SPTAN1 Encephalopathy: Distinct Phenotypes and Genotypes
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Human Periprostatic Adipose Tissue: Secretome from Patients With
CANCER GENOMICS & PROTEOMICS 16 : 29-58 (2019) doi:10.21873/cgp.20110 Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia PAULA ALEJANDRA SACCA 1, OSVALDO NÉSTOR MAZZA 2, CARLOS SCORTICATI 2, GONZALO VITAGLIANO 3, GABRIEL CASAS 4 and JUAN CARLOS CALVO 1,5 1Institute of Biology and Experimental Medicine (IBYME), CONICET, Buenos Aires, Argentina; 2Department of Urology, School of Medicine, University of Buenos Aires, Clínical Hospital “José de San Martín”, Buenos Aires, Argentina; 3Department of Urology, Deutsches Hospital, Buenos Aires, Argentina; 4Department of Pathology, Deutsches Hospital, Buenos Aires, Argentina; 5Department of Biological Chemistry, School of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina Abstract. Background/Aim: Periprostatic adipose tissue Prostate cancer (PCa) is the second most common cancer in (PPAT) directs tumour behaviour. Microenvironment secretome men worldwide. While most men have indolent disease, provides information related to its biology. This study was which can be treated properly, the problem consists in performed to identify secreted proteins by PPAT, from both reliably distinguishing between indolent and aggressive prostate cancer and benign prostate hyperplasia (BPH) disease. Evidence shows that the microenvironment affects patients. Patients and Methods: Liquid chromatography-mass tumour behavior. spectrometry-based proteomic analysis was performed in Adipose tissue microenvironment is now known to direct PPAT-conditioned media (CM) from patients with prostate tumour growth, invasion and metastases (1, 2). Adipose cancer (CMs-T) (stage T3: CM-T3, stage T2: CM-T2) or tissue is adjacent to the prostate gland and the site of benign disease (CM-BPH). Results: The highest number and invasion of PCa. -
Original Article Plasma CAMK2A Predicts Chemotherapy Resistance in Metastatic Triple Negative Breast Cancer
Int J Clin Exp Pathol 2018;11(2):650-663 www.ijcep.com /ISSN:1936-2625/IJCEP0069558 Original Article Plasma CAMK2A predicts chemotherapy resistance in metastatic triple negative breast cancer Bin Shao1*, Zhihua Tian2*, Huirong Ding2*, Qingsong Wang3, Guohong Song1, Lijun Di1, Hong Zhang2, Huiping Li1, Jing Shen2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 1Department of Medical Oncology, 2Central Laboratory, Peking University Cancer Hospital & Institute, Beijing, P. R. China; 3State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, P. R. China. *Equal contributors. Received November 21, 2017; Accepted December 15, 2017; Epub February 1, 2018; Published February 15, 2018 Abstract: Background: Chemotherapy resistance is a great obstacle in effective treatment for metastatic triple nega- tive breast cancer (TNBC). The ability to predict chemotherapy response would allow chemotherapy administration to be directed toward only those patients who would benefit, thus maximizing treatment efficiency. Differentially expressed plasma proteins may serve as putative biomarkers for predicting chemotherapy outcomes. Patients and methods: In this study, 26 plasma samples (10 samples with partial response (S) and 16 samples with progression disease (R)) from patients with metastatic TNBC were measured by Tandem Mass Tag (TMT)-based proteomics analysis to identify differentially expressed proteins between the S and R group. Potential proteinswere validated with enzyme-linked immunosorbent assay (ELISA) in another 67 plasma samples. Results: A total of 320 plasma proteins were identified, and statistical analysis showed that 108 proteins were significantly dysregulated between R and S groups in the screening stage. Bioinformatics revealed relevant pathways and regulatory networks of the differentially expressed proteins. -
KIF1A-Related Autosomal Dominant Spastic Paraplegias (SPG30) in Russian Families G
Rudenskaya et al. BMC Neurology (2020) 20:290 https://doi.org/10.1186/s12883-020-01872-4 RESEARCH ARTICLE Open Access KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families G. E. Rudenskaya1 , V. A. Kadnikova1* , O. P. Ryzhkova1 , L. A. Bessonova1, E. L. Dadali1 , D. S. Guseva1 , T. V. Markova1 , D. N. Khmelkova2 and A. V. Polyakov1 Abstract Background: Spastic paraplegia type 30 (SPG30) caused by KIF1A mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population. Methods: Clinical, genealogical and molecular methods were used. Molecular methods included massive parallel sequencing (MPS) of custom panel ‘spastic paraplegias’ with 62 target genes complemented by familial Sanger sequencing. One case was detected by the whole -exome sequencing. Results: AD SPG30 was detected in 10 unrelated families, making it the 3rd (8.4%) most common SPG form in the cohort of 118 families. No AR SPG30 cases were detected. In total, 9 heterozygous KIF1A mutations were detected, with 4 novel and 5 known mutations. All the mutations were located within KIF1A motor domain. Six cases had pure phenotypes, of which 5 were familial, where 2 familial cases demonstrated incomplete penetrance, early onset and slow relatively benign SPG course. -
