bluuebunny/crossref_metadata_2025 huggingface dataset:
The Drosophila Forkhead/Fox transcription factor Jumeau mediates specific cardiac progenitor cell divisions by regulating expression of the kinesin Nebbish
Authors: Kump Andrew J. , Panta Manoj , Schwab Kristopher R. , Inlow Mark H. , Ahmad Shaad M.
Published: February 2021

Forkhead (Fkh/Fox) domain transcription factors (TFs) mediate multiple cardiogenic processes in both mammals and Drosophila. We showed previously that the Drosophila Fox gene jumeau (jumu) controls three categories of cardiac progenitor cell division—asymmetric, symmetric, and cell division at an earlier stage—by regulating Polo kinase activity, and mediates the latter two categories in concert with the TF Myb. Those observations raised the question of whether other jumu-regulated genes also mediate all three categories of cardiac progenitor cell division or a subset thereof. By comparing microarray-based expression profiles of wild-type and jumu loss-of-function mesodermal cells, we identified nebbish (neb), a kinesin-encoding gene activated by jumu. Phenotypic analysis shows that neb is required for only two categories of jumu-regulated cardiac progenitor cell division: symmetric and cell division at an earlier stage. Synergistic genetic interactions between neb, jumu, Myb, and polo and the rescue of jumu mutations by ectopic cardiac mesoderm-specific expression of neb demonstrate that neb is an integral component of a jumu-regulated subnetwork mediating cardiac progenitor cell divisions. Our results emphasize the central role of Fox TFs in cardiogenesis and illustrate how a single TF can utilize different combinations of other regulators and downstream effectors to control distinct developmental processes.
Lipid tethering of breast tumor cells reduces cell aggregation during mammosphere formation
Authors: Bhandary Lekhana , Bailey Patrick C. , Chang Katarina T. , Underwood Karen F. , Lee Cornell J. , Whipple Rebecca A. , Jewell Christopher M. , Ory Eleanor , Thompson Keyata N. , Ju Julia A. , Mathias Trevor M. , Pratt Stephen J. P. , Vitolo Michele I. , Martin Stuart S.
Published: February 2021

Mammosphere assays are widely used in vitro to identify prospective cancer-initiating stem cells that can propagate clonally to form spheres in free-floating conditions. However, the traditional mammosphere assay inevitably introduces cell aggregation that interferes with the measurement of true mammosphere forming efficiency. We developed a method to reduce tumor cell aggregation and increase the probability that the observed mammospheres formed are clonal in origin. Tethering individual tumor cells to lipid anchors prevents cell drift while maintaining free-floating characteristics. This enables real-time monitoring of single tumor cells as they divide to form mammospheres. Monitoring tethered breast cancer cells provided detailed size information that correlates directly to previously published single cell tracking data. We observed that 71% of the Day 7 spheres in lipid-coated wells were between 50 and 150 μm compared to only 37% in traditional low attachment plates. When an equal mixture of MCF7-GFP and MCF7-mCherry cells were seeded, 65% of the mammospheres in lipid-coated wells demonstrated single color expression whereas only 32% were single-colored in low attachment wells. These results indicate that using lipid tethering for mammosphere growth assays can reduce the confounding factor of cell aggregation and increase the formation of clonal mammospheres.
Human, animal, water source interactions and leptospirosis in Thailand
Authors: Narkkul Udomsak , Thaipadungpanit Janjira , Srisawat Nattachai , Rudge James W. , Thongdee Metawee , Pawarana Rungrawee , Pan-ngum Wirichada
Published: February 2021

In Thailand, leptospirosis is primarily associated with those who work in agricultural occupations. Leptospirosis control is hampered by a poor understanding of the complex interactions between humans, animal reservoirs, Leptospira, and the variable spatial environment in which these factors coexist. We aimed to address key knowledge gaps concerning leptospirosis disease dynamics and the human–animal–water-source interface in two high-risk areas in Thailand. We conducted a cross-sectional survey among 746 study participants in two high-risk areas for leptospirosis in Thailand: Sisaket (SSK) and Nakhon Si Thammarat (NST). Interactions among humans, animals and water sources were quantified and analyzed. The presence of different animal species and thus contact patterns were different in NST and SSK. The consumption of water from the shared sources between the two areas was different. Those whose occupations were related to animals or environmental water and those who consumed water from more than two sources were more likely to have been infected with leptospirosis, with adjusted odds ratios 4.31 (95% CI 1.17–15.83) and 10.74 (95% CI 2.28–50.53), respectively. Understanding specific water-source sharing networks and human–animal contact patterns is useful when designing national and area-specific control programmes to prevent and control leptospirosis outbreaks.
Differentiation of physical and chemical cross-linking in gelatin methacryloyl hydrogels
Authors: Rebers Lisa , Reichsöllner Raffael , Regett Sophia , Tovar Günter E. M. , Borchers Kirsten , Baudis Stefan , Southan Alexander
Published: February 2021

