bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved resolution in single-molecule localization microscopy using QD-PAINT
Authors: Chang Yeonho , Kim Do-Hyeon , Zhou Kai , Jeong Min Gyu , Park Soyeon , Kwon Yonghoon , Hong Triet Minh , Noh Jungeun , Ryu Sung Ho
Published: March 2021

Single-molecule localization microscopy (SMLM) has allowed the observation of various molecular structures in cells beyond the diffraction limit using organic dyes. In principle, the SMLM resolution depends on the precision of photoswitching fluorophore localization, which is inversely correlated with the square root of the number of photons released from the individual fluorophores. Thus, increasing the photon number by using highly bright fluorophores, such as quantum dots (QDs), can theoretically fundamentally overcome the current resolution limit of SMLM. However, the use of QDs in SMLM has been challenging because QDs have no photoswitching property, which is essential for SMLM, and they exhibit nonspecificity and multivalency, which complicate their use in fluorescence imaging. Here, we present a method to utilize QDs in SMLM to surpass the resolution limit of the current SMLM utilizing organic dyes. We confer monovalency, specificity, and photoswitchability on QDs by steric exclusion via passivation and ligand exchange with ptDNA, PEG, and casein as well as by DNA point accumulation for imaging in nanoscale topography (DNA-PAINT) via automatic thermally driven hybridization between target-bound docking and dye-bound complementary imager strands. QDs are made monovalent and photoswitchable to enable SMLM and show substantially better photophysical properties than Cy3, with higher fluorescence intensity and an improved resolution factor. QD-PAINT displays improved spatial resolution with a narrower full width at half maximum (FWHM) than DNA-PAINT with Cy3. In summary, QD-PAINT shows great promise as a next-generation SMLM method for overcoming the limited resolution of the current SMLM.
Correction: Novel polygenic risk score as a translational tool linking depression-related changes in the corticolimbic transcriptome with neural face processing and anhedonic symptoms
Authors: Mareckova Klara , Hawco Colin , Santos Fernanda C. Dos , Bakht Arin , Calarco Navona , Miles Amy E. , Voineskos Aristotle N. , Sibille Etienne , Hariri Ahmad R. , Nikolova Yuliya S.
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41398-021-01277-y
Meta-analysis of neural systems underlying placebo analgesia from individual participant fMRI data
Authors: Zunhammer Matthias , Spisák Tamás , Wager Tor D. , Bingel Ulrike ,   The Placebo Imaging Consortium, Atlas Lauren , Benedetti Fabrizio , Büchel Christian , Choi Jae Chan , Colloca Luana , Duzzi Davide , Eippert Falk , Ellingsen Dan-Mikael , Elsenbruch Sigrid , Geuter Stephan , Kaptchuk Ted J. , Kessner Simon S. , Kirsch Irving , Kong Jian , Lamm Claus , Leknes Siri , Lui Fausta , Müllner-Huber Alexa , Porro Carlo A. , Rütgen Markus , Schenk Lieven A. , Schmid Julia , Theysohn Nina , Tracey Irene , Wrobel Nathalie , Zeidan Fadel
Published: March 2021

The brain systems underlying placebo analgesia are insufficiently understood. Here we performed a systematic, participant-level meta-analysis of experimental functional neuroimaging studies of evoked pain under stimulus-intensity-matched placebo and control conditions, encompassing 603 healthy participants from 20 (out of 28 eligible) studies. We find that placebo vs. control treatments induce small, widespread reductions in pain-related activity, particularly in regions belonging to ventral attention (including mid-insula) and somatomotor networks (including posterior insula). Behavioral placebo analgesia correlates with reduced pain-related activity in these networks and the thalamus, habenula, mid-cingulate, and supplementary motor area. Placebo-associated activity increases occur mainly in frontoparietal regions, with high between-study heterogeneity. We conclude that placebo treatments affect pain-related activity in multiple brain areas, which may reflect changes in nociception and/or other affective and decision-making processes surrounding pain. Between-study heterogeneity suggests that placebo analgesia is a multi-faceted phenomenon involving multiple cerebral mechanisms that differ across studies.
Unlocking history through automated virtual unfolding of sealed documents imaged by X-ray microtomography
Authors: Dambrogio Jana , Ghassaei Amanda , Smith Daniel Starza , Jackson Holly , Demaine Martin L. , Davis Graham , Mills David , Ahrendt Rebekah , Akkerman Nadine , van der Linden David , Demaine Erik D.
Published: March 2021

Computational flattening algorithms have been successfully applied to X-ray microtomography scans of damaged historical documents, but have so far been limited to scrolls, books, and documents with one or two folds. The challenge tackled here is to reconstruct the intricate folds, tucks, and slits of unopened letters secured shut with “letterlocking,” a practice—systematized in this paper—which underpinned global communications security for centuries before modern envelopes. We present a fully automatic computational approach for reconstructing and virtually unfolding volumetric scans of a locked letter with complex internal folding, producing legible images of the letter’s contents and crease pattern while preserving letterlocking evidence. We demonstrate our method on four letterpackets from Renaissance Europe, reading the contents of one unopened letter for the first time. Using the results of virtual unfolding, we situate our findings within a novel letterlocking categorization chart based on our study of 250,000 historical letters.
Imine as a linchpin approach for meta-C–H functionalization
Authors: Bag Sukdev , Jana Sadhan , Pradhan Sukumar , Bhowmick Suman , Goswami Nupur , Sinha Soumya Kumar , Maiti Debabrata
Published: March 2021

