on’ and ‘off’ states. These tools will aid those working with toxic genes or requiring precise regulation and propagation of cellular signals, plus illustrate the value of more diverse regulatory designs for synthetic biology.
Deep generative neural network for accurate drug response imputation
Authors: Jia Peilin , Hu Ruifeng , Pei Guangsheng , Dai Yulin , Wang Yin-Ying , Zhao Zhongming
Published: March 2021

Drug response differs substantially in cancer patients due to inter- and intra-tumor heterogeneity. Particularly, transcriptome context, especially tumor microenvironment, has been shown playing a significant role in shaping the actual treatment outcome. In this study, we develop a deep variational autoencoder (VAE) model to compress thousands of genes into latent vectors in a low-dimensional space. We then demonstrate that these encoded vectors could accurately impute drug response, outperform standard signature-gene based approaches, and appropriately control the overfitting problem. We apply rigorous quality assessment and validation, including assessing the impact of cell line lineage, cross-validation, cross-panel evaluation, and application in independent clinical data sets, to warrant the accuracy of the imputed drug response in both cell lines and cancer samples. Specifically, the expression-regulated component (EReX) of the observed drug response achieves high correlation across panels. Using the well-trained models, we impute drug response of The Cancer Genome Atlas data and investigate the features and signatures associated with the imputed drug response, including cell line origins, somatic mutations and tumor mutation burdens, tumor microenvironment, and confounding factors. In summary, our deep learning method and the results are useful for the study of signatures and markers of drug response.
Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner
Authors: Bithi Nazmin , Link Christopher , Henderson Yoko O. , Kim Suzie , Yang Jie , Li Ling , Wang Rui , Willard Belinda , Hine Christopher
Published: March 2021

Hydrogen sulfide (H2S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSnH). Despite the known importance of persulfidation, tissue-specific persulfidome profiles and their associated functions are not well characterized, specifically under conditions and interventions known to modulate H2S production. We hypothesize that dietary restriction (DR), which increases lifespan and can boost H2S production, expands tissue-specific persulfidomes. Here, we find protein persulfidation enriched in liver, kidney, muscle, and brain but decreased in heart of young and aged male mice under two forms of DR, with DR promoting persulfidation in numerous metabolic and aging-related pathways. Mice lacking cystathionine γ-lyase (CGL) have overall decreased tissue protein persulfidation numbers and fail to functionally augment persulfidomes in response to DR, predominantly in kidney, muscle, and brain. Here, we define tissue- and CGL-dependent persulfidomes and how diet transforms their makeup, underscoring the breadth for DR and H2S to impact biological processes and organismal health.
Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1
Authors: Zhang Yalan , Varela Luis , Szigeti-Buck Klara , Williams Adam , Stoiljkovic Milan , Šestan-Peša Matija , Henao-Mejia Jorge , D’Acunzo Pasquale , Levy Efrat , Flavell Richard A. , Horvath Tamas L. , Kaczmarek Leonard K.
Published: March 2021

Mutations in KCNC3, which encodes the Kv3.3 potassium channel, cause degeneration of the cerebellum, but exactly how the activity of an ion channel is linked to the survival of cerebellar neurons is not understood. Here, we report that Kv3.3 channels bind and stimulate Tank Binding Kinase 1 (TBK1), an enzyme that controls trafficking of membrane proteins into multivesicular bodies, and that this stimulation is greatly increased by a disease-causing Kv3.3 mutation. TBK1 activity is required for the binding of Kv3.3 to its auxiliary subunit Hax-1, which prevents channel inactivation with depolarization. Hax-1 is also an anti-apoptotic protein required for survival of cerebellar neurons. Overactivation of TBK1 by the mutant channel leads to the loss of Hax-1 by its accumulation in multivesicular bodies and lysosomes, and also stimulates exosome release from neurons. This process is coupled to activation of caspases and increased cell death. Our studies indicate that Kv3.3 channels are directly coupled to TBK1-dependent biochemical pathways that determine the trafficking of cellular constituents and neuronal survival.
trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo
Authors: Aron Zachary D. , Mehrani Atousa , Hoffer Eric D. , Connolly Kristie L. , Srinivas Pooja , Torhan Matthew C. , Alumasa John N. , Cabrera Mynthia , Hosangadi Divya , Barbor Jay S. , Cardinale Steven C. , Kwasny Steven M. , Morin Lucas R. , Butler Michelle M. , Opperman Timothy J. , Bowlin Terry L. , Jerse Ann , Stagg Scott M. , Dunham Christine M. , Keiler Kenneth C.
Published: March 2021

Bacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.
A computational workflow for the expansion of heterologous biosynthetic pathways to natural product derivatives
Authors: Hafner Jasmin , Payne James , MohammadiPeyhani Homa , Hatzimanikatis Vassily , Smolke Christina
Published: March 2021