Gelatin methacryloyl (GM) hydrogels have been investigated for almost 20 years, especially for biomedical applications. Recently, strengthening effects of a sequential cross-linking procedure, whereby GM hydrogel precursor solutions are cooled before chemical cross-linking, were reported. It was hypothesized that physical and enhanced chemical cross-linking of the GM hydrogels contribute to the observed strengthening effects. However, a detailed investigation is missing so far. In this contribution, we aimed to reveal the impact of physical and chemical cross-linking on strengthening of sequentially cross-linked GM and gelatin methacryloyl acetyl (GMA) hydrogels. We investigated physical and chemical cross-linking of three different GM(A) derivatives (GM10, GM2A8 and GM2), which provided systematically varied ratios of side-group modifications. GM10 contained the highest methacryloylation degree (DM), reducing its ability to cross-link physically. GM2 had the lowest DM and showed physical cross-linking. The total modification degree, determining the physical cross-linking ability, of GM2A8 was comparable to that of GM10, but the chemical cross-linking ability was comparable to GM2. At first, we measured the double bond conversion (DBC) kinetics during chemical GM(A) cross-linking quantitatively in real-time via near infrared spectroscopy-photorheology and showed that the DBC decreased due to sequential cross-linking. Furthermore, results of circular dichroism spectroscopy and differential scanning calorimetry indicated gelation and conformation changes, which increased storage moduli of all GM(A) hydrogels due to sequential cross-linking. The data suggested that the total cross-link density determines hydrogel stiffness, regardless of the physical or chemical nature of the cross-links.
Molecular characterization of atherosclerosis in HIV positive persons
Authors: Cornwell Adam , Palli Rohith , Singh Meera V. , Benoodt Lauren , Tyrell Alicia , Abe Jun-ichi , Schifitto Giovanni , Maggirwar Sanjay B. , Thakar Juilee
Published: February 2021

People living with HIV are at higher risk of atherosclerosis (AS). The pathogenesis of this risk is not fully understood. To assess the regulatory networks involved in AS we sequenced mRNA of the peripheral blood mononuclear cells (PBMCs) and measured cytokine and chemokine levels in the plasma of 13 persons living with HIV and 12 matched HIV-negative persons with and without AS. microRNAs (miRNAs) are known to play a role in HIV infection and may modulate gene regulation to drive AS. Hence, we further assessed miRNA expression in PBMCs of a subset of 12 HIV+ people with and without atherosclerosis. We identified 12 miRNAs differentially expressed between HIV+ AS+ and HIV+ , and validated 5 of those by RT-qPCR. While a few of these miRNAs have been implicated in HIV and atherosclerosis, others are novel. Integrating miRNA measurements with mRNA, we identified 27 target genes including SLC4A7, a critical sodium and bicarbonate transporter, that are potentially dysregulated during atherosclerosis. Additionally, we uncovered that levels of plasma cytokines were associated with transcription factor activity and miRNA expression in PBMCs. For example, BACH2 activity was associated with IL-1β, IL-15, and MIP-1α. IP10 and TNFα levels were associated with miR-124-3p. Finally, integration of all data types into a single network revealed increased importance of miRNAs in network regulation of the HIV+ group in contrast with increased importance of cytokines in the HIV+ AS+ group.
Rats show direct reciprocity when interacting with multiple partners
Authors: Kettler Nina , Schweinfurth Manon K. , Taborsky Michael
Published: February 2021

Direct reciprocity, where individuals apply the decision rule ‘help someone who has helped you’, is believed to be rare in non-human animals due to its high cognitive demands. Especially if previous encounters with several partners need to be correctly remembered, animals might either stop reciprocating favours previously received from an individual, or switch to the simpler generalized reciprocity mechanism. Here we tested the decision rules Norway rats apply when interacting with multiple partners before being able to return received help. In a sequential prisoner’s dilemma situation, focal subjects encountered four different partners that were either helpful or not, on four consecutive days. On the fifth day, the focal subject was paired with one of the previous four partners and given the opportunity to provide it with food. The focal rats returned received help by closely matching the quantity of help their partner had previously provided, independently of the time delay between received and given help, and independently of the ultimate interaction preceding the test. This shows that direct reciprocity is not limited to dyadic situations in Norway rats, suggesting that cognitive demands involved in applying the required decision rules can be met by non-human animals even when they interact with multiple partners differing in helping propensity.
N-linked glycosylation enzymes in the diatom Thalassiosira oceanica exhibit a diel cycle in transcript abundance and favor for NXT-type sites
Authors: Behnke Joerg , Cohen Alejandro M. , LaRoche Julie
Published: February 2021

N-linked glycosylation is a posttranslational modification affecting protein folding and function. The N-linked glycosylation pathway in algae is poorly characterized, and further knowledge is needed to understand the cell biology of algae and the evolution of N-linked glycosylation. This study investigated the N-linked glycosylation pathway in Thalassiosira oceanica, an open ocean diatom adapted to survive at growth-limiting iron concentrations. Here we identified and annotated the genes coding for the essential enzymes involved in the N-linked glycosylation pathway of T. oceanica. Transcript levels for genes coding for calreticulin, oligosaccharyltransferase (OST), N-acetylglucosaminyltransferase (GnT1), and UDP-glucose glucosyltransferase (UGGT) under high- and low-iron growth conditions revealed diel transcription patterns with a significant decrease of calreticulin and OST transcripts under iron-limitation. Solid-phase extraction of N-linked glycosylated peptides (SPEG) revealed 118 N-linked glycosylated peptides from cells grown in high- and low-iron growth conditions. The identified peptides had 81% NXT-type motifs, with X being any amino acids except proline. The presence of N-linked glycosylation sites in the iron starvation-induced protein 1a (ISIP1a) confirmed its predicted topology, contributing to the biochemical characterization of ISIP1 proteins. Analysis of extensive oceanic gene databases showed a global distribution of calreticulin, OST, and UGGT, reinforcing the importance of glycosylation in microalgae.
Low-dose exposure of glyphosate-based herbicides disrupt the urine metabolome and its interaction with gut microbiota
Authors: Hu Jianzhong , Lesseur Corina , Miao Yu , Manservisi Fabiana , Panzacchi Simona , Mandrioli Daniele , Belpoggi Fiorella , Chen Jia , Petrick Lauren
Published: February 2021

