bluuebunny/crossref_metadata_2025 huggingface dataset:
Posthypoxic behavioral impairment and mortality of Drosophila melanogaster are associated with high temperatures, enhanced predeath activity and oxidative stress
Authors: Habib Pardes , Jung Jennifer , Wilms Gina Maria , Kokott-Vuong Alma , Habib Shahin , Schulz Jörg B. , Voigt Aaron
Published: February 2021

Hypoxia is an underlying pathophysiological condition of a variety of devastating diseases, including acute ischemic stroke (AIS). We are faced with limited therapeutic options for AIS patients, and even after successful restoration of cerebral blood flow, the poststroke mortality is still high. More basic research is needed to explain mortality after reperfusion and to develop adjunct neuroprotective therapies.Drosophila melanogaster (D.m.)is a suitable model to analyze hypoxia; however, little is known about the impacts of hypoxia and especially of the subsequent reperfusion injury on the behavior and survival ofD.m. To address this knowledge gap, we subjected two wild-typeD.m. strains (Canton-S and Oregon-R) to severe hypoxia (<0.3% O2) under standardized environmental conditions in a well-constructed hypoxia chamber. During posthypoxic reperfusion (21% O2), we assessed fly activity (evoked and spontaneous) and analyzed molecular characteristics (oxidative stress marker abundance, reactive oxygen species (ROS) production, and metabolic activity) at various timepoints during reperfusion. First, we established standard conditions to induce hypoxia inD.m. to guarantee stable and reproducible experiments. Exposure to severe hypoxia under defined conditions impaired the climbing ability and reduced the overall activity of bothD.m. strains. Furthermore, a majority of the flies died during the early reperfusion phase (up to 24 h). Interestingly, the flies that died early exhibited elevated activity before death compared to that of the flies that survived the entire reperfusion period. Additionally, we detected increases in ROS and stress marker (Catalase, Superoxide Dismutase and Heat Shock Protein 70) levels as well as reductions in metabolic activity in the reperfusion phase. Finally, we found that changes in environmental conditions impacted the mortality rate. In particular, decreasing the temperature during hypoxia or the reperfusion phase displayed a protective effect. In conclusion, our data suggest that reperfusion-dependent death might be associated with elevated temperatures, predeath activity, and oxidative stress.
Clinical impact of panel-based error-corrected next generation sequencing versus flow cytometry to detect measurable residual disease (MRD) in acute myeloid leukemia (AML)
Authors: Patkar Nikhil , Kakirde Chinmayee , Shaikh Anam Fatima , Salve Rakhi , Bhanshe Prasanna , Chatterjee Gaurav , Rajpal Sweta , Joshi Swapnali , Chaudhary Shruti , Kodgule Rohan , Ghoghale Sitaram , Deshpande Nilesh , Shetty Dhanalaxmi , Khizer Syed Hasan , Jain Hasmukh , Bagal Bhausaheb , Menon Hari , Khattry Navin , Sengar Manju , Tembhare Prashant , Subramanian Papagudi , Gujral Sumeet
Published: February 2021

We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission, and evaluated MRD using sensitive error-corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients were PI NGS-MRD+ and 40.9% PC NGS-MRD+ (median VAF 0.76%). NGS-MRD+ patients had a significantly higher cumulative incidence of relapse (p = 0.003), inferior overall survival (p = 0.001) and relapse free survival (p < 0.001) as compared to NGS-MRD− patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. PI NGS-MRD− patients had a significantly improved survival as compared to patients who became NGS-MRD− subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS. Only a fraction of cases were NGS-MRD− but FCM-MRD+. NGS-MRD provided additional information of the risk of relapse when compared to FCM-MRD. We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and synergistic to FCM-MRD in AML treated with conventional therapies. Maximum clinical utility may be leveraged by combining FCM and NGS-MRD modalities.
Spray-coated electret materials with enhanced stability in a harsh environment for an MEMS energy harvesting device
Authors: Luo Anxin , Xu Yixin , Zhang Yulong , Zhang Mi , Zhang Xiaoqing , Lu Yan , Wang Fei
Published: February 2021

The charge stability of electret materials can directly affect the performance of electret-based devices such as electrostatic energy harvesters. In this paper, a spray-coating method is developed to deposit an electret layer with enhanced charge stability. The long-term stability of a spray-coated electret is investigated for 500 days and shows more stable performance than a spin-coated layer. A second-order linear model that includes both the surface charge and space charge is proposed to analyze the charge decay process of electrets in harsh environments at a high temperature (120 °C) and high humidity (99% RH); this model provides better accuracy than the traditional deep-trap model. To further verify the stability of the spray-coated electret, an electrostatic energy harvester is designed and fabricated with MEMS (micro-electromechanical systems) technology. The electret material can work as both the bonding interface and electret layer during fabrication. A maximum output power of 11.72 μW is harvested from a vibrating source at an acceleration of 28.5 m/s2. When the energy harvester with the spray-coated electret is exposed to a harsh environment (100 °C and 98% RH), an adequate amount of power can still be harvested even after 34 h and 48 h, respectively.
Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors
Authors: Saad Fred , Bögemann Martin , Suzuki Kazuhiro , Shore Neal
Published: February 2021

Background

Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as a rising prostate-specific antigen concentration, despite castrate levels of testosterone with ongoing androgen-deprivation therapy or orchiectomy, and no detectable metastases by conventional imaging. Patients with nmCRPC progress to metastatic disease and are at risk of developing cancer-related symptoms and morbidity, eventually dying of their disease. While patients with nmCRPC are generally asymptomatic from their disease, they are often older and have chronic comorbidities that require long-term concomitant medication. Therefore, careful consideration of the benefit–risk profile of potential treatments is required.

