bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultraviolet light-induced collagen degradation inhibits melanoma invasion
Authors: Budden Timothy , Gaudy-Marqueste Caroline , Porter Andrew , Kay Emily , Gurung Shilpa , Earnshaw Charles H. , Roeck Katharina , Craig Sarah , Traves Víctor , Krutmann Jean , Muller Patricia , Motta Luisa , Zanivan Sara , Malliri Angeliki , Furney Simon J. , Nagore Eduardo , Virós Amaya 
Published: May 2021

AbstractUltraviolet radiation (UVR) damages the dermis and fibroblasts; and increases melanoma incidence. Fibroblasts and their matrix contribute to cancer, so we studied how UVR modifies dermal fibroblast function, the extracellular matrix (ECM) and melanoma invasion. We confirmed UVR-damaged fibroblasts persistently upregulate collagen-cleaving matrix metalloprotein-1 (MMP1) expression, reducing local collagen (COL1A1), and COL1A1 degradation by MMP1 decreased melanoma invasion. Conversely, inhibiting ECM degradation and MMP1 expression restored melanoma invasion. Primary cutaneous melanomas of aged humans show more cancer cells invade as single cells at the invasive front of melanomas expressing and depositing more collagen, and collagen and single melanoma cell invasion are robust predictors of poor melanoma-specific survival. Thus, primary melanomas arising over collagen-degraded skin are less invasive, and reduced invasion improves survival. However, melanoma-associated fibroblasts can restore invasion by increasing collagen synthesis. Finally, high COL1A1 gene expression is a biomarker of poor outcome across a range of primary cancers.
Functional and diffusion MRI reveal the neurophysiological basis of neonates’ noxious-stimulus evoked brain activity
Authors: Baxter Luke , Moultrie Fiona , Fitzgibbon Sean , Aspbury Marianne , Mansfield Roshni , Bastiani Matteo , Rogers Richard , Jbabdi Saad , Duff Eugene , Slater Rebeccah 
Published: May 2021

AbstractUnderstanding the neurophysiology underlying neonatal responses to noxious stimulation is central to improving early life pain management. In this neonatal multimodal MRI study, we use resting-state and diffusion MRI to investigate inter-individual variability in noxious-stimulus evoked brain activity. We observe that cerebral haemodynamic responses to experimental noxious stimulation can be predicted from separately acquired resting-state brain activity (n = 18). Applying this prediction model to independent Developing Human Connectome Project data (n = 215), we identify negative associations between predicted noxious-stimulus evoked responses and white matter mean diffusivity. These associations are subsequently confirmed in the original noxious stimulation paradigm dataset, validating the prediction model. Here, we observe that noxious-stimulus evoked brain activity in healthy neonates is coupled to resting-state activity and white matter microstructure, that neural features can be used to predict responses to noxious stimulation, and that the dHCP dataset could be utilised for future exploratory research of early life pain system neurophysiology.
The role of non-axisymmetry of magnetic flux rope in constraining solar eruptions
Authors: Zhong Ze , Guo Yang , Ding M. D. 
Published: May 2021

AbstractWhether a solar eruption is successful or failed depends on the competition between different components of the Lorentz force exerting on the flux rope that drives the eruption. The present models only consider the strapping force generated by the background magnetic field perpendicular to the flux rope and the tension force generated by the field along the flux rope. Using the observed magnetic field on the photosphere as a time-matching bottom boundary, we perform a data-driven magnetohydrodynamic simulation for the 30 January 2015 confined eruption and successfully reproduce the observed solar flare without a coronal mass ejection. Here we show a Lorentz force component, resulting from the radial magnetic field or the non-axisymmetry of the flux rope, which can essentially constrain the eruption. Our finding contributes to the solar eruption model and presents the necessity of considering the topological structure of a flux rope when studying its eruption behaviour.
Distinct axial and lateral interactions within homologous filaments dictate the signaling specificity and order of the AIM2-ASC inflammasome
Authors: Matyszewski Mariusz , Zheng Weili , Lueck Jacob , Mazanek Zachary , Mohideen Naveen , Lau Albert Y. , Egelman Edward H. , Sohn Jungsan 
Published: May 2021