Despite the widespread applications of C–H functionalization, controlling site selectivity remains a significant challenge. Covalently attached directing groups (DGs) served as ancillary ligands to ensure ortho-, meta- and para-C–H functionalization over the last two decades. These covalently linked DGs necessitate two extra steps for a single C–H functionalization: introduction of DG prior to C–H activation and removal of DG post-functionalization. Here we report a temporary directing group (TDG) for meta-C–H functionalization via reversible imine formation. By overruling facile ortho-C–H bond activation by imine-N atom, a suitably designed pyrimidine-based TDG successfully delivered selective meta-C–C bond formation. Application of this temporary directing group strategy for streamlining the synthesis of complex organic molecules without any necessary pre-functionalization at the meta position has been explored.
Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques
Authors: Yadav Pragya D. , Ella Raches , Kumar Sanjay , Patil Dilip R. , Mohandas Sreelekshmy , Shete Anita M. , Vadrevu Krishna M. , Bhati Gaurav , Sapkal Gajanan , Kaushal Himanshu , Patil Savita , Jain Rajlaxmi , Deshpande Gururaj , Gupta Nivedita , Agarwal Kshitij , Gokhale Mangesh , Mathapati Basavaraj , Metkari Siddhanath , Mote Chandrashekhar , Nyayanit Dimpal , Patil Deepak Y. , Sai Prasad B. S. , Suryawanshi Annasaheb , Kadam Manoj , Kumar Abhimanyu , Daigude Sachin , Gopale Sanjay , Majumdar Triparna , Mali Deepak , Sarkale Prasad , Baradkar Shreekant , Gawande Pranita , Joshi Yash , Fulari Sidharam , Dighe Hitesh , Sharma Sharda , Gunjikar Rashmi , Kumar Abhinendra , Kalele Kaumudi , Srinivas Vellimedu K. , Gangakhedkar Raman R. , Ella Krishna M. , Abraham Priya , Panda Samiran , Bhargava Balram
Published: March 2021

The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.
Complete biosynthesis of a sulfated chondroitin in Escherichia coli
Authors: Badri Abinaya , Williams Asher , Awofiranye Adeola , Datta Payel , Xia Ke , He Wenqin , Fraser Keith , Dordick Jonathan S. , Linhardt Robert J. , Koffas Mattheos A. G.
Published: March 2021

Sulfated glycosaminoglycans (GAGs) are a class of important biologics that are currently manufactured by extraction from animal tissues. Although such methods are unsustainable and prone to contamination, animal-free production methods have not emerged as competitive alternatives due to complexities in scale-up, requirement for multiple stages and cost of co-factors and purification. Here, we demonstrate the development of single microbial cell factories capable of complete, one-step biosynthesis of chondroitin sulfate (CS), a type of GAG. We engineer E. coli to produce all three required components for CS production–chondroitin, sulfate donor and sulfotransferase. In this way, we achieve intracellular CS production of ~27 μg/g dry-cell-weight with about 96% of the disaccharides sulfated. We further explore four different factors that can affect the sulfation levels of this microbial product. Overall, this is a demonstration of simple, one-step microbial production of a sulfated GAG and marks an important step in the animal-free production of these molecules.
Graphene/MoS2/FeCoNi(OH)x and Graphene/MoS2/FeCoNiPx multilayer-stacked vertical nanosheets on carbon fibers for highly efficient overall water splitting
Authors: Ji Xixi , Lin Yanhong , Zeng Jie , Ren Zhonghua , Lin Zijia , Mu Yongbiao , Qiu Yejun , Yu Jie
Published: March 2021

Development of excellent and cheap electrocatalysts for water electrolysis is of great significance for application of hydrogen energy. Here, we show a highly efficient and stable oxygen evolution reaction (OER) catalyst with multilayer-stacked hybrid structure, in which vertical graphene nanosheets (VGSs), MoS2 nanosheets, and layered FeCoNi hydroxides (FeCoNi(OH)x) are successively grown on carbon fibers (CF/VGSs/MoS2/FeCoNi(OH)x). The catalyst exhibits excellent OER performance with a low overpotential of 225 and 241 mV to attain 500 and 1000 mA cm−2 and small Tafel slope of 29.2 mV dec−1. Theoretical calculation indicates that compositing of FeCoNi(OH)x with MoS2 could generate favorable electronic structure and decrease the OER overpotential, promoting the electrocatalytic activity. An alkaline water electrolyzer is established using CF/VGSs/MoS2/FeCoNi(OH)x anode for overall water splitting, which generates a current density of 100 mA cm−2 at 1.59 V with excellent stability over 100 h. Our highly efficient catalysts have great prospect for water electrolysis.
Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease
Authors: D’Cruz Nicholas , Vervoort Griet , Chalavi Sima , Dijkstra Bauke W. , Gilat Moran , Nieuwboer Alice
Published: March 2021