Methods

In this review, we will discuss the rationale for early treatment of patients with nmCRPC to delay metastatic progression and prolong survival, as well as the factors influencing this treatment decision. We will focus on oral pharmacotherapy with the second-generation androgen receptor inhibitors, apalutamide, enzalutamide, and darolutamide, and the importance of balancing the clinical benefit they offer with potential adverse events and the consequential impact on quality of life, physical capacity, and cognitive function.

Results and conclusions

While the definition of nmCRPC is well established, the advent of next-generation imaging techniques capable of detecting hitherto undetectable oligometastatic disease in patients with nmCRPC has fostered debate on the criteria that inform the management of these patients. However, despite these developments, published consensus statements have maintained that the absence of metastases on conventional imaging suffices to guide such therapeutic decisions. In addition, the prolonged metastasis-free survival and recently reported positive overall survival outcomes of the three second-generation androgen receptor inhibitors have provided further evidence for the early use of these agents in patients with nmCRPC in order to delay metastases and prolong survival. Here, we discuss the benefit–risk profiles of apalutamide, enzalutamide, and darolutamide based on the data available from their pivotal clinical trials in patients with nmCRPC.
Differential longitudinal changes of neuronal and glial damage markers in anorexia nervosa after partial weight restoration
Authors: Hellerhoff Inger , King Joseph A. , Tam Friederike I. , Pauligk Sophie , Seidel Maria , Geisler Daniel , Bahnsen Klaas , Kretschmann Nicole , Akgün Katja , Roessner Veit , Ziemssen Tjalf , Ehrlich Stefan
Published: February 2021

Atrophic brain changes in acute anorexia nervosa (AN) are often visible to the naked eye on computed tomography or magnetic resonance imaging scans, but it remains unclear what is driving these effects. In neurological diseases, neurofilament light (NF-L) and tau protein have been linked to axonal damage. Glial fibrillary acidic protein (GFAP) has been associated with astroglial injury. In an attempt to shed new light on factors potentially underlying past findings of structural brain alterations in AN, the current study investigated serum NF-L, tau protein, and GFAP levels longitudinally in AN patients undergoing weight restoration. Blood samples were obtained from 54 acutely underweight, predominantly adolescent female AN patients and 54 age-matched healthy control participants. AN patients were studied in the severely underweight state and again after short-term partial weight restoration. Group comparisons revealed higher levels of NF-L, tau protein, and GFAP in acutely underweight patients with AN compared to healthy control participants. Longitudinally, a decrease in NF-L and GFAP but not in tau protein levels was observed in AN patients upon short-term partial weight restoration. These results may be indicative of ongoing neuronal and astroglial injury during the underweight phase of AN. Normalization of NF-L and GFAP but not tau protein levels may indicate an only partial restoration of neuronal and astroglial integrity upon weight gain after initial AN-associated cell damage processes.
Individual inflammatory marker abnormalities or inflammatory marker scores to identify primary care patients with unexpected weight loss for cancer investigation?
Authors: Nicholson B. D. , Oke J. L. , Aveyard P. , Hamilton W. T. , Hobbs F. D. R.
Published: February 2021

Background

Combinations of inflammatory markers are used as prognostic scores in cancer patients with cachexia. We investigated whether they could also be used to prioritise patients attending primary care with unexpected weight loss for cancer investigation.

Methods

We used English primary care electronic health records data linked to cancer registry data from 12,024 patients with coded unexpected weight loss. For each individual inflammatory marker and score we estimated the sensitivity, specificity, likelihood ratios, positive predictive value (PPV) and the area under the curve along with 95% confidence intervals for a cancer diagnosis within six months.

Results

The risk of cancer associated with two abnormal inflammatory markers combined in a score was higher than the risk associated with individual inflammatory marker abnormalities. However, the risk of cancer in weight loss associated with individual abnormalities, notably a raised C-reactive protein, was sufficient to trigger further investigation for cancer under current NICE guidelines.

Conclusions

If scores including pairs of inflammatory marker abnormalities were to be used, in preference to individual abnormalities, fewer people would be investigated to diagnose one cancer with fewer false positives, but fewer people with cancer would be diagnosed overall.
Evaluating the potential of novel genetic approaches for the treatment of Duchenne muscular dystrophy
Authors: Himič Vratko , Davies Kay E.
Published: February 2021

