bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies and prospects of effective neural circuits reconstruction after spinal cord injury
Authors: Yang Biao , Zhang Feng , Cheng Feng , Ying Liwei , Wang Chenggui , Shi Kesi , Wang Jingkai , Xia Kaishun , Gong Zhe , Huang Xianpeng , Yu Cao , Li Fangcai , Liang Chengzhen , Chen Qixin 
Published: June 2020

AbstractDue to the disconnection of surviving neural elements after spinal cord injury (SCI), such patients had to suffer irreversible loss of motor or sensory function, and thereafter enormous economic and emotional burdens were brought to society and family. Despite many strategies being dealing with SCI, there is still no effective regenerative therapy. To date, significant progress has been made in studies of SCI repair strategies, including gene regulation of neural regeneration, cell or cell-derived exosomes and growth factors transplantation, repair of biomaterials, and neural signal stimulation. The pathophysiology of SCI is complex and multifaceted, and its mechanisms and processes are incompletely understood. Thus, combinatorial therapies have been demonstrated to be more effective, and lead to better neural circuits reconstruction and functional recovery. Combinations of biomaterials, stem cells, growth factors, drugs, and exosomes have been widely developed. However, simply achieving axon regeneration will not spontaneously lead to meaningful functional recovery. Therefore, the formation and remodeling of functional neural circuits also depend on rehabilitation exercises, such as exercise training, electrical stimulation (ES) and Brain–Computer Interfaces (BCIs). In this review, we summarize the recent progress in biological and engineering strategies for reconstructing neural circuits and promoting functional recovery after SCI, and emphasize current challenges and future directions.
PIK3C3 regulates the expansion of liver CSCs and PIK3C3 inhibition counteracts liver cancer stem cell activity induced by PI3K inhibitor
Authors: Liu Fengchao , Wu Xiaoling , Qian Yanzhi , Jiang Xin , Wang Yiying , Gao Jian 
Published: June 2020

AbstractThe existence of cancer stem cells (CSCs) accounts for hepatocellular carcinoma (HCC) treatment resistance, relapse, and metastasis. Although the elimination of cancer stem cells is crucial for cancer treatment, strategies for their elimination are limited. Here, we report that a remarkable increase in PIK3C3 was detected in HCC tissues and liver CSCs. Upregulated PIK3C3 facilitated liver CSC expansion in HCC cells; RNA interference-mediated silencing of PIK3C3 had an opposite effect. Furthermore, PIK3C3 inhibition by inhibitors effectively eliminated liver CSCs and inhibited the growth of tumors in vivo. The phosphoinositide 3-kinase (PI3K) pathway is considered an important hallmark of cancer. One of our recent studies found that prolonged inhibition by inhibitors of class I PI3K induces liver CSCs expansion. To our surprise, PIK3C3 inhibition blocked the expansion of CSCs induced by PI3K inhibitor; moreover, treatment with the combination of PIK3C3 inhibitor and PI3K inhibitor in maximal suppresses the expansion of liver CSCs of tumors in mice. Mechanistically, inhibition of PIK3C3 inhibit the activation of SGK3, a CSCs promoter, induced by PI3K inhibitor. We also show that PIK3C3 inhibitor suppresses liver CSCs by activation of the AMP-activated kinase (AMPK). Although PIK3C3 plays a critical role in autophagy, we find that PIK3C3 regulates liver CSCs independent of the autophagy process. These findings uncover the effective suppression of liver CSCs by targeting PIK3C3, and targeting PIK3C3 in combination with PI3K inhibitor inhibits the expansion of liver CSCs efficiently, which is an attractive therapeutic regimen for the treatment of HCC.
Increased AT2R expression is induced by AT1R autoantibody via two axes, Klf-5/IRF-1 and circErbB4/miR-29a-5p, to promote VSMC migration
Authors: Sun Yan , Li Yang , Wang Meili , Yue Mingming , Bai Lina , Bian Jingwei , Hao Weiwei , Sun Jing , Zhang Suli , Liu Huirong 
Published: June 2020