Plant natural products (PNPs) and their derivatives are important but underexplored sources of pharmaceutical molecules. To access this untapped potential, the reconstitution of heterologous PNP biosynthesis pathways in engineered microbes provides a valuable starting point to explore and produce novel PNP derivatives. Here, we introduce a computational workflow to systematically screen the biochemical vicinity of a biosynthetic pathway for pharmaceutical compounds that could be produced by derivatizing pathway intermediates. We apply our workflow to the biosynthetic pathway of noscapine, a benzylisoquinoline alkaloid (BIA) with a long history of medicinal use. Our workflow identifies pathways and enzyme candidates for the production of (S)-tetrahydropalmatine, a known analgesic and anxiolytic, and three additional derivatives. We then construct pathways for these compounds in yeast, resulting in platforms for de novo biosynthesis of BIA derivatives and demonstrating the value of cheminformatic tools to predict reactions, pathways, and enzymes in synthetic biology and metabolic engineering.
Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway
Authors: Alicea-Torres Kevin , Sanseviero Emilio , Gui Jun , Chen Jinyun , Veglia Filippo , Yu Qiujin , Donthireddy Laxminarasimha , Kossenkov Andrew , Lin Cindy , Fu Shuyu , Mulligan Charles , Nam Brian , Masters Gregory , Denstman Fred , Bennett Joseph , Hockstein Neil , Rynda-Apple Agnieszka , Nefedova Yulia , Fuchs Serge Y. , Gabrilovich Dmitry I.
Published: March 2021

Myeloid-derived suppressor cells (MDSC) are pathologically activated neutrophils and monocytes with potent immune suppressive activity. These cells play an important role in accelerating tumor progression and undermining the efficacy of anti-cancer therapies. The natural mechanisms limiting MDSC activity are not well understood. Here, we present evidence that type I interferons (IFN1) receptor signaling serves as a universal mechanism that restricts acquisition of suppressive activity by these cells. Downregulation of the IFNAR1 chain of this receptor is found in MDSC from cancer patients and mouse tumor models. The decrease in IFNAR1 depends on the activation of the p38 protein kinase and is required for activation of the immune suppressive phenotype. Whereas deletion of IFNAR1 is not sufficient to convert neutrophils and monocytes to MDSC, genetic stabilization of IFNAR1 in tumor bearing mice undermines suppressive activity of MDSC and has potent antitumor effect. Stabilizing IFNAR1 using inhibitor of p38 combined with the interferon induction therapy elicits a robust anti-tumor effect. Thus, negative regulatory mechanisms of MDSC function can be exploited therapeutically.
Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection
Authors: Wang Zhongfang , Yang Xiaoyun , Zhong Jiaying , Zhou Yumin , Tang Zhiqiang , Zhou Haibo , He Jun , Mei Xinyue , Tang Yonghong , Lin Bijia , Chen Zhenjun , McCluskey James , Yang Ji , Corbett Alexandra J. , Ran Pixin
Published: March 2021

T-cell immunity is important for recovery from COVID-19 and provides heightened immunity for re-infection. However, little is known about the SARS-CoV-2-specific T-cell immunity in virus-exposed individuals. Here we report virus-specific CD4+ and CD8+ T-cell memory in recovered COVID-19 patients and close contacts. We also demonstrate the size and quality of the memory T-cell pool of COVID-19 patients are larger and better than those of close contacts. However, the proliferation capacity, size and quality of T-cell responses in close contacts are readily distinguishable from healthy donors, suggesting close contacts are able to gain T-cell immunity against SARS-CoV-2 despite lacking a detectable infection. Additionally, asymptomatic and symptomatic COVID-19 patients contain similar levels of SARS-CoV-2-specific T-cell memory. Overall, this study demonstrates the versatility and potential of memory T cells from COVID-19 patients and close contacts, which may be important for host protection.
Large carbon sink potential of secondary forests in the Brazilian Amazon to mitigate climate change
Authors: Heinrich Viola H. A. , Dalagnol Ricardo , Cassol Henrique L. G. , Rosan Thais M. , de Almeida Catherine Torres , Silva Junior Celso H. L. , Campanharo Wesley A. , House Joanna I. , Sitch Stephen , Hales Tristram C. , Adami Marcos , Anderson Liana O. , Aragão Luiz E. O. C.
Published: March 2021

