bluuebunny/crossref_metadata_2025_split huggingface dataset:
A “spindle and thread”-mechanism unblocks translation of N-terminally disordered proteins
Authors: Kaldmäe Margit , Vosselman Thibault , Zhong Xueying , Lama Dilraj , Chen Gefei , Saluri Mihkel , Kronqvist Nina , Siau Jia Wei , Ng Aik Seng , Ghadessy Farid J. , Sabatier Pierre , Vojtesek Borivoj , Sarr Médoune , Sahin Cagla , Österlund Nicklas , Ilag Leopold L. , Väänänen Venla A. , Sedimbi Saikiran , Zubarev Roman A. , Nilsson Lennart , Koeck Philip J. B. , Rising Anna , Fritz Nicolas , Johansson Jan , Lane David P. , Landreh Michael 
Published: February 2021

AbstractProtein disorder is a major hurdle for structural biology. A prominent example is the tumour suppressor p53, whose low expression levels and poor conformational stability due to a high degree of disorder pose major challenges to the development of cancer therapeutics. Here, we address these issues by fusing p53 to an engineered spider silk domain termed NT*. The chimeric protein displays highly efficient translationin vitroand inE. coliand is fully active in human cancer cells. The transmission electron microscopy structure and native mass spectrometry reveal that the full-length p53 fusion protein adopts a compact conformation. Molecular dynamics simulations show that the disordered transactivation domain of p53 is wound around the NT*domain via a series of folding events, resulting in a globular structure. We find that expression of B-Raf, another partially disordered cancer target, is similarly enhanced by fusion to NT*. In summary, we demonstrate how inducing co-translational folding via a molecular “spindle and thread” mechanism can overcome poor translation efficiency of partially disordered proteins.
Systems approaches identify the consequences of monosomy in somatic human cells
Authors: Chunduri Narendra Kumar , Menges Paul , Gotsmann Vincent Leon , Zhang Xiaoxiao , Mardin Balca R. , Buccitelli Christopher , Korbel Jan O. , Willmund Felix , Kschischo Maik , Raeschle Markus , Storchova Zuzana 
Published: February 2021

AbstractChromosome loss that results in monosomy is detrimental to viability, yet, it is frequently observed in cancers. How cancers survive with monosomy is unknown. Using p53 deficient monosomic cell lines, we found that chromosome loss impairs proliferation and genomic stability. Transcriptome and proteome analysis revealed a partial compensation of the gene dosage changes that mitigates the effects of chromosome loss. Monosomy triggers global gene expression changes that differ from the effects of trisomy. We show that ribosome biogenesis and translation were commonly downregulated in monosomic cells, likely due to haploinsufficiency of ribosomal genes. The ensuing ribosome biogenesis stress triggers the p53 pathway and G1 arrest whenTP53is reintroduced into monosomic cells. Accordingly, impaired ribosome biogenesis and p53 inactivation are associated with monosomy in cancer. Our first systematic study of monosomy in human cells explains why monosomy is so detrimental and how loss of p53 enables its incidence in cancer.
Sulfur limitation increases duckweed starch accumulation without compromising growth
Authors: Sun Zuoliang , Guo Wenjun , Zhao Xuyao , Yang Jingjing , Duan Pengfei , Xu Shuqing , Hou Hongwei 
Published: February 2021

AbstractDuckweeds contain relatively high levels of starch and are a potential biomass feedstock for biofuel production. Here, the biomass and starch yield of duckweed under three different nutrient-limited conditions were analyzed to investigate possible ways of further increasing the efficiency of starch production. The results showed that sulfur limitation resulted in the highest starch yield, which was 42% and 73% higher than in nitrogen or phosphorus limitation, respectively. The high yield of sulfur-limited duckweed is largely due to the combinations of little effects on biomass and high accumulations of starch. Although nitrogen limitation led to higher starch content (67.4%), it severely reduced biomass production. The photosynthetic performance indicatorFv/Fmwas a simple and sensitive indicator of starch content in nutrient-limited duckweed. Taken together, this study demonstrates that sulfur limitation is a simple and efficient way to increase starch yield, highlighting the great potential of duckweed for biofuel production. We report that sulfur limitation is a practical approach to increase starch yields in duckweed without affecting growth or biomass.HighlightsSulfur limitation induces starch production in a duckweed specie.Nitrogen limitation triggers the highest starch content, but limits growth.Sulfur limitation results in the highest starch yield.Fv/Fmis a rapid and robust proxy of starch content in nutrient-limited duckweed.
Laser-facilitated epicutaneous immunization with SARS-CoV-2 spike protein induces ACE2 blocking antibodies in mice
Authors: Scheiblhofer Sandra , Drothler Stephan , Braun Werner , Braun Reinhard , Boesch Maximilian , Weiss Richard 
Published: February 2021