AbstractVascular remodeling can be caused by angiotensin II type 1 receptor (AT1R) autoantibody (AT1-AA), although the related mechanism remains unknown. Angiotensin II type 2 receptor (AT2R) plays multiple roles in vascular remodeling through cross-talk with AT1R in the cytoplasm. Here, we aimed to explore the role and mechanism of AT2R in AT1-AA-induced vascular smooth muscle cell (VSMC) migration, which is a key event in vascular remodeling. In vitro and in vivo, we found that AT2R can promote VSMC migration in AT1-AA-induced vascular remodeling. Moreover, AT2R expression was upregulated via Klf-5/IRF-1-mediated transcriptional and circErbB4/miR-29a-5p-mediated posttranscriptional mechanisms in response to AT1-AA. Our data provide a molecular basis for AT1-AA-induced AT2R expression by transcription factors, namely, a circular RNA and a microRNA, and showed that AT2R participated in AT1-AA-induced VSMC migration during the development of vascular remodeling. AT2R may be a potential target for the treatment of AT1-AA-induced vascular diseases.
A PROTAC peptide induces durable β-catenin degradation and suppresses Wnt-dependent intestinal cancer
Authors: Liao Hongwei , Li Xiang , Zhao Lianzheng , Wang Yalong , Wang Xiaodan , Wu Ye , Zhou Xin , Fu Wei , Liu Lei , Hu Hong-Gang , Chen Ye-Guang 
Published: June 2020

AbstractAberrant activation of Wnt/β-catenin signaling has been associated with the onset and progression of many types of tumors and thus β-catenin represents one attractive intracellular target for cancer therapy. Based on the Axin-derived peptide that binds to β-catenin, two stapled peptides SAHPA1 and xStAx were reported to enhance or impair Wnt/β-catenin signaling, respectively. In this study, we designed PROTACs (proteolysis targeting chimeras) by coupling SAHPA1 or xStAx with the VHL ligand to achieve efficient β-catenin degradation. The obtained xStAx-VHLL sustained β-catenin degradation and manifested strong inhibition of Wnt signaling in cancer cells and in APC−/− organoids. Furthermore, xStAx-VHLL could effectively restrain tumor formation in BALB/C nude mice, and diminish the existing tumors in APCmin/+ mice. More importantly, xStAx-VHLL could potently inhibit the survival of colorectal cancer patient-derived organoids. These findings suggest that xStAx-VHLL exhibits the ability of cancer prevention and cure, highlighting the potential of β-catenin degrader PROTACs as a new class of promising anticancer agent.
Is HSPG2 a modifier gene for Marfan syndrome?
Authors: Gerdes Gyuricza Isabela , Barbosa de Souza Rodrigo , Farinha-Arcieri Luis Ernesto , Ribeiro Fernandes Gustavo , Veiga Pereira Lygia 
Published: June 2020

AbstractMarfan syndrome (MFS) is a connective tissue disease caused by variants in the FBN1 gene. Nevertheless, other genes influence the manifestations of the disease, characterized by high clinical variability even within families. We mapped modifier loci for cardiovascular and skeletal manifestations in the mg∆loxPneo mouse model for MFS and the synthenic loci in the human genome. Corroborating our findings, one of those loci was identified also as a modifier locus in MFS patients. Here, we investigate the HSPG2 gene, located in this region, as a candidate modifier gene for MFS. We show a correlation between Fbn1 and Hspg2 expression in spinal column and aorta in non-isogenic mg∆loxPneo mice. Moreover, we show that mice with severe phenotypes present lower expression of Hspg2 than those mildly affected. Thus, we propose that HSPG2 is a strong candidate modifier gene for MFS and its role in modulating disease severity should be investigated in patients.
Structure and dynamics of the ASB9 CUL-RING E3 Ligase
Authors: Lumpkin Ryan J. , Baker Richard W. , Leschziner Andres E. , Komives Elizabeth A. 
Published: June 2020

AbstractThe Cullin 5 (CUL5) Ring E3 ligase uses adaptors Elongins B and C (ELOB/C) to bind different SOCS-box-containing substrate receptors, determining the substrate specificity of the ligase. The 18-member ankyrin and SOCS box (ASB) family is the largest substrate receptor family. Here we report cryo-EM data for the substrate, creatine kinase (CKB) bound to ASB9-ELOB/C, and for full-length CUL5 bound to the RING protein, RBX2, which binds various E2s. To date, no full structures are available either for a substrate-bound ASB nor for CUL5. Hydrogen–deuterium exchange (HDX-MS) mapped onto a full structural model of the ligase revealed long-range allostery extending from the substrate through CUL5. We propose a revised allosteric mechanism for how CUL-E3 ligases function. ASB9 and CUL5 behave as rigid rods, connected through a hinge provided by ELOB/C transmitting long-range allosteric crosstalk from the substrate through CUL5 to the RBX2 flexible linker.
Assessing the severity of psoriasis through multivariate analysis of optical images from non-lesional skin
Authors: Žurauskas Mantas , Barkalifa Ronit , Alex Aneesh , Marjanovic Marina , Spillman Darold R. , Mukherjee Prabuddha , Neitzel Craig D. , Lee Warren , Medler Jeremy , Arp Zane , Cleveland Matthew , Hood Steve , Boppart Stephen A. 
Published: June 2020