Glyphosate-based herbicides (GBHs) can disrupt the host microbiota and influence human health. In this study, we explored the potential effects of GBHs on urinary metabolites and their interactions with gut microbiome using a rodent model. Glyphosate and Roundup (equal molar for glyphosate) were administered at the USA glyphosate ADI guideline (1.75 mg/kg bw/day) to the dams and their pups. The urine metabolites were profiled using non-targeted liquid chromatography—high resolution mass spectrometry (LC-HRMS). Our results found that overall urine metabolite profiles significantly differed between dams and pups and between female and male pups. Specifically, we identified a significant increase of homocysteine, a known risk factor of cardiovascular disease in both Roundup and glyphosate exposed pups, but in males only. Correlation network analysis between gut microbiome and urine metabolome pointed to Prevotella to be negatively correlated with the level of homocysteine. Our study provides initial evidence that exposures to commonly used GBH, at a currently acceptable human exposure dose, is capable of modifying urine metabolites in both rat adults and pups. The link between Prevotella-homocysteine suggests the potential role of GBHs in modifying the susceptibility of homocysteine, which is a metabolite that has been dysregulated in related diseases like cardiovascular disease or inflammation, through commensal microbiome.
Variable selection methods for predicting clinical outcomes following allogeneic hematopoietic cell transplantation
Authors: Pasin Chloé , Moy Ryan H. , Reshef Ran , Yates Andrew J.
Published: February 2021

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative procedure for a large number of diseases. However, the greatest barriers to the success of allo-HCT are relapse and graft-versus-host-disease (GVHD). Many studies have examined the reconstitution of the immune system after allo-HCT and searched for factors associated with clinical outcome. Serum biomarkers have also been studied to predict the incidence and prognosis of GVHD. However, the use of multiparametric immunophenotyping has been less extensively explored: studies usually focus on preselected and predefined cell phenotypes and so do not fully exploit the richness of flow cytometry data. Here we aimed to identify cell phenotypes present 30 days after allo-HCT that are associated with clinical outcomes in 37 patients participating in a trial relating to the prevention of GVHD, derived from 82 flow cytometry markers and 13 clinical variables. To do this we applied variable selection methods in a competing risks modeling framework, and identified specific subsets of T, B, and NK cells associated with relapse. Our study demonstrates the value of variable selection methods for mining rich, high dimensional clinical data and identifying potentially unexplored cell subpopulations of interest.
Genome-scale phylogenetic analyses confirm Olpidium as the closest living zoosporic fungus to the non-flagellated, terrestrial fungi
Authors: Chang Ying , Rochon D’Ann , Sekimoto Satoshi , Wang Yan , Chovatia Mansi , Sandor Laura , Salamov Asaf , Grigoriev Igor V. , Stajich Jason E. , Spatafora Joseph W.
Published: February 2021

The zoosporic obligate endoparasites,Olpidium,hold a pivotal position to the reconstruction of the flagellum loss in fungi, one of the key morphological transitions associated with the colonization of land by the early fungi. We generated genome and transcriptome data from non-axenic zoospores ofOlpidium bornovanusand used a metagenome approach to extract phylogenetically informative fungal markers. Our phylogenetic reconstruction strongly supportedOlpidiumas the closest zoosporic relative of the non-flagellated terrestrial fungi. Super-alignment analyses resolvedOlpidiumas sister to the non-flagellated terrestrial fungi, whereas a super-tree approach recovered different placements ofOlpidium,but without strong support. Further investigations detected little conflicting signal among the sampled markers but revealed a potential polytomy in early fungal evolution associated with the branching order amongOlpidium, Zoopagomycota and Mucoromycota. The branches defining the evolutionary relationships of these lineages were characterized by short branch lengths and low phylogenetic content and received equivocal support for alternative phylogenetic hypotheses from individual markers. These nodes were marked by important morphological innovations, including the transition to hyphal growth and the loss of flagellum, which enabled early fungi to explore new niches and resulted in rapid and temporally concurrent Precambrian diversifications of the ancestors of several phyla of fungi.
Lipidomic analysis of facial skin surface lipid reveals the causes of pregnancy-related skin barrier weakness
Authors: Yang Manli , Zhou Mingyue , Li Yuan , Huang Hong , Jia Yan
Published: February 2021

Self-reported skin discomfort is a common problem during pregnancy, but it is not clear whether skin barrier function is altered in the process. Few studies have described the skin barrier function during pregnancy. In this work, we used highly sensitive and high-resolution ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to distinguish skin surface lipid (SSL) combined with multivariate analysis of lipids and metabolic changes to determine the relationship between SSL changes and skin physiology during pregnancy in order to better understand the skin condition of pregnant women. The results showed a significant reduction in the total lipid content in pregnant women. A total of 2270 lipids were detected, and the relative abundances of fatty acyls and glycerolipids were significantly reduced, while glycerophospholipids (GPs), sphingolipids, and saccharolipids was significantly increased in the pregnancy group. Multivariate data analysis indicated that 23 entities constituted the most important individual species responsible for the discrimination and phosphatidylcholine was the most abundant lipid in pregnancy group. In addition, compared to SSL profile of control group, it was observed that the average chain length of ceramides and fatty acids both decreased in SSL profile of pregnancy group. The main and most commonly affected pathway was that of GP pathways. These findings indicate that skin lipids are significantly altered in mid-pregnancy compared to the control group. Changes in ostrogen during pregnancy also make the skin more susceptible to inflammatory factors and lead to more fragile and susceptible skin, weakening the skin barrier along with the lipid alterations.
Submarine mud volcanoes as a source of chromophoric dissolved organic matter to the deep waters of the Gulf of Cádiz
Authors: Amaral Valentina , Romera-Castillo Cristina , Forja Jesús
Published: February 2021

