bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanisms of K+ clearance and extracellular space shrinkage—Glia cells as the stars
Authors: MacAulay Nanna 
Published: March 2020

AbstractNeuronal signaling in the central nervous system (CNS) associates with release of K+ into the extracellular space resulting in transient increases in [K+]o. This elevated K+ is swiftly removed, in part, via uptake by neighboring glia cells. This process occurs in parallel to the [K+]o elevation and glia cells thus act as K+ sinks during the neuronal activity, while releasing it at the termination of the pulse. The molecular transport mechanisms governing this glial K+ absorption remain a point of debate. Passive distribution of K+ via Kir4.1‐mediated spatial buffering of K+ has become a favorite within the glial field, although evidence for a quantitatively significant contribution from this ion channel to K+ clearance from the extracellular space is sparse. The Na+/K+‐ATPase, but not the Na+/K+/Cl− cotransporter, NKCC1, shapes the activity‐evoked K+ transient. The different isoform combinations of the Na+/K+‐ATPase expressed in glia cells and neurons display different kinetic characteristics and are thereby distinctly geared toward their temporal and quantitative contribution to K+ clearance. The glia cell swelling occurring with the K+ transient was long assumed to be directly associated with K+ uptake and/or AQP4, although accumulating evidence suggests that they are not. Rather, activation of bicarbonate‐ and lactate transporters appear to lead to glial cell swelling via the activity‐evoked alkaline transient, K+‐mediated glial depolarization, and metabolic demand. This review covers evidence, or lack thereof, accumulated over the last half century on the molecular mechanisms supporting activity‐evoked K+ and extracellular space dynamics.
Nurr1Cd11bcreconditional knockout mice display inflammatory injury to nigrostriatal dopaminergic neurons
Authors: Dong Jie , Liu Xinyao , Wang Yuanyuan , Cai Huaibin , Le Weidong 
Published: March 2020

AbstractNuclear receptor‐related 1 protein (NURR1) is essential for the development and maintenance of midbrain dopaminergic (DAergic) neurons. NURR1 also protects DAergic neurons against neuroinflammation. However, it remains to be determined to what extent does NURR1 exerts its protective function through acting autonomously in the microglia. Using Cre/lox gene targeting system, we deletedNurr1in the microglia ofNurr1Cd11bcreconditional knockout (cKO) mice. TheNurr1Cd11bcrecKO mice displayed age‐dependent motor abnormalities and increased microglial activation, but with no obvious DAergic neurodegeneration. To boost the inflammatory injury, we systemically administered endotoxin lipopolysaccharide (LPS) toNurr1Cd11bcremice. As expected, LPS treatment exacerbated the motor phenotypes and inflammatory reactions inNurr1Cd11bcrecKO mice. More importantly, LPS administration caused DAergic neuron loss and α‐synuclein aggregation, two pathological hallmarks of Parkinson's disease (PD). Therefore, our findings provide in vivo evidence supporting a critical protective role of NURR1 in the microglia against inflammation‐induced degeneration of DAergic neurons in PD.
Spatiotemporal and spectral dynamics of multi‐item working memory as revealed by the n‐back task using MEG
Authors: Costers Lars , Van Schependom Jeroen , Laton Jorne , Baijot Johan , Sjøgård Martin , Wens Vincent , De Tiège Xavier , Goldman Serge , D'Haeseleer Miguel , D'hooghe Marie Beatrice , Woolrich Mark , Nagels Guy 
Published: March 2020

AbstractMulti‐item working memory (WM) is a complex cognitive function thought to arise from specific frequency band oscillations and their interactions. While some theories and consistent findings have been established, there is still a lot of unclarity about the sources, temporal dynamics, and roles of event‐related fields (ERFs) and theta, alpha, and beta oscillations during WM activity. In this study, we performed an extensive whole‐brain ERF and time‐frequency analysis on n‐back magnetoencephalography data from 38 healthy controls. We identified the previously unknown sources of the n‐back M300, the right inferior temporal and parahippocampal gyrus and left inferior temporal gyrus, and frontal theta power increase, the orbitofrontal cortex. We shed new light on the role of the precuneus during n‐back activity, based on an early ERF and theta power increase, and suggest it to be a crucial link between lower‐level and higher‐level information processing. In addition, we provide strong evidence for the central role of the hippocampus in multi‐item WM behavior through the dynamics of theta and alpha oscillatory changes. Almost simultaneous alpha power decreases observed in the hippocampus and occipital fusiform gyri, regions known to be involved in letter processing, suggest that these regions together enable letter recognition, encoding and storage in WM. In summary, this study offers an extensive investigation into the spatial, temporal, and spectral characteristics of n‐back multi‐item WM activity.
The effectiveness of long‐acting injectable antipsychotics versus oral antipsychotics in the maintenance treatment of outpatients with chronic schizophrenia
Authors: Fang Su‐Chen , Liao Ding‐Lieh , Huang Cheng‐Yi , Hsu Chun‐Chi , Cheng Shu‐Li , Shao Yu‐Hsuan J. 
Published: March 2020