Tropical secondary forests sequester carbon up to 20 times faster than old-growth forests. This rate does not capture spatial regrowth patterns due to environmental and disturbance drivers. Here we quantify the influence of such drivers on the rate and spatial patterns of regrowth in the Brazilian Amazon using satellite data. Carbon sequestration rates of young secondary forests (<20 years) in the west are ~60% higher (3.0 ± 1.0 Mg C ha−1 yr−1) compared to those in the east (1.3 ± 0.3 Mg C ha−1 yr−1). Disturbances reduce regrowth rates by 8–55%. The 2017 secondary forest carbon stock, of 294 Tg C, could be 8% higher by avoiding fires and repeated deforestation. Maintaining the 2017 secondary forest area has the potential to accumulate ~19.0 Tg C yr−1 until 2030, contributing ~5.5% to Brazil’s 2030 net emissions reduction target. Implementing legal mechanisms to protect and expand secondary forests whilst supporting old-growth conservation is, therefore, key to realising their potential as a nature-based climate solution.
Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers
Authors: Vaclova Tereza , Grazini Ursula , Ward Lewis , O’Neill Daniel , Markovets Aleksandra , Huang Xiangning , Chmielecki Juliann , Hartmaier Ryan , Thress Kenneth S. , Smith Paul D. , Barrett J. Carl , Downward Julian , de Bruin Elza C.
Published: March 2021

Advanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the size of the EGFR T790M-positive clone impacts response to osimertinib. T790M subclonality, as assessed by a retrospective NGS analysis of 289 baseline plasma ctDNA samples from T790M‐positive advanced NSCLC patients from the AURA3 phase III trial, is associated with shorter progression-free survival (PFS), both in the osimertinib and the chemotherapy-treated patients. Both baseline and longitudinal ctDNA profiling indicate that the T790M subclonal tumours are enriched for PIK3CA alterations, which we demonstrate to confer resistance to osimertinib in vitro that can be partially reversed by PI3K pathway inhibitors. Overall, our results elucidate the impact of tumour heterogeneity on response to osimertinib in advanced stage NSCLC patients and could help define appropriate combination therapies in these patients.
The decrease of intraflagellar transport impairs sensory perception and metabolism in ageing
Authors: Zhang Yincong , Zhang Xiaona , Dai Yumin , Song Mengjiao , Zhou Yifei , Zhou Jun , Yan Xiumin , Shen Yidong
Published: March 2021

Sensory perception and metabolic homeostasis are known to deteriorate with ageing, impairing the health of aged animals, while mechanisms underlying their deterioration remain poorly understood. The potential interplay between the declining sensory perception and the impaired metabolism during ageing is also barely explored. Here, we report that the intraflagellar transport (IFT) in the cilia of sensory neurons is impaired in the aged nematode Caenorhabditis elegans due to a daf-19/RFX-modulated decrease of IFT components. We find that the reduced IFT in sensory cilia thus impairs sensory perception with ageing. Moreover, we demonstrate that whereas the IFT-dependent decrease of sensory perception in aged worms has a mild impact on the insulin/IGF-1 signalling, it remarkably suppresses AMP-activated protein kinase (AMPK) signalling across tissues. We show that upregulating daf-19/RFX effectively enhances IFT, sensory perception, AMPK activity and autophagy, promoting metabolic homeostasis and longevity. Our study determines an ageing pathway causing IFT decay and sensory perception deterioration, which in turn disrupts metabolism and healthy ageing.
Evidence for sponges as sister to all other animals from partitioned phylogenomics with mixture models and recoding
Authors: Redmond Anthony K. , McLysaght Aoife
Published: March 2021

Resolving the relationships between the major lineages in the animal tree of life is necessary to understand the origin and evolution of key animal traits. Sponges, characterized by their simple body plan, were traditionally considered the sister group of all other animal lineages, implying a gradual increase in animal complexity from unicellularity to complex multicellularity. However, the availability of genomic data has sparked tremendous controversy as some phylogenomic studies support comb jellies taking this position, requiring secondary loss or independent origins of complex traits. Here we show that incorporating site-heterogeneous mixture models and recoding into partitioned phylogenomics alleviates systematic errors that hamper commonly-applied phylogenetic models. Testing on real datasets, we show a great improvement in model-fit that attenuates branching artefacts induced by systematic error. We reanalyse key datasets and show that partitioned phylogenomics does not support comb jellies as sister to other animals at either the supermatrix or partition-specific level.
Fine silt and clay content is the main factor defining maximal C and N accumulations in soils: a meta-analysis
Authors: Matus Francisco J.
Published: March 2021

When studying carbon (C) sequestration in soil, it is necessary to recognize the maximal storage potential and the main influencing factors, including the climate, land use, and soil properties. Here, we hypothesized that the silt and clay contents in soils as well as the clay mineralogy are the main factors affecting the maximal C and N storage levels of soils. This hypothesis was evaluated using a database containing the organic C contents of topsoils separated by ultrasonic dispersion to determine the particle size fractions. The slopes of the linear regressions between the C contents in silt and clay to the soil organic C (SOC) and between the N contents in silt and clay to the total N content were independent of the clay mineralogy (2:1, 1:1, calcareous soil, amorphous clays), climate type (tropical, temperate, and Mediterranean), and land use type (cropland, grassland, and forest). This clearly shows that the silt and clay content is the main factor defining an upper SOC level, which allowed us to propose a generalized linear regression (R2 > 0.95) model with a common slope, independent of the land use and climate type, to estimate the soil C sequestration potential. The implications of these findings are as follows: (1) a common slope regression was accurately calculated (0.83 ± 0.02 for C-silt + clay < 63 μm and 0.81 ± 0.02 for C-silt + clay < 20 μm) and (2) there was no asymptotic pattern found to support the existence of an SOC saturation pool.
Clinical measures of foot posture and ankle joint dorsiflexion do not differ in adults with and without plantar heel pain
Authors: Landorf Karl B. , Kaminski Michelle R. , Munteanu Shannon E. , Zammit Gerard V. , Menz Hylton B.
Published: March 2021