The onset of freezing of gait (FOG) in Parkinson’s disease (PD) is a critical milestone, marked by a higher risk of falls and reduced quality of life. FOG is associated with alterations in subcortical neural circuits, yet no study has assessed whether subcortical morphology can predict the onset of clinical FOG. In this prospective multimodal neuroimaging cohort study, we performed vertex-based analysis of grey matter morphology in fifty-seven individuals with PD at study entry and two years later. We also explored the behavioral correlates and resting-state functional connectivity related to these local volume differences. At study entry, we found that freezers (N = 12) and persons who developed FOG during the course of the study (converters) (N = 9) showed local inflations in bilateral thalamus in contrast to persons who did not (non-converters) (N = 36). Longitudinally, converters (N = 7) also showed local inflation in the left thalamus, as compared to non-converters (N = 36). A model including sex, daily levodopa equivalent dose, and local thalamic inflation predicted conversion with good accuracy (AUC: 0.87, sensitivity: 88.9%, specificity: 77.8%). Exploratory analyses showed that local thalamic inflations were associated with larger medial thalamic sub-nuclei volumes and better cognitive performance. Resting-state analyses further revealed that converters had stronger thalamo-cortical coupling with limbic and cognitive regions pre-conversion, with a marked reduction in coupling over the two years. Finally, validation using the PPMI cohort suggested FOG-specific non-linear evolution of thalamic local volume. These findings provide markers of, and deeper insights into conversion to FOG, which may foster earlier intervention and better mobility for persons with PD.
Probable REM sleep behavior disorder is associated with longitudinal cortical thinning in Parkinson’s disease
Authors: Yoon Eun Jin , Monchi Oury
Published: March 2021

REM sleep behavior disorder (RBD) has a poor prognostic implication in both motor and non-motor functions in Parkinson’s disease (PD) patients. However, to the best of our knowledge no study to date investigated the longitudinal cerebral changes underlying RBD symptoms in PD. We performed the longitudinal study to investigate the association between probable RBD and cortical and subcortical changes in early, de novo PD patients. We studied 78 participants from the Parkinson’s Progression Marker Initiative who underwent structural MRI at baseline and after 2 years. The presence of probable RBD (pRBD) was evaluated using the RBD screening questionnaire. We compared the cross-sectional and longitudinal cortical thickness and subcortical volume changes, between PD patients with and without pRBD. At baseline, we found bilateral inferior temporal cortex thinning in the PD-pRBD group compared with the PD-noRBD group. Longitudinally, the PD-pRBD group revealed a significant increase in the rate of thinning in the left insula compared with the PD-noRBD group, and the increased thinning correlated with decreased cognitive performance. In subcortical volume analyses, the presence of pRBD was linked with volume decrease over time in the left caudate nucleus, pallidum and amygdala. The volume changes in the left caudate nucleus revealed correlations with global cognition. These results support the idea that RBD is an important marker of rapid progression in PD motor and non-motor symptoms and suggest that the atrophy in the left insula and caudate nucleus might be the underlying neurobiological mechanisms of the poorer prognosis in PD patients with RBD.
Rheumatoid arthritis decreases risk for Parkinson’s disease: a Mendelian randomization study
Authors: Li ChunYu , Ou RuWei , Shang HuiFang
Published: March 2021

Epidemiological and clinical studies have suggested comorbidity between rheumatoid arthritis and Parkinson’s disease (PD), but whether there exists a causal association and the effect direction of rheumatoid arthritis on PD is controversial and elusive. To evaluate the causal relationship, we first estimated the genetic correlation between rheumatoid arthritis and PD, and then performed a two-sample Mendelian randomization analysis based on summary statistics from large genome-wide association studies of rheumatoid arthritis (N = 47,580) and PD (N = 482,703). We identified negative and significant correlation between rheumatoid arthritis and PD (genetic correlation: −0.10, P = 0.0033). Meanwhile, one standard deviation increase in rheumatoid arthritis risk was associated with a lower risk of PD (OR: 0.904, 95% CI: 0.866–0.943, P: 2.95E–06). The result was robust under all sensitivity analyses. Our results provide evidence supporting a protective role of rheumatoid arthritis on PD. A deeper understanding of the inflammation and immune response is likely to elucidate the potential pathogenesis of PD and identify therapeutic targets for PD.
Human moral decision-making through the lens of Parkinson’s disease
Authors: Ponsi Giorgia , Scattolin Marina , Villa Riccardo , Aglioti Salvatore Maria
Published: March 2021

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the basal ganglia (BG) and thalamocortical circuitry. While defective motor control has long been considered the defining symptom of PD, mounting evidence indicates that the BG are fundamentally important for a multitude of cognitive, emotional, and motivational processes in addition to motor function. Here, we review alterations in moral decision-making in people with PD, specifically in the context of deceptive behavior. We report that PD patients exhibit two opposite behavioral patterns: hyper- and hypo-honesty. The hyper-honest subgroup engages in deception less often than matched controls, even when lying is associated with a monetary payoff. This behavioral pattern seems to be linked to dopaminergic hypo-activity, implying enhanced harm avoidance, risk aversion, non-impulsivity, and reduced reward sensitivity. On the contrary, the hypo-honest subgroup—often characterized by the additional diagnosis of impulse control disorders (ICDs) and dopamine dysregulation syndrome (DDS)—deceives more often than both PD patients without ICDs/DDS and controls. This behavioral pattern appears to be associated with dopaminergic hyperactivity, which underpins enhanced novelty-seeking, risk-proneness, impulsivity, and reward sensitivity. We posit that these two complementary behavioral patterns might be related to dysfunction of the dopaminergic reward system, leading to reduced or enhanced motivation to deceive. Only a few studies have directly investigated moral decision-making in PD and other neurodegenerative disorders affecting the BG, and further research on the causal role of subcortical structures in shaping moral behavior is needed.
Spin-induced negative thermal expansion and spin–phonon coupling in van der Waals material CrBr3
Authors: Kozlenko D. P. , Lis O. N. , Kichanov S. E. , Lukin E. V. , Belozerova N. M. , Savenko B. N.
Published: March 2021

The two-dimensional van der Waals (vdW) magnets retaining magnetic order in atomically thin limit demonstrate challenging physical phenomena and they are considered as prospective building blocks for construction of advanced spintronics and nanoelectronics devices. Here, we present experimental evidence for negative thermal expansion of lattice volume and vdW layers and strong spin–phonon coupling effects, caused by formation of the long-range ferromagnetic order in the vdW material CrBr3. The neutron and X-ray diffraction measurements revealed anomalous temperature variation of lattice parameters and interatomic distances and angles in the vicinity of Curie temperature (TC). A pronounced rise of the frequencies of the most of the observed vibrational modes and unusual reversal broadening of their full widths at half maximum below TC was found from Raman spectroscopy measurements.
Structural phase transition and superconductivity hierarchy in 1T-TaS2 under pressure up to 100 GPa
Authors: Dong Qing , Li Quanjun , Li Shujia , Shi Xuhan , Niu Shifeng , Liu Shijie , Liu Ran , Liu Bo , Luo Xuan , Si Jianguo , Lu Wenjian , Hao Ning , Sun Yuping , Liu Bingbing
Published: March 2021

The adoption of high pressure not only reinforces the comprehension of the structure and exotic electronic states of transition metal dichalcogenides (TMDs) but also promotes the discovery of intriguing phenomena. Here, 1T-TaS2 was investigated up to 100 GPa, and re-enhanced superconductivity was found with structural phase transitions. The discovered I4/mmm TaS2 presents strong electron–phonon coupling, revealing a good superconductivity of the nonlayered structure. The P–T phase diagram shows a dome shape centered at ~20 GPa, which is attributed to the distortion of the 1T structure. Accompanied by the transition to nonlayered structure above 44.5 GPa, the superconducting critical temperature shows an increasing trend and reaches ~7 K at the highest studied pressure, presenting superior superconductivity compared to the original layered structure. It is unexpected that the pressure-induced re-enhanced superconductivity was observed in TMDs, and the transition from a superconductor with complicated electron-pairing mechanism to a phonon-mediated superconductor would expand the field of pressure-modified superconductivity.
Author Correction: Mitochondrial dysfunction in neurological disorders: exploring mitochondrial transplantation
Authors: Norat Pedro , Soldozy Sauson , Sokolowski Jennifer D. , Gorick Catherine M. , Kumar Jeyan S. , Chae Youngrok , Yağmurlu Kaan , Prada Francesco , Walker Melanie , Levitt Michael R. , Price Richard J. , Tvrdik Petr , Kalani M. Yashar S.
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41536-021-00125-3
Compilation of longitudinal microbiota data and hospitalome from hematopoietic cell transplantation patients
Authors: Liao Chen , Taylor Bradford P. , Ceccarani Camilla , Fontana Emily , Amoretti Luigi A. , Wright Roberta J. , Gomes Antonio L. C. , Peled Jonathan U. , Taur Ying , Perales Miguel-Angel , van den Brink Marcel R. M. , Littmann Eric , Pamer Eric G. , Schluter Jonas , Xavier Joao B.
Published: March 2021

The impact of the gut microbiota in human health is affected by several factors including its composition, drug administrations, therapeutic interventions and underlying diseases. Unfortunately, many human microbiota datasets available publicly were collected to study the impact of single variables, and typically consist of outpatients in cross-sectional studies, have small sample numbers and/or lack metadata to account for confounders. These limitations can complicate reusing the data for questions outside their original focus. Here, we provide comprehensive longitudinal patient dataset that overcomes those limitations: a collection of fecal microbiota compositions (>10,000 microbiota samples from >1,000 patients) and a rich description of the “hospitalome” experienced by the hosts, i.e., their drug exposures and other metadata from patients with cancer, hospitalized to receive allogeneic hematopoietic cell transplantation (allo-HCT) at a large cancer center in the United States. We present five examples of how to apply these data to address clinical and scientific questions on host-associated microbial communities.
Author Correction: A Machine-learning Approach to Forecast Aggravation Risk in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Clinical Indicators
Authors: Peng Junfeng , Chen Chuan , Zhou Mi , Xie Xiaohua , Zhou Yuqi , Luo Ching-Hsing
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Spatio-temporal selection of reference genes in the two congeneric species of Glycyrrhiza
Authors: Li Yuping , Liang Xiaoju , Zhou Xuguo , An Yu , Li Ming , Yuan Ling , Li Yongqing , Wang Ying
Published: March 2021

