bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-195 rescues ApoE4-induced cognitive deficits and lysosomal defects in Alzheimer’s disease pathogenesis
Authors: Cao Jiqing , Huang Min , Guo Lei , Zhu Li , Hou Jianwei , Zhang Larry , Pero Adriana , Ng Sabrina , El Gaamouch Farida , Elder Gregory , Sano Mary , Goate Alison , TCW Julia , Haroutunian Vahram , Zhang Bin , Cai Dongming 
Published: July 2020

AbstractOur recent findings link the apolipoprotein E4 (ApoE4)-specific changes in brain phosphoinositol biphosphate (PIP2) homeostasis to the susceptibility of developing Alzheimer’s Disease (AD). In the present study, we have identified miR-195 as a top micro-RNA candidate involved in the ApoE/PIP2 pathway using miRNA profiles in human ROSMAP datasets and mouse microarray studies. Further validation studies have demonstrated that levels of miR-195 are significantly lower in human brain tissue of ApoE4+/− patients with clinical diagnosis of mild cognitive impairment (MCI) or early AD when compared to ApoE4−/− subjects. In addition, brain miR-195 levels are reduced along with disease progression from normal aging to early AD, and cerebrospinal fluid (CSF) miR-195 levels of MCI subjects are positively correlated with cognitive performances as measured by mini-mental status examination (MMSE) and negatively correlated with CSF tau levels, suggesting the involvement of miR-195 in early development of AD with a potential impact on cognition. Similar differences in miR-195 levels are seen in ApoE4+/+ mouse hippocampal brain tissue and cultured neurons when compared to ApoE3+/+ counterparts. Over-expressing miR-195 reduces expression levels of its top predicted target synaptojanin 1 (synj1), a brain PIP2-degrading enzyme. Furthermore, elevating miR-195 ameliorates cognitive deficits, amyloid plaque burden, and tau hyper-phosphorylation in ApoE4+/+ mice. In addition, elevating miR-195 rescues AD-related lysosomal defects in inducible pluripotent stem cells (iPSCs)-derived brain cells of ApoE4+/+ AD subjects while inhibiting miR-195 exacerbates these phenotypes. Together, our data uncover a novel regulatory mechanism of miR-195 targeted at ApoE4-associated brain PIP2 dyshomeostasis, cognitive deficits, and AD pathology.
Topology predicts long-term functional outcome in early psychosis
Authors: Fournier Margot , Scolamiero Martina , Gholam-Rezaee Mehdi M. , Cleusix Martine , Jenni Raoul , Ferrari Carina , Golay Philippe , Baumann Philipp S. , Cuenod Michel , Conus Philippe , Do Kim Q. , Hess Kathryn 
Published: July 2020

AbstractEarly intervention in psychosis is crucial to improving patient response to treatment and the functional deficits that critically affect their long-term quality of life. Stratification tools are needed to personalize functional deficit prevention strategies at an early stage. In the present study, we applied topological tools to analyze symptoms of early psychosis patients, and detected a clear stratification of the cohort into three groups. One of the groups had a significantly better psychosocial outcome than the others after a 3-year clinical follow-up. This group was characterized by a metabolic profile indicative of an activated antioxidant response, while that of the groups with poorer outcome was indicative of oxidative stress. We replicated in a second cohort the finding that the three distinct clinical profiles at baseline were associated with distinct outcomes at follow-up, thus validating the predictive value of this new stratification. This approach could assist in personalizing treatment strategies.
Exercise modulation of tumour perfusion and hypoxia to improve radiotherapy response in prostate cancer
Authors: Schumacher Oliver , Galvão Daniel A. , Taaffe Dennis R. , Chee Raphael , Spry Nigel , Newton Robert U. 
Published: July 2020