Foot posture and ankle joint dorsiflexion have long been proposed to be risk factors for plantar heel pain, however body mass may be a confounder when investigating these factors. The aim of this study was to determine if clinical measures of foot posture and ankle joint dorsiflexion differ in adults with and without plantar heel pain after accounting for body mass. This was a cross-sectional observational study that compared 50 participants with plantar heel pain to 25 control participants without plantar heel pain who were matched for age, sex and body mass index. Foot posture was assessed using the Foot Posture Index and the Arch Index. Ankle joint dorsiflexion was assessed with a weightbearing lunge test with the knee extended and with the knee flexed. No significant differences (P < 0.05) were found between the groups for foot posture, whether measured with the Foot Posture Index or the Arch Index. Similarly, no significant differences were found in the weightbearing lunge test whether measured with the knee extended or with the knee flexed. Clinical measures of foot posture and ankle joint dorsiflexion do not differ in adults with and without plantar heel pain when body mass is accounted for. Therefore, clinicians should not focus exclusively on foot posture and ankle dorsiflexion and ignore the contribution of overweight or obesity.
Behavioural movement strategies in cyclic models
Authors: Moura B. , Menezes J.
Published: March 2021

The spatial segregation of species is fundamental to ecosystem formation and stability. Behavioural strategies may determine where species are located and how their interactions change the local environment arrangement. In response to stimuli in the environment, individuals may move in a specific direction instead of walking randomly. This behaviour can be innate or learned from experience, and allow the individuals to conquer or the maintain territory, foraging or taking refuge. We study a generalisation of the spatial rock-paper-scissors model where individuals of one out of the species may perform directional movement tactics. Running a series of stochastic simulations, we investigate the effects of the behavioural tactics on the spatial pattern formation and the maintenance of the species diversity. We also explore a more realistic scenario, where not all individuals are conditioned to perform the behavioural strategy or have different levels of neighbourhood perception. Our outcomes show that self-preservation behaviour is more profitable in terms of territorial dominance, with the best result being achieved when all individuals are conditioned and have a long-range vicinity perception. On the other hand, invading is more advantageous if part of individuals is conditioned and if they have short-range neighbourhood perception. Finally, our findings reveal that the self-defence strategy is the least jeopardising to biodiversity which can help biologists to understand population dynamics in a setting where individuals may move strategically.
Identification of macrophage activation-related biomarkers in obese type 2 diabetes that may be indicative of enhanced respiratory risk in COVID-19
Authors: Moin Abu Saleh Md , Sathyapalan Thozhukat , Diboun Ilhame , Atkin Stephen L. , Butler Alexandra E.
Published: March 2021

Hyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS). The objective was to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects. A case-controlled interventional pilot study in OT2D (n = 23) and control subjects (n = 23). OT2D subjects underwent hyperinsulinemic clamp to normalize serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-h of insulin clamp (OT2D subjects only). Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers, CXCL9 and CXCL10, were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGβ-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia. In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences could potentially predispose diabetic individuals to increased infection severity complicated by ARDS.

Clinical trial reg. no: NCT03102801; registration date April 6, 2017.
Surface localized magnetism in transition metal doped alumina
Authors: Nykwest Erik C. , Trujillo Dennis , Alpay S. Pamir
Published: March 2021

Alumina is a structural ceramic that finds many uses in a broad range of applications. It is widely employed in the aerospace and biomedical sectors due to its stability at high temperatures and in harsh chemical environments. Here, we show that magnetism can be induced at alumina surfaces by doping with 3d transition metals. We analyze the electronic structure, spin magnetic moments, and spin density of $$\alpha $$
α
-Al$$_{2}$$

2

O$$_{3}$$

3

as a function of both dopant species (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu) and depth using first principles calculations. Our results show that all dopants, with the exception of Sc, produce magnetic moments that are concentrated to the surface of alumina with varying degrees of delocalization. It is seen that all of the dopants are at least meta-stable on the surface and must overcome an energy barrier of 0.19–1.14 eV in order to diffuse from the surface into the bulk. As a result of judiciously doping with select 3d transition metals the surface of alumina can be made magnetic. This could lead to novel applications in data storage, catalysis, and biomedical engineering through an added surface functionality.
Role of fluctuations in epidemic resurgence after a lockdown
Authors: Neri I. , Gammaitoni L.
Published: March 2021