AbstractThe skin represents an attractive target tissue for vaccination against respiratory viruses such as SARS-CoV-2. Laser-facilitated epicutaneous immunization (EPI) has been established as a novel technology to overcome the skin barrier, which combines efficient delivery via micropores with an inherent adjuvant effect due to the release of danger-associated molecular patterns. Here we delivered the S1 subunit of the Spike protein of SARS-CoV-2 to the skin of BALB/c mice via laser-generated micropores with or without CpG-ODN1826 or the B subunit of heat-labile enterotoxin of E.coli (LT-B). EPI induced serum IgG titers of 1:3200 that could be boosted 5 to 10-fold by co-administration of LT-B and CpG, respectively. Sera were able to inhibit binding of the spike protein to its receptor ACE2. Our data indicate that delivery of recombinant spike protein via the skin may represent an alternative route for vaccines against Covid-19.
Suppression of alpha-band power underlies exogenous attention to emotional distractors
Authors: Arana Lydia , Melcón María , Kessel Dominique , Hoyos Sandra , Albert Jacobo , Carretié Luis , Capilla Almudena 
Published: February 2021

AbstractAlpha-band oscillations (8-14 Hz) are essential for attention and perception processes by facilitating the selection of relevant information. Directing visuospatial endogenous (voluntary) attention to a given location consistently results in a power suppression of alpha activity over occipito-parietal areas contralateral to the attended visual field. In contrast, the neural oscillatory dynamics underlying the involuntary capture of attention, or exogenous attention, are currently under debate. By exploiting the inherent capacity of emotionally salient visual stimuli to capture attention, we aimed to investigate whether exogenous attention is characterized by either a reduction or an increase in alpha-band activity. Electroencephalographic activity was recorded while participants completed a Posner visuospatial cueing task, in which a lateralized image with either positive, negative, or neutral emotional content competed with a target stimulus presented in the opposite hemifield. Compared with trials with no distractors, alpha power was reduced over occipital regions contralateral to distracting images. This reduction of alpha activity turned out to be functionally relevant, as it correlated with impaired behavioural performance on the ongoing task and was enhanced for distractors with negative valence. Taken together, our results demonstrate that visuospatial exogenous attention is characterized by a suppression of alpha-band activity contralateral to distractor location, similar to the oscillatory underpinnings of endogenous attention. Further, these results highlight the key role of exogenous attention as an adaptive mechanism for the efficient detection of biologically salient stimuli.HighlightsExogenous attention is indexed by alpha suppression contralateral to distractors.Alpha power decrease is enhanced by distractors with negative emotional valence.Lower levels of alpha power correlate with poorer task performance accuracy.The negativity bias in exogenous attention might reflect an adaptive mechanism.
Milk-Way Algorithm applied in Imbalanced Dataset
Authors: Leite Carmelina Figueiredo Vieira , dos Santos Marcos Augusto 
Published: February 2021

AbstractWe wish to evaluate the algorithm Milk-Way, using a known dataset deposited in a public repository. The new algorithm, which converges various techniques from different areas of knowledge, can classify ligands and select potential new drugs. It was used a dataset of ligands, organized by 15 Bioassays and described by different fingerprints. Full details of the dataset architecture were already published in a public repository. Through the stratified feature selection, using the Milk-Way algorithm, the True Positive and False Positive Rates reached a higher performance compared to the published paper. Using all the features available for each Bioassay, we reached the lowest metrics in all of them. We demonstrated that adding more features have not made a significant impact on the performance. In all the Bioassays, the True Positives and False Positives reached 100% and 0%, respectively, only using 50% and 75% of the features available. The Milk-Way algorithm suggests a holistic approach, which will contribute to the machine-learning area, namely to classified ligands in the virtual screening.
Female manipulation of offspring sex ratio in the gregarious parasitoidAnaphes flavipesfrom a new two-generation approach
Authors: Samková Alena , Raška Jan , Hadrava Jiří , Skuhrovec Jiří , Janšta Petr 
Published: February 2021