Seafloor structures related to the emission of different fluids, such as submarine mud volcanoes (MVs), have been recently reported to largely contribute with dissolved organic matter (DOM) into the oceans. Submarine MVs are common structures in the Gulf of Cádiz. However, little is known about the biogeochemical processes that occur in these peculiar environments, especially those involving DOM. Here, we report DOM characterization in the sediment pore water of three MVs of the Gulf of Cádiz. Estimated benthic fluxes of dissolved organic carbon (DOC) and chromophoric DOM (CDOM) were higher than in other marine sediments with an average of 0.11 ± 0.04 mmol m−2 d−1 for DOC and ranging between 0.11 and 2.86 m−1 L m−2 d−1, for CDOM. Protein-like components represented ~ 70% of the total fluorescent DOM (FDOM). We found that deep fluids migration from MVs (cold seeps) and anaerobic production via sulfate-reducing bacteria represent a source of DOC and FDOM to the overlying water column. Our results also indicate that fluorescent components can have many diverse sources not captured by common classifications. Overall, MVs act as a source of DOC, CDOM, and FDOM to the deep waters of the Gulf of Cádiz, providing energy to the microbial communities living there.
Targeting barrel field spiny stellate cells using a vesicular monoaminergic transporter 2-Cre mouse line
Authors: Freitag Fabio B. , Ahemaiti Aikeremu , Weman Hannah M. , Ambroz Katharina , Lagerström Malin C.
Published: February 2021

Rodent primary somatosensory cortex (S1) is organized in defined layers, where layer IV serves as the main target for thalamocortical projections. Serotoninergic signaling is important for the organization of thalamocortical projections and consequently proper barrel field development in rodents, and the vesicular monoamine transporter 2 (VMAT2) can be detected locally in layer IV S1 cortical neurons in mice as old as P10, but the identity of the Vmat2-expressing neurons is unknown. We here show thatVmat2mRNA and also Vmat2-Cre recombinase are still expressed in adult mice in a sub-population of the S1 cortical neurons in the barrel field. The Vmat2-Cre cells showed a homogenous intrinsically bursting firing pattern determined by whole-cell patch-clamp, localized radial densely spinous basal dendritic trees and almost exclusively lack of apical dendrite, indicative of layer IV spiny stellate cells. Single cell mRNA sequencing analysis showed that S1 cortical Vmat2-Cre;tdTomatocells express the layer IV markerRorband mainly cluster with layer IV neurons, and RNAscope analysis revealed that adult Vmat2-Cre neurons expressVmat2and vesicular glutamate transporter 1 (Vglut1) andVglut2mRNA to a high extent. In conclusion, our analysis shows that corticalVmat2expression is mainly confined to layer IV neurons with morphological, electrophysiological and transcriptional characteristics indicative of spiny stellate cells.
Molecular diversity and evolutionary trends of cysteine-rich peptides from the venom glands of Chinese spider Heteropoda venatoria
Authors: Luo Jie , Ding Yiying , Peng Zhihao , Chen Kezhi , Zhang Xuewen , Xiao Tiaoyi , Chen Jinjun
Published: February 2021

Heteropoda venatoria in the family Sparassidae is highly valued in pantropical countries because the species feed on domestic insect pests. Unlike most other species of Araneomorphae, H. venatoria uses the great speed and strong chelicerae (mouthparts) with toxin glands to capture the insects instead of its web. Therefore, H. venatoria provides unique opportunities for venom evolution research. The venom of H. venatoria was explored by matrix-assisted laser desorption/ionization tandem time-of-flight and analyzing expressed sequence tags. The 154 sequences coding cysteine-rich peptides (CRPs) revealed 24 families based on the phylogenetic analyses of precursors and cysteine frameworks in the putative mature regions. Intriguingly, four kinds of motifs are first described in spider venom. Furthermore, combining the diverse CRPs of H. venatoria with previous spider venom peptidomics data, the structures of precursors and the patterns of cysteine frameworks were analyzed. This work revealed the dynamic evolutionary trends of venom CRPs in H. venatoria: the precursor has evolved an extended mature peptide with more cysteines, and a diminished or even vanished propeptides between the signal and mature peptides; and the CRPs evolved by multiple duplications of an ancestral ICK gene as well as recruitments of non-toxin genes.
Complete chloroplast genomes shed light on phylogenetic relationships, divergence time, and biogeography of Allioideae (Amaryllidaceae)
Authors: Namgung Ju , Do Hoang Dang Khoa , Kim Changkyun , Choi Hyeok Jae , Kim Joo‑Hwan
Published: February 2021