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle-wasting disorder that is caused by a lack of functional dystrophin, a cytoplasmic protein necessary for the structural integrity of muscle. As variants in the dystrophin gene lead to a disruption of the reading frame, pharmacological treatments have only limited efficacy; there is currently no effective therapy and consequently, a significant unmet clinical need for DMD. Recently, novel genetic approaches have shown real promise in treating DMD, with advancements in the efficacy and tropism of exon skipping and surrogate gene therapy. CRISPR-Cas9 has the potential to be a ‘one-hit’ curative treatment in the coming decade. The current limitations of gene editing, such as off-target effects and immunogenicity, are in fact partly constraints of the delivery method itself, and thus research focus has shifted to improving the viral vector. In order to halt the loss of ambulation, early diagnosis and treatment will be pivotal. In an era where genetic sequencing is increasingly utilised in the clinic, genetic therapies will play a progressively central role in DMD therapy. This review delineates the relative merits of cutting-edge genetic approaches, as well as the challenges that still need to be overcome before they become clinically viable.
Dry anophthalmic socket syndrome – morphological alterations in meibomian glands
Authors: Rokohl Alexander C. , Trester Marc , Naderi Parsa , Loreck Niklas , Zwingelberg Sarah , Bucher Franziska , Pine Keith R. , Heindl Ludwig M.
Published: February 2021

Purpose

To evaluate morphological alterations of meibomian glands (MGs) in the dry anophthalmic socket syndrome (DASS).

Methods

Fifteen unilateral anophthalmic patients wearing cryolite glass prosthetic eyes were enrolled. All patients with clinical blepharitis or other significant eyelid abnormalities were excluded. In vivo laser scanning confocal microscopy (LSCM) of the MGs in the lower eyelids both on the anophthalmic side and the healthy fellow eye was performed to quantify acinar unit density, acinar unit diameter, acinar unit area, meibum secretion reflectivity, the inhomogeneous appearance of the glandular interstice, and inhomogeneous appearance of the acinar walls.

Results

The lower eyelids of the anophthalmic sockets revealed a significant reduction of the acinar unit density (p = 0.003) as well as a significantly more inhomogeneous appearance of the periglandular interstices (p = 0.018) and the acinar unit walls (p = 0.015) than the healthy fellow eyelid. However, there were no significant differences regarding the acinar unit diameter, acinar unit area, and meibum secretion reflectivity of the MGs on the anophthalmic side compared to the healthy fellow eyelid (p ≥ 0.05, respectively).

Conclusions

The eyelids of anophthalmic sockets without clinical blepharitis demonstrate a reduced density of MG acinar units and a more inhomogeneous appearance of the periglandular interstices and the acinar unit walls. This can cause meibomian gland dysfunction contributing to DASS and suggests early treatment of these symptomatic patients, even in the clinical absence of any blepharitis signs.
The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes
Authors: Davydova Erna , Shimazu Tadahiro , Schuhmacher Maren Kirstin , Jakobsson Magnus E. , Willemen Hanneke L. D. M. , Liu Tongri , Moen Anders , Ho Angela Y. Y. , Małecki Jędrzej , Schroer Lisa , Pinto Rita , Suzuki Takehiro , Grønsberg Ida A. , Sohtome Yoshihiro , Akakabe Mai , Weirich Sara , Kikuchi Masaki , Olsen Jesper V. , Dohmae Naoshi , Umehara Takashi , Sodeoka Mikiko , Siino Valentina , McDonough Michael A. , Eijkelkamp Niels , Schofield Christopher J. , Jeltsch Albert , Shinkai Yoichi , Falnes Pål Ø.
Published: February 2021

Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where “x” is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.
Genetic predictors of participation in optional components of UK Biobank
Authors: Tyrrell Jessica , Zheng Jie , Beaumont Robin , Hinton Kathryn , Richardson Tom G. , Wood Andrew R. , Davey Smith George , Frayling Timothy M. , Tilling Kate
Published: February 2021

Large studies such as UK Biobank are increasingly used for GWAS and Mendelian randomization (MR) studies. However, selection into and dropout from studies may bias genetic and phenotypic associations. We examine genetic factors affecting participation in four optional components in up to 451,306 UK Biobank participants. We used GWAS to identify genetic variants associated with participation, MR to estimate effects of phenotypes on participation, and genetic correlations to compare participation bias across different studies. 32 variants were associated with participation in one of the optional components (P < 6 × 10−9), including loci with links to intelligence and Alzheimer’s disease. Genetic correlations demonstrated that participation bias was common across studies. MR showed that longer educational duration, older menarche and taller stature increased participation, whilst higher levels of adiposity, dyslipidaemia, neuroticism, Alzheimer’s and schizophrenia reduced participation. Our effect estimates can be used for sensitivity analysis to account for selective participation biases in genetic or non-genetic analyses.
Salmonella Typhimurium reprograms macrophage metabolism via T3SS effector SopE2 to promote intracellular replication and virulence
Authors: Jiang Lingyan , Wang Peisheng , Song Xiaorui , Zhang Huan , Ma Shuangshuang , Wang Jingting , Li Wanwu , Lv Runxia , Liu Xiaoqian , Ma Shuai , Yan Jiaqi , Zhou Haiyan , Huang Di , Cheng Zhihui , Yang Chen , Feng Lu , Wang Lei
Published: February 2021

