bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of PHF6 leads to aberrant development of human neuron-like cells
Authors: Fliedner Anna , Gregor Anne , Ferrazzi Fulvia , Ekici Arif B. , Sticht Heinrich , Zweier Christiane 
Published: November 2020

AbstractPathogenic variants in PHD finger protein 6 (PHF6) cause Borjeson–Forssman–Lehmann syndrome (BFLS), a rare X-linked neurodevelopmental disorder, which manifests variably in both males and females. To investigate the mechanisms behind overlapping but distinct clinical aspects between genders, we assessed the consequences of individual variants with structural modelling and molecular techniques. We found evidence that de novo variants occurring in females are more severe and result in loss of PHF6, while inherited variants identified in males might be hypomorph or have weaker effects on protein stability. This might contribute to the different phenotypes in male versus female individuals with BFLS. Furthermore, we used CRISPR/Cas9 to induce knockout of PHF6 in SK-N-BE (2) cells which were then differentiated to neuron-like cells in order to model nervous system related consequences of PHF6 loss. Transcriptome analysis revealed a broad deregulation of genes involved in chromatin and transcriptional regulation as well as in axon and neuron development. Subsequently, we could demonstrate that PHF6 is indeed required for proper neuron proliferation, neurite outgrowth and migration. Impairment of these processes might therefore contribute to the neurodevelopmental and cognitive dysfunction in BFLS.
Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status
Authors: Morilla Ian , Léger Thibaut , Marah Assiya , Pic Isabelle , Zaag Hatem , Ogier-Denis Eric 
Published: November 2020

AbstractThe conditions used to describe the presence of an immune disease are often represented by interaction graphs. These informative, but intricate structures are susceptible to perturbations at different levels. The mode in which that perturbation occurs is still of utmost importance in areas such as cell reprogramming and therapeutics models. In this sense, module identification can be useful to well characterise the global graph architecture. To help us with this identification, we perform topological overlap-related measures. Thanks to these measures, the location of highly disease-specific module regulators is possible. Such regulators can perturb other nodes, potentially causing the entire system to change behaviour or collapse. We provide a geometric framework explaining such situations in the context of inflammatory bowel diseases (IBD). IBD are severe chronic disorders of the gastrointestinal tract whose incidence is dramatically increasing worldwide. Our approach models different IBD status as Riemannian manifolds defined by the graph Laplacian of two high throughput proteome screenings. It also identifies module regulators as singularities within the manifolds (the so-called singular manifolds). Furthermore, it reinterprets the characteristic nonlinear dynamics of IBD as compensatory responses to perturbations on those singularities. Then, particular reconfigurations of the immune system could make the disease status move towards an innocuous target state.
Circulating expression of Hsa_circRNA_102893 contributes to early gestational diabetes mellitus detection
Authors: Yang Hongling , Ye Weitao , Chen Ruihua , Zeng Fangling , Long Yan , Zhang Xiaoyan , Ma Jun , Gan Qiangsheng , Rehemutula Rehemayi , Zhu Chunyan 
Published: November 2020

AbstractDue to a poor availability of reliable biomarkers, detecting gestational diabetes mellitus (GDM) in early pregnancy remains a challenge. Novel biomarkers like Circular RNAs (circRNAs) may be a promising diagnostic tool. The aim of this study was (a) to identify circRNAs deregulated in GDM and (b) evaluate the potential of circRNAs in detecting GDM. The circRNAs expression profiling in 6 paired women (with and without GDM) was measured by microarray. The levels of five most relevant circRNAs were validated in 12 paired participants by qRT-PCR. To verify the reproducibility of qRT-PCR, significantly differential expressed circRNA levels were confirmed in 18 paired participants. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. The areas under ROC curves of hsa_circRNA_102893 were 0.806 (95% CI 0.594–0.937) and 0.741 (0.568–0.872) in training set and test set, respectively. Circulating circRNAs reflect the presence of GDM. Hsa_circRNA_102893 may be a potential novel and stable noninvasive biomarker for detecting GDM in early pregnancy.
Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice
Authors: Baxter Sally L. , Keenan William T. , Athanas Argus J. , Proudfoot James A. , Zangwill Linda M. , Ayyagari Radha , Liebmann Jeffrey M. , Girkin Christopher A. , Patapoutian Ardem , Weinreb Robert N. 
Published: November 2020