Intrinsic Indicators for Specimen Degradation
Laboratory Investigation (2013) 93, 242–253 & 2013 USCAP, Inc All rights reserved 0023-6837/13 $32.00 Intrinsic indicators for specimen degradation Jie Li1, Catherine Kil1, Kelly Considine1, Bartosz Smarkucki1, Michael C Stankewich1, Brian Balgley2 and Alexander O Vortmeyer1 Variable degrees of molecular degradation occur in human surgical specimens before clinical examination and severely affect analytical results. We therefore initiated an investigation to identify protein markers for tissue degradation assessment. We exposed 4 cell lines and 64 surgical/autopsy specimens to defined periods of time at room temperature before procurement (experimental cold ischemic time (CIT)-dependent tissue degradation model). Using two-dimen- sional fluorescence difference gel electrophoresis in conjunction with mass spectrometry, we performed comparative proteomic analyses on cells at different CIT exposures and identified proteins with CIT-dependent changes. The results were validated by testing clinical specimens with western blot analysis. We identified 26 proteins that underwent dynamic changes (characterized by continuous quantitative changes, isoelectric changes, and/or proteolytic cleavages) in our degradation model. These changes are strongly associated with the length of CIT. We demonstrate these proteins to represent universal tissue degradation indicators (TDIs) in clinical specimens. We also devised and implemented a unique degradation measure by calculating the quantitative ratio between TDIs’ intact forms and their respective degradation- -
2020.07.27.20162974V1.Full.Pdf
medRxiv preprint doi: https://doi.org/10.1101/2020.07.27.20162974; this version posted July 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. 1 Title: Genotype and defects in microtubule-based motility correlate with clinical severity in 2 KIF1A Associated Neurological Disorder 3 Authors: Lia Boyle,1 Lu Rao,2 Simranpreet Kaur,3 Xiao Fan,1,4 Caroline Mebane,1 Laura 4 Hamm,5 Andrew Thornton,6 Jared T Ahrendsen,7 Matthew P Anderson,7,8 John Christodoulou,3 5 Arne Gennerich,2 Yufeng Shen,4,9 Wendy K Chung1,10 6 7 Abstract: KIF1A Associated Neurological Disorder (KAND) encompasses a recently identified 8 group of rare neurodegenerative conditions caused by variants in KIF1A, a member of the 9 kinesin-3 family of microtubule (MT) motor proteins. Here we characterize the natural history of 10 KAND in 117 individuals using a combination of caregiver or self-reported medical history, a 11 standardized measure of adaptive behavior, clinical records, and neuropathology. We developed 12 a heuristic severity score using a weighted sum of common symptoms to assess disease severity. 13 Focusing on 100 individuals, we compared the average clinical severity score for each variant 14 with in silico predictions of deleteriousness and location in the protein. We found increased 15 severity is strongly associated with variants occurring in regions involved with ATP and MT- 16 binding: the P-loop, switch I, and switch II. -
Mackenzie's Mission Gene & Condition List
Mackenzie’s Mission Gene & Condition List What conditions are being screened for in Mackenzie’s Mission? Genetic carrier screening offered through this research study has been carefully developed. It is focused on providing people with information about their chance of having children with a severe genetic condition occurring in childhood. The screening is designed to provide genetic information that is relevant and useful, and to minimise uncertain and unclear information. How the conditions and genes are selected The Mackenzie’s Mission reproductive genetic carrier screen currently includes approximately 1300 genes which are associated with about 750 conditions. The reason there are fewer conditions than genes is that some genetic conditions can be caused by changes in more than one gene. The gene list is reviewed regularly. To select the conditions and genes to be screened, a committee comprised of experts in genetics and screening was established including: clinical geneticists, genetic scientists, a genetic pathologist, genetic counsellors, an ethicist and a parent of a child with a genetic condition. The following criteria were developed and are used to select the genes to be included: • Screening the gene is technically possible using currently available technology • The gene is known to cause a genetic condition • The condition affects people in childhood • The condition has a serious impact on a person’s quality of life and/or is life-limiting o For many of the conditions there is no treatment or the treatment is very burdensome for the child and their family. For some conditions very early diagnosis and treatment can make a difference for the child. -