AbstractInflammasomes are filamentous signaling platforms integral to innate immunity. Currently, little is known about how these structurally similar filaments recognize and distinguish one another. A cryo-EM structure of the AIM2PYD filament reveals that the architecture of the upstream filament is essentially identical to that of the adaptor ASCPYD filament. In silico simulations using Rosetta and molecular dynamics followed by biochemical and cellular experiments consistently demonstrate that individual filaments assemble bidirectionally. By contrast, the recognition between AIM2 and ASC requires at least one to be oligomeric and occurs in a head-to-tail manner. Using in silico mutagenesis as a guide, we also identify specific axial and lateral interfaces that dictate the recognition and distinction between AIM2 and ASC filaments. Together, the results here provide a robust framework for delineating the signaling specificity and order of inflammasomes.
Water-oriented magnetic anisotropy transition
Authors: Su Sheng-Qun , Wu Shu-Qi , Hagihala Masato , Miao Ping , Tan Zhijian , Torii Shuki , Kamiyama Takashi , Xiao Tongtong , Wang Zhenxing , Ouyang Zhongwen , Miyazaki Yuji , Nakano Motohiro , Nakanishi Takumi , Li Jun-Qiu , Kanegawa Shinji , Sato Osamu 
Published: May 2021

AbstractWater reorientation is essential in a wide range of chemical and biological processes. However, the effects of such reorientation through rotation around the metal–oxygen bond on the chemical and physical properties of the resulting complex are usually ignored. Most studies focus on the donor property of water as a recognized σ donor-type ligand rather than a participant in the π interaction. Although a theoretical approach to study water-rotation effects on the functionality of a complex has recently been conducted, it has not been experimentally demonstrated. In this study, we determine that the magnetic anisotropy of a Co(II) complex can be effectively controlled by the slight rotation of coordinating water ligands, which is achieved by a two-step structural phase transition. When the water molecule is rotated by 21.2 ± 0.2° around the Co–O bond, the directional magnetic susceptibility of the single crystal changes by approximately 30% along the a-axis due to the rotation of the magnetic anisotropy axis through the modification of the π interaction between cobalt(II) and the water ligand. The theoretical calculations further support the hypothesis that the reorientation of water molecules is a key factor contributing to the magnetic anisotropy transition of this complex.
Genes and pathways monotonically dysregulated during progression from normal through leukoplakia to gingivo-buccal oral cancer
Authors: Das Debodipta , Maitra Arindam , Panda Chinmay K. , Ghose Sandip , Roy Bidyut , Sarin Rajiv , Majumder Partha P. 
Published: May 2021

AbstractOral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) accounts for the highest cancer morbidity and mortality among men in India. It has been observed that about one-third of individuals with oral leukoplakia, a dysplastic precancerous lesion in the oral cavity, progress to oral cancer. We aimed to identify systematic transcriptomic changes as a normal tissue in the oral cavity progresses to frank OSCC-GB. Seventy-two OSCC-GB patients, from multiple hospitals, were recruited, and transcriptome analysis of tumor and adjacent normal tissue (of all patients) and adjacent leukoplakia tissue (of a subset of 25 unselected patients with concomitant leukoplakia) was performed. We have identified many differences in the transcriptomic profiles between OSCC-GB and squamous cell carcinoma of the head and neck regions. Compared to the normal/precancerous tissue, significant enrichment of ECM−receptor interaction, PI3K-Akt signaling, cytokine−cytokine receptor interaction, focal adhesion, and cell cycle pathways were observed in OSCC-GB. Using gene set enrichment analysis, we identified a profound role of interferon receptor signaling in tumor growth by activating immune evasion mechanisms. The role of tumor-infiltrating immune cells further supported the growth and immunosuppressive mechanism of tumor tissues. Some immune evasion genes—CD274, CD80, and IDO1—were found to be activated even in the precancerous tissue. Taken together, our findings provide a clear insight into the sequential genetic dysregulation associated with progression to oral cancer. This insight provides a window to the development of predictive biomarkers and therapeutic targets for gingivo-buccal oral cancer.
Macrophage morphological plasticity and migration is Rac signalling and MMP9 dependant
Authors: Travnickova Jana , Nhim Sandra , Abdellaoui Naoill , Djouad Farida , Nguyen-Chi Maï , Parmeggiani Andrea , Kissa Karima 
Published: May 2021