Salmonella Typhimurium establishes systemic infection by replicating in host macrophages. Here we show that macrophages infected with S. Typhimurium exhibit upregulated glycolysis and decreased serine synthesis, leading to accumulation of glycolytic intermediates. The effects on serine synthesis are mediated by bacterial protein SopE2, a type III secretion system (T3SS) effector encoded in pathogenicity island SPI-1. The changes in host metabolism promote intracellular replication of S. Typhimurium via two mechanisms: decreased glucose levels lead to upregulated bacterial uptake of 2- and 3-phosphoglycerate and phosphoenolpyruvate (carbon sources), while increased pyruvate and lactate levels induce upregulation of another pathogenicity island, SPI-2, known to encode virulence factors. Pharmacological or genetic inhibition of host glycolysis, activation of host serine synthesis, or deletion of either the bacterial transport or signal sensor systems for those host glycolytic intermediates impairs S. Typhimurium replication or virulence.
The mechanism for the enhanced piezoelectricity in multi-elements doped (K,Na)NbO3 ceramics
Authors: Gao Xiaoyi , Cheng Zhenxiang , Chen Zibin , Liu Yao , Meng Xiangyu , Zhang Xu , Wang Jianli , Guo Qinghu , Li Bei , Sun Huajun , Gu Qinfen , Hao Hua , Shen Qiang , Wu Jinsong , Liao Xiaozhou , Ringer Simon P. , Liu Hanxing , Zhang Lianmeng , Chen Wen , Li Fei , Zhang Shujun
Published: February 2021

(K,Na)NbO3 based ceramics are considered to be one of the most promising lead-free ferroelectrics replacing Pb(Zr,Ti)O3. Despite extensive studies over the last two decades, the mechanism for the enhanced piezoelectricity in multi-elements doped (K,Na)NbO3 ceramics has not been fully understood. Here, we combine temperature-dependent synchrotron x-ray diffraction and property measurements, atomic-scale scanning transmission electron microscopy, and first-principle and phase-field calculations to establish the dopant–structure–property relationship for multi-elements doped (K,Na)NbO3 ceramics. Our results indicate that the dopants induced tetragonal phase and the accompanying high-density nanoscale heterostructures with low-angle polar vectors are responsible for the high dielectric and piezoelectric properties. This work explains the mechanism of the high piezoelectricity recently achieved in (K,Na)NbO3 ceramics and provides guidance for the design of high-performance ferroelectric ceramics, which is expected to benefit numerous functional materials.
Complete and cooperative in vitro assembly of computationally designed self-assembling protein nanomaterials
Authors: Wargacki Adam J. , Wörner Tobias P. , van de Waterbeemd Michiel , Ellis Daniel , Heck Albert J. R. , King Neil P.
Published: February 2021

Recent advances in computational methods have enabled the predictive design of self-assembling protein nanomaterials with atomic-level accuracy. These design strategies focus exclusively on a single target structure, without consideration of the mechanism or dynamics of assembly. However, understanding the assembly process, and in particular its robustness to perturbation, will be critical for translating this class of materials into useful technologies. Here we investigate the assembly of two computationally designed, 120-subunit icosahedral complexes in detail using several complementary biochemical methods. We found that assembly of each material from its two constituent protein building blocks was highly cooperative and yielded exclusively complete, 120-subunit complexes except in one non-stoichiometric regime for one of the materials. Our results suggest that in vitro assembly provides a robust and controllable route for the manufacture of designed protein nanomaterials and confirm that cooperative assembly can be an intrinsic, rather than evolved, feature of hierarchically structured protein complexes.
Publisher Correction: Exploring the effect of network topology, mRNA and protein dynamics on gene regulatory network stability
Authors: Guo Yipei , Amir Ariel
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21415-w
Human heart-forming organoids recapitulate early heart and foregut development
Authors: Drakhlis Lika , Biswanath Santoshi , Farr Clara-Milena , Lupanow Victoria , Teske Jana , Ritzenhoff Katharina , Franke Annika , Manstein Felix , Bolesani Emiliano , Kempf Henning , Liebscher Simone , Schenke-Layland Katja , Hegermann Jan , Nolte Lena , Meyer Heiko , de la Roche Jeanne , Thiemann Stefan , Wahl-Schott Christian , Martin Ulrich , Zweigerdt Robert
Published: February 2021

Organoid models of early tissue development have been produced for the intestine, brain, kidney and other organs, but similar approaches for the heart have been lacking. Here we generate complex, highly structured, three-dimensional heart-forming organoids (HFOs) by embedding human pluripotent stem cell aggregates in Matrigel followed by directed cardiac differentiation via biphasic WNT pathway modulation with small molecules. HFOs are composed of a myocardial layer lined by endocardial-like cells and surrounded by septum-transversum-like anlagen; they further contain spatially and molecularly distinct anterior versus posterior foregut endoderm tissues and a vascular network. The architecture of HFOs closely resembles aspects of early native heart anlagen before heart tube formation, which is known to require an interplay with foregut endoderm development. We apply HFOs to study genetic defects in vitro by demonstrating thatNKX2.5-knockout HFOs show a phenotype reminiscent of cardiac malformations previously observed in transgenic mice.
Nickel excess affects phenology and reproductive attributes of Asterella wallichiana and Plagiochasma appendiculatum growing in natural habitats
Authors: Sharma Anil , Bhagat Madhu , Urfan Mohammad , Ahmed Bilal , Langer Anima , Ali Villayat , Vyas Dhiraj , Yadav Narendra Singh , Hakla Haroon Rashid , Sharma Shubham , Pal Sikander
Published: February 2021