AbstractPatients with psoriasis represent a heterogeneous population with individualized disease expression. Psoriasis can be monitored through gold standard histopathology of biopsy specimens that are painful and permanently scar. A common associated measure is the use of non-invasive assessment of the Psoriasis Area and Severity Index (PASI) or similarly derived clinical assessment based scores. However, heterogeneous manifestations of the disease lead to specific PASI scores being poorly reproducible and not easily associated with clinical severity, complicating the efforts to monitor the disease. To address this issue, we developed a methodology for non-invasive automated assessment of the severity of psoriasis using optical imaging. Our analysis shows that two-photon fluorescence lifetime imaging permits the identification of biomarkers present in both lesional and non-lesional skin that correlate with psoriasis severity. This ability to measure changes in lesional and healthy-appearing skin provides a new pathway for independent monitoring of both the localized and systemic effects of the disease. Non-invasive optical imaging was conducted on lesions and non-lesional (pseudo-control) skin of 33 subjects diagnosed with psoriasis, lesional skin of 7 subjects diagnosed with eczema, and healthy skin of 18 control subjects. Statistical feature extraction was combined with principal component analysis to analyze pairs of two-photon fluorescence lifetime images of stratum basale and stratum granulosum layers of skin. We found that psoriasis is associated with biochemical and structural changes in non-lesional skin that can be assessed using clinically available two-photon fluorescence lifetime microscopy systems.
Role of Superoxide Reductase FA796 in Oxidative Stress Resistance in Filifactor alocis
Authors: Mishra Arunima , Aja Ezinne , Fletcher Hansel M 
Published: June 2020

AbstractFilifactor alocis, a Gram-positive anaerobic bacterium, is now a proposed diagnostic indicator of periodontal disease. Because the stress response of this bacterium to the oxidative environment of the periodontal pocket may impact its pathogenicity, an understanding of its oxidative stress resistance strategy is vital. Interrogation of the F. alocis genome identified the HMPREF0389_00796 gene that encodes for a putative superoxide reductase (SOR) enzyme. SORs are non-heme, iron-containing enzymes that can catalyze the reduction of superoxide radicals to hydrogen peroxide and are important in the protection against oxidative stress. In this study, we have functionally characterized the putative SOR (FA796) from F. alocis ATCC 35896. The recombinant FA796 protein, which is predicted to be a homotetramer of the 1Fe-SOR class, can reduce superoxide radicals. F. alocis FLL141 (∆FA796::ermF) was significantly more sensitive to oxygen/air exposure compared to the parent strain. Sensitivity correlated with the level of intracellular superoxide radicals. Additionally, the FA796-defective mutant had increased sensitivity to hydrogen peroxide-induced stress, was inhibited in its ability to form biofilm and had reduced survival in epithelial cells. Collectively, these results suggest that the F. alocis SOR protein is a key enzymatic scavenger of superoxide radicals and protects the bacterium from oxidative stress conditions.
Protection and immune modulation of activated human vaginal epithelial cells by Aurea helianthus extract
Authors: Park Yoonjin , Lee Kyunghwa , Lee Chayul , Song Ahran , Kim Jinkwan , Kim Boyong , Lee SeungGwan 
Published: June 2020