AbstractGlaucoma disproportionately affects individuals of African descent. Prior studies of the PIEZO1 mechanoreceptor have suggested a possible role in glaucoma pathophysiology. Here, we investigated associations between a Piezo1 gain-of-function variant common in individuals of African descent with glaucoma-related phenotypes. We analyzed whole genome sequences to identify Piezo1 variants and their frequencies among 1565 human participants. For the most common variant (e756del), we compared phenotypes between heterozygotes, homozygotes, and wildtypes. Longitudinal mixed effects models of visual field mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness were used to evaluate progression. Based on trends in the models, further investigation was conducted using Piezo1 gain-of-function mice. About 30% of African descent individuals had at least one e756del allele. There were trends suggesting e756del was associated with higher IOPs, thinner RNFLs, lower optic nerve head capillary densities, and greater decreases in MD and RNFL thickness over time, but these did not reach statistical significance. Among mice, increased Piezo1 activity was not significantly associated with IOP or retinal ganglion cell density. Our study confirms that the Piezo1 e756del gain-of-function variant is a frequent polymorphism present in African descent individuals but is unrelated to examined differences in glaucoma phenotypes. Ongoing work is needed to elucidate the role of Piezo1-mediated mechanotransduction in glaucoma.
Growth and development of the third permanent molar in Paranthropus robustus from Swartkrans, South Africa
Authors: Dean Christopher , Zanolli Clément , Le Cabec Adeline , Tawane Mirriam , Garrevoet Jan , Mazurier Arnaud , Macchiarelli Roberto 
Published: November 2020

AbstractThird permanent molars (M3s) are the last tooth to form but have not been used to estimate age at dental maturation in early fossil hominins because direct histological evidence for the timing of their growth has been lacking. We investigated an isolated maxillary M3 (SK 835) from the 1.5 to 1.8-million-year-old (Mya) site of Swartkrans, South Africa, attributed to Paranthropus robustus. Tissue proportions of this specimen were assessed using 3D X-ray micro-tomography. Thin ground sections were used to image daily growth increments in enamel and dentine. Transmitted light microscopy and synchrotron X-ray fluorescence imaging revealed fluctuations in Ca concentration that coincide with daily growth increments. We used regional daily secretion rates and Sr marker-lines to reconstruct tooth growth along the enamel/dentine and then cementum/dentine boundaries. Cumulative growth curves for increasing enamel thickness and tooth height and age-of-attainment estimates for fractional stages of tooth formation differed from those in modern humans. These now provide additional means for assessing late maturation in early hominins. M3 formation took ≥ 7 years in SK 835 and completion of the roots would have occurred between 11 and 14 years of age. Estimated age at dental maturation in this fossil hominin compares well with what is known for living great apes.
Broadband absorption using all-graphene grating-coupled nanoparticles on a reflector
Authors: Raad Shiva Hayati , Atlasbaf Zahra , Zapata-Rodríguez Carlos J. 
Published: November 2020

AbstractIn this paper, the hybridized localized surface plasmon resonances (LSPRs) of a periodic assembly of graphene-wrapped nanoparticles are used to design a nanoparticle assisted optical absorber. Bandwidth enhancement of this structure via providing multiple types of plasmonic resonances in the associated unit cell using two densely packed crossly stacked graphene strips is proposed. The designed graphene strips support fundamental propagating surface plasmons on the ribbons, and gap plasmons in the cavity constructed by the adjacent sections. Graphene strips exhibit a hyperbolic dispersion region in the operating spectrum and assist in the bandwidth enhancement. Moreover, since the nanoparticles are deposited on the top strips, real-time biasing of them can be easily conducted by exciting the surface plasmons of the strip without the necessity to electrically connect the adjacent nanoparticles. The overall dynamic bandwidth of the structure, using a two-state biasing scheme, covers the frequencies of 18.16–40.47 THz with 90% efficiency. Due to the symmetry of the structure, the device performs similarly for both transverse electric (TE) and transverse magnetic (TM) waves and it has a high broadband absorption rate regarding different incident angles up to 40°. Due to the presence of 2D graphene material and also using hollow spherical particles, our proposed absorber is also lightweight and it is suitable for novel compact optoelectronic devices due to its sub-wavelength dimensions.
Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis
Authors: Alvarez Carla , Suliman Salwa , Almarhoumi Rawan , Vega Maria Elena , Rojas Carolina , Monasterio Gustavo , Galindo Mario , Vernal Rolando , Kantarci Alpdogan 
Published: November 2020