ABSTRACTBoth theoretical and empirical work suggests that offspring sex ratio has important consequences on fitness. Within insects, gregarious parasitoids with haplodiploid sex determination represent an ideal model for studying the decision-making process behind the assignment of offspring sex. To gain insight into the offspring sex ratio of gregarious parasitoids, we performed experiments onAnaphes flavipes, interpreting our results through a two-generation approach. We confirm the existence of a relationship between offspring sex ratio and clutch size: the proportion of males increases with larger clutch size. Based on this finding, we assumed that the proportion of males among one female’s offspring would also increase with external factors such as a low population density of the host or the presence of the host’s predator, which may pressure the mothers to lay a higher-sized clutch. Contrary to our initial expectations, we show that if it is the pressure of external factors that leads to an increase in clutch size, these larger clutches tend to be more female-biased and the overall offspring sex ratio of a particular female does not change. While in our previous work, we showed that higher clutch sizes reduce body sizes of the offspring and their future fertility, here we conclude that the differences in fertility affect the offspring sex ratio. Taken together, we highlight our two-generation approach which reveals that while the above external factors do not affect the sex ratio ofA. flavipesin the F1 generation, they do have an effect in the F2 generation.
Dietary Vitamin B12reduces amyloid-β proteotoxicity by alleviating oxidative stress and mitochondrial dysfunction
Authors: Lam Andy B. , Kervin Kirsten , Tanis Jessica E. 
Published: February 2021

SUMMARYAlzheimer’s disease (AD) is a devastating neurodegenerative disorder with no effective treatment. Diet, as a modifiable risk factor for AD, could potentially be targeted to slow disease onset and progression. However, complexity of the human diet and indirect effects of the microbiome make it challenging to identify protective nutrients. Multiple factors contribute to AD pathogenesis including amyloid beta (Aβ) deposition, mitochondrial dysfunction, and oxidative stress. Here we usedCaenorhabditis elegansto define the impact of diet on Aβ proteotoxicity. We discovered that dietary vitamin B12alleviated mitochondrial fragmentation, bioenergetic defects, and oxidative stress, delaying Aβ-induced paralysis without affecting Aβ accumulation. Vitamin B12had this protective effect by acting as a cofactor for methionine synthase rather than as an antioxidant. Vitamin supplementation of B12deficient adult Aβ animals was beneficial, demonstrating potential for vitamin B12as a therapy to target pathogenic features of AD triggered by both aging and proteotoxic stress.
Hydrophobic-cationic peptides enhance RNA polymerase ribozyme activity by accretion
Authors: Li Peiying , Holliger Philipp , Tagami Shunsuke 
Published: February 2021

ABSTRACTAccretion and the resulting increase in local concentration to enhance target stability and function is a widespread mechanism in biology (for example in the liquid-liquid demixing phases and coacervates). It is widely believed that such macromolecular aggregates (formed through ionic and hydrophobic interactions) may have played a role in the origin of life. Here, we report on the behaviour of a hydrophobic-cationic RNA binding peptide selected by phage display (P43: AKKVWIIMGGS) that forms insoluble aggregates, accrete RNA on their surfaces in a size-dependent manner, and thus enhance the activities of various ribozymes. At low Mg2+concentrations ([Mg2+]: 25 mM MgCl2), the activity of a small ribozyme (hammerhead ribozyme) was enhanced by P43, while larger ribozymes (RNA polymerase ribozyme (RPR), RNase P, F1* ligase) were inhibited. In contrast, at high [Mg2+] (≥200 mM), the RPR activity was enhanced. Another hydrophobic-cationic peptide with a simpler sequence (K2V6: KKVVVVVV) also exhibited similar regulatory effects on the RPR activity. Furthermore, inactive RPR captured on P43 aggregates at low [Mg2+] could be reactivated in a high [Mg2+] buffer. Therefore, in marked contrast to previously studied purely cationic peptides (like K10) that enhance RPR only at low ionic strength, hydrophobic-cationic peptides can reversibly concentrate RNA and enhance the RPR activity even at high ionic strength conditions such as in eutectic ice phases. Such peptides could have aided the emergence of longer and functional RNAs in a fluctuating environment (e.g., dry-wet / freeze-thaw cycles) on the prebiotic earth.
Mass cytometry reveals immunological response to radiation-induced cardiac fibrosis in mice
Authors: Tang Yi , Wang Bing , Sun Mingjiao , Liu Pan , Zhang Xue , You Mingliang , Xia Bing 
Published: February 2021