Bryophytes are potent metal absorbers, thriving well on heavy metal (HM)-polluted soils. Mechanisms controlling uptake, compartmentalization and impacts of HMs on bryophytes life cycle are largely unknown. The current study is an effort to decipher mechanisms of nickel (Ni) excess-induced effects on the phenological events of two bryophytes, Asterella wallichiana and Plagiochasma apendiculatum growing in natural habitats. Observations revealed Ni-excess induced negative impacts on abundance, frequency of occurrence of reproductive organs, population viability and morphological traits, spore viability and physiological attributes of both the liverworts. Results led us conclude that P. appendiculatum survived better with the lowest impact on its life cycle events than A. wallichiana under Ni excess in natural habitats. Our findings collectively provide insights into the previously unknown mechanisms of Ni-induced responses in liverworts with respect to phenological attributes, as well as demonstrate the potential of P. appendiculatum to survive better in Ni excess habitats.
Ancient mitogenomics elucidates diversity of extinct West Indian tortoises
Authors: Kehlmaier Christian , Albury Nancy A. , Steadman David W. , Graciá Eva , Franz Richard , Fritz Uwe
Published: February 2021

We present 10 nearly complete mitochondrial genomes of the extinct tortoiseChelonoidis alburyorumfrom the Bahamas. While our samples represent morphologically distinct populations from six islands, their genetic divergences were shallow and resembled those among Galápagos tortoises. Our molecular clock estimates revealed that divergence among Bahamian tortoises began ~ 1.5 mya, whereas divergence among the Galápagos tortoises (C. nigercomplex) began ~ 2 mya. The inter-island divergences of tortoises from within the Bahamas and within the Galápagos Islands are much younger (0.09–0.59 mya, and 0.08–1.43 mya, respectively) than the genetic differentiation between any other congeneric pair of tortoise species. The shallow mitochondrial divergences of the two radiations on the Bahamas and the Galápagos Islands suggest that each archipelago sustained only one species of tortoise, and that the taxa currently regarded as distinct species in the Galápagos should be returned to subspecies status. The extinct tortoises from the Bahamas have two well-supported clades: the first includes one sample from Great Abaco and two from Crooked Island; the second clade includes tortoises from Great Abaco, Eleuthera, Crooked Island, Mayaguana, Middle Caicos, and Grand Turk. Tortoises belonging to both clades on Great Abaco and Crooked Island suggest late Holocene inter-island transport by prehistoric humans.
Structural and morphological tuning of Cu-based metal oxide nanoparticles by a facile chemical method and highly electrochemical sensing of sulphite
Authors: Sudha Velayutham , Murugadoss Govindhasamy , Thangamuthu Rangasamy
Published: February 2021

A facile one-step chemical method is introduced for the successful synthesis of Cu2O, CuO and CuNa2(OH)4crystal structures and their electrochemical properties were also investigated. X-ray diffraction studies revealed that these copper-based oxide nanoparticles display different crystal structures such as cubic (Cu2O), monoclinic (CuO) and orthorhombic [CuNa2(OH)4]. The microstructural information of nanoparticles was investigated by transmission electron microscopy. It shows attractive morphologies of different orientation such as rod like structure, nanobeads and well-aligned uniform nanorod for Cu2O, CuO and CuNa2(OH)4, respectively. Electrochemical sensing of sulphite (SO32−) on these three copper-based oxide modified electrodes was investigated. Among the three different crystal structures, CuO shows promising electrocatalytic activity towards oxidation of sulphite. A linear variation in peak current was obtained for SO32−oxidation from 0.2 to 15 mM under the optimum experimental condition. The sensitivity and detection limit were in the order of 48.5 µA cm−2 mM−1and 1.8 µM, respectively. Finally, practical utility of CuO modified electrode was demonstrated for the estimation of sulphite in commercial wine samples.
Retraction Note: JNK confers 5-fluorouracil resistance in p53-deficient and mutant p53-expressing colon cancer cells by inducing survival autophagy
Authors: Sui Xinbing , Kong Na , Wang Xian , Fang Yong , Hu Xiaotong , Xu Yinghua , Chen Wei , Wang Kaifeng , Li Da , Jin Wei , Lou Fang , Zheng Yu , Hu Hong , Gong Liu , Zhou Xiaoyun , Pan Hongming , Han Weidong
Published: February 2021

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-82870-5.
One-step photonic curing of screen-printed conductive Ni flake electrodes for use in flexible electronics
Authors: Altay Bilge Nazli , Turkani Vikram S. , Pekarovicova Alexandra , Fleming Paul D. , Atashbar Massood Z. , Bolduc Martin , Cloutier Sylvain G.
Published: February 2021