AbstractThe alveolar bone resorption is a distinctive feature of periodontitis progression and determinant for tooth loss. Regulatory T lymphocytes (Tregs) display immuno-suppressive mechanisms and tissue repairing functions, which are critical to support periodontal health. Tregs may become unstable and dysfunctional under inflammatory conditions, which can even accelerate tissue destruction. In this study, experimental periodontitis was associated with the progressive and increased presence of Th17 and Treg-related mediators in the gingiva (IL-6, IL-17A, IL-17F, RANKL, IL-10, TGF-β and GITR; P < 0.05), and the proliferation of both Treg and Th17 cells in cervical lymph nodes. Tregs from cervical lymph nodes had reduced Foxp3 expression (> 25% MFI loss) and increased IL-17A expression (> 15%), compared with Tregs from spleen and healthy controls. Tregs gene expression analysis showed a differential signature between health and disease, with increased expression of Th17-associated factors in periodontitis-derived Tregs. The ex vivo suppression capacity of Tregs on osteoclastic differentiation was significantly lower in Tregs obtained from periodontally diseased animals compared to controls (P < 0.05), as identified by the increased number of TRAP+ osteoclasts (P < 0.01) in the Tregs/pre-osteoclast co-cultures. Taken together, these results demonstrate that Tregs become phenotypically unstable and lose anti-osteoclastogenic properties during experimental periodontitis; thus, further promoting the Th17-driven bone loss.
Characterization of somatic mutation-associated microenvironment signatures in acute myeloid leukemia patients based on TCGA analysis
Authors: Wang Jun , Dao Feng-Ting , Yang Lu , Qin Ya-Zhen 
Published: November 2020

AbstractRecurrent genetic mutations occur in acute myeloid leukemia (AML) and have been incorporated into risk stratification to predict the prognoses of AML patients. The bone marrow microenvironment plays a critical role in the development and progression of AML. However, the characteristics of the genetic mutation-associated microenvironment have not been comprehensively identified to date. In this study, we obtained the gene expression profiles of 173 AML patients from The Cancer Genome Atlas (TCGA) database and calculated their immune and stromal scores by applying the ESTIMATE algorithm. Immune scores were significantly associated with OS and cytogenetic risk. Next, we categorized the intermediate and poor cytogenetic risk patients into individual-mutation and wild-type groups according to RUNX1, ASXL1, TP53, FLT3-ITD, NPM1 and biallelic CEBPA mutation status. The relationships between the immune microenvironment and each genetic mutation were investigated by identifying differentially expressed genes (DEGs) and conducting functional enrichment analyses of them. Significant immune- and stromal-relevant DEGs associated with each mutation were identified, and most of the DEGs (from the FLT3-ITD, NPM1 and biallelic CEBPA mutation groups) were validated in the GSE14468 cohort downloaded from the Gene Expression Omnibus (GEO) database. In summary, we identified key immune- and stromal-relevant gene signatures associated with genetic mutations in AML, which may provide new biomarkers for risk stratification and personalized immunotherapy.
Distraction decreases rIFG-putamen connectivity during goal-directed effort for food rewards
Authors: Duif Iris , Wegman Joost , de Graaf Kees , Smeets Paul A. M. , Aarts Esther 
Published: November 2020