AbstractObjectiveTo compare the psychiatric service utilization between patients who only received long‐acting injectable antipsychotics (LAIAs) and those who only received oral antipsychotics (OAPs) in the maintenance treatment of chronic schizophrenia.MethodsWe constructed a cohort of chronic schizophrenia patients who underwent maintenance treatment from the Taiwan National Health Insurance Research Database in 2011 and followed these patients for 12 months. We included patients who had been diagnosed with schizophrenia for at least 3 years, were not hospitalized in 2011, and had received 1 year of maintenance treatment. Inverse probability of treatment weighting logistic, linear, and negative binomial regression models were used to estimate associated psychiatric services utilization and adjust for covariate imbalances between the LAIAs and OAPs groups.ResultsAmong 40,194 patients, 948 (2.36%) received only LAIAs and 39,246 (97.64%) received only OAPs. Compared with those who received only OAPs, the sole LAIAs users were associated with a lower percentage of psychiatric hospitalization (8.4% and 5.8%, respectively; odds ratio: 0.63, p < .01), shorter lengths of hospitalization days (82.8 and 65.9, respectively; coefficient [b]: −16.87, p = .03), and fewer emergency room visits (2.3 and 1.8, respectively; b: −0.24, p < .01) per patient.ConclusionsChronic schizophrenia patients who received only LAIs had a lower risk of disease relapse and a reduction in psychiatric service utilization than those receiving only OAPs.
Excessive ADAM17 activation occurs in uremic patients and may contribute to their immunocompromised status
Authors: Yashiro Mitsuru , Ohya Masaki , Mima Toru , Nakashima Yuri , Kawakami Kazuki , Sonou Tomohiro , Tatsuta Koichi , Yamano Yukiko , Negi Shigeo , Shigematsu Takashi 
Published: March 2020

AbstractIntroductionWe previously reported that fibroblast growth factor 23 (FGF23)‐klotho signaling plays a role in B cell immunity. Despite high serum levels of FGF23, a decline in immunity is frequently observed in patients on hemodialysis (HD); thus, abnormalities in the FGF23‐klotho signaling pathway in immune cells may occur in these patients.MethodsWe analyzed the number of klotho‐positive cells in peripheral blood mononuclear cells from 10 male and 6 female patients on HD and 5 healthy male subjects using flow cytometry. We analyzed the abundance of cleaved klotho protein in the murine B cell line, A20, and in the serum of HD patients and healthy subjects (HS) using flow cytometry and Western blotting. The serum level of A disintegrin and metalloprotease 17 (ADAM17) was measured in HD patients and HS using enzyme‐linked immunosorbent assay.ResultsThe number of klotho‐positive B cells was reduced in HD patients. Serum ADAM17 was responsible for the reduction in klotho, as a specific ADAM17 inhibitor reversed this change. The total serum levels of ADAM17 were similar in HD patients and HS; however, activated ADAM17 was increased in the serum of HD patients.ConclusionsWe concluded that abnormal ADAM17 activation could contribute to the immunocompromised status in patients on HD, in line with the reported role of ADAM17 as an anti‐inflammatory and immunosuppressive factor.
MicroRNA‐34a‐mediated death of acute myeloid leukemia stem cells through apoptosis induction and exosome shedding inhibition via histone deacetylase 2 targeting
Authors: Hu Yanning , Ma Xiaotang , Wu Zhimei , Nong Qingwei , Liu Feng , Wang Yue , Dong Min 
Published: March 2020