Allioideae includes economically important bulb crops such as garlic, onion, leeks, and some ornamental plants in Amaryllidaceae. Here, we reported the complete chloroplast genome (cpDNA) sequences of 17 species of Allioideae, five of Amaryllidoideae, and one of Agapanthoideae. These cpDNA sequences represent 80 protein-coding, 30 tRNA, and four rRNA genes, and range from 151,808 to 159,998 bp in length. Loss and pseudogenization of multiple genes (i.e., rps2, infA, and rpl22) appear to have occurred multiple times during the evolution of Alloideae. Additionally, eight mutation hotspots, including rps15-ycf1, rps16-trnQ-UUG, petG-trnW-CCA, psbA upstream, rpl32-trnL-UAG, ycf1, rpl22, matK, and ndhF, were identified in the studied Allium species. Additionally, we present the first phylogenomic analysis among the four tribes of Allioideae based on 74 cpDNA coding regions of 21 species of Allioideae, five species of Amaryllidoideae, one species of Agapanthoideae, and five species representing selected members of Asparagales. Our molecular phylogenomic results strongly support the monophyly of Allioideae, which is sister to Amaryllioideae. Within Allioideae, Tulbaghieae was sister to Gilliesieae-Leucocoryneae whereas Allieae was sister to the clade of Tulbaghieae- Gilliesieae-Leucocoryneae. Molecular dating analyses revealed the crown age of Allioideae in the Eocene (40.1 mya) followed by differentiation of Allieae in the early Miocene (21.3 mya). The split of Gilliesieae from Leucocoryneae was estimated at 16.5 mya. Biogeographic reconstruction suggests an African origin for Allioideae and subsequent spread to Eurasia during the middle Eocene. Cool and arid conditions during the late Eocene led to isolation between African and Eurasian species. African Allioideae may have diverged to South American taxa in the late Oligocene. Rather than vicariance, long-distance dispersal is the most likely explanation for intercontinental distribution of African and South American Allioideae species.
Simultaneous bidirectional hindlimb locomotion in decerebrate cats
Authors: Lyakhovetskii V. , Merkulyeva N. , Gorskii O. , Musienko Pavel
Published: February 2021

We show that epidural spinal cord stimulation can elicit stable bidirectional locomotion of decerebrate cats on a split-belt treadmill. The stepping pattern of one limb was similar to unidirectional forward walking and, the other—was similar to unidirectional backward walking. This confirms that spinal and brainstem circuitry are sufficient to control such complex and extraordinary motor tasks driven by somatosensory input. Interlimb coordination during forward and backward walking was preserved in 2 out of 4 animals during ‘extreme’ conditions when one of the treadmill belts was stopped. Bidirectional locomotion worsened but was still possible after temporary spinalization by cooling the spinal cord on a low thoracic level. These present evidence for the great degree of the automatism for this stepping mode defined by the spinal neuronal networks.
NLRC5/CITA expression correlates with efficient response to checkpoint blockade immunotherapy
Authors: Yoshihama Sayuri , Cho Steven X. , Yeung Jason , Pan Xuedong , Lizee Gregory , Konganti Kranti , Johnson Valen E. , Kobayashi Koichi S.
Published: February 2021

Checkpoint blockade-mediated immunotherapy is emerging as an effective treatment modality for multiple cancer types. However, cancer cells frequently evade the immune system, compromising the effectiveness of immunotherapy. It is crucial to develop screening methods to identify the patients who would most benefit from these therapies because of the risk of the side effects and the high cost of treatment. Here we show that expression of the MHC class I transactivator (CITA), NLRC5, is important for efficient responses to anti-CTLA-4 and anti-PD1 checkpoint blockade therapies. Melanoma tumors derived from patients responding to immunotherapy exhibited significantly higher expression of NLRC5 and MHC class I-related genes compared to non-responding patients. In addition, multivariate analysis that included the number of tumor-associated non-synonymous mutations, predicted neo-antigen load and PD-L2 expression was capable of further stratifying responders and non-responders to anti-CTLA4 therapy. Moreover, expression or methylation of NLRC5 together with total somatic mutation number were significantly correlated with increased patient survival. These results suggest that NLRC5 tumor expression, alone or together with tumor mutation load constitutes a valuable predictive biomarker for both prognosis and response to anti-CTLA-4 and potentially anti-PD1 blockade immunotherapy in melanoma patients.
Genetic and environmental architecture of conscientiousness in adolescence
Authors: Takahashi Yusuke , Zheng Anqing , Yamagata Shinji , Ando Juko
Published: February 2021

Using a genetically informative design (about 2000 twin pairs), we investigated the phenotypic and genetic and environmental architecture of a broad construct of conscientiousness (including conscientiousness per se, effortful control, self-control, and grit). These four different measures were substantially correlated; the coefficients ranged from 0.74 (0.72–0.76) to 0.79 (0.76–0.80). Univariate genetic analyses revealed that individual differences in conscientiousness measures were moderately attributable to additive genetic factors, to an extent ranging from 62 (58–65) to 64% (61–67%); we obtained no evidence that shared environmental influences were observed. Multivariate genetic analyses showed that for the four measures used to assess conscientiousness, genetic correlations were stronger than the corresponding non-shared environmental correlations, and that a latent common factor accounted for over 84% of the genetic variance. Our findings suggest that individual differences in the four measures of conscientiousness are not distinguishable at both the phenotypic and behavioural genetic levels, and that the overlap was substantially attributable to genetic factors.
Local electromechanical alterations determine the left ventricle rotational dynamics in CRT-eligible heart failure patients
Authors: Jadczyk Tomasz , Kurzelowski Radoslaw , Golba Krzysztof S. , Wilczek Jacek , Caluori Guido , Maffessanti Francesco , Biernat Jolanta , Gruszczynska Katarzyna , Cybulska Magdalena , Emmert Maximilian Y. , Parma Zofia , Baranski Kamil , Dutka Mieczyslaw , Kalanska-Lukasik Barbara , Starek Zdenek , Wojakowski Wojciech
Published: February 2021