Glycyrrhiza, a genus of perennial medicinal herbs, has been traditionally used to treat human diseases, including respiratory disorders. Functional analysis of genes involved in the synthesis, accumulation, and degradation of bioactive compounds in these medicinal plants requires accurate measurement of their expression profiles. Reverse transcription quantitative real-time PCR (RT-qPCR) is a primary tool, which requires stably expressed reference genes to serve as the internal references to normalize the target gene expression. In this study, the stability of 14 candidate reference genes from the two congeneric species G. uralensis and G. inflata, including ACT, CAC, CYP, DNAJ, DREB, EF1, RAN, TIF1, TUB, UBC2, ABCC2, COPS3, CS, R3HDM2, were evaluated across different tissues and throughout various developmental stages. More importantly, we investigated the impact of interactions between tissue and developmental stage on the performance of candidate reference genes. Four algorithms, including geNorm, NormFinder, BestKeeper, and Delta Ct, were used to analyze the expression stability and RefFinder, a comprehensive software, provided the final recommendation. Based on previous research and our preliminary data, we hypothesized that internal references for spatio-temporal gene expression are different from the reference genes suited for individual factors. In G. uralensis, the top three most stable reference genes across different tissues were R3HDM2, CAC and TUB, while CAC, CYP and ABCC2 were most suited for different developmental stages. CAC is the only candidate recommended for both biotic factors, which is reflected in the stability ranking for the spatio (tissue)-temporal (developmental stage) interactions (CAC, R3HDM2 and DNAJ). Similarly, in G. inflata, COPS3, R3HDM2 and DREB were selected for tissues, while RAN, COPS3 and CS were recommended for developmental stages. For the tissue-developmental stage interactions, COPS3, DREB and ABCC2 were the most suited reference genes. In both species, only one of the top three candidates was shared between the individual factors and their interactions, specifically, CAC in G. uralensis and COPS3 in G. inflata, which supports our overarching hypothesis. In summary, spatio-temporal selection of reference genes not only lays the foundation for functional genomics research in Glycyrrhiza, but also facilitates these traditional medicinal herbs to reach/maximize their pharmaceutical potential.
Importance of HBsAg recognition by HLA molecules as revealed by responsiveness to different hepatitis B vaccines
Authors: Nishida Nao , Sugiyama Masaya , Ohashi Jun , Kawai Yosuke , Khor Seik-Soon , Nishina Sohji , Yamasaki Kazumi , Yazaki Hirohisa , Okudera Kaori , Tamori Akihiro , Eguchi Yuichiro , Sakai Aiko , Kakisaka Keisuke , Sawai Hiromi , Tsuchiura Takayo , Ishikawa Miyuki , Hino Keisuke , Sumazaki Ryo , Takikawa Yasuhiro , Kanda Tatsuo , Yokosuka Osamu , Yatsuhashi Hiroshi , Tokunaga Katsushi , Mizokami Masashi
Published: March 2021

Hepatitis B (HB) vaccines (Heptavax-II and Bimmugen) designed based on HBV genotypes A and C are mainly used for vaccination against HB in Japan. To determine whether there are differences in the genetic background associated with vaccine responsiveness, genome-wide association studies were performed on 555 Heptavax-II and 1193 Bimmugen recipients. Further HLA imputation and detailed analysis of the association with HLA genes showed that two haplotypes, DRB1*13:02-DQB1*06:04 and DRB1*04:05-DQB1*04:01, were significantly associated in comparison with high-responders (HBsAb > 100 mIU/mL) for the two HB vaccines. In particular, HLA-DRB1*13:02-DQB1*06:04 haplotype is of great interest in the sense that it could only be detected by direct analysis of the high-responders in vaccination with Heptavax-II or Bimmugen. Compared with healthy controls, DRB1*13:02-DQB1*06:04 was significantly less frequent in high-responders when vaccinated with Heptavax-II, indicating that high antibody titers were less likely to be obtained with Heptavax-II. As Bimmugen and Heptavax-II tended to have high and low vaccine responses to DRB1*13:02, 15 residues were found in the Heptavax-II-derived antigenic peptide predicted to have the most unstable HLA-peptide binding. Further functional analysis of selected hepatitis B patients with HLA haplotypes identified in this study is expected to lead to an understanding of the mechanisms underlying liver disease.
Influence of age on sperm characteristics evaluated by light and electron microscopies
Authors: Collodel Giulia , Ferretti Fabio , Masini Maurizio , Gualtieri Giacomo , Moretti Elena
Published: March 2021

The impact of male aging on male fertility has only recently become of interest to the scientific community. This study aims to assess the relationship between age and fertility among a sample of men, considering the individual and pathological characteristics. In this retrospective study data of semen analysis and medical history of 1294 Italian male patients were considered. Semen analysis was performed by light microscopy and transmission electron microscopy mathematically elaborated. A generalized linear model was used to explore the influence of male age on semen quality, considering as confounders wine consumption, smoking habits, presence of varicocele, consanguinity and positive semen bacteriological analysis and urethral swab. The mean age of the participants was 36.41 ± 6.379. Male aging without impact of confounders was correlated with a decrease in sperm concentration and motility and an increased in sperm necrosis. Sperm concentration and progressive motility were negatively related to the presence of confounders as wine consumption (sperm motility), urogenital infection (sperm concentration and motility), varicocele (sperm concentration) and consanguinity (sperm motility). Urogenital infection, varicocele and consanguinity positively correlated with sperm necrosis. The most important finding was the observation of a negative effect of male aging on sperm parameters such as concentration, motility, and viability. It is possible to hypothesize age-dependent changes of testicular environment, probably related to reactive oxygen species production. The demonstration, in a large sample of patients, that aging influences sperm quality strongly motivates further research focused on the mechanisms involved in this phenomenon and its effects on offspring fitness.
Major oscillations in spontaneous home-cage activity in C57BL/6 mice housed under constant conditions
Authors: Pernold Karin , Rullman Eric , Ulfhake Brun
Published: March 2021