Most popular statistical models in epidemic evolution focus on the dynamics of average relevant quantities and overlooks the role of small fluctuations on the model parameters. Models for Covid-19 are no exception. In this paper we show that the role of time-correlated fluctuations, far from being negligible, can in fact determine the spreading of an epidemic and, most importantly, the resurgence of the exponential diffusion in the presence of time-limited episodes in promiscuity behaviours. The results found in this work are not only relevant and specific for the Covid-19 epidemic but are more general and can be applied to other epidemics.
Edemas of the face and lymphoscintigraphic examination
Authors: Bourgeois Pierre , Peters E. , Van Mieghem A. , Vrancken A. , Giacalone G. , Zeltzer A.
Published: March 2021

Facial edemas not secondary to surgery and/or radiotherapy for head and neck cancer are relatively uncommon. Our aim is to report a retrospective analysis of the lymphoscintigraphic and SPECT-CT investigations obtained in patients with such facial edema. Retrospective review of exams (planar imagings in all and with SPECT-CT in 5) obtained after the subcutaneous injection of 99mTc HSA Nanosized colloids between the eyebrows in five men and seven women. Four main lymphatic pathways were identified on sequential planar imagings: para-nasal left and right and supra- ocular left and right. For eleven patients, the absence of visualization of lymphatic drainage and/or their delayed appearance correlated well with the localisation of the edematous areas. In two patients with post-traumatic and post- surgical edemas, SPECT-CT showed one deep left sided cervical lymph node (LN) in front of the first cervical vertebra. This lymphoscintigraphic approach represents a simple and valuable way to assess the lymphatic drainage pathways of the face and to establish the diagnosis of facial lymphedema.
Towards a new pseudo-quantitative approach to evaluate the ionization response of nitrogen compounds in complex matrices
Authors: Guillemant Julie , Lacoue-Nègre Marion , Berlioz-Barbier Alexandra , Albrieux Florian , de Oliveira Luis P. , Joly Jean-François , Duponchel Ludovic
Published: March 2021

Ultra high-resolution mass spectrometry (FT-ICR MS) coupled to electrospray ionization (ESI) provides unprecedented molecular characterization of complex matrices such as petroleum products. However, ESI faces major ionization competition phenomena that prevent the absolute quantification of the compounds of interest. On the other hand, comprehensive two-dimensional gas chromatography (GC × GC) coupled to specific detectors (HRMS or NCD) is able to quantify the main families identified in these complex matrices. In this paper, this innovative dual approach has been used to evaluate the ionization response of nitrogen compounds in gas oils as a case study. To this extent, a large gas oil dataset has been analyzed by GC × GC/HRMS, GC × GC-NCD and ESI(+/−)-FT-ICR MS. Then, the concentrations obtained from GC × GC-NCD have been compared to those obtained from FT-ICR MS hence proving that strong ionization competitions are taking place and also depending on the origin of the sample. Finally, multilinear regressions (MLR) have been used to quantitatively predict nitrogen families from FT-ICR MS measurements as well as start rationalizing the ionization competition phenomena taking place between them in different types of gas oils.
The factors influencing clinical outcomes after leukapheresis in acute leukaemia
Authors: Lee Howon , Park Silvia , Yoon Jae-Ho , Cho Byung-Sik , Kim Hee-Je , Lee Seok , Kim Dong-Wook , Chung Nack-Gyun , Cho Bin , Kim Kyoung Bo , Yoo Jaeeun , Jekarl Dong Wook , Chae Hyojin , Lim Jihyang , Kim Myungshin , Oh Eun-Jee , Kim Yonggoo
Published: March 2021

Leukapheresis is used for the mechanical removal of leukaemic cells in hyperleukocytosis. However, the effectiveness of leukapheresis remains unclear due to selection and confounding factors in the cohorts. We compared the effectiveness of leukapheresis among the subgroups according to either the 2016 World Health Organization classification or the number of cytogenetic abnormalities with a retrospective, single-centre study from January 2009 to December 2018. Acute myeloid leukaemia (AML, n = 212) and acute lymphoblastic leukaemia (ALL, n = 97) were included. The 30-day survival rates (95% confidence interval, 95% CI) for AML and ALL were 86.3% (81.6–90.9%) and 94.8% (90.3–99.2%), respectively. For AML, ‘primary AML with myelodysplasia-related changes’ and ‘AML with biallelic mutation of CEBPA’ showed better 30-day survival outcomes (P = 0.026) than the other subgroups. A higher platelet count after leukapheresis was associated with better 30-day survival in AML patients (P = 0.029). A decrease in blast percentage count after leukapheresis was associated with better 30-day survival in ALL patients (P = 0.034). Our study suggested that prophylactic platelet transfusion to raise the platelet count to 50 × 109/L or greater might improve clinical outcome in AML patients undergoing leukapheresis.
Microplastic pollution in seawater and marine organisms across the Tropical Eastern Pacific and Galápagos
Authors: Alfaro-Núñez Alonzo , Astorga Diana , Cáceres-Farías Lenin , Bastidas Lisandra , Soto Villegas Cynthia , Macay Kewrin , Christensen Jan H.
Published: March 2021