AbstractAurea helianthus extract is associated with various properties including anti-melanogenesis, anti-oxidation, tumorigenic suppression, and immunoregulation; however, the mechanism by which it executes the immunomodulation of human vaginal epithelial cells (HVECs) remains elusive. We established three immunological functions of the extract. First, it mediated tumorigenic suppression in HVECs. Expression of cytokeratin 8, cancer antigen-125, and vimentin was dramatically downregulated in HVECs exposed to the extract under oxidative and fungal stresses. Second, the extract activated dendritic cells and macrophages. On exposing progenitor dendritic cells to the extract, the number of CD304+ cells increased by 40%; further, under oxidative and fungal stresses, this number was approximately 1.8 and 1.3 times lower, respectively, compared to that in the stressed cells. In monocytic differentiation, the number of dendritic cells and macrophages increased 9 and 6 times, respectively, compared to that in the control. Additionally, the extract enhanced and recovered polarisation by approximately 1.5 and 2 times, respectively, than that under stressed conditions. Third, the phagocytic activity of macrophages, against HPV16, 18, and 33 peptides, was enhanced by 12–35 times compared with that under stressed conditions. Thus, A. helianthus extract is a strong stimulator of the immune system and tumorigenic suppression under stress conditions.
Activation of cortical M1 muscarinic receptors and related intracellular signaling is necessary for reactivation-induced object memory updating
Authors: Jardine Kristen H. , Wideman Cassidy E. , MacGregor Chelsea , Sgarbossa Cassandra , Orr Dean , Mitchnick Krista A. , Winters Boyer D. 
Published: June 2020

AbstractReactivated long-term memories can become labile and sensitive to modification. Memories in this destabilized state can be weakened or strengthened, but there is limited research characterizing the mechanisms underlying retrieval-induced qualitative updates (i.e., information integration). We have previously implicated cholinergic transmission in object memory destabilization. Here we present a novel rodent paradigm developed to assess the role of this cholinergic mechanism in qualitative object memory updating. The post-reactivation object memory modification (PROMM) task exposes rats to contextual information following object memory reactivation. Subsequent object exploratory performance suggests that the contextual information is integrated with the original memory in a reactivation- and time-dependent manner. This effect is blocked by interference with M1 muscarinic receptors and several downstream signals in perirhinal cortex. These findings therefore demonstrate a hitherto unacknowledged cognitive function for acetylcholine with important implications for understanding the dynamic nature of long-term memory storage in the normal and aging brain.
Population dynamics of threatened Lahontan cutthroat trout in Summit Lake, Nevada
Authors: Simmons James B. , Campbell Teresa , Jerde Christopher L. , Chandra Sudeep , Cowan William , Hogan Zeb , Saenz Jessica , Shoemaker Kevin 
Published: June 2020

AbstractSummit Lake, Nevada (USA) is the last high-desert terminal lake to have a native self-sustaining population of threatened Lahontan cutthroat trout (Oncorhynchus clarkii henshawi). From spring 2015 to fall 2017, we quantified adult abundance and survival and the total annual spawning run. Abundance and survival were estimated with mark-recapture using PIT tags, and the annual spawning run was estimated with PIT tag detections and counts of spawners. Adult abundance fluctuated from 830 (95% CI 559–1248) to 1085 (95% CI 747–1614), with no overall temporal trend, as a decrease in male abundance was generally offset by an equal increase in female abundance. Estimated mean adult survival was 0.51 (95% CI 0.44–0.58). The spawning run increased from 645 (2015) to 868 (2016), but then decreased slightly to 824 (2017, mean = 789 ± 118). Female spawners increased in 2016 but decreased slightly in 2017, whereas male spawners decreased each year. In addition, the proportion of adults that spawned each year increased overall. Our study suggests that the adult population remained stable although most of the study period included the recent, severe regional drought in the western United States (2012–2016).
Polygenic analysis of the effect of common and low-frequency genetic variants on serum uric acid levels in Korean individuals
Authors: Cho Sung Kweon , Kim Beomsu , Myung Woojae , Chang Yoosoo , Ryu Seungho , Kim Han-Na , Kim Hyung-Lae , Kuo Po-Hsiu , Winkler Cheryl A. , Won Hong-Hee 
Published: June 2020

AbstractIncreased serum uric acid (SUA) levels cause gout and are associated with multiple diseases, including chronic kidney disease. Previous genome-wide association studies (GWAS) have identified more than 180 loci that contribute to SUA levels. Here, we investigated genetic determinants of SUA level in the Korean population. We conducted a GWAS for SUA in 6,881 Korean individuals, calculated polygenic risk scores (PRSs) for common variants, and validated the association of low-frequency variants and PRS with SUA levels in 3,194 individuals. We identified two low-frequency and six common independent variants associated with SUA. Despite the overall similar effect sizes of variants in Korean and European populations, the proportion of variance for SUA levels explained by the variants was greater in the Korean population. A rare, nonsense variant SLC22A12 p.W258X showed the most significant association with reduced SUA levels, and PRSs of common variants associated with SUA levels were significant in multiple Korean cohorts. Interestingly, an East Asian-specific missense variant (rs671) in ALDH2 displayed a significant association on chromosome 12 with the SUA level. Further genetic epidemiological studies on SUA are needed in ethnically diverse cohorts to investigate rare or low-frequency variants and determine the influence of genetic and environmental factors on SUA.
Impact-induced amino acid formation on Hadean Earth and Noachian Mars
Authors: Takeuchi Yuto , Furukawa Yoshihiro , Kobayashi Takamichi , Sekine Toshimori , Terada Naoki , Kakegawa Takeshi 
Published: June 2020

