bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of methotrexate and etanercept biosimilar rhTNFR:Fc in Chinese patients with active rheumatoid arthritis: A controlled, randomized and multicenter study
Authors: Wu Qingjun , Zhao Yan , Xu Dong , Zhang Zhuoli , Li Zhenbin 
Published: August 2020

AbstractRheumatoid arthritis is a chronic inflammatory disease which could lead to severe joint damage and disability. This study was performed to determine the efficacy and safety of methotrexate (MTX) therapy combined with maintenance or discontinuation of etanercept biosimilar rhTNFR:Fc in active rheumatoid arthritis patients in Chinese patients. In this controlled, randomized and open-label study, 89 patients with active rheumatoid arthritis were enrolled at 7 institutions in China between September 2010 and May 2011. In a period of 52 weeks, patients were randomly assigned to one of three treatment groups: MTX plus rhTNFR:Fc for 52 weeks, MTX plus rhTNFR:Fc for 24 weeks, or MTX monotherapy. The primary endpoint was the joint damage evaluated by change from baseline (CFB) of van de Heijde modified Total Sharp Score (mTSS). Intention-to-treat population were used for analysis. A total of 89 enrolled patients were eligible for this study, of whom 32 were assigned to MTX plus rhTNFR:Fc52 group, 31 to MTX plus rhTNFR:Fc24, and 26 to MTX monotherapy. Only one patient was lost to follow up in the MTX plus rhTNFR:Fc24 group. The mTSS CFB was lower in the rhTNFR:Fc pooled group (combination of data in the MTX plus rhTNFR:Fc52 group and MTX plus rhTNFR:Fc24 group) comparing with MTX monotherapy at week 24 and 52 (P = 0.03 and P < 0.01). Additionally, ACR50 and ACR70 response rates were both higher in the rhTNFR:Fc pooled group than MTX monotherapy (P < 0.05). Combination of MTX and rhTNFR:Fc in patients with active rheumatoid arthritis could effectively inhibit joint structure damage.
Single-cell RNA sequencing uncovers heterogenous transcriptional signatures in macrophages during efferocytosis
Authors: Lantz Connor , Radmanesh Behram , Liu Esther , Thorp Edward B. , Lin Jennie 
Published: August 2020

AbstractEfferocytosis triggers cellular reprogramming, including the induction of mRNA transcripts which encode anti-inflammatory cytokines that promote inflammation resolution. Our current understanding of this transcriptional response is largely informed from analysis of bulk phagocyte populations; however, this precludes the resolution of heterogeneity between individual macrophages and macrophage subsets. Moreover, phagocytes may contain so called “passenger” transcripts that originate from engulfed apoptotic bodies, thus obscuring the true transcriptional reprogramming of the phagocyte. To define the transcriptional diversity during efferocytosis, we utilized single-cell mRNA sequencing after co-cultivating macrophages with apoptotic cells. Importantly, transcriptomic analyses were performed after validating the disappearance of apoptotic cell-derived RNA sequences. Our findings reveal new heterogeneity of the efferocytic response at a single-cell resolution, particularly evident between F4/80+ MHCIILO and F4/80− MHCIIHI macrophage sub-populations. After exposure to apoptotic cells, the F4/80+ MHCIILO subset significantly induced pathways associated with tissue and cellular homeostasis, while the F4/80− MHCIIHI subset downregulated these putative signaling axes. Ablation of a canonical efferocytosis receptor, MerTK, blunted efferocytic signatures and led to the escalation of cell death-associated transcriptional signatures in F4/80+ MHCIILO macrophages. Taken together, our results newly elucidate the heterogenous transcriptional response of single-cell peritoneal macrophages after exposure to apoptotic cells.
Chromatin and transcriptome changes in human myoblasts show spatio-temporal correlations and demonstrate DPP4 inhibition in differentiated myotubes
Authors: Kolanowski Tomasz J. , Rozwadowska Natalia , Zimna Agnieszka , Nowaczyk Magdalena , Siatkowski Marcin , Łabędź Wojciech , Wiland Ewa , Gapiński Jacek , Jurga Stefan , Kurpisz Maciej 
Published: August 2020