AbstractBackgroundRadiation-induced cardiac injury results in complex clinical presentations, unique management issues, and increased morbidity and mortality. But the underlying mechanism of radiation-induced cardiac injury is still unclear. The aim of this study is to explain the compositional alterations of innate and adaptive cells after thoracic irradiation and the relationship of macrophage with other adaptive cells.MethodsC57BL/6 mice were anesthetized and performed with 20Gy single dose cardiac irradiation. We carried out mice echocardiography to examine cardiac function. Masson and immunohistochemical staining were adopted to analyze cardiac fibrosis. Blood and cardiac tissue were collected 7 days, 4 weeks and 8 weeks after irradiation and sham-irradiated mice were set as a control group. Part of blood and tissue samples were analyzed with mass cytometry. We also used remaining blood samples to measure pro-fibrotic cytokines.ResultsWe observed reduced cardiac diastolic function and pathologically confirmed cardiac fibrosis after thoracic irradiation. Through mass cytometry, we identified that the proportion of neutrophils, macrophages and monocytes elevated. The ratio of T and B cells decreased after irradiation in the blood samples. For tissue samples, the proportion of macrophages, monocytes and neutrophils increased, endothelial cells reduced, but T and B cells also increased. The level of TGF-β, TNF-α, IL-6 climbed considerably, all of them are closely associated with the evolution of macrophage function during recovering phase of cardiac injury. In the correlation plot, we also discovered that CD4+T and CD8+T cells were strongly positively correlated with macrophages.ConclusionWe illustrated the immunological response after radiation-induced cardiac fibrosis, and macrophage may play a crucial role during the process. The results might have therapeutic potential for targeting macrophages in order to reduce radiation-induced cardiac fibrosis.
Cross-sectional analysis of the microbiota of human gut and their direct environment (exposome) in a household cohort in northern Vietnam
Authors: Bich Vu Thi Ngoc , Hai Ho Bich , Galazzo Gianluca , Viet Dung Vu Tien , Oomen Melissa , Nguyen Minh Trang Nghiem , Hoang Tran Huy , van Doorn H. Rogier , Wertheim Heiman FL , Penders John 
Published: February 2021

AbstractComprehensive insight into the human gut microbiota and the interaction with their environment in communities with a high background of antibiotic use and antibiotic resistance genes is currently largely lacking. In a cohort (Vietnam), individuals within the same household, also individuals within their geographical cluster share more bacterial taxa than individuals from different households or geographical clusters. The microbial diversity among individuals who used antibiotics in the past four months was significantly lower than those who did not. Fecal microbiota of humans was more diverse than non-human samples, shared a small part of its amplicon sequence variants (ASVs) with feces from animals (7.4%), water (2.2%) and food (3.1%). Sharing of ASVs between humans and companion animals was not associated with household. There is a correlation between an Enterobacteriaceae ASV and the presence of blactx-m-2 in feces from humans and animals, hinting towards an exchange of antimicrobial resistant strains between reservoirs.
Structural and functional characterization of SARS-CoV-2 RBD domains produced in mammalian cells
Authors: Gstöttner Christoph , Zhang Tao , Resemann Anja , Ruben Sophia , Pengelley Stuart , Suckau Detlev , Welsink Tim , Wuhrer Manfred , Domínguez-Vega Elena 
Published: February 2021