AbstractWe investigated the role of leukemia stem cells in chemoresistance and recurrence of acute myeloid leukemia. Total RNA was isolated from cells or tissues using TRIzol reagent. Cell viability was assessed with the tetrazolium assay. MicroRNA‐34a (miR‐34a), which acts on cell death regulation pathways, was noticeably downregulated in non‐M3 acute myeloid leukemia stem cells compared with normal hematopoietic stem cells. Furthermore, inhibition of miR‐34a‐mediated suppression in leukemia stem cells was associated with poor clinical outcomes and impaired treatment efficacy in acute myeloid leukemia. Transfection with a miR‐34a mimic triggered leukemia stem cell death and prevented leukemia. Bioinformatics analysis and a dual‐luciferase reporter assay showed that miR‐34a targeted the 3′‐untranslated region of histone deacetylase 2, and the reinforced expression of miR‐34a remarkably stimulated the expression of histone deacetylase 2 in leukemia stem cells. Ectopic miR‐34a expression triggered death of leukemia stem cells via pathways involving the Janus kinase 1‐signal transducer and activator of transcription 2‐p53 axis. Targeting leukemia stem cells to trigger cell death through upregulation of miR‐34a expression could be used to diagnose and treat acute myeloid leukemia.
Conjugating homogenized liver‐extracellular matrix into decellularized hepatic scaffold for liver tissue engineering
Authors: Saleh Tarek , Ahmed Ebtehal , Yu Lina , Song Su‐Hyeon , Park Kyung‐Mee , Kwak Ho‐Hyun , Woo Heung‐Myong 
Published: March 2020

AbstractThe generation of a transplantable liver scaffold is crucial for the treatment of end‐stage liver failure. Unfortunately, decellularized liver scaffolds suffer from lack of bioactive molecules and functionality. In this study, we conjugated homogenized liver‐extracellular matrix (ECM) into a decellularized liver in a rat model to improve its structural and functional properties. The homogenized ECM was prepared, characterized, and subsequently perfused into ethyl carbodiimide hydrochloride (EDC)/N‐hydroxysuccinimide (NHS) activated liver scaffolds. Various techniques were performed to confirm the improvements that were accomplished through the conjugation process; these included micro/ultra‐structural analyses, biochemical analysis of ECM components, DNA quantification, swelling ratio, structural stability, calcification properties, platelet activation study, static and dynamic seeding with EAhy926 endothelial cells and HepG2 hepatocarcinoma cells, subcutaneous implantation and intrahepatic transplantation. The results showed that the conjugated scaffolds have superior micro‐ and ultrastructural and biochemical characteristics. In addition, DNA contents, swelling ratios, calcification properties, platelet reactions, and host inflammatory reactions were not altered with the conjugation process. The conjugated scaffolds revealed better cellular spreading and popularity compared to the non‐conjugated scaffolds. Intrahepatic transplantation showed that the conjugated scaffold had higher popularity of hepatic regenerative cells with better angiogenesis. The conjugation of the decellularized liver scaffold with homogenized liver‐ECM is a promising tool to improve the quality of the generated scaffold for further transplantation.
Cell–cell interaction in a coculture system consisting of CRISPR/Cas9 mediated GFP knock‐in HUVECs and MG‐63 cells in alginate‐GelMA based nanocomposites hydrogel as a 3D scaffold
Authors: Shahabipour Fahimeh , Oskuee Reza K. , Dehghani Hesam , Shokrgozar Mohammad A. , Aninwene George E. , Bonakdar Shahin 
Published: March 2020