Left ventricle, LV wringing wall motion relies on physiological muscle fiber orientation, fibrotic status, and electromechanics (EM). The loss of proper EM activation can lead to rigid-body-type (RBT) LV rotation, which is associated with advanced heart failure (HF) and challenges in resynchronization. To describe the EM coupling and scar tissue burden with respect to rotational patterns observed on the LV in patients with ischemic heart failure with reduced ejection fraction (HFrEF) left bundle branch block (LBBB). Thirty patients with HFrEF/LBBB underwent EM analysis of the left ventricle using an invasive electro-mechanical catheter mapping system (NOGA XP, Biosense Webster). The following parameters were evaluated: rotation angle; rotation velocity; unipolar/bipolar voltage; local activation time, LAT; local electro-mechanical delay, LEMD; total electro-mechanical delay, TEMD. Patients underwent late-gadolinium enhancement cMRI when possible. The different LV rotation pattern served as sole parameter for patients’ grouping into two categories: wringing rotation (Group A, n = 6) and RBT rotation (Group B, n = 24). All parameters were aggregated into a nine segment, three sector and whole LV models, and compared at multiple scales. Segmental statistical analysis in Group B revealed significant inhomogeneities, across the LV, regarding voltage level, scar burdening, and LEMD changes: correlation analysis showed correspondently a loss of synchronization between electrical (LAT) and mechanical activation (TEMD). On contrary, Group A (relatively low number of patients) did not present significant differences in LEMD across LV segments, therefore electrical (LAT) and mechanical (TEMD) activation were well synchronized. Fibrosis burden was in general associated with areas of low voltage. The rotational behavior of LV in HF/LBBB patients is determined by the local alteration of EM coupling. These findings serve as a strong basic groundwork for a hypothesis that EM analysis may predict CRT response.

Clinical trial registration: SUM No. KNW/0022/KB1/17/15.
Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis
Authors: Luo Chengxin , Wu Guixian , Huang Xiangtao , Ma Yanni , Zhang Yali , Song Qiuyue , Xie Mingling , Sun Yanni , Huang Yarui , Huang Zhen , Hou Yu , Xu Shuangnian , Chen Jieping , Li Xi
Published: February 2021

Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20+ B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel–Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20+ B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73–0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13–1.48, P < 0.001). Ofatumumab was inferior to rituximab in consideration of ORR (OR 0.73, 95% CI 0.55–0.96, P = 0.02), and had no significant differences with rituximab in regard to PFS, OS and CRR. 131I-tositumomab yielded similar PFS, OS, ORR and CRR with rituximab. 90Y-ibritumomab tiuxetan increased ORR (OR 3.07, 95% CI 1.47–6.43, P = 0.003), but did not improve PFS, DFS, OS and CRR compared with rituximab. In conclusion, compared with rituximab in induction therapy of CD20+ B-NHL, obinutuzumab significantly improves PFS but with higher incidence of AEs, ofatumumab decreases ORR, 90Y-ibritumomab tiuxetan increases ORR.
Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection
Authors: Cruz-Chan Julio V. , Villanueva-Lizama Liliana E. , Versteeg Leroy , Damania Ashish , Villar Maria José , González-López Cristina , Keegan Brian , Pollet Jeroen , Gusovsky Fabian , Hotez Peter J. , Bottazzi Maria Elena , Jones Kathryn M.
Published: February 2021

Chagas disease resulting fromTrypanosoma cruziinfection leads to a silent, long-lasting chronic neglected tropical disease affecting the poorest and underserved populations around the world. Antiparasitic treatment with benznidazole does not prevent disease progression or death in patients with established cardiac disease. Our consortium is developing a therapeutic vaccine based on theT. cruziflagellar—derived antigen Tc24-C4 formulated with a Toll-like receptor 4 agonist adjuvant, to complement existing chemotherapy and improve treatment efficacy. Here we demonstrate that therapeutic treatment of acutely infected mice with a reduced dose of benznidazole concurrently with vaccine treatment – also known as “vaccine-linked chemotherapy”—induced a TH17 like immune response, with significantly increased production of antigen specific IL-17A, IL-23 and IL-22, and CD8 + T lymphocytes, as well as significantly increasedT. cruzispecific IFNγ-producing CD4 + T lymphocytes. Significantly reduced cardiac inflammation, fibrosis, and parasite burdens and improved survival were achieved by vaccine-linked chemotherapy and individual treatments. Importantly, low dose treatments were comparably efficacious to high dose treatments, demonstrating potential dose sparing effects. We conclude that through induction of TH17 immune responses vaccine-linked chemotherapeutic strategies could bridge the tolerability and efficacy gaps of current drug treatment in Chagasic patients.
Meta-omics characteristics of intestinal microbiota associated to HBeAg seroconversion induced by oral antiviral therapy
Authors: Zeng Yu-Li , Qin Lei , Wei Wen-Jun , Cai Hong , Yu Xiao-Fang , Zhang Wei , Wu Xiao-Lu , Liu Xiao-Bin , Chen Wei-Ming , You Pan , Hong Mei-Zhu , Liu Yaming , Dong Xuan , Shia Ben-Chang , Niu Jian-Jun , Pan Jin-Shui
Published: February 2021