Photonic curing has shown great promise in maintaining the integrity of flexible thin polymer substrates without structural degradation due to shrinkage, charring or decomposition during the sintering of printed functional ink films in milliseconds at high temperatures. In this paper, single-step photonic curing of screen-printed nickel (Ni) electrodes is reported for sensor, interconnector and printed electronics applications. Solid bleached sulphate paperboard (SBS) and polyethylene terephthalate polymer (PET) substrates are employed to investigate the electrical performance, ink transfer and ink spreading that directly affect the fabrication of homogeneous ink films. Ni flake ink is selected, particularly since its effects on sintering and rheology have not yet been examined. The viscosity of Ni flake ink yields shear-thinning behavior that is distinct from that of screen printing. The porous SBS substrate is allowed approximately 20% less ink usage. With one-step photonic curing, the electrodes on SBS and PET exhibited electrical performances of a minimum of 4 Ω/sq and 16 Ω/sq, respectively, at a pulse length of 1.6 ms, which is comparable to conventional thermal heating at 130 °C for 5 min. The results emphasize the suitability of Ni flake ink to fabricate electronic devices on flexible substrates by photonic curing.
Initiating Ullmann-like coupling of Br2Py by a semimetal surface
Authors: Hu Jinping , Hu Jinbang , Wang Hongbing , Shen Kongchao , Zhang Huan , Huang Chaoqin , Xie Lei , Tian Qiwei , Huang Han , Jiang Zheng , Song Fei
Published: February 2021

Intensive efforts have been devoted to surface Ullmann-like coupling in recent years, due to its appealing success towards on-surface synthesis of tailor-made nanostructures. While attentions were mostly drawn on metallic substrates, however, Ullmann dehalogenation and coupling reaction on semimetal surfaces has been seldom addressed. Herein, we demonstrate the self-assembly of 2, 7-dibromopyrene (Br2Py) and the well controllable dehalogenation reaction of Br2Py on the Bi(111)–Ag substrate with a combination of scanning tunnelling microscopy (STM) and density functional theory calculations (DFT). By elaborately investigating the reaction path and formed organic nanostructures, it is revealed that the pristinely inert bismuth layer supported on the silver substrate can initiate Ullmann-like coupling in a desired manner by getting alloyed with Ag atoms underneath, while side products have not been discovered. By clarifying the pristine nature of Bi–Ag(111) and Ullmann-like reaction mechanisms, our report proposes an ideal template for thoroughly exploring dehalogenative coupling reaction mechanisms with atomic insights and on-surface synthesis of carbon-based architectures.
Big trees drive forest structure patterns across a lowland Amazon regrowth gradient
Authors: Caron Tassiana Maylla Fontoura , Chuma Victor Juan Ulises Rodriguez , Sandi Alexander Arévalo , Norris Darren
Published: February 2021

Degraded Amazonian forests can take decades to recover and the ecological results of natural regeneration are still uncertain. Here we use field data collected across 15 lowland Amazon smallholder properties to examine the relationships between forest structure, mammal diversity, regrowth type, regrowth age, topography and hydrology. Forest structure was quantified together with mammal diversity in 30 paired regrowth-control plots. Forest regrowth stage was classified into three groups: late second-regrowth, early second-regrowth and abandoned pasture. Basal area in regrowth plots remained less than half that recorded in control plots even after 20–25 years. Although basal area did increase in sequence from pasture, early to late-regrowth plots, there was a significant decline in basal area of late-regrowth control plots associated with a decline in the proportion of large trees. Variation in different forest structure responses was explained by contrasting variables, with the proportion of small trees (DBH < 20 cm) most strongly explained by topography (altitude and slope) whereas the proportion of large trees (DBH > 60 cm) was explained by plot type (control vs. regrowth) and regrowth class. These findings support calls for increased efforts to actively conserve large trees to avoid retrogressive succession around edges of degraded Amazon forests.
Investigations on the effect of different influencing factors on film cooling effectiveness under the injection of synthetic coolant
Authors: Chang Jianlong , Duan Xinlei , Du Yang , Guo Baoquan , Pan Yutian
Published: February 2021

By combining the synthetic jet and film cooling, the incident cooling flow is specially treated to find a better film cooling method. Numerical simulations of the synthetic coolant ejected are carried out for analyzing the cooling performance in detail, under different blowing ratios, hole patterns, Strouhal numbers, and various orders of incidence for the two rows of holes. By comparing the flow structures and the cooling effect corresponding to the synthetic coolant and the steady coolant fields, it is found that within the scope of the investigations, the best cooling effect can be obtained under the incident conditions of an elliptical hole with the aspect ratio of 0.618, the blow molding ratio of 2.5, and the Strouhal number St = 0.22. Due to the strong controllability of the synthetic coolant, the synthetic coolant can be controlled through adjusting the frequency of blowing and suction, so as to change the interaction between vortex structures for improving film cooling effect in turn. As a result, the synthetic coolant ejection is more advisable in certain conditions to achieve better outcomes.
Improved spectral resolution of the femtosecond stimulated Raman spectroscopy achieved by the use of the 2nd-order diffraction method
Authors: Kang Dong-gu , Woo Kyung Chul , Kang Do Hyung , Park Chanho , Kim Sang Kyu
Published: February 2021