AbstractThe interaction between osteogenic and angiogenic cells through a coculturing system in biocompatible materials has been considered for successfully engineering vascularized bone tissue equivalents. In this study, we developed a hydrogel‐blended scaffold consisted of gelatin methacryloyl (GelMA) and alginate enriched with hydroxyapatite nanoparticles (HAP) to model an in vitro prevascularized bone construct. The hydrogel‐based scaffold revealed a higher mechanical stiffness than those of pure (GelMA), alginate, and (GelMA+ HAP) hydrogels. In the present study, we generated a green fluorescent protein (GFP) knock‐in umbilical vein endothelial cells (HUVECs) cell line using the CRISPR/Cas9 technology. The GFP was inserted into the human‐like ROSA locus of HUVECs genome. HUVECs expressing GFP were cocultured with OB‐like cells (MG‐63) within three‐dimensionally (3D) fabricated hydrogel to investigate the response of cocultured osteoblasts and endothelial cells in a 3D structure. Cell viability under the 3D cocultured gel was higher than the 3D monocultured. Compared to the 3D monocultured condition, the cells were aligned and developed into the vessel‐like structures. During 14 days of culture periods, the cells displayed actin protrusions by the formation of spike‐like filopodia in the 3D cocultured model. Angiogenic and osteogenic‐related genes such as CD31, vWF, and osteocalcin showed higher expression in the cocultured versus the monocultured. These results have collectively indicated that the 3D cocultured hydrogel facilitates interaction among cells, thereby having a greater effect on angiogenic and osteogenic properties in the absence of induction media.
RUNX1 and RUNX2 transcription factors function in opposing roles to regulate breast cancer stem cells
Authors: Fritz Andrew J. , Hong Deli , Boyd Joseph , Kost Jason , Finstaad Kristiaan H. , Fitzgerald Mark P. , Hanna Sebastian , Abuarqoub Alqassem H. , Malik Miles , Bushweller John , Tye Coralee , Ghule Prachi , Gordon Jonathan , Frietze Seth , Zaidi Sayyed K. , Lian Jane B. , Stein Janet L. , Stein Gary S. 
Published: March 2020

AbstractBreast cancer stem cells (BCSCs) are competent to initiate tumor formation and growth and refractory to conventional therapies. Consequently BCSCs are implicated in tumor recurrence. Many signaling cascades associated with BCSCs are critical for epithelial‐to‐mesenchymal transition (EMT). We developed a model system to mechanistically examine BCSCs in basal‐like breast cancer using MCF10AT1 FACS sorted for CD24 (negative/low in BCSCs) and CD44 (positive/high in BCSCs). Ingenuity Pathway Analysis comparing RNA‐seq on the CD24−/low versus CD24+/high MCF10AT1 indicates that the top activated upstream regulators include TWIST1, TGFβ1, OCT4, and other factors known to be increased in BCSCs and during EMT. The top inhibited upstream regulators include ESR1, TP63, and FAS. Consistent with our results, many genes previously demonstrated to be regulated by RUNX factors are altered in BCSCs. The RUNX2 interaction network is the top significant pathway altered between CD24−/low and CD24+/high MCF10AT1. RUNX1 is higher in expression at the RNA level than RUNX2. RUNX3 is not expressed. While, human‐specific quantitative polymerase chain reaction primers demonstrate that RUNX1 and CDH1 decrease in human MCF10CA1a cells that have grown tumors within the murine mammary fat pad microenvironment, RUNX2 and VIM increase. Treatment with an inhibitor of RUNX binding to CBFβ for 5 days followed by a 7‐day recovery period results in EMT suggesting that loss of RUNX1, rather than increase in RUNX2, is a driver of EMT in early stage breast cancer. Increased understanding of RUNX regulation on BCSCs and EMT will provide novel insight into therapeutic strategies to prevent recurrence.
A guideline for homology modeling of the proteins from newly discovered betacoronavirus, 2019 novel coronavirus (2019‐nCoV)
Authors: Dong Shengjie , Sun Jiachen , Mao Zhuo , Wang Lu , Lu Yi‐Lin , Li Jiesen 
Published: March 2020

AbstractDuring an outbreak of respiratory diseases including atypical pneumonia in Wuhan, a previously unknown β‐coronavirus was detected in patients. The newly discovered coronavirus is similar to some β‐coronaviruses found in bats but different from previously known SARS‐CoV and MERS‐CoV. High sequence identities and similarities between 2019‐nCoV and SARS‐CoV were found. In this study, we searched the homologous templates of all nonstructural and structural proteins of 2019‐nCoV. Among the nonstructural proteins, the leader protein (nsp1), the papain‐like protease (nsp3), the nsp4, the 3C‐like protease (nsp5), the nsp7, the nsp8, the nsp9, the nsp10, the RNA‐directed RNA polymerase (nsp12), the helicase (nsp13), the guanine‐N7 methyltransferase (nsp14), the uridylate‐specific endoribonuclease (nsp15), the 2'‐O‐methyltransferase (nsp16), and the ORF7a protein could be built on the basis of homology templates. Among the structural proteins, the spike protein (S‐protein), the envelope protein (E‐protein), and the nucleocapsid protein (N‐protein) can be constructed based on the crystal structures of the proteins from SARS‐CoV. It is known that PL‐Pro, 3CL‐Pro, and RdRp are important targets for design antiviral drugs against 2019‐nCoV. And S protein is a critical target candidate for inhibitor screening or vaccine design against 2019‐nCoV because coronavirus replication is initiated by the binding of S protein to cell surface receptors. It is believed that these proteins should be useful for further structure‐based virtual screening and related computer‐aided drug development and vaccine design.
Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)
Authors: Dale Jessica M. , Hood Simon P. , Bowen Ori , Bright Helen , Cutler Keith L. , Berry Neil , Almond Neil , Goldin Robert , Karayiannis Peter , Rose Nicola J. 
Published: March 2020