Tenofovir and entecavir are currently designated as the preferred oral antiviral drugs for chronic hepatitis B. However, only less than 40% of patients can achieve HBeAg seroconversion. We aim at investigating the role of intestinal microbiome in HBeAg seroconversion induced by oral antiviral therapy and describe multi-omics characteristics of HBeAg seroconversion associated intestinal flora. In this study, we prospectively collected fecal samples at baseline from the patients with HBeAg positive chronic hepatitis B who would have oral antiviral therapy. 16S rDNA sequencing and metabolomics were performed. We identified HBeAg seroconversion-related microbial signature and constructed prediction model for HBeAg seroconversion. Thirty-seven of these subjects achieved HBeAg seroconversion within 156 weeks after the initiation of oral antiviral therapy, while 41 subjects remained HBeAg positive even after over 156 weeks of therapy. A computational statistical and machine learning approach allowed us to identify a microbial signature for HBeAg seroconversion. Using random forest method, we further constructed a classifier based on the microbial signature, with area under curve being 0.749 for the test set. Patients who achieved HBeAg seroconversion tended to have lower abundance of certain fecal metabolites such as essential amino acids, and several dipeptides. By analyzing the fecal microbiota from the patients with and without HBeAg seroconversion, we showed intestinal microbiome play a critical role in HBeAg seroconversion induced by oral antiviral therapy. We also identified intestinal microbial signature that is associated with HBeAg seroconversion after oral antiviral therapy.
Binary scaffold facilitates in situ regeneration of axons and neurons for complete spinal cord injury repair
Authors: Liu Dingyang , Shu Muya , Liu Weiyuan , Shen Yeyu , Long Ge , Zhao Yannan , Hou Xianglin , Xiao Zhifeng , Dai Jianwu , Li Xing
Published: February 2021

A binary-drug modified scaffold is able to promote both axonal and neuronal regeneration in complete spinal cord injury model. Moreover, it also facilitates synaptic formation of the regenerated neurons and axons for motor function improvement.
Stability of pyruvic acid clusters upon slow electron attachment
Authors: Pysanenko Andriy , Grygoryeva Kateryna , Kočišek Jaroslav , Kumar T. P. Ragesh , Fedor Juraj , Ončák Milan , Fárník Michal
Published: February 2021

Fragmentation of pyruvic acid upon slow electron attachment is investigated in relevance to its formation on ice grains in the interstellar medium.
Intrinsic enhancement of the rate capability and suppression of the phase transition via p-type doping in Fe–Mn based P2-type cathodes used for sodium ion batteries
Authors: Hwang Taesoon , Lim Jin-Myoung , Oh Rye-Gyeong , Cho Woosuk , Cho Maenghyo , Cho Kyeongjae
Published: February 2021

First principles design of a P2-type Fe–Mn oxide cathode for Na ion batteries with improved electrochemical performance and suppression of its phase transition by Cu doping. The improvements are confirmed using experimental cathode synthesis and battery test.
Catalytic cycle of the partial oxidation of methane to methanol over Cu-ZSM-5 revealed using DFT calculations
Authors: Yu Xi , Zhong Liangshu , Li Shenggang
Published: February 2021

Methane oxidation to methanol over Cu-ZSM-5 is found using DFT calculations to involve both [Cu2(O2)]2+ and [Cu2(μ-O)]2+ active sites.
Advances in multiplexed techniques for the detection and quantification of microRNAs
Authors: Jet Thomas , Gines Guillaume , Rondelez Yannick , Taly Valérie
Published: February 2021

Multiplex miRNA detection is a promising way to non-invasive diagnostics. In this review, we discuss the recent advances to the multiplexing of miRNA quantification.
Effects of the morphology and heteroatom doping of CeO2 support on the hydrogenation activity of Pt single-atoms
Authors: Ma Yanfu , Zhang Xiaohui , Cao Lina , Lu Junling
Published: February 2021

Doping the spherical CeO2 support using N enhances the hydrogenation activity of Pt single atoms remarkably, which can be even higher than that of spherical CeO2 supported Pt clusters.
Versatile quantitative biopsy: an approach for cost-effective detection of hydrogen peroxide in tissue specimens
Authors: Nan Yanxia , Gu Yu , Liu Zhen , Zhou Qiulan , Zhao Wenjie , Xu Weijian
Published: February 2021

In the presence of H2O2, the amylose released by the micelles is converted into glucose by glucoamylase and detected by a PGM.
Post-synthesis modification of functionalised polyhedral oligomeric silsesquioxanes with encapsulated fluoride – enhancing reactivity of T8-F POSS for materials synthesis
Authors: Laird Mathilde , Gaveau Philippe , Trens Philippe , Carcel Carole , Unno Masafumi , Bartlett John R. , Wong Chi Man Michel
Published: February 2021

The first successful approach for modifying poorly reactive POSS containing F− (T8-F) and incorporating intact T8-F within a nanohybrid material is described.
Highly effective catalytic reduction of nitrobenzene compounds with gold nanoparticle-immobilized hydroxyapatite nanowire-sintered porous ceramic beads
Authors: Li Jie , Wu Minjie , Du Hongchen , Wang Buchuan , Li Yinglong , Huan Weiwei
Published: February 2021

A catalytic ceramic bead with micron-sized and interconnected porous channels, adjustable porosity, high catalytic activity, and long-term stability is prepared.
Solar-driven valorisation of glycerol on BiVO4 photoanodes: effect of co-catalyst and reaction media on reaction selectivity
Authors: Wu Yi-Hsuan , Kuznetsov Denis A. , Pflug Nicholas C. , Fedorov Alexey , Müller Christoph R.
Published: February 2021

Photoelectrodes based on bismuth vanadate demonstrate excellent performance in photoelectrochemical glycerol reforming.
Alloy engineering in mixed Sn–Ge perovskites for photovoltaic application
Authors: Zhou Yu-Qian , Xu Jian , Liu Jian-Bo , Liu Bai-Xin
Published: February 2021

The concerted action of alloying on both band edges and defect states leads to the most benign defect properties (SnI and GeI) in CsGe0.5Sn0.5I3, compared to the other components.
Expecting the unexpected: high pressure crystallization significantly boosts up triboelectric outputs of microbial polyesters
Authors: Wang Chuanfeng , Peng Zhou , Huang Xi , Yan Cheng , Yang Tao , Zhang Chaoliang , Lu Jun , Yang Weiqing
Published: January 2021