IDENTIFICATION and CHARACTERIZATION of ACTIN-REGULATORY PROTEINS in the HAIR CELL's CUTICULAR PLATE by LANA MARY POLLOCK Subm
IDENTIFICATION AND CHARACTERIZATION OF ACTIN-REGULATORY PROTEINS IN THE HAIR CELL’S CUTICULAR PLATE by LANA MARY POLLOCK Submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy Dissertation advisor: Brian M. McDermott Jr., Ph.D. Department of Genetics and Genome Sciences CASE WESTERN RESERVE UNIVERSITY January 2016 Case Western Reserve University School of Graduate Studies We, the thesis committee, hereby approve the thesis/dissertation of Lana Pollock, candidate for the degree of Doctor of Philosophy (PhD).* (signed)_________Zhenghe Wang, Ph.D._________________ (chair of committee) ___________Brian McDermott, Ph.D._______________ ___________ Hua Lou, Ph.D._____________________ ___________Stephen Maricich, Ph.D., M.D.___________ ___________Anthony Wynshaw-Boris, Ph.D., M.D._____ Date of defense_____September 8th, 2015_______________ *we also certify that written approval has been obtained for release of any proprietary material contained therein 2 This thesis is dedicated to Daniel Margevicius. Thank you for your unwavering love and support. Ačiū!! 3 Table of contents List of Tables ........................................................................................................ 7 List of Figures ....................................................................................................... 8 List of abbreviations ............................................................................................ 13 Abstract ............................................................................................................. -
Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in -
Cytoskeletal Remodeling in Cancer
biology Review Cytoskeletal Remodeling in Cancer Jaya Aseervatham Department of Ophthalmology, University of Texas Health Science Center at Houston, Houston, TX 77054, USA; [email protected]; Tel.: +146-9767-0166 Received: 15 October 2020; Accepted: 4 November 2020; Published: 7 November 2020 Simple Summary: Cell migration is an essential process from embryogenesis to cell death. This is tightly regulated by numerous proteins that help in proper functioning of the cell. In diseases like cancer, this process is deregulated and helps in the dissemination of tumor cells from the primary site to secondary sites initiating the process of metastasis. For metastasis to be efficient, cytoskeletal components like actin, myosin, and intermediate filaments and their associated proteins should co-ordinate in an orderly fashion leading to the formation of many cellular protrusions-like lamellipodia and filopodia and invadopodia. Knowledge of this process is the key to control metastasis of cancer cells that leads to death in 90% of the patients. The focus of this review is giving an overall understanding of these process, concentrating on the changes in protein association and regulation and how the tumor cells use it to their advantage. Since the expression of cytoskeletal proteins can be directly related to the degree of malignancy, knowledge about these proteins will provide powerful tools to improve both cancer prognosis and treatment. Abstract: Successful metastasis depends on cell invasion, migration, host immune escape, extravasation, and angiogenesis. The process of cell invasion and migration relies on the dynamic changes taking place in the cytoskeletal components; actin, tubulin and intermediate filaments. This is possible due to the plasticity of the cytoskeleton and coordinated action of all the three, is crucial for the process of metastasis from the primary site. -
Inhibition of the MID1 Protein Complex