AbstractAlthough less attention was paid to understanding physical localization changes in cell nuclei recently, depicting chromatin interaction maps is a topic of high interest. Here, we focused on defining extensive physical changes in chromatin organization in the process of skeletal myoblast differentiation. Based on RNA profiling data and 3D imaging of myogenic (NCAM1, DES, MYOG, ACTN3, MYF5, MYF6, ACTN2, and MYH2) and other selected genes (HPRT1, CDH15, DPP4 and VCAM1), we observed correlations between the following: (1) expression change and localization, (2) a gene and its genomic neighbourhood expression and (3) intra-chromosome and microscopical locus-centromere distances. In particular, we demonstrated the negative regulation of DPP4 mRNA (p < 0.001) and protein (p < 0.05) in differentiated myotubes, which coincided with a localization change of the DPP4 locus towards the nuclear lamina (p < 0.001) and chromosome 2 centromere (p < 0.001). Furthermore, we discuss the possible role of DPP4 in myoblasts (supported by an inhibition assay). We also provide positive regulation examples (VCAM1 and MYH2). Overall, we describe for the first time existing mechanisms of spatial gene expression regulation in myoblasts that might explain the issue of heterogenic responses observed during muscle regenerative therapies.
Females of the red damselfly Mnesarete pudica are attracted to more ornamented males and attract rival males
Authors: Pena-Firme Paloma , Guillermo-Ferreira Rhainer 
Published: August 2020

AbstractMale calopterygid damselflies often exhibit colourful wings used during aggressive contests and courtship displays. Evidence suggests that male wing coloration is a secondary sexual character assessed by males and females to identify male quality. In some species, males adopt a lekking strategy, where females visit exhibition arenas and choose the best mate. Here, we addressed whether the behaviour ofMnesarete pudicamales is influenced by female visitation when gathering in leks. We hypothesized that female visitation would increase male investment in courtship and fighting, while reducing patrolling flights and harassment attempts. Moreover, we tested the hypothesis that more ornamented males attract more females to the territory, following the hotshot model of lek evolution. Our results suggest that, indeed, males with more pigmented wings attract more visiting females, independently of male size. Our results also show that the number of females in a territory attracts more males and elicits male contest behaviour, reducing male harassment. We conclude that male ornament and male clustering is a good predictor of female visitation rates, suggesting that females may exert mate choice.
Plasma β-III tubulin, neurofilament light chain and glial fibrillary acidic protein are associated with neurodegeneration and progression in schizophrenia
Authors: Rodrigues-Amorim Daniela , Rivera-Baltanás Tania , del Carmen Vallejo-Curto María , Rodriguez-Jamardo Cynthia , de las Heras Elena , Barreiro-Villar Carolina , Blanco-Formoso María , Fernández-Palleiro Patricia , Álvarez-Ariza María , López Marta , García-Caballero Alejandro , Olivares José Manuel , Spuch Carlos 
Published: August 2020

AbstractSchizophrenia is a progressive disorder characterized by multiple psychotic relapses. After every relapse, patients may not fully recover, and this may lead to a progressive loss of functionality. Pharmacological treatment represents a key factor to minimize the biological, psychological and psychosocial impact of the disorder. The number of relapses and the duration of psychotic episodes induce a potential neuronal damage and subsequently, neurodegenerative processes. Thus, a comparative study was performed, including forty healthy controls and forty-two SZ patients divided into first-episode psychosis (FEP) and chronic SZ (CSZ) subgroups, where the CSZ sub group was subdivided by antipsychotic treatment. In order to measure the potential neuronal damage, plasma levels of β-III tubulin, neurofilament light chain (Nf-L), and glial fibrillary acidic protein (GFAP) were performed. The results revealed that the levels of these proteins were increased in the SZ group compared to the control group (P < 0.05). Moreover, multiple comparison analysis showed highly significant levels of β-III tubulin (P = 0.0002), Nf-L (P = 0.0403) and GFAP (P < 0.015) in the subgroup of CSZ clozapine-treated. In conclusion, β-III tubulin, Nf-L and GFAP proteins may be potential biomarkers of neurodegeneration and progression in SZ.
The bHLH transcription factor VfTT8 underlies zt2, the locus determining zero tannin content in faba bean (Vicia faba L.)
Authors: Gutierrez Natalia , Avila Carmen M. , Torres Ana M. 
Published: August 2020

