Francesca Tozzi, Grazia Rutigliano, Marco Borsò, Chiara Falcicchia, Riccardo Zucchi, Nicola Origlia
Abnormalities in thyroid hormones (TH) availability and/or metabolism have been hypothesized to contribute to Alzheimer's disease (AD) and to be a risk factor for stroke. Recently, 3-iodothyronamine (T1 AM), an endogenous amine putatively derived from TH metabolism, gained interest for its ability to promote learning and memory in the mouse. Moreover, T1 AM has been demonstrated to rescue the β-Amyloid dependent LTP impairment in the entorhinal cortex (EC), a brain area crucially involved in learning and memory and early affected during AD...
January 19, 2021: Neurobiology of Disease
Jiuling Zhu, Huimin Xu, Hui Song, Xiang Li, Ning Wang, Junli Zhao, Xiaojing Zheng, Kwang-Youn Kim, Hui Zhang, Qinwen Mao, Haibin Xia
Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions in early embryogenesis, anti-inflammation, and neurodegeneration. A good model for the functional study of PGRN is the zebrafish with knockdown or knockout of grn, the gene encoding PGRN. Morpholino oligonucleotides (MOs) and zinc finger nucleases have been used to generate zebrafish grn models, yet they have shown inconsistent phenotypes due to either the neurotoxicity of the MOs or possible genetic compensation responses during gene editing...
January 22, 2021: Journal of Neurochemistry
Isabella Loughland, Alexander Little, Frank Seebacher
BACKGROUND: Thermal plasticity is pivotal for evolution in changing climates and in mediating resilience to its potentially negative effects. The efficacy to respond to environmental change depends on underlying mechanisms. DNA methylation induced by DNA methyltransferase 3 enzymes in the germline or during early embryonic development may be correlated with responses to environmental change. This developmental plasticity can interact with reversible acclimation within adult organisms, which would increase the speed of response and could alleviate potential mismatches between parental or early embryonic environments and those experienced at later life stages...
January 21, 2021: BMC Biology
Jingzhen Li, Fei Liu, Yuexia Lv, Kui Sun, Yuntong Zhao, Jamas Reilly, Yangjun Zhang, Jiayi Tu, Shanshan Yu, Xiliang Liu, Yayun Qin, Yuwen Huang, Pan Gao, Danna Jia, Xiang Chen, Yunqiao Han, Xinhua Shu, Daji Luo, Zhaohui Tang, Mugen Liu
Dysfunction of splicing factors often result in abnormal cell differentiation and apoptosis, especially in neural tissues. Mutations in pre-mRNAs processing factor 31 (PRPF31) cause autosomal dominant retinitis pigmentosa, a progressive retinal degeneration disease. The transcriptome-wide splicing events specifically regulated by PRPF31 and their biological roles in the development and maintenance of retina are still unclear. Here, we showed that the differentiation and viability of retinal progenitor cells (RPCs) are severely perturbed in prpf31 knockout zebrafish when compared with other tissues at an early embryonic stage...
January 21, 2021: Nucleic Acids Research
Tomohisa Iwai, Mitsuhiro Kida, Hiroshi Yamauchi, Kosuke Okuwaki, Toru Kaneko, Rikiya Hasegawa, Masafumi Watanabe, Takahiro Kurosu, Hiroshi Imaizumi, Wasaburo Koizumi
Background and Objectives: Balloon enteroscopy-assisted ERCP (BE-ERCP) has become the first-line therapy for biliopancreatic anastomotic strictures. However, it is not always successful, and salvage methods have not been established. This study aimed to evaluate the outcomes of EUS-guided transanastomotic drainage using a forward-viewing (FV) echoendoscope. Patients and Methods: Of eight cases wherein BE-ERCP treatment failed due to severe or complete benign anastomotic stricture, seven cases underwent EUS-guided choledochojejunostomy, and EUS-guided pancreaticojejunostomy was applied in one case after intubating an FV echoendoscope into the anastomotic site...
January 20, 2021: Endoscopic Ultrasound
Mingang Hao, Syn Kok Yeo, Kevin Turner, Alexis Harold, Yongguang Yang, Xiaoting Zhang, Jun-Lin Guan
Autophagy modulation is an emerging strategy for cancer therapy. By deleting an essential autophagy gene or disrupting its autophagy function, we determined a mechanism of HER2+ breast cancer tumorigenesis by directly regulating the oncogenic driver. Disruption of FIP200-mediated autophagy reduced HER2 expression on the tumor cell surface and abolished mammary tumorigenesis in MMTV-Neu mice. Decreased HER2 surface expression was due to trafficking from the Golgi to the endocytic pathways instead of the plasma membrane...