Detection of plastic debris degrading into micro particles across all oceanic environments and inside of marine organisms is no longer surprising news. Microplastic contamination now appears as one of the world’s environmental main concerns. To determine the levels of microplastic pollution at sea, water samples were collected across a 4000 km-trajectory in the Tropical Eastern Pacific and the Galápagos archipelago, covering an area of 453,000 square kilometres. Furthermore, 240 specimens of 16 different species of fish, squid, and shrimp, all of human consumption, were collected along the continental coast. Microplastic particles were found in 100% of the water samples and marine organisms. Microplastic particles ranging from 150 to 500 µm in size were the most predominant. This is one of the first reports simultaneously detecting and quantifying microplastic particles abundance and their impact on marine organisms of this region.
Author Correction: Strontium isotope evidence for a trade network between southeastern Arabia and India during Antiquity
Authors: Ryan Saskia E. , Dabrowski Vladimir , Dapoigny Arnaud , Gauthier Caroline , Douville Eric , Tengberg Margareta , Kerfant Céline , Mouton Michel , Desormeau Xavier , Zazzo Antoine , Bouchaud Charlène
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Cross-continental emergence of Nannizziopsis barbatae disease may threaten wild Australian lizards
Authors: Peterson Nicola R. , Rose Karrie , Shaw Stephanie , Hyndman Tim H. , Sigler Lynne , Kurtböke D. İpek , Llinas Josh , Littleford‑Colquhoun Bethan L. , Cristescu Romane , Frère Celine
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Application of Whole Genome Resequencing in Mapping of a Tomato Yellow Leaf Curl Virus Resistance Gene
Authors: Wang Yinlei , Jiang Jing , Zhao Liping , Zhou Rong , Yu Wengui , Zhao Tongmin
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Copy number-dependent DNA methylation of the Pyricularia oryzae MAGGY retrotransposon is triggered by DNA damage
Authors: Van Vu Ba , Nguyen Quyet , Kondo-Takeoka Yuki , Murata Toshiki , Kadotani Naoki , Thi Nguyen Giang , Arazoe Takayuki , Ohsato Shuichi , Nakayashiki Hitoshi
Published: March 2021

Transposable elements are common targets for transcriptional and post-transcriptional gene silencing in eukaryotic genomes. However, the molecular mechanisms responsible for sensing such repeated sequences in the genome remain largely unknown. Here, we show that machinery of homologous recombination (HR) and RNA silencing play cooperative roles in copy number-dependent de novo DNA methylation of the retrotransposon MAGGY in the fungus Pyricularia oryzae. Genetic and physical interaction studies revealed that RecA domain-containing proteins, including P. oryzae homologs of Rad51, Rad55, and Rad57, together with an uncharacterized protein, Ddnm1, form complex(es) and mediate either the overall level or the copy number-dependence of de novo MAGGY DNA methylation, likely in conjunction with DNA repair. Interestingly, P. oryzae mutants of specific RNA silencing components (MoDCL1 and MoAGO2) were impaired in copy number-dependence of MAGGY methylation. Co-immunoprecipitation of MoAGO2 and HR components suggested a physical interaction between the HR and RNA silencing machinery in the process.
A combinatorial action of GmMYB176 and GmbZIP5 controls isoflavonoid biosynthesis in soybean (Glycine max)
Authors: Anguraj Vadivel Arun Kumaran , McDowell Tim , Renaud Justin B. , Dhaubhadel Sangeeta
Published: March 2021

GmMYB176 is an R1 MYB transcription factor that regulates multiple genes in the isoflavonoid biosynthetic pathway, thereby affecting their levels in soybean roots. While GmMYB176 is important for isoflavonoid synthesis, it is not sufficient for the function and requires additional cofactor(s). The aim of this study was to identify the GmMYB176 interactome for the regulation of isoflavonoid biosynthesis in soybean. Here, we demonstrate that a bZIP transcription factor GmbZIP5 co-immunoprecipitates with GmMYB176 and shows protein–protein interaction in planta. RNAi silencing of GmbZIP5 reduced the isoflavonoid level in soybean hairy roots. Furthermore, co-overexpression of GmMYB176 and GmbZIP5 enhanced the level of multiple isoflavonoid phytoallexins including glyceollin, isowighteone and a unique O-methylhydroxy isoflavone in soybean hairy roots. These findings could be utilized to develop biotechnological strategies to manipulate the metabolite levels either to enhance plant defense mechanisms or for human health benefits in soybean or other economically important crops.
GmBTB/POZ promotes the ubiquitination and degradation of LHP1 to regulate the response of soybean to Phytophthora sojae
Authors: Zhang Chuanzhong , Cheng Qun , Wang Huiyu , Gao Hong , Fang Xin , Chen Xi , Zhao Ming , Wei Wanling , Song Bo , Liu Shanshan , Wu Junjiang , Zhang Shuzhen , Xu Pengfei
Published: March 2021

Phytophthora sojaeis a pathogen that causes stem and root rot in soybean (Glycine max[L.] Merr.). We previously demonstrated that GmBTB/POZ, a BTB/POZ domain-containing nuclear protein, enhances resistance toP. sojaein soybean, via a process that depends on salicylic acid (SA). Here, we demonstrate that GmBTB/POZ associates directly with soybean LIKE HETEROCHROMATIN PROTEIN1 (GmLHP1) in vitro and in vivo and promotes its ubiquitination and degradation. Both overexpression and RNA interference analysis of transgenic lines demonstrate that GmLHP1 negatively regulates the response of soybean toP. sojaeby reducing SA levels and repressingGmPR1expression. The WRKY transcription factor gene,GmWRKY40, a SA-induced gene in the SA signaling pathway, is targeted by GmLHP1, which represses its expression via at least two mechanisms (directly binding to its promoter and impairing SA accumulation). Furthermore, the nuclear localization of GmLHP1 is required for the GmLHP1-mediated negative regulation of immunity, SA levels and the suppression ofGmWRKY40expression. Finally, GmBTB/POZ releases GmLHP1-regulatedGmWRKY40suppression and increases resistance toP. sojaeinGmLHP1-OEhairy roots. These findings uncover a regulatory mechanism by which GmBTB/POZ-GmLHP1 modulates resistance toP. sojaein soybean, likely by regulating the expression of downstream target geneGmWRKY40.
Simultaneous immunodetection of ionophore antibiotics, salinomycin and narasin, in poultry products and milk
Authors: Burkin Maksim A. , Galvidis Inna A.
Published: March 2021

Immunoassay of ionophore antibiotics, salinomycin and narasin, was first developed for milk analysis. Good recovery was promoted by the absence of Na+–K+ ions in tested samples.
Simultaneous sulfidation of Mo and Co oxides supported on Au(111)
Authors: Prabhu M. K. , Groot I. M. N.
Published: March 2021

Co-Promoted MoS2 model catalyst for fundamental hydrodesulfurization studies can be synthesized from a mixed Co and Mo oxide precursor.
Boosting charge carrier separation efficiency by constructing an intramolecular DA system towards efficient photoreduction of CO2
Authors: Zhang Xinyu , Wang Mei , Song Xianghai , Yan Yongsheng , Huo Pengwei , Yan Yan , Yang Boting
Published: March 2021

The charge carrier excitation–recombination process between the donor and acceptor, and the photocatalytic reduction of CO2to CO over CN based DA composites.
High-throughput computational discovery of ternary-layered MAX phases and prediction of their exfoliation for formation of 2D MXenes
Authors: Khaledialidusti Rasoul , Khazaei Mohammad , Khazaei Somayeh , Ohno Kaoru
Published: March 2021

The rush to synthesize novel two-dimensional (2D) materials has excited the research community studying ternary-layered carbide and nitride compounds, known as MAX phases, for the past two decades in the quest to develop new 2D material precursors.
Enhanced field emission performance of MXene–TiO2 composite films
Authors: Yang Bingjun , Chen Jiangtao , Wu Xiaonan , Liu Bao , Liu Lingyang , Tang Yu , Yan Xingbin
Published: March 2021

A MXene–TiO2 composite emitter with enhanced field emission performance is prepared, and the emission current density is up to 289 mA cm−2. The field emission of the composite is also realized under the driving of a TENG.
Improved thermoelectric properties of WS2–WSe2 phononic crystals: insights from first-principles calculations
Authors: Han Dan , Yang Xiaoheng , Du Mu , Xin Gongming , Zhang Jingchao , Wang Xinyu , Cheng Lin
Published: March 2021

Improved thermoelectric properties of different WS2–WSe2 phononic crystals are evaluated by combining first-principles calculations with Boltzmann transport theory.
Sound damping in soft particle packings: the interplay between configurational disorder and inelasticity
Authors: Saitoh Kuniyasu , Mizuno Hideyuki
Published: March 2021

We numerically investigate sound damping in disordered two-dimensional soft particle packings. Our findings suggest that sound damping in soft particle packings is determined by the interplay between elastic heterogeneities and inelasticity.
Electrosynthesized CuOx/graphene by a four-electrode electrolysis system for the oxygen reduction reaction to hydrogen peroxide
Authors: Xiao He , Li Bo , Zhao Man , Li Ya , Hu Tianjun , Jia Jianfeng , Wu Haishun
Published: March 2021