AbstractBackgroundAn increasing number of studies indicate that exercise plays an important role in the overall care of prostate cancer (PCa) patients before, during and after treatment. Historically, research has focused on exercise as a modulator of physical function, psychosocial well-being as well as a countermeasure to cancer- and treatment-related adverse effects. However, recent studies reveal that exercise may also directly influence tumour physiology that could beneficially affect the response to radiotherapy.MethodsIn this narrative review, we provide an overview of tumour vascular characteristics that limit the effect of radiation and establish a rationale for exercise as adjunct therapy during PCa radiotherapy. Further, we summarise the existing literature on exercise as a modulator of tumour perfusion and hypoxia and outline potential future research directions.ResultsPreclinical research has shown that exercise can reduce intratumoral hypoxia—a major limiting factor in radiotherapy—by improving tumour perfusion and vascularisation. In addition, preliminary evidence suggests that exercise training can improve radiotherapy treatment outcomes by increasing natural killer cell infiltration in a murine PCa model.ConclusionsExercise is a potentially promising adjunct therapy for men with PCa undergoing radiotherapy that may increase its effectiveness. However, exercise-induced tumour radiosensitisation remains to be confirmed in preclinical and clinical trials, as does the optimal exercise prescription to elicit such effects.
PAICS contributes to gastric carcinogenesis and participates in DNA damage response by interacting with histone deacetylase 1/2
Authors: Huang Nan , Xu Chang , Deng Liang , Li Xue , Bian Zhixuan , Zhang Yue , Long Shuping , Chen Yan , Zhen Ni , Li Guohui , Sun Fenyong 
Published: July 2020

AbstractPhosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), an essential enzyme involved in de novo purine biosynthesis, is connected with formation of various tumors. However, the specific biological roles and related mechanisms of PAICS in gastric cancer (GC) remain unclear. In the present study, we identified for the first time that PAICS was significantly upregulated in GC and high expression of PAICS was correlated with poor prognosis of patients with GC. In addition, knockdown of PAICS significantly induced cell apoptosis, and inhibited GC cell growth both in vitro and in vivo. Mechanistic studies first found that PAICS was engaged in DNA damage response, and knockdown of PAICS in GC cell lines induced DNA damage and impaired DNA damage repair efficiency. Further explorations revealed that PAICS interacted with histone deacetylase HDAC1 and HDAC2, and PAICS deficiency decreased the expression of DAD51 and inhibited its recruitment to DNA damage sites by impairing HDAC1/2 deacetylase activity, eventually preventing DNA damage repair. Consistently, PAICS deficiency enhanced the sensitivity of GC cells to DNA damage agent, cisplatin (CDDP), both in vitro and in vivo. Altogether, our findings demonstrate that PAICS plays an oncogenic role in GC, which act as a novel diagnosis and prognostic biomarker for patients with GC.
TIGAR/AP-1 axis accelerates the division of Lgr5− reserve intestinal stem cells to reestablish intestinal architecture after lethal radiation
Authors: Chen Fei , Zhang Yushuo , Hu Songling , Shi Xiaolin , Wang Zhongmin , Deng Zicheng , Lin Longxin , Zhang Jianghong , Pan Yan , Bai Yang , Liu Fenju , Zhang Haowen , Shao Chunlin 
Published: July 2020

AbstractDuring radiologic or nuclear accidents, high-dose ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a deadly disorder that urgently needs effective therapy. Unfortunately, current treatments based on natural products and antioxidants have shown very limited effects in alleviating deadly GIS. Reserve intestinal stem cells (ISCs) and secretory progenitor cells are both reported to replenish damaged cells and contribute to crypt regeneration. However, the suppressed β-catenin/c-MYC axis within these slow-cycling cells leads to limited regenerative response to restore intestinal integrity during fatal accidental injury. Current study demonstrates that post-IR overexpression of TIGAR, a critical downstream target of c-MYC in mouse intestine, mounts a hyperplastic response in Bmi1-creERT+ reserve ISCs, and thus rescues mice from lethal IR exposure. Critically, by eliminating damaging reactive oxygen species (ROS) yet retaining the proliferative ROS signals, TIGAR-overexpression enhances the activity of activator protein 1, which is indispensable for initiating reserve-ISC division after lethal radiation. In addition, it is identified that TIGAR-induction exclusively gears the Lgr5− subpopulation of reserve ISCs to regenerate crypts, and intestinal TIGAR-overexpression displays equivalent intestinal reconstruction to reserve-ISC-restricted TIGAR-induction. Our findings imply that precise administrations toward Lgr5− reserve ISCs are promising strategies for unpredictable lethal injury, and TIGAR can be employed as a therapeutic target for unexpected radiation-induced GIS.
Maximizing lentiviral vector gene transfer in the CNS
Authors: Humbel Morgane , Ramosaj Mergim , Zimmer Virginie , Regio Sara , Aeby Ludiwine , Moser Sylvain , Boizot Alexia , Sipion Mélanie , Rey Maria , Déglon Nicole 
Published: July 2020