AbstractGB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology.
Global pattern of short‐term concurrent hot and dry extremes and its relationship to large‐scale climate indices
Authors: Zhang Haoyue , Wu Chuanhao , Yeh Pat J.‐F. , Hu Bill X. 
Published: March 2020

AbstractThe short‐term concurrent hot and dry extreme (SCHDE) event has recently stimulated intensive scientific interests due to its rapid onset, severe intensity, and devastating impacts on agriculture and natural ecosystems. The SCHDE is mainly caused by an increase in actual evapotranspiration (ET) accompanied with a decrease in soil moisture (SM) due to anomalously high surface temperature (Tair). Based on the daily datasets of precipitation (P), Tair, ET, and SM from four global modelling products as well as large‐scale climate indices, we analyse globally the spatio‐temporal evolution of SCHDE events at both grid and basin scales. Results indicate that SCHDE events occur mostly in Northern Hemisphere regions with relatively low P. During 1980–2010, due to significant global warming (0.30°C·decade−1) the global mean occurrence frequency of SCHDE has an increasing trend (0.34%·decade−1) along with a weakly decreasing trend of SM (~−0.08%·decade−1) and a significantly increasing trend of ET (~8.34 mm·decade−1). Overall, North America and Asia have a higher frequency of SCHDE occurrence than other continents. The variability of Tair is mainly responsible for the variability of SCHDE occurrence over the equator regions, while the variability of ET (SM) plays an important role in SCHDE occurrence variability in the cropland‐dominant (mid‐ and high‐latitude) regions. Globally, the relative contribution of Tair to SCHDE variability is the largest, followed by ET and SM. Lastly, we found that the cold phases of the Pacific Decadal Oscillation during the La Niña events (i.e., negative Multivariate ENSO Index) are conducive to the intensification of SCHDE events in southern South America and Australia.
Athletes after anterior cruciate ligament reconstruction demonstrate asymmetric intracortical facilitation early after surgery
Authors: Zarzycki Ryan , Morton Susanne M. , Charalambous Charalambos C. , Pietrosimone Brian , Williams Glenn N. , Snyder‐Mackler Lynn 
Published: March 2020

AbstractQuadriceps dysfunction persists after anterior cruciate ligament reconstruction (ACLR), yet the etiology remains elusive. Inhibitory and facilitatory intracortical networks (ie, intracortical excitability) may be involved in quadriceps dysfunction, yet the investigation of these networks early after ACLR is sparse. The purposes of this study were to examine (a) changes in intracortical excitability in athletes after ACLR compared to uninjured athletes during the course of postoperative rehabilitation, (b) the association between intracortical excitability and quadriceps strength in athletes after ACLR. Eighteen level I/II athletes after ACLR between the ages of 18 to 30 years and eighteen healthy sex, age, and activity matched athletes were tested at three‐time points: (a) 2 weeks after surgery, (b) achievement of a “quiet knee” defined as full range of motion and minimal effusion, (c) return to running time point defined as achievement of a quadriceps index ≥80% and at least 12 weeks post‐ACLR. Short‐interval intracortical inhibition (SICI) and intracortical facilitation (ICF), measured via transcranial magnetic stimulation and isometric quadriceps strength were examined bilaterally at each time point. There was a significant group × limb interaction (P = .017) for ICF. The ACLR group demonstrated asymmetric ICF (greater in the nonsurgical limb) compared to controls and a significant relationship between SICI and quadriceps strength of the surgical limb at the quiet knee time point (P = .018). ACLR individuals demonstrate differential effects on ICF between limbs. Also, SICI is associated with isometric quadriceps strength after ACLR, suggesting increased inhibition of the motor cortex may contribute to impaired quadriceps strength following ACLR.