A facile four-electrode electrolysis system is firstly applied to synthesize CuOx/graphene hybrid for oxygen reduction to hydrogen peroxide.
Successes, challenges, and opportunities for quantum chemistry in understanding metalloenzymes for solar fuels research
Authors: Orio Maylis , Pantazis Dimitrios A.
Published: March 2021

Overview of the rich and diverse contributions of quantum chemistry to understanding the structure and function of the biological archetypes for solar fuel research, photosystem II and hydrogenases.
Multiple reflection optimization package for X-ray diffraction
Authors: Magalhães S. , S. Cabaço J. , Araújo J. P. , Alves E.
Published: March 2021

New software for the simulation and fitting of 2θ–ω scans of symmetric and asymmetric reflections based on the dynamical theory of X-ray diffraction is presented.
Magnetron sputtered ZnO electron transporting layers for high performance perovskite solar cells
Authors: Niu Haihong , Fang Cunlong , Wei Xiantao , Wang Huan , Wan Lei , Li Yuan , Mao Xiaoli , Xu Jinzhang , Zhou Ru
Published: March 2021

Efficient low-temperature magnetron sputtered ZnO based ETLs with reasonable energy levels, high electrical conductivity and excellent charge extraction are designed for high-efficiency PSCs.
Preparation of organocobalt(iii) complexes via O2 activation
Authors: Møller Mads Sondrup , Kongsted Jacob , McKenzie Christine J.
Published: March 2021

Understanding an old dog’s old tricks: The coupling of selective C–H activation with O2 activation by Co(salen).
Recyclable, reprocessable, self-adhered and repairable carbon fiber reinforced polymers using full biobased matrices from camphoric acid and epoxidized soybean oil
Authors: Zhang Weiwei , Wu Jianqiao , Gao Liang , Zhang Baoyan , Jiang Jianxin , Hu Jun
Published: March 2021

Recyclable carbon fiber composites were prepared using full biobased dynamic matrices from camphoric acid and epoxidized soybean oil.
An effective photocatalytic hydrogen evolution strategy based on tunable band gap (CuIn)xZn2(1−x)S2combined with amorphous molybdenum sulfide
Authors: Cao Yanren , Li Haiyan , Jin Jingyi , Li Yanxin , Feng Ting , Wang Wei , Dong Bohua , Cao Lixin
Published: March 2021

The combination of crystalline band-tunable (CuIn)xZn2(1−x)S2and amorphous a-MoSxprovides a good strategy for photocatalysts.
A rapid and sensitive fluorescence biosensor based on plasmonic PCR
Authors: Wu Jingrui , Jiang Kunlun , Mi Hua , Qiu Yuwei , Son Jiwoong , Park Hyun June , Nam Jwa-Min , Lee Jung-Hoon
Published: March 2021

Herein, we demonstrate plasmonic photothermal PCR utilizing plasmonic magnetic nanoparticles as nano-sized heater and magnetic separator for fluorescence detection. Plasmonic photothermal PCR can be completed in 5.5 min with LOD of 3.3 copies per μL.
Synaptic transistors and neuromorphic systems based on carbon nano-materials
Authors: Du Chunyu , Ren Yanyun , Qu Zhiyang , Gao Lili , Zhai Yongbiao , Han Su-Ting , Zhou Ye
Published: March 2021

Carbon nano-material based synaptic transistors and neuromorphic systems are systematically reviewed.
A review of Mn-based catalysts for low-temperature NH3-SCR: NOxremoval and H2O/SO2resistance
Authors: Xu Guiying , Guo Xiaolong , Cheng Xingxing , Yu Jian , Fang Baizeng
Published: March 2021

Mn-Based catalysts with various morphologies, structures and compositions for improved NOxremoval and H2O/SO2resistance performance for low-temperature NH3-SCR are reviewed.
Copper-catalyzed [3 + 2]-cycloaddition of α-halonitroalkenes with azomethine ylides: facile synthesis of multisubstituted pyrrolidines and pyrroles
Authors: Motornov Vladimir A. , Tabolin Andrey A. , Nelyubina Yulia V. , Nenajdenko Valentine G. , Ioffe Sema L.
Published: March 2021

An approach to multisubstituted pyrrolidines, pyrrolines and pyrroles is developed based on [3 + 2]-cycloaddition of α-halo (F, Cl, Br) nitroalkenes.
Copper(i)-catalyzed [4 + 2] cycloaddition of aza-ortho-quinone methides with bicyclic alkenes
Authors: Lei Lu , Liang Yu-Feng , Liang Cui , Qin Jiang-Ke , Pan Cheng-Xue , Su Gui-Fa , Mo Dong-Liang
Published: March 2021

An efficient copper(i)-catalyzed [4 + 2] cycloaddition of aza-ortho-quinone methides (ao-QMs) and bicyclic alkenes to prepare tetrahydroquinoline-fused bicycles bearing multiple stereocenters in good yields is reported.