AbstractGene transfer is a widely developed technique for studying and treating genetic diseases. However, the development of therapeutic strategies is challenging, due to the cellular and functional complexity of the central nervous system (CNS), its large size and restricted access. We explored two parameters for improving gene transfer efficacy and capacity for the selective targeting of subpopulations of cells with lentiviral vectors (LVs). We first developed a second-generation LV specifically targeting astrocytes for the efficient expression or silencing of genes of interest, and to better study the importance of cell subpopulations in neurological disorders. We then made use of the retrograde transport properties of a chimeric envelope to target brain circuits affected in CNS diseases and achieve a broad distribution. The combination of retrograde transport and specific tropism displayed by this LV provides opportunities for delivering therapeutic genes to specific cell populations and ensuring high levels of transduction in interconnected brain areas following local administration. This new LV and delivery strategy should be of greater therapeutic benefit and opens up new possibilities for the preclinical development of gene therapy for neurodegenerative diseases.
Contactless probing of polycrystalline methane hydrate at pore scale suggests weaker tensile properties than thought
Authors: Atig Dyhia , Broseta Daniel , Pereira Jean-Michel , Brown Ross 
Published: July 2020

AbstractMethane hydrate is widely distributed in the pores of marine sediments or permafrost soils, contributing to their mechanical properties. Yet the tensile properties of the hydrate at pore scales remain almost completely unknown, notably the influence of grain size on its own cohesion. Here we grow thin films of the hydrate in glass capillaries. Using a novel, contactless thermal method to apply stress, and video microscopy to observe the strain, we estimate the tensile elastic modulus and strength. Ductile and brittle characteristics are both found, dependent on sample thickness and texture, which are controlled by supercooling with respect to the dissociation temperature and by ageing. Relating the data to the literature suggests the cohesive strength of methane hydrate was so far significantly overestimated.
Proton-transfer-induced 3D/2D hybrid perovskites suppress ion migration and reduce luminance overshoot
Authors: Kim Hobeom , Kim Joo Sung , Heo Jung-Min , Pei Mingyuan , Park In-Hyeok , Liu Zhun , Yun Hyung Joong , Park Min-Ho , Jeong Su-Hun , Kim Young-Hoon , Park Jin-Woo , Oveisi Emad , Nagane Satyawan , Sadhanala Aditya , Zhang Lijun , Kweon Jin Jung , Lee Sung Keun , Yang Hoichang , Jang Hyun Myung , Friend Richard H. , Loh Kian Ping , Nazeeruddin Mohammad Khaja , Park Nam-Gyu , Lee Tae-Woo 
Published: July 2020

AbstractPerovskite light-emitting diodes (PeLEDs) based on three-dimensional (3D) polycrystalline perovskites suffer from ion migration, which causes overshoot of luminance over time during operation and reduces its operational lifetime. Here, we demonstrate 3D/2D hybrid PeLEDs with extremely reduced luminance overshoot and 21 times longer operational lifetime than 3D PeLEDs. The luminance overshoot ratio of 3D/2D hybrid PeLED is only 7.4% which is greatly lower than that of 3D PeLED (150.4%). The 3D/2D hybrid perovskite is obtained by adding a small amount of neutral benzylamine to methylammonium lead bromide, which induces a proton transfer from methylammonium to benzylamine and enables crystallization of 2D perovskite without destroying the 3D phase. Benzylammonium in the perovskite lattice suppresses formation of deep-trap states and ion migration, thereby enhances both operating stability and luminous efficiency based on its retardation effect in reorientation.
Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state
Authors: Kawabe Takeshi , Yi Jaeu , Kawajiri Akihisa , Hilligan Kerry , Fang Difeng , Ishii Naoto , Yamane Hidehiro , Zhu Jinfang , Jankovic Dragana , Kim Kwang Soon , Trinchieri Giorgio , Sher Alan 
Published: July 2020