AbstractAbiotic synthesis of biomolecules is an essential step for the chemical origin of life. Many attempts have succeeded in synthesizing biomolecules, including amino acids and nucleobases (e.g., via spark discharge, impact shock, and hydrothermal heating), from reduced compounds that may have been limited in their availabilities on Hadean Earth and Noachian Mars. On the other hand, formation of amino-acids and nucleobases from CO2 and N2 (i.e., the most abundant C and N sources on Earth during the Hadean) has been limited via spark discharge. Here, we demonstrate the synthesis of amino acids by laboratory impact-induced reactions among simple inorganic mixtures: Fe, Ni, Mg2SiO4, H2O, CO2, and N2, by coupling the reduction of CO2, N2, and H2O with the oxidation of metallic Fe and Ni. These chemical processes simulated the possible reactions at impacts of Fe-bearing meteorites/asteroids on oceans with a CO2 and N2 atmosphere. The results indicate that hypervelocity impact was a source of amino acids on the Earth during the Hadean and potentially on Mars during the Noachian. Amino acids formed during such events could more readily polymerize in the next step of the chemical evolution, as impact events locally form amino acids at the impact sites.
The neovascularization effect of dedifferentiated fat cells
Authors: Watanabe Hirofumi , Goto Shumpei , Kato Reona , Komiyama Shogo , Nagaoka Yuki , Kazama Tomohiko , Yamamoto Chii , Li Yuxin , Konuma Noriyoshi , Hagikura Kazuhiro , Matsumoto Taro 
Published: June 2020

AbstractMature adipocyte-derived dedifferentiated fat (DFAT) cells can be prepared efficiently and with minimal invasiveness to the donor. They can be utilized as a source of transplanted cells during therapy. Although the transplantation of DFAT cells into an ischemic tissue enhances angiogenesis and increases vascular flow, there is little information regarding the mechanism of the therapeutic angiogenesis. To further study this, mice ischemic hindlimb model was used. It was confirmed that in comparison with the adipose derived stem cells and fibroblasts, the transplantation of DFAT cells led to a significant improvement in the blood flow and increased mature blood vessel density. The ability of DFAT cells to secrete angiogenic factors in hypoxic conditions and upon co-culture with vascular endothelial cells was then examined. Furthermore, we examined the possibility that DFAT cells differentiating into pericytes. The therapeutic angiogenic effects of DFAT cells were observed by the secretion of angiogenic factors and pericyte differentiation by transforming growth factor β1 signalling via Smad2/3. DFAT cells can be prepared with minimal invasiveness and high efficiency and are expected to become a source of transplanted cells in the future of angiogenic cell therapy.
Spatial relationship between land-use/land-cover change and land surface temperature in the Dongting Lake area, China
Authors: Tan Jie , Yu De , Li Qiang , Tan Xuelan , Zhou Weijun 
Published: June 2020

AbstractThe Dongting Lake area (China) is a climate change-sensitive and ecologically fragile area and plays a crucial role in the regulation of the regional climate. In recent decades, rapid social and economic development has led to increased land use/land cover (LULC) changes in the Dongting Lake area, which affect the surface energy balance and hydrological processes. Its contemporary variability under climate change remains highly uncertain. Therefore, we retrieved the Land surface temperature (LST) from the Landsat 7 data and explored its relationship with the LULC types. The results showed that LST is significantly affected by surface type. LST varied significantly across LULC types, with higher LSTs in built-up land, reed beach land, forest land, and paddy fields than in water bodies, mud beaches, marshlands, and riparian forests. Water bodies play an important regulatory role in reducing LST and mitigating thermal effects on the ground. The winter LST in the study area increased by approximately 3.5 °C, which may be related to the decrease in the area of Dongting Lake water bodies, water fields and reed flats after the Three Gorges Reservoir was impounded. Compared with the relationship between the NDVI, DEM, and distance from the water body, the negative correlation between the NDMI and LST was stronger and more stable and had the greatest effect on LST. These insights improve the understanding of the land change consequences on the temporal dynamics of LST.