The mouse is the most important mammalian model in life science research and the behavior of the mouse is a key read-out of experimental interventions and genetic manipulations. To serve this purpose a solid understanding of the mouse normal behavior is a prerequisite. Using 14–19 months of cumulative 24/7 home-cage activity recorded with a non-intrusive technique, evidence is here provided for a highly significant circannual oscillation in spontaneous activity (1–2 SD of the mean, on average 65% higher during peak of highs than lows; P = 7E−50) of male and female C57BL/6 mice held under constant conditions. The periodicity of this hitherto not recognized oscillation is in the range of 2–4 months (average estimate was 97 days across cohorts of cages). It off-sets responses to environmental stimuli and co-varies with the feeding behavior but does not significantly alter the preference for being active during the dark hours. The absence of coordination of this rhythmicity between cages with mice or seasons of the year suggest that the oscillation of physical activity is generated by a free-running intrinsic oscillator devoid of external timer. Due to the magnitude of this rhythmic variation it may be a serious confounder in experiments on mice if left unrecognized.
A 3D taphonomic model of long bone modification by lions in medium-sized ungulate carcasses
Authors: Domínguez-Rodrigo Manuel , Gidna Agness , Baquedano Enrique , Cobo-Sánchez Lucía , Mora Rocio , Courtenay Lloyd A. , Gonzalez-Aguilera Diego , Mate-Gonzalez Miguel A. , Prieto-Herráez Diego
Published: March 2021

Here, we present the first three-dimensional taphonomic analysis of a carnivore-modified assemblage at the anatomical scale of the appendicular skeleton. A sample of ten carcasses composed of two taxa (zebra and wildebeest) consumed by wild lions in the Tarangire National Park (Tanzania) has been used to determine element-specific lion damage patterns. This study presents a novel software for the 3D spatial documentation of bone surface modifications at the anatomical level. Combined with spatial statistics, the present analysis has been able to conclude that despite variable degrees of competition during carcass consumption, lions generate bilateral patterning consisting of substantial damage of proximal ends of stylopodials and zeugopodials, moderate damage of the distal ends of femora and marginal damage of distal ends of humeri and zeugopodials. Of special interest is, specifically, the patterning of tooth marks on shafts according to element, since these are crucial to determine not only the type of carnivore involved in any given bone assemblage, but also the interaction with other agents (namely, hominins, in the past). Lions leave few tooth marks on mid-shaft sections, mostly concentrated on certain sections and orientations of stylopodials and, to a lesser extent, of the proximal tibia. Redundant occurrence of tooth marks on certain bone sections renders them as crucial to attest lion agency in carcass initial consumption. Indirectly, this can also be used to determine whether hominins ever acquired carcasses at lion kills.
Ultrafast carbon nanotubes growth on recycled carbon fibers and their evaluation on interfacial shear strength in reinforced composites
Authors: Salas A. , Medina C. , Vial J. T. , Flores P. , Canales C. , Tuninetti V. , Jaramillo A. F. , Meléndrez M. F.
Published: March 2021

The global demand for products manufactured with carbon fibers (CFs) has increased in recent years; however, the waste generated at the end of the product lifetime has also increased. In this research, the impact of the addition of carbon nanotubes (CNTs) on the interlaminated resistance of recycled carbon fibers (RCFs) was studied. In this work, a recycling process of the composite material was applied via thermolysis to obtain the CFs, followed by the growth of CNTs on their surface using the Poptube technique. The recycling temperature were 500 °C and 700 °C; and ferrocene and polypyrrole were used to grow CNTs on CFs surface. CNTs were verified by Raman spectroscopy and scanning electron microscopy (SEM). Finally, to determine the interlaminar resistance, a double cantilever beam (DCB) test was performed. The results indicate that with Poptube technique, CNTs can be grown on RCFs using both impregnations. Thermolysis recycling process at 500 °C allowed CFs without resin residues and without visible damage. The DCB tests showed a decrease in the fracture resistance in mode I loading of 34.9% for the polypyrrole samples and 29.3% for the ferrocene samples compared with the virgin carbon fibers (VCFs) samples with a resistance of 1052.5 J/m2.
Preparation and application of a thidiazuron·diuron ultra-low-volume spray suitable for plant protection unmanned aerial vehicles
Authors: Liu Qin , Wei Kun , Yang Liyun , Xu Weiming , Xue Wei
Published: March 2021

Spraying of defoliant can promote centralized defoliation of cotton and advance maturity to facilitate harvesting. Modern pesticide application equipment includes plant protection unmanned aerial vehicles (UAVs), which are used widely for spraying defoliants. However, commonly used defoliant formulations are mainly suspension concentrates and water-dispersible granules, which need to be diluted with water when used. These are not suitable for plant protection UAVs with limited load capacity, especially in arid areas such as Xinjiang, China. Therefore, we prepared a thidiazuron·diuron ultra-low-volume (ULV) spray, which can be used directly without dilution in water. We found that ULV sprays had better wettability than the commercially available suspension concentrate, could quickly wet cotton leaves and spread fully. The volatilization rate was lower. ULV sprays also showed better atomization performance and more uniform droplet distribution than the commercially available suspension concentrate. At a dosage of 4.50–9.00 L/ha, the coverage rate on cotton leaves was 0.85–4.15% and droplet deposition densities were 15.63–42.57 pcs/cm2; defoliation rate and spitting rate were also greater than those of the reference product. This study could be contributed to the development of special pesticide formulations suitable for UAVs.
Polymorphic variants in Sweet and Umami taste receptor genes and birthweight
Authors: Farinella Riccardo , Erbi Ilaria , Bedini Alice , Donato Sara , Gentiluomo Manuel , Angelucci Claudia , Lupetti Antonella , Cuttano Armando , Moscuzza Francesca , Tuoni Cristina , Rizzato Cosmeri , Ciantelli Massimiliano , Campa Daniele
Published: March 2021