AbstractFaba bean (Vicia faba L.) is an important protein-rich fodder crop, which is widely cultivated in temperate areas. However, antinutritional compounds such as condensed tannins, limit the use of this protein source in monogastric feed formulations. Previous studies demonstrated that two recessive and complementary genes, zt1 and zt2, control absence of tannin and white flower colour in faba bean. An ortholog of the Medicago WD40 transcription factor TTG1 was reported to encode the zt1 phenotype, but the responsible gene for zt2 is still unknown. Here we used a candidate gene approach combined with linkage mapping, comparative genomics and gene expression to fine map the zt2 genomic region and to identify the regulatory gene controlling both traits. Seventy-two genes, including 23 MYB and bHLH regulatory genes predicted to be associated with anthocyanin expression together with WRKY proteins, were screened and genotyped in three mapping populations. The linkage groups constructed identified the regulatory gene, TRANSPARENT TESTA8 (TT8), encoding a basic helix-loop-helix (bHLH) transcription factor, as the candidate for zt2. This finding was supported by qPCR analysis and further validated in different genetic backgrounds. Accordingly, VfTT8 was downregulated in white flowered types while showing high levels of expression in wild genotypes. Our results provide new insights on the regulatory mechanisms of tannin biosynthesis in faba bean and will facilitate the development of an ultimate zt2 diagnostic marker for the fast generation of new value-added cultivars free of tannins and with improved nutritional value.
CXCR4hi effector neutrophils in sickle cell anemia: potential role for elevated circulating serotonin (5-HT) in CXCR4hi neutrophil polarization
Authors: Garcia Flavia , Mendonça Rafaela , Miguel Lediana I. , Dominical Venina M. , Saad Sara T. O. , Costa Fernando F. , Conran Nicola 
Published: August 2020

AbstractLeukocyte recruitment and heterocellular aggregate formation drive the inflammatory vaso-occlusive processes associated with sickle cell anemia (SCA). We characterized neutrophils in a population of patients with SCA and investigated whether platelet-derived molecules can induce phenotypic alterations in this cell type. Imaging flow cytometry analysis demonstrated that the frequency of circulating CXCR4hi neutrophils was significantly higher in steady-state SCA individuals than in healthy control individuals and that these cells presented increased CD11b activation and toll-like receptor-4 expression. SCA neutrophils display increased neutrophil-platelet aggregation, and CXCR4hi neutrophils demonstrated augmented neutrophil-platelet aggregate frequency with a higher mean number of platelets adhered per neutrophil. Importantly, incubation of neutrophils with platelets significantly elevated their CXCR4 expression, while SCA plasma was found to induce CXCR4hi neutrophil polarization significantly more than control plasma. SCA individuals had significantly increased plasma levels of serotonin (5-HT), and serotonin molecule and SCA plasma induced neutrophil CXCR4 expression in a serotonin-receptor-dependent manner. Thus, the augmented CXCR4hi neutrophil population may contribute to mechanisms that promote vaso-occlusion in SCA; furthermore, circulating serotonin, derived from platelet activation, may play a role in the polarization of neutrophils, suggesting that serotonin-receptor antagonists or serotonin reuptake inhibitors could represent therapeutic approaches to reduce neutrophil activation in SCA.
A novel epitope tagging system to visualize and monitor antigens in live cells with chromobodies
Authors: Traenkle Bjoern , Segan Sören , Fagbadebo Funmilayo O. , Kaiser Philipp D. , Rothbauer Ulrich 
Published: August 2020