AbstractDistracted eating can lead to increased food intake, but it is unclear how. We aimed to assess how distraction affects motivated, goal-directed responses for food reward after satiation. Thirty-eight healthy normal-weight participants (28F; 10M) performed a visual detection task varying in attentional load (high vs. low distraction) during fMRI. Simultaneously, they exerted effort for sweet and savory food rewards by repeated button presses. Two fMRI runs were separated by sensory-specific satiation (outcome devaluation) of one of the (sweet or savory) reward outcomes, to assess outcome-sensitive, goal-directed, responses (valued vs. devalued reward, post vs. pre satiation). We could not verify our primary hypothesis that more distraction leads to less activation in ventromedial prefrontal cortex (vmPFC) during goal-directed effort. Behaviorally, distraction also did not affect effort for food reward following satiation across subjects. For our secondary hypothesis, we assessed whether distraction affected other fronto-striatal regions during goal-directed effort. We did not obtain such effects at our whole-brain corrected threshold, but at an exploratory uncorrected threshold (p < 0.001), distraction decreased goal-directed responses (devalued vs. valued) in the right inferior frontal gyrus (rIFG). We continued with this rIFG region for the next secondary hypothesis; specifically, that distraction would reduce functional connectivity with the fronto-striatal regions found in the previous analyses. Indeed, distraction decreased functional connectivity between the rIFG and left putamen for valued versus devalued food rewards (pFWE(cluster) < 0.05). In an exploratory brain-behavior analysis, we showed that distraction-sensitive rIFG-responses correlated negatively (r = − 0.40; p = 0.014) with the effect of distraction on effort. Specifically, decreased distraction-related rIFG-responses were associated with increased effort for food reward after satiation. We discuss the absence of distraction effects on goal-directed responses in vmPFC and in behavior across participants. Moreover, based on our significant functional connectivity and brain-behavior results, we suggest that distraction might attenuate the ability to inhibit responses for food reward after satiation by affecting the rIFG and its connection to the putamen.
Two lichens differing in element concentrations have similar spatial patterns of element concentrations responding to road traffic and soil input
Authors: Wu Yuan-yuan , Gao Jing , Zhang Guo-zhan , Zhao Run-kang , Liu Ai-qin , Sun Lian-wei , Li Xing , Tang Hong-liang , Zhao Liang-cheng , Guo Xiu-ping , Liu Hua-jie 
Published: November 2020

AbstractTwo epiphytic lichens (Xanthoria alfredii, XAa; X. ulophyllodes, XAu) and soil were sampled at three sites with varied distances to a road in a semiarid sandland in Inner Mongolia, China and analyzed for concentrations of 42 elements to assess the contribution of soil input and road traffic to lichen element burdens, and to compare element concentration differences between the two lichens. The study showed that multielement patterns, Fe:Ti and rare earth element ratios were similar between the lichen and soil samples. Enrichment factors (EFs) showed that ten elements (Ca, Cd, Co, Cu, K, P, Pb, S, Sb, and Zn) were enriched in the lichens relative to the local soil. Concentrations of most elements were higher in XAu than in XAa regardless of sites, and increased with proximity to the road regardless of lichen species. These results suggested that lichen element compositions were highly affected by soil input and road traffic. The narrow-lobed sorediate species were more efficient in particulate entrapment than the broad-lobed nonsorediate species. XAa and XAu are good bioaccumulators for road pollution in desert and have similar spatial patterns of element concentrations for most elements as response to road traffic emissions and soil input.
Experimental study of superheating of tin powders
Authors: Na Han Gil , Byoun Youngmin , Park Suyoung , Choi Myung Sik , Jin Changhyun 
Published: November 2020

AbstractAn unstable energy-unbalanced state such as superheating or supercooling is often unexpectedly observed because a factor of energy depends not only on the temperature but is a product of temperature (T) and entropy (S). Thus, at the same temperature, if the entropy is different, the total energy of the system can be different. In such cases, the temperature-change-rate cannot match the entropy-change-rate, which results in a hysteresis curve for the temperature/entropy relationship. Due to the difference between the temperature- and entropy-change-rates, properties of a material, such as the boiling and freezing points, can be extended from point to area. This study confirmed that depending on the heating rate, tin powders exhibit different melting points. Given the contemporary reinterpretation of many energy-non-equilibrium phenomena that have only been discussed on the basis of temperature, this study is expected to contribute to the actual expansion of scientific/engineering applications.
Coxsackievirus infection induces a non-canonical autophagy independent of the ULK and PI3K complexes
Authors: Mohamud Yasir , Shi Junyan , Tang Hui , Xiang Pinhao , Xue Yuan Chao , Liu Huitao , Ng Chen Seng , Luo Honglin 
Published: November 2020