The first thousand days of life from conception have a significant impact on the health status with short, and long-term effects. Among several anthropometric and maternal lifestyle parameters birth weight plays a crucial role on the growth and neurological development of infants. Recent genome wide association studies (GWAS) have demonstrated a robust foetal and maternal genetic background of birth weight, however only a small proportion of the genetic hereditability has been already identified. Considering the extensive number of phenotypes on which they are involved, we focused on identifying the possible effect of genetic variants belonging to taste receptor genes and birthweight. In the human genome there are two taste receptors family the bitter receptors (TAS2Rs) and the sweet and umami receptors (TAS1Rs). In particular sweet perception is due to a heterodimeric receptor encoded by the TAS1R2 and the TAS1R3 gene, while the umami taste receptor is encoded by the TAS1R1 and the TAS1R3 genes. We observed that carriers of the T allele of the TAS1R1-rs4908932 SNPs showed an increase in birthweight compared to GG homozygotes Coeff: 87.40 (35.13–139.68) p-value = 0.001. The association remained significant after correction for multiple testing. TAS1R1-rs4908932 is a potentially functional SNP and is in linkage disequilibrium with another polymorphism that has been associated with BMI in adults showing the importance of this variant from the early stages of conception through all the adult life.
The food web in a subterranean ecosystem is driven by intraguild predation
Authors: Parimuchová Andrea , Dušátková Lenka Petráková , Kováč Ľubomír , Macháčková Táňa , Slabý Ondřej , Pekár Stano
Published: March 2021

Trophic interactions of cave arthropods have been understudied. We used molecular methods (NGS) to decipher the food web in the subterranean ecosystem of the Ardovská Cave (Western Carpathians, Slovakia). We collected five arthropod predators of the speciesParasitus loricatus(gamasid mites),Eukoenenia spelaea(palpigrades),Quedius mesomelinus(beetles), andPorrhomma profundumandCentromerus cavernarum(both spiders) and prey belonging to several orders. Various arthropod orders were exploited as prey, and trophic interactions differed among the predators. Linear models were used to compare absolute and relative prey body sizes among the predators.Quediusexploited relatively small prey, whileEukoeneniaandParasitusfed on relatively large prey. Exploitation of eggs or cadavers is discussed. In contrast to previous studies,Eukoeneniawas found to be carnivorous. A high proportion of intraguild predation was found in all predators. Intraspecific consumption (most likely cannibalism) was detected only in mites and beetles. Using Pianka’s index, the highest trophic niche overlaps were found betweenPorrhommaandParasitusand betweenCentromerusandEukoenenia, while the lowest niche overlap was found betweenParasitusandQuedius. Contrary to what we expected, the high availability of Diptera and Isopoda as a potential prey in the studied system was not corroborated. Our work demonstrates that intraguild diet plays an important role in predators occupying subterranean ecosystems.
Author Correction: Microvascular impairment as a biomarker of diabetic retinopathy progression in the long-term follow up in type 1 diabetes
Authors: Scarinci Fabio , Picconi Fabiana , Virgili Gianni , Varano Monica , Giorno Paola , Frontoni Simona , Parravano Mariacristina
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication
Authors: Li Yueshuo , Shi Feng , Hu Jianmin , Xie Longlong , Zhao Lin , Tang Min , Luo Xiangjian , Ye Mao , Zheng Hui , Zhou Min , Liu Na , Bode Ann M. , Fan Jia , Zhou Jian , Gao Qiang , Qiu Shuangjian , Wu Weizhong , Zhang Xin , Liao Weihua , Cao Ya
Published: March 2021

p18 is a key negative regulator of cell cycle progression and mediates cell cycle arrest at the G1/S phase. Ubiquitination is the prime mechanism in regulating p18 protein abundance. However, so far no post- translational regulator, especially DUBs, has been identified to regulate the protein stability of p18. In this paper, we identified CYLD as a deubiquitinase of p18, which binds to and removes the K48-linked polyubiquitylation chains conjugated onto p18, thus stabilizing the p18 protein. Loss of CYLD causes the degradation of p18 and induces the G1/S transition. Epstein–Barr virus (EBV), is the human oncovirus etiologically linked to nasopharyngeal carcinoma (NPC). Here we found that EBV drives a replication passive environment by deregulating the CYLD-p18 axis. Functionally, CYLD inhibits cell proliferation and tumorigenesis through p18 in vivo. Restoring CYLD prevents EBV induced viral replication and tumor growth. Collectively, our results identify CYLD directly stabilizes p18 to regulate the cellular G1/S transition. The reconstitution of CYLD-p18 axis could be a promising approach for EBV-positive cancer therapy.
Structural variant detection in cancer genomes: computational challenges and perspectives for precision oncology
Authors: van Belzen Ianthe A. E. M. , Schönhuth Alexander , Kemmeren Patrick , Hehir-Kwa Jayne Y.
Published: March 2021

Cancer is generally characterized by acquired genomic aberrations in a broad spectrum of types and sizes, ranging from single nucleotide variants to structural variants (SVs). At least 30% of cancers have a known pathogenic SV used in diagnosis or treatment stratification. However, research into the role of SVs in cancer has been limited due to difficulties in detection. Biological and computational challenges confound SV detection in cancer samples, including intratumor heterogeneity, polyploidy, and distinguishing tumor-specific SVs from germline and somatic variants present in healthy cells. Classification of tumor-specific SVs is challenging due to inconsistencies in detected breakpoints, derived variant types and biological complexity of some rearrangements. Full-spectrum SV detection with high recall and precision requires integration of multiple algorithms and sequencing technologies to rescue variants that are difficult to resolve through individual methods. Here, we explore current strategies for integrating SV callsets and to enable the use of tumor-specific SVs in precision oncology.
Protective effect of Que Zui tea hot-water and aqueous ethanol extract against acetaminophen-induced liver injury in miceviainhibition of oxidative stress, inflammation, and apoptosis
Authors: Wang Yongpeng , Tian Lei , Wang Yudan , Zhao Tianrui , Khan Afsar , Wang Yifen , Cao Jianxin , Cheng Guiguang
Published: March 2021