Prolongation of the picosecond Raman pump laser pulse in the femtosecond stimulated Raman spectroscopy (FSRS) setup is essential for achieving the high spectral resolution of the time-resolved vibrational Raman spectra. In this work, the 2nd-order diffraction has been firstly employed in the double-pass grating filter technique for realizing the FSRS setup with the sub-5 cm−1 spectral resolution. It has been experimentally demonstrated that our new FSRS setup gives rise to a highly-resolved Raman spectrum of the excited trans-stilbene, which is much improved from those reported in the literatures. The spectral resolution of the present FSRS system has been estimated to be the lowest value ever reported to date, giving Δν = 2.5 cm−1.
Association mapping for maize stover yield and saccharification efficiency using a multiparent advanced generation intercross (MAGIC) population
Authors: López-Malvar A. , Butron A. , Malvar R. A. , McQueen-Mason S. J. , Faas L. , Gómez L. D. , Revilla P. , Figueroa-Garrido D. J. , Santiago R.
Published: February 2021

Cellulosic ethanol derived from fast growing C4 grasses could become an alternative to finite fossil fuels. With the potential to generate a major source of lignocellulosic biomass, maize has gained importance as an outstanding model plant for studying the complex cell wall network and also to optimize crop breeding strategies in bioenergy grasses. A genome-wide association study (GWAS) was conducted using a subset of 408 Recombinant Inbred Lines (RILs) from a Multi-Parent Advanced Generation Intercross (MAGIC) Population in order to identify single nucleotide polymorphisms (SNPs) associated with yield and saccharification efficiency of maize stover. We identified 13 SNPs significantly associated with increased stover yield that corresponded to 13 QTL, and 2 SNPs significantly associated with improved saccharification efficiency, that could be clustered into 2 QTL. We have pointed out the most interesting SNPs to be implemented in breeding programs based on results from analyses of averaged and yearly data. Association mapping in this MAGIC population highlight genomic regions directly linked to traits that influence the final use of maize. Markers linked to these QTL could be used in genomic or marker-assisted selection programs to improve biomass quality for ethanol production. This study opens a possible optimisation path for improving the viability of second-generation biofuels.
Alterations in reward network functional connectivity are associated with increased food addiction in obese individuals
Authors: Ravichandran Soumya , Bhatt Ravi R. , Pandit Bilal , Osadchiy Vadim , Alaverdyan Anita , Vora Priten , Stains Jean , Naliboff Bruce , Mayer Emeran A. , Gupta Arpana
Published: February 2021

Functional neuroimaging studies in obesity have identified alterations in the connectivity within the reward network leading to decreased homeostatic control of ingestive behavior. However, the neural mechanisms underlying sex differences in the prevalence of food addiction in obesity is unknown. The aim of the study was to identify functional connectivity alterations associated with: (1) Food addiction, (2) Sex- differences in food addiction, (3) Ingestive behaviors. 150 participants (females: N = 103, males: N = 47; food addiction: N = 40, no food addiction: N = 110) with high BMI ≥ 25 kg/m2 underwent functional resting state MRIs. Participants were administered the Yale Food Addiction Scale (YFAS), to determine diagnostic criteria for food addiction (YFAS Symptom Count ≥ 3 with clinically significant impairment or distress), and completed ingestive behavior questionnaires. Connectivity differences were analyzed using a general linear model in the CONN Toolbox and images were segmented using the Schaefer 400, Harvard–Oxford Subcortical, and Ascending Arousal Network atlases. Significant connectivities and clinical variables were correlated. Statistical significance was corrected for multiple comparisons at q < .05. (1) Individuals with food addiction had greater connectivity between brainstem regions and the orbital frontal gyrus compared to individuals with no food addiction. (2) Females with food addiction had greater connectivity in the salience and emotional regulation networks and lowered connectivity between the default mode network and central executive network compared to males with food addiction. (3) Increased connectivity between regions of the reward network was positively associated with scores on the General Food Cravings Questionnaire-Trait, indicative of greater food cravings in individuals with food addiction. Individuals with food addiction showed greater connectivity between regions of the reward network suggesting dysregulation of the dopaminergic pathway. Additionally, greater connectivity in the locus coeruleus could indicate that the maladaptive food behaviors displayed by individuals with food addiction serve as a coping mechanism in response to pathological anxiety and stress. Sex differences in functional connectivity suggest that females with food addiction engage more in emotional overeating and less cognitive control and homeostatic processing compared to males. These mechanistic pathways may have clinical implications for understanding the sex-dependent variability in response to diet interventions.
Light environment drives evolution of color vision genes in butterflies and moths
Authors: Sondhi Yash , Ellis Emily A. , Bybee Seth M. , Theobald Jamie C. , Kawahara Akito Y.
Published: February 2021

Opsins, combined with a chromophore, are the primary light-sensing molecules in animals and are crucial for color vision. Throughout animal evolution, duplications and losses of opsin proteins are common, but it is unclear what is driving these gains and losses. Light availability is implicated, and dim environments are often associated with low opsin diversity and loss. Correlations between high opsin diversity and bright environments, however, are tenuous. To test if increased light availability is associated with opsin diversification, we examined diel niche and identified opsins using transcriptomes and genomes of 175 butterflies and moths (Lepidoptera). We found 14 independent opsin duplications associated with bright environments. Estimating their rates of evolution revealed that opsins from diurnal taxa evolve faster—at least 13 amino acids were identified with higher dN/dS rates, with a subset close enough to the chromophore to tune the opsin. These results demonstrate that high light availability increases opsin diversity and evolution rate in Lepidoptera.
Glycolipid-dependent and lectin-driven transcytosis in mouse enterocytes
Authors: Ivashenka Alena , Wunder Christian , Chambon Valerie , Sandhoff Roger , Jennemann Richard , Dransart Estelle , Podsypanina Katrina , Lombard Bérangère , Loew Damarys , Lamaze Christophe , Poirier Francoise , Gröne Hermann-Josef , Johannes Ludger , Shafaq-Zadah Massiullah
Published: February 2021