AbstractCoxsackievirus B3 (CVB3) is a single-stranded positive RNA virus that usurps cellular machinery, including the evolutionarily anti-viral autophagy pathway, for productive infections. Despite the emergence of double-membraned autophagosome-like vesicles during CVB3 infection, very little is known about the mechanism of autophagy initiation. In this study, we investigated the role of established autophagy factors in the initiation of CVB3-induced autophagy. Using siRNA-mediated gene-silencing and CRISPR-Cas9-based gene-editing in culture cells, we discovered that CVB3 bypasses the ULK1/2 and PI3K complexes to trigger autophagy. Moreover, we found that CVB3-induced LC3 lipidation occurred independent of WIPI2 and the transmembrane protein ATG9 but required components of the late-stage ubiquitin-like ATG conjugation system including ATG5 and ATG16L1. Remarkably, we showed the canonical autophagy factor ULK1 was cleaved through the catalytic activity of the viral proteinase 3C. Mutagenesis experiments identified the cleavage site of ULK1 after Q524, which separates its N-terminal kinase domain from C-terminal substrate binding domain. Finally, we uncovered PI4KIIIβ (a PI4P kinase), but not PI3P or PI5P kinases as requisites for CVB3-induced LC3 lipidation. Taken together, our studies reveal that CVB3 initiates a non-canonical form of autophagy that bypasses ULK1/2 and PI3K signaling pathways to ultimately converge on PI4KIIIβ- and ATG5–ATG12–ATG16L1 machinery.
Ryder Glacier in northwest Greenland is shielded from warm Atlantic water by a bathymetric sill
Authors: Jakobsson Martin , Mayer Larry A. , Nilsson Johan , Stranne Christian , Calder Brian , O’Regan Matthew , Farrell John W. , Cronin Thomas M. , Brüchert Volker , Chawarski Julek , Eriksson Björn , Fredriksson Jonas , Gemery Laura , Glueder Anna , Holmes Felicity A. , Jerram Kevin , Kirchner Nina , Mix Alan , Muchowski Julia , Prakash Abhay , Reilly Brendan , Thornton Brett , Ulfsbo Adam , Weidner Elizabeth , Åkesson Henning , Handl Tamara , Ståhl Emelie , Boze Lee-Gray , Reed Sam , West Gabriel , Padman June 
Published: November 2020

AbstractThe processes controlling advance and retreat of outlet glaciers in fjords draining the Greenland Ice Sheet remain poorly known, undermining assessments of their dynamics and associated sea-level rise in a warming climate. Mass loss of the Greenland Ice Sheet has increased six-fold over the last four decades, with discharge and melt from outlet glaciers comprising key components of this loss. Here we acquired oceanographic data and multibeam bathymetry in the previously uncharted Sherard Osborn Fjord in northwest Greenland where Ryder Glacier drains into the Arctic Ocean. Our data show that warmer subsurface water of Atlantic origin enters the fjord, but Ryder Glacier’s floating tongue at its present location is partly protected from the inflow by a bathymetric sill located in the innermost fjord. This reduces under-ice melting of the glacier, providing insight into Ryder Glacier’s dynamics and its vulnerability to inflow of Atlantic warmer water.
Bioinformatics identification of CCL8/21 as potential prognostic biomarkers in breast cancer microenvironment
Authors: Chen Bowen , Zhang Shuyuan , Li Qiuyu , Wu Shiting , He Han , Huang Jinbo 
Published: November 2020

Abstract
Background: Breast cancer (BC) is the most common malignancy among females worldwide. The tumor microenvironment usually prevents effective lymphocyte activation and infiltration, and suppresses infiltrating effector cells, leading to a failure of the host to reject the tumor. CC chemokines play a significant role in inflammation and infection.
Methods: In our study, we analyzed the expression and survival data of CC chemokines in patients with BC using several bioinformatics analyses tools.
Results: The mRNA expression of CCL2/3/4/5/7/8/11/17/19/20/22 was remarkably increased while CCL14/21/23/28 was significantly down-regulated in BC tissues compared with normal tissues. Methylation could down-regulate expression of CCL2/5/15/17/19/20/22/23/24/25/26/27 in BC. Low expression of CCL3/4/23 was found to be associated with drug resistance in BC. Results from Kaplan–Meier plotter and BC Gene-Expression Miner v4.2 (bcGenExMiner) v4.2 demonstrated that BC patients with high CCL8 and low CCL19/21/22 expression were more likely to have a worse prognosis. CCL8 expression was significantly up-regulated in BC tissues compared with normal tissues. High CCL8 expression was significantly correlated with negative PR, negative ER, positive nodal status, triple-negative BC subtype, basal-like BC subtype, triple-negative and basal-like BC subtype and high grades. CCL21 was down-regulated in BC, while high levels of CCL21 was associated with negative PR, triple-negative subtype, basal-like subtype and low tumor grade. Functional analysis demonstrated that CCL8 and CCL21 were involved in carcinogenesis, tumor immune escape and chemoresistance in BC.
Conclusion: Integrative bioinformatics analysis demonstrated CCL8/21 as potential prognostic biomarkers in BC microenvironment.