The tender leaves and buds ofVaccinium dunalianumWight have been traditionally processed as folk tea, known as Que Zui tea (QT), with a wide range of benefits to humans.
Effect of pulsed electric fields on carotenoid and phenolic bioaccessibility and their relationship with carrot structure
Authors: López-Gámez Gloria , Elez-Martínez Pedro , Quiles-Chuliá Amparo , Martín-Belloso Olga , Hernando-Hernando Isabel , Soliva-Fortuny Robert
Published: March 2021

Pulsed electric fields application to whole carrots is a feasible strategy to enhance carotenoids and phenolic bioaccessibility.
Apoptotic mechanisms of gastric cancer cells induced by isolated erinacine S through epigenetic histone H3 methylation of FasL and TRAIL
Authors: Tung Shui-Yi , Lee Ko-Chao , Lee Kam-Fai , Yang Ya-Ling , Huang Wen-Shih , Lee Li-Ya , Chen Wan-Ping , Chen Chin-Chu , Teng Chih-Chuan , Shen Chien-Heng , Hsieh Meng-Chiao , Huang Cheng-Yi , Sheen Jiunn-Ming , Kuo Hsing-Chun
Published: March 2021

Erinacine S, the new bioactive diterpenoid compound isolated from the ethanol extract of the mycelia of Hericium erinaceus, displays great health-promoting properties.
Ultralow magnetostrictive flexible ferromagnetic nanowires
Authors: Muscas Giuseppe , Jönsson Petra E. , Serrano I. G. , Vallin Örjan , Kamalakar M. Venkata
Published: March 2021

Highly resilient flexible magnetic nanowires realized with ultralow magnetostriction, high endurance and enhanced elastic limit for stable flexible and bendable spintronics.
Using nuclear magnetic resonance proton relaxation to probe the surface chemistry of carbon 2D materials
Authors: Marchesini Sofia , Paton Keith R. , Brennan Barry , Turner Piers , Pollard Andrew J.
Published: March 2021

Using NMR proton relaxation to rapidly identify surface chemical functionalisation changes of carbon nanomaterials in liquid.
A template-directed synthesis of metal–organic framework (MOF-74) ultrathin nanosheets for oxygen reduction electrocatalysis
Authors: Fan Rui , Kang Ning , Li Yuzhen , Gao Lizhen
Published: March 2021

Layered double hydroxide (LDH) is employed as a layered template to synthesize ultrathin Ni-MOF-74 nanosheets. The two-dimensional structure brings numerous exposed unsaturated active sites and enhanced conductivity for Ni-MOF-74.
Porous graphene nanocages with wrinkled surfaces enhancing electrocatalytic activity of lithium/sulfuryl chloride batteries
Authors: Li Xiangyang , Kheimeh Sari Hirbod Maleki , Niu Lanjie , He Gege , Zhou Yao , Li Xifei , Sun Zhanbo
Published: March 2021

Nitrogen-doped graphene nanocages with high surface roughness highly overcome the defect of lithium/sulfuryl chloride batteries, which is attributed to the superior interface properties from the porous graphene layer and N-doping effect.
Molecular recognition of SARS-CoV-2 spike glycoprotein: quantum chemical hot spot and epitope analyses
Authors: Watanabe Chiduru , Okiyama Yoshio , Tanaka Shigenori , Fukuzawa Kaori , Honma Teruki
Published: March 2021

Quantum chemical calculations investigated molecular recognition of SARS-CoV-2 spike glycoproteins including its N501Y variant for ACE2 and antibody. Hot spot and epitope analyses revealed key residues to design drugs and antibodies against COVID-19.
N-Glycosylated Ganoderma lucidum immunomodulatory protein improved anti-inflammatory activity via inhibition of the p38 MAPK pathway
Authors: Li Qi-Zhang , Chen Xin , Mao Pei-Wen , Jin Meng-Yuan , Wu Qin , Zhou Xuan-Wei
Published: March 2021

The global health emergency generated by coronavirus disease-2019 has prompted the search for immunomodulatory agents.
New π-stacking motifs for molecular semiconducting materials: bis(bis(8-quinolinyl)amide)metal(ii) complexes of Cr, Mn, Fe, and Zn
Authors: Albrecht Georg , Locke Harald , Schweitzer Pascal , Becker Jonathan , Chen Limei , Schreiner Peter R. , Schlettwein Derck
Published: March 2021

Metal–organic complexes with a pair of orthogonal π-systems lead to a new stacking motif in solid state and open the way to a new branch in the family of molecular semiconductors.
The synthesis of thermoresponsive POSS-based eight-arm star poly(N-isopropylacrylamide): A comparison between Z-RAFT and R-RAFT strategies
Authors: Pang Bo , Liu Rui , Han Guang , Wang Wei , Zhang Wangqing
Published: March 2021

Z-Type POSS-based eight-arm star poly(N-isopropylacrylamide), POSS-(PNIPAM)8-Z, is synthesized and demonstrated to be a thermoresponsive switchable emulsifier.