AbstractEpitope tagging is a versatile approach to study different proteins using a well-defined and established methodology. To date, most epitope tags such as myc, HA, V5 and FLAG tags are recognized by antibodies, which limits their use to fixed cells, tissues or protein samples. Here we introduce a broadly applicable tagging strategy utilizing a short peptide tag (PepTag) which is specifically recognized by a nanobody (PepNB). We demonstrated that the PepNB can be easily functionalized for immunoprecipitation or direct immunofluorescence staining of Pep-tagged proteins in vitro. For in cellulo studies we converted the PepNB into a fluorescently labeled Pep-chromobody (PepCB) which is functionally expressed in living cells. The addition of the small PepTag does not interfere with the examined structures in different cellular compartments and its detection with the PepCB enables optical antigen tracing in real time. By employing the phenomenon of antigen-mediated chromobody stabilization (AMCBS) using a turnover-accelerated PepCB we demonstrated that the system is suitable to visualize and quantify changes in Pep-tagged antigen concentration by quantitative live-cell imaging. We expect that this novel tagging strategy offers new opportunities to study the dynamic regulation of proteins, e.g. during cellular signaling, cell differentiation, or upon drug action.
Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro
Authors: Kostopoulos Ioannis , Elzinga Janneke , Ottman Noora , Klievink Jay T. , Blijenberg Bernadet , Aalvink Steven , Boeren Sjef , Mank Marko , Knol Jan , de Vos Willem M. , Belzer Clara 
Published: August 2020

AbstractAkkermansia muciniphila is a well-studied anaerobic bacterium specialized in mucus degradation and associated with human health. Because of the structural resemblance of mucus glycans and free human milk oligosaccharides (HMOs), we studied the ability of A. muciniphila to utilize human milk oligosaccharides. We found that A. muciniphila was able to grow on human milk and degrade HMOs. Analyses of the proteome of A. muciniphila indicated that key-glycan degrading enzymes were expressed when the bacterium was grown on human milk. Our results display the functionality of the key-glycan degrading enzymes (α-l-fucosidases, β-galactosidases, exo-α-sialidases and β-acetylhexosaminidases) to degrade the HMO-structures 2′-FL, LNT, lactose, and LNT2. The hydrolysation of the host-derived glycan structures allows A. muciniphila to promote syntrophy with other beneficial bacteria, contributing in that way to a microbial ecological network in the gut. Thus, the capacity of A. muciniphila to utilize human milk will enable its survival in the early life intestine and colonization of the mucosal layer in early life, warranting later life mucosal and metabolic health.
Active vision in immersive, 360° real-world environments
Authors: Haskins Amanda J. , Mentch Jeff , Botch Thomas L. , Robertson Caroline E. 
Published: August 2020

AbstractHow do we construct a sense of place in a real-world environment? Real-world environments are actively explored via saccades, head turns, and body movements. Yet, little is known about how humans process real-world scene information during active viewing conditions. Here, we exploited recent developments in virtual reality (VR) and in-headset eye-tracking to test the impact of active vs. passive viewing conditions on gaze behavior while participants explored novel, real-world, 360° scenes. In one condition, participants actively explored 360° photospheres from a first-person perspective via self-directed motion (saccades and head turns). In another condition, photospheres were passively displayed to participants while they were head-restricted. We found that, relative to passive viewers, active viewers displayed increased attention to semantically meaningful scene regions, suggesting more exploratory, information-seeking gaze behavior. We also observed signatures of exploratory behavior in eye movements, such as quicker, more entropic fixations during active as compared with passive viewing conditions. These results show that active viewing influences every aspect of gaze behavior, from the way we move our eyes to what we choose to attend to. Moreover, these results offer key benchmark measurements of gaze behavior in 360°, naturalistic environments.
Cerebrospinal fluid ctDNA and metabolites are informative biomarkers for the evaluation of CNS germ cell tumors
Authors: Takayasu Takeshi , Shah Mauli , Dono Antonio , Yan Yuanqing , Borkar Roshan , Putluri Nagireddy , Zhu Jay-Jiguang , Hama Seiji , Yamasaki Fumiyuki , Tahara Hidetoshi , Sugiyama Kazuhiko , Kurisu Kaoru , Esquenazi Yoshua , Ballester Leomar Y. 
Published: August 2020