Glycoproteins and glycolipids at the plasma membrane contribute to a range of functions from growth factor signaling to cell adhesion and migration. Glycoconjugates undergo endocytic trafficking. According to the glycolipid-lectin (GL-Lect) hypothesis, the construction of tubular endocytic pits is driven in a glycosphingolipid-dependent manner by sugar-binding proteins of the galectin family. Here, we provide evidence for a function of the GL-Lect mechanism in transcytosis across enterocytes in the mouse intestine. We show that galectin-3 (Gal3) and its newly identified binding partner lactotransferrin are transported in a glycosphingolipid-dependent manner from the apical to the basolateral membrane. Transcytosis of lactotransferrin is perturbed in Gal3 knockout mice and can be rescued by exogenous Gal3. Inside enterocytes, Gal3 is localized to hallmark structures of the GL-Lect mechanism, termed clathrin-independent carriers. These data pioneer the existence of GL-Lect endocytosis in vivo and strongly suggest that polarized trafficking across the intestinal barrier relies on this mechanism.
Impact of mid Eocene greenhouse warming on America’s southernmost floras
Authors: Fernández Damián A. , Palazzesi Luis , González Estebenet M. Sol , Tellería M. Cristina , Barreda Viviana D.
Published: February 2021

A major climate shift took place about 40 Myr ago—the Middle Eocene Climatic Optimum or MECO—triggered by a significant rise of atmospheric CO2 concentrations. The biotic response to this MECO is well documented in the marine realm, but poorly explored in adjacent landmasses. Here, we quantify the response of the floras from America’s southernmost latitudes based on the analysis of terrestrially derived spores and pollen grains from the mid-late Eocene (~46–34 Myr) of southern Patagonia. Robust nonparametric estimators indicate that floras in southern Patagonia were in average ~40% more diverse during the MECO than pre-MECO and post-MECO intervals. The high atmospheric CO2 and increasing temperatures may have favored the combination of neotropical migrants with Gondwanan species, explaining in part the high diversity that we observed during the MECO. Our reconstructed biota reflects a greenhouse world and offers a climatic and ecological deep time scenario of an ice-free sub-Antarctic realm.
Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Authors: Kim Youngchang , Wower Jacek , Maltseva Natalia , Chang Changsoo , Jedrzejczak Robert , Wilamowski Mateusz , Kang Soowon , Nicolaescu Vlad , Randall Glenn , Michalska Karolina , Joachimiak Andrzej
Published: February 2021

SARS-CoV-2 Nsp15 is a uridine-specific endoribonuclease with C-terminal catalytic domain belonging to the EndoU family that is highly conserved in coronaviruses. As endoribonuclease activity seems to be responsible for the interference with the innate immune response, Nsp15 emerges as an attractive target for therapeutic intervention. Here we report the first structures with bound nucleotides and show how the enzyme specifically recognizes uridine moiety. In addition to a uridine site we present evidence for a second base binding site that can accommodate any base. The structure with a transition state analog, uridine vanadate, confirms interactions key to catalytic mechanisms. In the presence of manganese ions, the enzyme cleaves unpaired RNAs. This acquired knowledge was instrumental in identifying Tipiracil, an FDA approved drug that is used in the treatment of colorectal cancer, as a potential anti-COVID-19 drug. Using crystallography, biochemical, and whole-cell assays, we demonstrate that Tipiracil inhibits SARS-CoV-2 Nsp15 by interacting with the uridine binding pocket in the enzyme’s active site. Our findings provide new insights for the development of uracil scaffold-based drugs.
Molecular mechanisms of cell cryopreservation with polyampholytes studied by solid-state NMR
Authors: Matsumura Kazuaki , Hayashi Fumiaki , Nagashima Toshio , Rajan Robin , Hyon Suong-Hyu
Published: February 2021

Polyampholytes are emerging macromolecular membrane non-penetrating cryoprotectants; however, the mechanism behind their cryopreservation remains unclear. Here, we investigated the mechanism using solid-state NMR spectroscopy. The polymer-chain dynamics and the water and ion mobilities in the presence of various membrane penetrating and non-penetrating cryoprotectants were monitored at low temperatures to mimic cryopreservation conditions. NMR experiments revealed that the water, Sodium-ion, and polymer-chain signals in a carboxylated poly-ʟ-lysine (COOH-PLL) solution broadened upon cooling, indicating increasingly restricted mobility and increased solution viscosity. Moreover, strong intermolecular interactions facilitated the COOH-PLL glass transition, trapping water and salt in the gaps of the reversible matrix, preventing intracellular ice formation and osmotic shock during freezing; this reduced cell stress is responsible for cryoprotection. This simple NMR technique enabled the correlation of the cryoprotective properties of polymers that operate through mechanisms different from those of current cryoprotectants, and will facilitate the future molecular design of cryoprotectants.