AbstractCD4+T lymphocytes consist of naïve, antigen-specific memory, and memory-phenotype (MP) cell compartments at homeostasis. We recently showed that MP cells exert innate-like effector function during host defense, but whether MP CD4+T cells are functionally heterogeneous and, if so, what signals specify the differentiation of MP cell subpopulations under homeostatic conditions is still unclear. Here we characterize MP lymphocytes as consisting of T-bethigh, T-betlow, and T-bet−subsets, with innate, Th1-like effector activity exclusively associated with T-bethighcells. We further show that the latter population depends on IL-12 produced by CD8α+type 1 dendritic cells (DC1) for its differentiation. Finally, our data demonstrate that this tonic IL-12 production requires TLR-MyD88 signaling independent of foreign agonists, and is further enhanced by CD40-CD40L interactions between DC1 and CD4+T lymphocytes. We propose that optimal differentiation of T-bethighMP lymphocytes at homeostasis is driven by self-recognition signals at both the DC and Tcell levels.
Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease
Authors: Doi Daisuke , Magotani Hiroaki , Kikuchi Tetsuhiro , Ikeda Megumi , Hiramatsu Satoe , Yoshida Kenji , Amano Naoki , Nomura Masaki , Umekage Masafumi , Morizane Asuka , Takahashi Jun 
Published: July 2020

AbstractInduced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neurons are an expected source for cell-based therapies for Parkinson’s disease (PD). The regulatory criteria for the clinical application of these therapies, however, have not been established. Here we show the results of our pre-clinical study, in which we evaluate the safety and efficacy of dopaminergic progenitors (DAPs) derived from a clinical-grade human iPSC line. We confirm the characteristics of DAPs by in vitro analyses. We also verify that the DAP population include no residual undifferentiated iPSCs or early neural stem cells and have no genetic aberration in cancer-related genes. Furthermore, in vivo studies using immunodeficient mice reveal no tumorigenicity or toxicity of the cells. When the DAPs are transplanted into the striatum of 6-OHDA-lesioned rats, the animals show behavioral improvement. Based on these results, we started a clinical trial to treat PD patients in 2018.
A flat carborane with multiple aromaticity beyond Wade–Mingos’ rules
Authors: Lu Wei , Do Dinh Cao Huan , Kinjo Rei 
Published: July 2020

AbstractIt is widely known that the skeletal structure of clusters reflects the number of skeletal bonding electron pairs involved, which is called the polyhedral skeletal electron pair theory (PSEPT) or Wade and Mingos rules. While recent computational studies propose that the increase of skeletal electrons of polyhedral clusters leads to the flat structure beyond the PSEPT, little experimental evidence has been demonstrated. Herein, we report the synthesis of a C2B4R4 carborane 2 featuring a flat ribbon-like structure. The C2B4 core of 2 bearing 16 skeletal electrons in the singlet-ground state defies both the [4n + 2] Hückel’s rule and Baird’s rule. Nevertheless, the delocalization of those electrons simultaneously induces two independent π- and two independent σ-aromatic ring currents, rendering quadruple aromaticity.
An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment
Authors: GeurtsvanKessel Corine H. , Okba Nisreen M. A. , Igloi Zsofia , Bogers Susanne , Embregts Carmen W. E. , Laksono Brigitta M. , Leijten Lonneke , Rokx Casper , Rijnders Bart , Rahamat-Langendoen Janette , van den Akker Johannes P. C. , van Kampen Jeroen J. A. , van der Eijk Annemiek A. , van Binnendijk Rob S. , Haagmans Bart , Koopmans Marion 
Published: July 2020