Polyhydroxybutyrate (PHB) with special wrinkled spherulites enables significant improvement in triboelectric outputs of the microbial polyester.
Microwave-assisted solvothermal synthesis of LiVyM1−yOPO4 (M = Mn, Cr, Ti, Zr, Nb, Mo, W) cathode materials for lithium-ion batteries
Authors: Kaplan Carol , Hidalgo Marc Francis V. , Zuba Mateusz J. , Chernova Natasha A. , Piper Louis F. J. , Whittingham M. Stanley
Published: February 2021

LiVOPO4 (LVP) is a promising next generation multi-electron material with a theoretical capacity of 305 mA h g−1, higher than any commercially used cathode material.
Understanding the lattice nitrogen stability and deactivation pathways of cubic CrN nanoparticles in the electrochemical nitrogen reduction reaction
Authors: Guo Wenhan , Liang Zibin , Tang Yanqun , Cai Kunting , Qiu Tianjie , Wu Yingxiao , Zhang Kexin , Gao Song , Zou Ruqiang
Published: February 2021

CrN nanoparticles with a cubic rocksalt structure are investigated for the lattice stability during the electrochemical nitrogen reduction reaction. Lattice collapse and ammonia poisoning are proposed as the two possible deactivation pathways.
Adsorption energy as a promising single-parameter descriptor for single atom catalysis in the oxygen evolution reaction
Authors: Huang Hai-Cai , Li Jun , Zhao Yang , Chen Jing , Bu Yu-Xiang , Cheng Shi-Bo
Published: February 2021

A highly efficient and reliable single-parameter descriptor for offering a strategy to rationally design SACs for the OER.
Applications of oxidized alginate in regenerative medicine
Authors: Kong Xiaoli , Chen Long , Li Bo , Quan Changyun , Wu Jun
Published: February 2021

Because of its ideal degradation rate and features, oxidized alginate (OA) is selected as an appropriate substitute and has been introduced into hydrogels, microspheres, 3D-printed/composite scaffolds, membranes, and electrospinning and coating materials.
Biomarker imprinted magnetic core–shell nanoparticles for rapid, culture free detection of pathogenic bacteria
Authors: Rajpal Soumya , Bhakta Snehasis , Mishra Prashant
Published: February 2021

A facile method for the fabrication of pyocyanin imprinted magnetic nanoparticles for the capture of toxin and culture free detection of pathogenic bacteria.
Recent progress in intrinsic and stimulated room-temperature gas sensors enabled by low-dimensional materials
Authors: Cheng Yinfen , Ren Baiyu , Xu Kai , Jeerapan Itthipon , Chen Hui , Li Zhong , Ou Jian Zhen
Published: February 2021

Room temperature (RT) gas sensors based on low-dimensional materials that mainly included three strategies. (1) Nanostructures optimisation; (2) driven by voltage biasing; (3) assisting with light illumination.
Doping of silicon with phosphorus end-terminated polymers: source characterization and dopant diffusion in SiO2
Authors: Perego Michele , Seguini Gabriele , Mascheroni Edoardo , Arduca Elisa , Gianotti Valentina , Laus Michele
Published: February 2021

A polystyrene homopolymer with narrow molecular weight distribution (Mn = 2.3 ± 0.3 kg mol−1, Đ = 1.05 ± 0.01) and end-terminated with a phosphorus containing moiety has been used to form P δ-layers embedded into a SiO2 matrix.
The green synthesis of a palm empty fruit bunch-derived sulfonated carbon acid catalyst and its performance for cassava peel starch hydrolysis
Authors: Nata Iryanti Fatyasari , Irawan Chairul , Putra Meilana Dharma , Lee Cheng-Kang
Published: February 2021

A sulfonated carbon acid catalyst (C–SO3H) was successfully generated from palm empty fruit bunch (PEFB) carbon via hydrothermal sulfonation via the addition of hydroxyethylsulfonic acid and citric acid.
Fe ultra-small particles anchored on carbon aerogels to enhance the oxygen reduction reaction in Zn-air batteries
Authors: Shi Jinjin , Shu Xinxin , Xiang Chensheng , Li Hong , Li Yang , Du Wei , An Pengfei , Tian He , Zhang Jintao , Xia Haibing
Published: February 2021

The Fe–N4–O–Fe–N4 moiety as active sites in ultra-small Fe particles anchored on carbon aerogel exhibited superior performance towards the oxygen reduction reaction.
Cation optimization for burn-in loss-free perovskite solar devices
Authors: Paek Sanghyun , Khan Sher Bahadar , Franckevičius Marius , Gegevičius Rokas , A. Syzgantseva Olga , Syzgantseva Maria A. , Kinche Sachin , Asiri Abdullah M. , Roldán-Carmona Cristina , Nazeeruddin Mohammed Khaja
Published: February 2021

The photovoltaic stability of nonencapsulated cells containing Csx(FAMAGua)1−x (x = 0.1; x = 0.2; x = 0.3) stored in the dark under air conditions for 4000 h (a), and devices under continuous light soaking at MPP tracking (b).
Nickel-Catalyzed Ligand-Free Hiyama Coupling of Aryl Bromides and Vinyltrimethoxysilane
Authors: Mao Yongjun , Shi Shi-Liang , Wei Shichao
Published: January 2021

We herein disclose the first Ni-catalyzed Hiyama coupling of aryl halides with vinylsilanes. This protocol uses cheap, nontoxic, and stable vinyltrimethoxysilane as the vinyl donor, proceeds under mild and ligand-free conditions, furnishing a diverse variety of styrene derivatives in high yields with excellent functional group compatibility.