AbstractIn vitro, depending on extracellular matrix (ECM) architecture, macrophages migrate either in amoeboid or mesenchymal mode; while the first is a general trait of leukocytes, the latter is associated with tissue remodelling via Matrix Metalloproteinases (MMPs). To assess whether these stereotyped migrations could be also observed in a physiological context, we used the zebrafish embryo and monitored macrophage morphology, behaviour and capacity to mobilise haematopoietic stem/progenitor cells (HSPCs), as a final functional readout. Morphometric analysis identified 4 different cell shapes. Live imaging revealed that macrophages successively adopt all four shapes as they migrate through ECM. Treatment with inhibitors of MMPs or Rac GTPase to abolish mesenchymal migration, suppresses both ECM degradation and HSPC mobilisation while differently affecting macrophage behaviour. This study depicts real time macrophage behaviour in a physiological context and reveals extreme reactivity of these cells constantly adapting and switching migratory shapes to achieve HSPCs proper mobilisation.
Scaffolding depth cues and perceptual learning in VR to train stereovision: a proof of concept pilot study
Authors: Godinez Angelica , Martín-González Santiago , Ibarrondo Oliver , Levi Dennis M. 
Published: May 2021

AbstractStereopsis is a valuable feature of human visual perception, which may be impaired or absent in amblyopia and/or strabismus but can be improved through perceptual learning (PL) and videogames. The development of consumer virtual reality (VR) may provide a useful tool for improving stereovision. We report a proof of concept study, especially useful for strabismic patients and/or those with reduced or null stereoacuity. Our novel VR PL strategy is based on a principled approach which included aligning and balancing the perceptual input to the two eyes, dichoptic tasks, exposure to large disparities, scaffolding depth cues and perception for action. We recruited ten adults with normal vision and ten with binocular impairments. Participants played two novel PL games (DartBoard and Halloween) using a VR-HMD. Each game consisted of three depth cue scaffolding conditions, starting with non-binocular and binocular cues to depth and ending with only binocular disparity. All stereo-anomalous participants improved in the game and most (9/10) showed transfer to clinical and psychophysical stereoacuity tests (mean stereoacuity changed from 569 to 296 arc seconds, P < 0.0001). Stereo-normal participants also showed in-game improvement, which transferred to psychophysical tests (mean stereoacuity changed from 23 to a ceiling value of 20 arc seconds, P = 0.001). We conclude that a VR PL approach based on depth cue scaffolding may provide a useful method for improving stereoacuity, and the in-game performance metrics may provide useful insights into principles for effective treatment of stereo anomalies.This study was registered as a clinical trial on 04/05/2010 with the identifier NCT01115283 at ClinicalTrials.gov.
A comprehensive retrospective cohort study of the journey of B-cell lymphoma in Taiwan
Authors: Pei Sung-Nan , Wang Ming-Chung , Ma Ming-Chun , Kuo Ching-Yuan , Liao Chun-Kai , Qiu Hong , Rothwell Lee Anne , Liu Yanfang 
Published: May 2021

AbstractComplete disease journey and risk factors for poor outcomes are needed to facilitate effectiveness evaluations of new therapies and clinical decision-making in B-cell Non-Hodgkin lymphoma (B-NHL), particularly in Asia where such data are lacking. This retrospective cohort study used electronic medical records from a regional medical centre in southern Taiwan to follow-up 441 patients newly diagnosed with common B-NHL subtypes: Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone Lymphoma (MZL), Mantle Cell Lymphoma (MCL), and Waldenström macroglobulinemia (WM), between 01-Jan-2008 and 31-Dec-2013, until 31-Dec-2017. Treatment pathways were modelled using a Markov approach. Stage III/IV disease at diagnosis was frequent for patients with DLBCL, FL, MCL and WM. Hepatitis B surface antigen/hepatitis C virus seropositivity was 18.6%/12.3%. Clinical responses to 1st-line treatment were observed in 76.0% (DLBCL), 87.3% (FL), 86.0% (MZL), 60.0% (MCL), and 42.9% (WM) of patients. For DLBCL, disease control was achieved by ~ 50% after 1st-line, ~ 24% after 2nd-line, ~ 17% after 3rd-line. Patients with Stage III/IV DLBCL or age > 65 years at diagnosis had lower rates of active treatment, poorer disease control and higher mortality than patients with early stage disease or age ≤ 65 years. Disease flare < 6 months after 1st-line treatment was significantly associated with mortality. Despite good clinical response rates for some sub-types, survival remains poor. New treatments are needed to improve the outcome of B-NHL.
Stray light characterization with ultrafast time-of-flight imaging
Authors: Clermont L. , Uhring W. , Georges M. 
Published: May 2021