January 16, 2021: Developmental Cell
Harshini Surendran, Swapna Nandakumar, Vijay Bhaskar Reddy K, Jonathan Stoddard, Varsha Mohan K, Pramod K Upadhyay, Trevor J McGill, Rajarshi Pal
BACKGROUND: Age-related macular degeneration (AMD) is a result of degeneration/damage of the retinal pigment epithelium (RPE) while retinitis pigmentosa (RP), an inherited early-onset disease, results from premature loss of photoreceptors. A promising therapeutic approach for both is the replacement of lost/damaged cells with human induced pluripotent stem cell (hiPSC)-derived retinal cells. METHODS: The aim of this study was to investigate the in vivo functionality of RPE and photoreceptor progenitor (PRP) cells derived from a clinical-grade hiPSC line through a unified protocol...
January 19, 2021: Stem Cell Research & Therapy
Weiwei Wang, Yu Huang, Zhonghua Ji, Guo Chen, Yan Zhang, Yuanzheng Qiao, Mengya Shi, Min Li, Teng Huang, Tianchao Wei, Meilan Mo, Xiumiao He, Ping Wei
Infectious Bursal Disease Virus (IBDV) has haunted the poultry industry with severe, prolonged immunosuppression of chickens when infected at an early age and can easily lead to other secondary infections. Understanding the pathogenic mechanisms could lead to effective prevention and control of Infectious Bursal Disease (IBD). Evidence suggests that the N-terminal domain of polymerase in segment B plays an important role, but it is not clear which part or residual is crucial for the pathogenicity. Using a reverse genetics technique, a molecular clone (rNN1172) of the parental vvIBDV strain NN1172 was generated, and its pathogenicity was found to be the same as the parental virus...
January 14, 2021: Viruses
Jaeho Yoon, Jerlin Garo, Moonsup Lee, Jian Sun, Yoo-Seok Hwang, Ira O Daar
Rab11 family-interacting protein 5 (Rab11fip5) is an adaptor protein that binds to the small GTPase Rab11, which has an important function in endosome recycling and trafficking of cellular proteins to the plasma membrane. Rab11fip5 is involved in many cellular processes, such as cytoskeleton rearrangement, iron uptake, and exocytosis in neuroendocrine cells and also known as a candidate gene for autism-spectrum disorder. However, the role of Rab11fip5 during early embryonic development is not clearly understood...
January 18, 2021: Development
Jian Song, Nan Jiang, Xueqi Gan, Wei Zhi, Zhuoli Zhu
AIMS: Coagulation is a common event that play a double-edged role in physiological and pathological process. Anti-coagulation methods were applied in joint surgery or scaffolds implantation to encourage new vascular formation and avoid coagulation block. However, whether anti-coagulation drug perform regulatory roles in regulating bone structure is unknown. This study aims to explore a direct thrombin inhibitor, argatroban, effects on bone marrow stromal cells (BMSCs) and decipher the underlying mechanisms...
January 15, 2021: Life Sciences
Hitoshi Ishii, Brian B Hansen, Jakob Langer, Hiroshi Horio
INTRODUCTION: In the randomized Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) 10 trial, once-daily orally administered semaglutide-the first oral glucagon-like peptide 1 receptor agonist (GLP-1RA)-was similarly tolerated with comparable (at 7 mg) or better (at 14 mg) efficacy versus the injectable GLP-1RA dulaglutide 0.75 mg. Health-related quality of life (HRQoL) in PIONEER 10 was assessed using the Japanese-specific Diabetes Therapy-Related Quality of Life (DTR-QoL) questionnaire...
January 18, 2021: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Shuxian Lu, Zhaojie Lyu, Zhihao Wang, Yao Kou, Cong Liu, Shengyue Li, Mengyan Hu, Hongjie Zhu, Wenxing Wang, Ce Zhang, Yung-Shu Kuan, Yi-Wen Liu, Jianming Chen, Jing Tian
Lipin 1 is an intracellular protein acting as a phosphatidic acid phosphohydrolase enzyme controlling lipid metabolism. Human recessive mutations in LPIN1 cause recurrent, early-onset myoglobinuria, a condition normally associated with muscle pain and weakness. Whether and how lipin 1 deficiency in humans leads to peripheral neuropathy is yet unclear. Herein, two novel compound heterozygous mutations in LPIN1 with neurological disorders, but no myoglobinuria were identified in an adult-onset syndromic myasthenia family...
2021: Theranostics
N Lipták, Z Gál, B Biró, L Hiripi, O I Hoffmann
Approximately 35 % of the mouse genes are indispensable for life, thus, global knock-out (KO) of those genes may result in embryonic or early postnatal lethality due to developmental abnormalities. Several KO mouse lines are valuable human disease models, but viable homozygous mutant mice are frequently required to mirror most symptoms of a human disease. The site-specific gene editing systems, the transcription activator-like effector nucleases (TALENs), Zinc-finger nucleases (ZFNs) and the clustered regularly interspaced short palindrome repeat-associated Cas9 nuclease (CRISPR/Cas9) made the generation of KO mice more efficient than before, but the homozygous lethality is still an undesired side-effect in case of many genes...