AbstractAs the SARS-CoV-2 pandemic is still ongoing and dramatically influences our life, the need for recombinant proteins for diagnostics, vaccine development, and research is very high. The spike (S) protein, and particularly its receptor binding domain (RBD), mediates the interaction with the ACE2 receptor on host cells and may be modulated by its structural features. Therefore, well characterized recombinant RBDs are essential. We have performed an in-depth structural and functional characterization of RBDs expressed in Chinese hamster ovary (CHO) and human embryonic kidney (HEK293) cells. To structurally characterize the native RBDs (comprisingN- andO-glycans and additional posttranslational modifications) a multilevel mass spectrometric approach was employed. Released glycan and glycopeptide analysis were integrated with intact mass analysis, glycan-enzymatic dissection and top-down sequencing for comprehensive annotation of RBD proteoforms. The data showed distinct glycosylation for CHO- and HEK293-RBD with the latter exhibiting antenna fucosylation, higher level of sialylation and a combination of core 1 and core 2 typeO-glycans. Additionally, from both putativeO-glycosylation sites, we could confirm thatO-glycosylation was exclusively present at T323, which was previously unknown. For both RBDs, the binding to SARS-CoV-2 antibodies of positive patients and affinity to ACE2 receptor was addressed showing comparable results. This work not only offers insights into RBD structural and functional features but also provides a workflow for characterization of new RBDs and batch-to-batch comparison.
Stabilin-1 plays a protective role againstListeriamonocytogenes infection through the regulation of cytokine and chemokine production and immune cell recruitment
Authors: Pombinho Rita , Pinheiro Jorge , Resende Mariana , Meireles Diana , Jalkanen Sirpa , Sousa Sandra , Cabanes Didier 
Published: February 2021

ABSTRACTScavenger receptors are part of a complex surveillance system expressed by host cells to efficiently orchestrate innate immune response against bacterial infections. Stabilin-1 (STAB-1) is a scavenger receptor involved in cell trafficking, inflammation and cancer, however its role in infection remains to be elucidated.Listeria monocytogenes(Lm) is a major intracellular human food-borne pathogen causing severe infections in susceptible hosts. Using a mouse model of infection, we demonstrate here that STAB-1 controlsLm-induced cytokine and chemokine production and immune cell accumulation inLm-infected organs. We show that STAB-1 also regulates the recruitment of myeloid cells in response toLminfection and contributes to clear circulating bacteria. In addition, whereas STAB-1 appears to promote bacterial uptake by macrophages, infection by pathogenicListeriainduces the down regulation of STAB-1 expression and its delocalization from the host cell membrane.We propose STAB-1 as a new SR involved in the control ofLminfection through the regulation of host defense mechanisms, a process that would be targeted by bacterial virulence factors to promote infection.
Prevention of quality loss and melanosis of white leg shrimp by Sargassum horneri extracts
Authors: Fang Hua , Zhang Jianyu , Hong Zhuan , Chen Weizhu , Zhang Yiping , Fang Meijuan 
Published: February 2021

PurposeBeing interested in developing a natural preservative for the prolongation of shrimp shelf life, this study aims to evaluate the Sargassum horneri extracts for their antioxidant effect, copper reducing power, copper chelating activity and polyphenol oxidase (PPO) inhibitory activity, as well as explored their potential preservative activity in white leg shrimp.Design/methodology/approachThe antioxidant properties of Sargassum horneri 75% ethanol aqueous extracts were measured by 2,2-diphenyl-1-picryl hydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) and PPO inhibitory activity. Sample III displayed the highest antioxidant activity, PPO inhibitory activity, copper reducing power and copper chelating activity, so it was selected for further studying its impact on shrimp's quality changes such as pH value, total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS), melanosis and sensory score during storage at 4°C.FindingsAmong all three samples, sample III containing 49.88% total phenolic contents was selected for the further study on the prevention of quality loss and melanosis of shrimp, because it yielded the highest antioxidant activity, PPO inhibitory activity, copper reducing power and copper chelating activity than the other two samples (samples II and IV). It was found that shrimp treated with 0.2% sample III had the lowest melanosis scores throughout the storage (p < 0.05). During ten days of storage at 4°C, shrimp treated with 0.2% sample III had a higher score in sensory properties (color, segments, texture and odor), compared with the control, 0.1% kojic acid and 0.1% sample III treated shrimp (p < 0.05). The results indicated that the treatment of shrimp with 0.2% sample III could extend the shelf life to eight days at 4°C.Social implicationsThe extracts of Sargassum horneri displayed potent PPO inhibition, antimicrobial and antioxidant properties. Importantly, the 75% extracts of Sargassum horneri could extend the shelf life. Considering these results, the extracts of Sargassum horneri may be used as natural preservatives in the food industry after further evaluation of their other properties such as toxicity, as well as provide a choice target to source natural products intended for cosmetics.Originality/valueThe originality of this paper lies in the development and application of the extracts of edible algae. To extend the shelf life of seafood, the polyphenolic-rich extract of Sargassum horneri provided another possible selection.