AbstractUnderstanding stray light (SL) is a crucial aspect in the development of high-end optical instruments, for instance space telescopes. As it drives image quality, SL must be controlled by design and characterized experimentally. However, conventional SL characterization methods are limited as they do not provide information on its origins. The problem is complex due to the diversity of light interaction processes with surfaces, creating various SL contributors. Therefore, when SL level is higher than expected, it can be difficult to determine how to improve the system. We demonstrate a new approach, ultrafast time-of-flight SL characterization, where a pulsed laser source and a streak camera are used to record individually SL contributors which travel with a specific optical path length. Furthermore, the optical path length offers a means of identification to determine its origin. We demonstrate this method in an imaging system, measuring and identifying individual ghosts and scattering components. We then show how it can be used to reverse-engineer the instrument SL origins.
Generation of a chemical genetic model for JAK3
Authors: Remenyi Judit , Naik Rangeetha Jayaprakash , Wang Jinhua , Razsolkov Momchil , Verano Alyssa , Cai Quan , Tan Li , Toth Rachel , Raggett Samantha , Baillie Carla , Traynor Ryan , Hastie C. James , Gray Nathanael S. , Arthur J. Simon C. 
Published: May 2021

AbstractJanus Kinases (JAKs) have emerged as an important drug target for the treatment of a number of immune disorders due to the central role that they play in cytokine signalling. 4 isoforms of JAKs exist in mammalian cells and the ideal isoform profile of a JAK inhibitor has been the subject of much debate. JAK3 has been proposed as an ideal target due to its expression being largely restricted to the immune system and its requirement for signalling by cytokine receptors using the common γ-chain. Unlike other JAKs, JAK3 possesses a cysteine in its ATP binding pocket and this has allowed the design of isoform selective covalent JAK3 inhibitors targeting this residue. We report here that mutating this cysteine to serine does not prevent JAK3 catalytic activity but does greatly increase the IC50 for covalent JAK3 inhibitors. Mice with a Cys905Ser knockin mutation in the endogenous JAK3 gene are viable and show no apparent welfare issues. Cells from these mice show normal STAT phosphorylation in response to JAK3 dependent cytokines but are resistant to the effects of covalent JAK3 inhibitors. These mice therefore provide a chemical-genetic model to study JAK3 function.
Physiological and transcriptomic analyses characterized high temperature stress response mechanisms in Sorbus pohuashanensis
Authors: Pei Xin , Zhang Yan , Zhu Lingyi , Zhao Dongxue , Lu Yizeng , Zheng Jian 
Published: May 2021

AbstractSorbus pohuashanensis (Hance) Hedl. is a Chinese native alpine tree species, but the problem of introducing S. pohuashanensis to low altitude areas has not been solved. In this study, we aimed to explore the molecular regulatory network of S. pohuashanensis in response to high-temperature stress using RNA-Sequencing technology and physiological and biochemical determination. Based on transcriptomic data, we obtained 1221 genes (752 up-regulated and 469 down-regulated) that were differentially expressed during 8 h 43℃ treatment and candidate genes were related to calcium signaling pathway, plant hormone signal transduction, heat shock factors, chaperones, ubiquitin mediated proteolysis, cell wall modification, ROS scavenging enzymes, detoxification and energy metabolism. The analysis of high temperature response at the physiological level and biochemical level were performed. The chlorophyll fluorescence parameters of leaf cells decreased, the content of osmotic regulators increased, and the activity of ROS scavenging enzymes decreased. The molecular regulatory network of S. pohuashanensis in response to high-temperature stress was preliminarily revealed in this study, which provides fundamental information improving introducing methods and discovering heat-tolerant genes involved in high-temperature stress in this species and provides a reference for other plants of the genus Sorbus.
The expansion of Acheulean hominins into the Nefud Desert of Arabia
Authors: Scerri Eleanor M. L. , Frouin Marine , Breeze Paul S. , Armitage Simon J. , Candy Ian , Groucutt Huw S. , Drake Nick , Parton Ash , White Tom S. , Alsharekh Abdullah M. , Petraglia Michael D. 
Published: May 2021