January 14, 2021: Physiological Research
Fumiaki Nasu, Yutaro Obara, Yosuke Okamoto, Hiroaki Yamaguchi, Kazuya Kurakami, Ikuo Norota, Kuniaki Ishii
AIMS: Azelnidipine, a third-generation dihydropyridine calcium channel blocker (DHP CCB), has a characteristic hypotensive effect that persists even after it has disappeared from the plasma, which is thought to be due to its high hydrophobicity. However, because azelnidipine is unique, it might have other unknown effects on L-type Cav 1.2 channels that result in the long-lasting decrease of blood pressure. The aim of this study was to investigate the potential quantitative modification of Cav 1...
January 13, 2021: Life Sciences
Yuan-Hung Lo, Kevin S Kolahi, Yuhong Du, Chiung-Ying Chang, Andrey Krokhotin, Ajay Nair, Walter D Sobba, Kasper Karlsson, Sunny J Jones, Teri A Longacre, Amanda T Mah, Bahar Tercan, Alexandra Sockell, Hang Xu, Jose A Seoane, Jin Chen, Ilya Shmulevich, Jonathan S Weissman, Christina Curtis, Andrea Califano, Haian Fu, Gerald R Crabtree, Calvin J Kuo
Mutations in ARID1A rank amongst the most common molecular aberrations in human cancer. However, oncogenic consequences of ARID1A mutation in human cells remain poorly defined due to lack of forward genetic models. Here, CRISPR/Cas9-mediated ARID1A knockout in primary TP53-/- human gastric organoids induced morphologic dysplasia, tumorigenicity and mucinous differentiation. Genetic Wnt/B-catenin activation rescued mucinous differentiation, but not hyperproliferation, suggesting alternative pathways of ARID1A KO-mediated transformation...
January 15, 2021: Cancer Discovery
Nancy J Newman, Patrick Yu-Wai-Man, Valerio Carelli, Mark L Moster, Valerie Biousse, Catherine Vignal-Clermont, Robert C Sergott, Thomas Klopstock, Alfredo A Sadun, Piero Barboni, Adam A DeBusk, Jean François Girmens, Günther Rudolph, Rustum Karanjia, Magali Taiel, Laure Blouin, Gerard Smits, Barrett Katz, José-Alain Sahel
PURPOSE: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). DESIGN: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial. PARTICIPANTS: Subjects with the m.11778G>A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included. METHODS: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 1010 viral genomes in 90 μl) or to sham injection...
January 12, 2021: Ophthalmology
Chunhui Xu, Yun Shen, Cuiling Li, Fan Lu, Meng-Di Zhang, Robert B Meeley, Donald R McCarty, Bao-Cai Tan
Ribosome assembly factors guide the complex process by which ribosomal proteins and the ribosomal RNAs form a functional ribosome. However, the assembly of plant plastid ribosomes is poorly understood. In the present study, we discovered a maize (Zea mays) plastid ribosome assembly factor based on our characterization of the embryo defective 15 (emb15) mutant. Loss of function of Emb15 retards embryo development at an early stage, but does not substantially affect the endosperm, and causes an albino phenotype in other genetic backgrounds...
January 15, 2021: Plant Journal
Jennifer Horwitz, Annie Huang, David McAuley, Gerard H Jansen, Donna Johnston
Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2...
January 11, 2021: Journal of Pediatric Hematology/oncology
Polly Soo Xi Yap, Chun Wie Chong, Azanna Ahmad Kamar, Ivan Kok Seng Yap, Yao Mun Choo, Nai Ming Lai, Cindy Shuan Ju Teh
Emerging evidence has shown a link between the perturbations and development of the gut microbiota in infants with their immediate and long-term health. To better understand the assembly of the gut microbiota in preterm infants, faecal samples were longitudinally collected from the preterm (n = 19) and term (n = 20) infants from birth until month 12. 16S rRNA gene sequencing (n = 141) and metabolomics profiling (n = 141) using nuclear magnetic resonance spectroscopy identified significant differences between groups in various time points...
January 14, 2021: Scientific Reports
Alison F Feder, Pleuni S Pennings, Dmitri A Petrov
HIV can evolve remarkably quickly in response to antiretroviral therapies and the immune system. This evolution stymies treatment effectiveness and prevents the development of an HIV vaccine. Consequently, there has been a great interest in using population genetics to disentangle the forces that govern the HIV adaptive landscape (selection, drift, mutation, and recombination). Traditional population genetics approaches look at the current state of genetic variation and infer the processes that can generate it...
January 2021: PLoS Genetics
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