AbstractSerum and cerebrospinal fluid (CSF) levels of α-fetoprotein and β-subunit of human chorionic gonadotropin are used as biomarkers for the management of central nervous system (CNS) germ cell tumors (GCTs). However, additional discriminating biomarkers are required. Especially, biomarkers to differentiate non-germinomatous germ cell tumors (NGGCTs) from germinomas are critical, as these have a distinct prognosis. We investigated CSF samples from 12 patients with CNS-GCT patients (8 germinomas and 4 NGGCTs). We analyzed circulating tumor DNA (ctDNA) in CSF to detect mutated genes. We also used liquid chromatography-mass spectrometry to characterize metabolites in CSF. We detectedKITand/orNRASmutation, known as frequently mutated genes in GCTs, in 3/12 (25%) patients. We also found significant differences in the abundance of 15 metabolites between control and GCT, with unsupervised hierarchical clustering analysis. Metabolites related to the TCA cycle were increased in GCTs. Urea, ornithine, and short-chain acylcarnitines were decreased in GCTs. Moreover, we also detected several metabolites (e.g., betaine, guanidine acetic acid, and 2-aminoheptanoic acid) that displayed significant differences in abundance in patients with germinomas and NGGCTs. Our results suggest that ctDNA and metabolites in CSF can serve as novel biomarkers for CNS-GCTs and can be useful to differentiate germinomas from NGGCTs.
3D imaging and morphometry of the heart capillary system in spontaneously hypertensive rats and normotensive controls
Authors: Olianti Camilla , Costantini Irene , Giardini Francesco , Lazzeri Erica , Crocini Claudia , Ferrantini Cecilia , Pavone Francesco Saverio , Camici Paolo Guido , Sacconi Leonardo 
Published: August 2020

AbstractSystemic arterial hypertension is a highly prevalent chronic disease associated with hypertensive cardiomyopathy. One important feature of this condition is remodelling of intramural small coronary arteries and arterioles. Here, we investigated the implications of this remodelling in the downstream vascular organization, in particular at the capillary level. We used Spontaneously Hypertensive Rats (SHR) exhibiting many features of the human hypertensive cardiomyopathy. We generated 3D high-resolution mesoscopic reconstructions of the entire network of SHR hearts combining gel-based fluorescent labelling of coronaries with a CLARITY-based tissue clearing protocol. We performed morphometric quantification of the capillary network over time to assess capillary diameter, linear density, and angular dispersion. In SHRs, we found significant remodelling of the capillary network density and dispersion. SHR capillary density is increased in both ventricles and at all ages, including before the onset of systemic hypertension. This result suggests that remodelling occurs independently from the onset of systemic hypertension and left ventricular hypertrophy. On the contrary, capillary angular dispersion increases with time in SHR. Consistently, our multicolor imaging underlined a strong correlation between vascular dispersion and cellular disarray. Together our data show that 3D high-resolution reconstruction of the capillary network can unveil anatomic signatures in both physiological and pathological cardiac conditions, thus offering a reliable method for integrated quantitative analyses.
Outcome saliency modulates behavioral decision switching
Authors: Sun Sai , Yu Rongjun , Wang Shuo 
Published: August 2020

AbstractGoal-directed decision making often requires evaluating the outcomes of our decisions, assessing any gains or losses, learning from performance-related feedback, and deciding whether to alter our future decisions. However, it is unclear how these processes can be influenced by the saliency of an outcome (e.g., when one aspect of the outcome is accentuated more than another). Here we investigated whether decision strategies changed when certain aspects of the task outcome (win/loss or correct/incorrect) became more salient and how our brain encoded such saliency signals. We employed a simple two-alternative forced choice gambling task and quantified the frequency at which participants switched decisions to an alternative option in the subsequent trial after receiving feedback on their current selection. We conducted three experiments. In Experiment 1, we established the baseline decision switching behavior: participants switched more frequently following incorrect trials than correct trials, but there was no significant difference between win and loss trials. In Experiment 2, we highlighted the utility (win or loss) or performance (correct or incorrect) dimension of thechosenoutcome and we found that the difference in switching frequency was enlarged along the highlighted dimension. However, Experiment 3 showed that when using non-specific saliency emphasis of the outcome, the saliency effect was abolished. We further conducted simultaneous EEG recordings using specific saliency emphasis and found that the feedback-related negativity, P300, and late positive potential could collectively encode saliency modulation of behavioral switching. Lastly, both the frontal and parietal theta-band power encoded the outcome when it was made more salient. Together, our findings suggest that specific outcome saliency can modulate behavioral decision switching between choices and our results have further revealed the neural signatures underlying such saliency modulation. Altering the saliency of an outcome may change how information is weighed during outcome evaluation and thus influence future decisions.