AbstractThe world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.
Long-term Parkinson’s disease quality of life after staged DBS: STN vs GPi and first vs second lead
Authors: Cernera Stephanie , Eisinger Robert S. , Wong Joshua K. , Ho Kwo Wei David , Lopes Janine Lobo , To Kevin , Carbunaru Samuel , Ramirez-Zamora Adolfo , Almeida Leonardo , Foote Kelly D. , Okun Michael S. , Gunduz Aysegul 
Published: July 2020

AbstractDeep brain stimulation (DBS) for Parkinson’s disease (PD) improves quality of life (QoL), but longitudinal follow-up data are scarce. We sought to quantify long-term benefits of subthalamic nucleus (STN) vs globus pallidus internus (GPi), and unilateral vs staged bilateral PD-DBS on postoperative QoL. This is a retrospective, longitudinal, non-randomized study using the PD QoL questionnaire (PDQ)-39 in patients with STN- or GPi-DBS, and with unilateral (N = 191) or staged bilateral (an additional contralateral lead implant) surgery (N = 127 and 156 for the first and second lead, respectively). Changes in PDQ-39 summary index (PDQ-39SI) and subscores throughout 60 months of follow-up were used as the primary analysis. We applied mixed models that included levodopa and covariates that differed at baseline across groups. For unilateral implantation, we observed an initial improvement in PDQ-39SI of 15.55 ± 3.29% (µ ± SE) across both brain targets at 4 months postoperatively. Unilateral STN patients demonstrated greater improvement in PDQ-39SI than GPi patients at 4 and 18 months postoperatively. Analysis of patients with staged bilateral leads revealed an initial 25.34 ± 2.74% (µ ± SE) improvement in PDQ-39SI at 4 months after the first lead with further improvement until 18 months, with no difference across targets. Scores did not improve after the second lead with gradual worsening starting at 18 months postoperatively. STN-DBS provided greater short-term QoL improvement than GPi-DBS for unilateral surgery. For staged bilateral DBS, overall QoL improvement was explained primarily by the first lead. Decision-making for patients considering DBS should include a discussion surrounding the potential risks and benefits from a second DBS lead.
Database of literature derived cellular measurements from the murine basal ganglia
Authors: Bjerke Ingvild E. , Puchades Maja A. , Bjaalie Jan G. , Leergaard Trygve B. 
Published: July 2020

AbstractQuantitative measurements and descriptive statistics of different cellular elements in the brain are typically published in journal articles as text, tables, and example figures, and represent an important basis for the creation of biologically constrained computational models, design of intervention studies, and comparison of subject groups. Such data can be challenging to extract from publications and difficult to normalise and compare across studies, and few studies have so far attempted to integrate quantitative information available in journal articles. We here present a database of quantitative information about cellular parameters in the frequently studied murine basal ganglia. The database holds a curated and normalised selection of currently available data collected from the literature and public repositories, providing the most comprehensive collection of quantitative neuroanatomical data from the basal ganglia to date. The database is shared as a downloadable resource from the EBRAINS Knowledge Graph (https://kg.ebrains.eu), together with a workflow that allows interested researchers to update and expand the database with data from future reports.
DiB-splits: nature-guided design of a novel fluorescent labeling split system
Authors: Bozhanova Nina G. , Gavrikov Alexey S. , Mishin Alexander S. , Meiler Jens 
Published: July 2020

AbstractFluorogen-activating proteins (FAPs) are innovative fluorescent probes combining advantages of genetically-encoded proteins such as green fluorescent protein and externally added fluorogens that allow for highly tunable and on demand fluorescent signaling. Previously, a panel of green- and red-emitting FAPs has been created from bacterial lipocalin Blc (named DiBs). Here we present a rational design as well as functional and structural characterization of the first self-assembling FAP split system, DiB-splits. This new system decreases the size of the FAP label to ~8–12 kDa while preserving DiBs’ unique properties: strong increase in fluorescence intensity of the chromophore upon binding, binding affinities to the chromophore in nanomolar to low micromolar range, and high photostability of the protein-ligand complex. These properties allow for use of DiB-splits for wide-field, confocal, and super-resolution fluorescence microscopy. DiB-splits also represent an attractive starting point for further design of a protein-protein interaction detection system as well as novel FAP-based sensors.