AbstractThe Arabian Peninsula is a critical geographic landmass situated between Africa and the rest of Eurasia. Climatic shifts across the Pleistocene periodically produced wetter conditions in Arabia, dramatically altering the spatial distribution of hominins both within and between continents. This is particularly true of Acheulean hominins, who appear to have been more tethered to water sources than Middle Palaeolithic hominins. However, until recently, chrono-cultural knowledge of the Acheulean of Arabia has been limited to one dated site, which indicated a hominin presence in Marine Isotope Stages (MIS) 7–6. Here, we report the first dated Acheulean site from the Nefud Desert of northern Saudi Arabia, together with palaeoecological evidence for an associated deep, probably fresh-water, lake. The site of An Nasim features varied and often finely flaked façonnage handaxes. Luminescence ages together with geomorphological and palaeoecological evidence indicates that the associated artefacts date to MIS 9. At present, An Nasim represents the oldest yet documented Acheulean sites in Arabia, and adds to a growing picture of regionally diverse stone tool assemblages used by Middle Pleistocene hominins, and likely indicative of repeated population re-entry into the peninsula in wet ‘Green Arabia’ phases.
A discovery about the positional distribution pattern among candidate homologous pixels and its potential application in aerial multi-view image matching
Authors: Zhang Ka , Xiao Wen , Sheng Yehua , Wang Junshu , Zhang Shan , Ye Longjie 
Published: May 2021

AbstractIn aerial multi-view photogrammetry, whether there is a special positional distribution pattern among candidate homologous pixels of a matching pixel in the multi-view images? If so, can this positional pattern be used to precisely confirm the real homologous pixels? These problems have not been studied at present. Therefore, the study of the positional distribution pattern among candidate homologous pixels based on the adjustment theory in surveying is investigated in this paper. Firstly, the definition and computing method of pixel’s pseudo object-space coordinates are given, which can transform the problem of multi-view matching for confirming real homologous pixels into the problem of surveying adjustment for computing the pseudo object-space coordinates of the matching pixel. Secondly, according to the surveying adjustment theory, the standardized residual of each candidate homologous pixel of the matching pixel is figured out, and the positional distribution pattern among these candidate pixels is theoretically inferred utilizing the quantitative index of standardized residual. Lastly, actual aerial images acquired by different sensors are used to carry out experimental verification of the theoretical inference. Experimental results prove not only that there is a specific positional distribution pattern among candidate homologous pixels, but also that this positional distribution pattern can be used to develop a new object-side multi-view image matching method. The proposed study has an important reference value on resolving the defects of existing image-side multi-view matching methods at the mechanism level.
Maternal HIV infection is associated with distinct systemic cytokine profiles throughout pregnancy in South African women
Authors: Akoto Charlene , Norris Shane A. , Hemelaar Joris 
Published: May 2021

AbstractMaternal HIV infection is associated with adverse pregnancy outcomes, but the mechanisms remain unknown. The course of pregnancy is regulated by immunological processes and HIV infection and antiretroviral therapy (ART) impact key immune mechanisms, which may disrupt the immune programme of pregnancy. We evaluated a broad range of systemic cytokines at each trimester of pregnancy in 56 women living with HIV (WLHIV) and 68 HIV-negative women, who were enrolled in a prospective pregnancy cohort study in Soweto, South Africa. The pro-inflammatory cytokine IP-10 was detected in each trimester in all WLHIV, which was significantly more than in HIV-negative women. The anti-viral cytokine IFNλ1 was detected more frequently in WLHIV, whereas IFNβ and IFNλ2/3 were detected more frequently in HIV-negative women. Th1 cytokines IL-12 and IL-12p70, Th2 cytokine IL-5, and Th17 cytokine IL-17A were detected more frequently in WLHIV throughout pregnancy. Il-6, IL-9, and IL-10 were more commonly detected in WLHIV in the first trimester. Trends of increased detection of Th1 (IL-2, IL-12p70), Th2 (IL-4, Il-5, Il-13) and Th17 (IL-17A, Il-17F, IL-21, IL-22) cytokines were associated with small-for-gestational-age babies. Our findings indicate that maternal HIV/ART is associated with distinct systemic cytokine profiles throughout pregnancy.