Matthes et al. Cell Death Discovery (2018) 4:4 DOI 10.1038/s41420-017-0003-8 Cell Death Discovery ARTICLE Open Access Inhibition of the MID1 protein complex: a novel approach targeting APP protein synthesis Frank Matthes1,MoritzM.Hettich1, Judith Schilling1, Diana Flores-Dominguez1, Nelli Blank1, Thomas Wiglenda2, Alexander Buntru2,HannaWolf1, Stephanie Weber1,InaVorberg 1, Alina Dagane2, Gunnar Dittmar2,3,ErichWanker2, Dan Ehninger1 and Sybille Krauss1 Abstract Alzheimer’s disease (AD) is characterized by two neuropathological hallmarks: senile plaques, which are composed of amyloid-β (Aβ) peptides, and neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. Aβ peptides are derived from sequential proteolytic cleavage of the amyloid precursor protein (APP). In this study, we identified a so far unknown mode of regulation of APP protein synthesis involving the MID1 protein complex: MID1 binds to and regulates the translation of APP mRNA. The underlying mode of action of MID1 involves the mTOR pathway. Thus, inhibition of the MID1 complex reduces the APP protein level in cultures of primary neurons. Based on this, we used one compound that we discovered previously to interfere with the MID1 complex, metformin, for in vivo experiments. Indeed, long-term treatment with metformin decreased APP protein expression levels and consequently Aβ in an AD mouse model. Importantly, we have initiated the metformin treatment late in life, at a time-point where mice were in an already progressed state of the disease, and could observe an improved behavioral phenotype. These 1234567890 1234567890 findings together with our previous observation, showing that inhibition of the MID1 complex by metformin also decreases tau phosphorylation, make the MID1 complex a particularly interesting drug target for treating AD. -
SCIENCE CHINA Spectrin: Structure, Function and Disease
SCIENCE CHINA Life Sciences • REVIEW • December 2013 Vol.56 No.12: 1076–1085 doi: 10.1007/s11427-013-4575-0 Spectrin: Structure, function and disease ZHANG Rui1, ZHANG ChenYu1, ZHAO Qi2 & LI DongHai1* 1Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China; 2Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China Received November 21, 2012; accepted March 20, 2013 Spectrin is a large, cytoskeletal, and heterodimeric protein composed of modular structure of and subunits, it typically contains 106 contiguous amino acid sequence motifs called “spectrin repeats”. Spectrin is crucial for maintaining the stability and structure of the cell membrane and the shape of a cell. Moreover, it contributes to diverse cell functions such as cell adhe- sion, cell spreading, and the cell cycle. Mutations of spectrin lead to various human diseases such as hereditary hemolytic anemia, type 5 spinocerebellar ataxia, cancer, as well as others. This review focuses on recent advances in determining the structure and function of spectrin as well as its role in disease. erythrocyte, spectrin, cell cycle, mass spectrometry, disease Citation: Zhang R, Zhang C Y, Zhao Q, et al. Spectrin: Structure, function and disease. Sci China Life Sci, 2013, 56: 1076–1085, doi: 10.1007/s11427-013-4575-0 Spectrin is a cytoskeletal protein that was first discovered in subunits are encoded by SPTA1 and SPTAN1, respectively. erythrocytes and is important for maintaining the stability, SPTA1 is expressed in erythroid cells. In contrast to SPTA1, structure, and shape of the cell membrane. -
Prediction and Verification of the AD-FTLD Common Pathomechanism Based on Dynamic Molecular Network Analysis
ARTICLE https://doi.org/10.1038/s42003-021-02475-6 OPEN Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis ✉ Meihua Jin1,6, Xiaocen Jin1,6, Hidenori Homma1,6 , Kyota Fujita1, Hikari Tanaka1, Shigeo Murayama2,3, ✉ Hiroyasu Akatsu4, Kazuhiko Tagawa1 & Hitoshi Okazawa1,5 Multiple gene mutations cause familial frontotemporal lobar degeneration (FTLD) while no single gene mutations exists in sporadic FTLD. Various proteins aggregate in variable regions of the brain, leading to multiple pathological and clinical prototypes. The heterogeneity of 1234567890():,; FTLD could be one of the reasons preventing development of disease-modifying therapy. We newly develop a mathematical method to analyze chronological changes of PPI networks with sequential big data from comprehensive phosphoproteome of four FTLD knock-in (KI) mouse models (PGRNR504X-KI, TDP43N267S-KI, VCPT262A-KI and CHMP2BQ165X-KI mice) together with four transgenic mouse models of Alzheimer’s disease (AD) and with APPKM670/671NL-KI mice at multiple time points. The new method reveals the common core pathological network across FTLD and AD, which is shared by mouse models and human postmortem brains. Based on the prediction, we performed therapeutic intervention of the FTLD models, and confirmed amelioration of pathologies and symptoms of four FTLD mouse models by inter- ruption of the core molecule HMGB1, verifying the new mathematical method to predict dynamic molecular networks. 1 Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. 2 Department of Neuropathology, Brain Bank for Aging Research, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan. 3 Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan.