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Jenna-Lynn B Senger, Valerie M K Verge, K Ming Chan, Christine A Webber
By altering the intrinsic metabolism of the cell, including the upregulation of regeneration-associated genes (RAGs) and the production of structural proteins for axonal outgrowth, the conditioning lesion sets up an environment highly conducive to regeneration. In this review, we assess forty years of research to provide a comprehensive overview of the conditioning lesion literature, directed at: a) discussing the mechanisms of, and barriers to nerve regeneration that can be mitigated by the conditioning lesion; b) describing the cellular and molecular pathways implicated in the conditioning lesion effect; and c) deliberating on how these insights might be applied clinically...
March 14, 2018: Annals of Neurology
Gunnar Poplawski, Tetsuhiro Ishikawa, Coralie Brifault, Corinne Lee-Kubli, Robert Regestam, Kenneth W Henry, Yasuhiro Shiga, HyoJun Kwon, Seiji Ohtori, Steven L Gonias, Wendy M Campana
Sensory neurons in the PNS demonstrate substantial capacity for regeneration following injury. Recent studies have identified changes in the transcriptome of sensory neurons, which are instrumental for axon regeneration. The role of Schwann cells (SCs) in mediating these changes remains undefined. We tested the hypothesis that SCs regulate expression of genes in sensory neurons before and after PNS injury by comparing mice in which LDL Receptor-related Protein-1 (LRP1) is deleted in SCs (scLRP1-/- mice) with wild-type (scLRP1+/+ ) littermates...
March 9, 2018: Glia
Elisa Rubino, Ming Zhang, Tiziana Mongini, Silvia Boschi, Liliana Vercelli, Alessandro Vacca, Flora Govone, Annalisa Gai, Maria Teresa Giordana, Mark Grinberg, Ekaterina Rogaeva, Innocenzo Rainero
Mutations in CHCHD2 and CHCHD10 were recently reported in a broad spectrum of neurodegenerative diseases, for example, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, or mitochondrial myopathy (MM). The aim of the study was to evaluate the prevalence of CHCHD2 and CHCHD10 mutations in Italian MM patients without mitochondrial DNA mutations. The coding regions of CHCHD2 and CHCHD10 were sequenced in 62 MM patients. None of the patients showed CHCHD2 mutations, whereas 1 sporadic MM patient carried a homozygous Pro96Thr substitution in CHCHD10...
February 14, 2018: Neurobiology of Aging
Ziyang Jing, Hui Deng, Junfan Ma, Yanhong Guo, Yaoxian Liang, Rui Wu, Lata A, Zihan Geng, Xiaoyan Qiu, Yue Wang
Podocyte injury occurs during the initiation and development of numerous forms of glomerular disease, and antibodies targeting podocytes have become a biomarker for diagnosis and monitoring treatment response. Accumulating evidence has suggested that immunoglobulin (Ig) is expressed in non‑B lineage cells, including epithelial cancer cells, myeloid cells and several types of normal cells. The main aim of the present study was to ascertain the expression of IgG in human podocytes and to determine its potential role in cellular bioactivity...
March 1, 2018: International Journal of Molecular Medicine
Cynthia L Hsu, Elian X Lee, Kara L Gordon, Edwin A Paz, Wen-Chuan Shen, Kohta Ohnishi, Jill Meisenhelder, Tony Hunter, Albert R La Spada
Autophagy is the major cellular pathway by which macromolecules are degraded, and amino acid depletion powerfully activates autophagy. MAP4K3, or germinal-center kinase-like kinase, is required for robust cell growth in response to amino acids, but the basis for MAP4K3 regulation of cellular metabolic disposition remains unknown. Here we identify MAP4K3 as an amino acid-dependent regulator of autophagy through its phosphorylation of transcription factor EB (TFEB), a transcriptional activator of autophagy, and through amino acid starvation-dependent lysosomal localization of MAP4K3...
March 5, 2018: Nature Communications
Takahiro Hatayama, Ryosuke Segawa, Natsumi Mizuno, Sumiko Eguchi, Hiroshi Akamatsu, Misaki Fukuda, Fumihisa Nakata, Warren J Leonard, Masahiro Hiratsuka, Noriyasu Hirasawa
Many classical vaccines contain whole pathogens and, thus, may occasionally induce adverse effects, such as inflammation. Vaccines containing purified rAgs resolved this problem, but, owing to their low antigenicity, they require adjuvants. Recently, the use of several cytokines, including thymic stromal lymphopoietin (TSLP), has been proposed for this purpose. However, it is difficult to use cytokines as vaccine adjuvants in clinical practice. In this study, we examined the effects of all- trans retinoic acid (atRA) on TSLP production and Ag-induced Ab production...
March 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Kazuyoshi Takeda, Katashi Nagamatsu, Ko Okumura
ETHNOPHARMACOLOGICAL RELEVANCE: Propolis, a resinous material collected from numerous plants by honeybees, has historically been used as a health-promoting food. Recently, due to its potential anti-tumor effects, use of propolis has been proposed as an adjuvant therapy to chemotherapy; however, the effects of propolis on immune responses remain unclear. AIM OF THE STUDY: In this study, we examined the effects of the oral ingestion of propolis on natural killer (NK) cell activity, which is important in immune surveillance against cancer and viral infections...
February 26, 2018: Journal of Ethnopharmacology
Blerta Green, Alberto Martin, Antoaneta Belcheva
C-Myc overexpression mediates lymphomagenesis, however, secondary genetic lesions are required for its full oncogenic potential. The origin and the mechanism of formation of these mutations are unclear. Using the lacI-mutation detection system, we show that secondary mutations occur early in B-cell development and are repaired by Msh2. The mutations at the lacI gene were predominantly at C:G base pairs and CpG motifs suggesting that they were formed due to cytosine deamination or oxidative damage of G. Hence, we investigated the role of Ogg1 and UNG glycosylases in c-Myc driven lymphomagenesis but found that their deficiencies did not influence the disease outcome in the Eµ c-Myc mouse model...
February 26, 2018: Experimental Hematology
Chuanjian Lu, Huazhen Liu, Xiaowei Jin, Yuchao Chen, Chun-Ling Liang, Feifei Qiu, Zhenhua Dai
A recipient usually rejects a transplanted organ and thus needs immunosuppressive treatments to prevent rejection. Achieving long-term allograft survival without continuous global immunosuppression is highly desirable in transplantation as long-term immunosuppression causes various side effects. Therefore, it is necessary to search for medicine with potentially less side effects. Traditional Chinese medicine PSORI-CM01 (Yin Xie Ling), a formula with seven natural herbs, has been used to treat patients with psoriasis...
2018: Frontiers in Pharmacology
Yoon Sang Jeon, Rag Gyu Kim, Sang-Jin Shin
No abstract text is available yet for this article.
February 23, 2018: Clinical Orthopaedics and related Research
Dylan Lawless, Christoph B Geier, Jocelyn R Farmer, Hana Allen Lango, Daniel Thwaites, Faranaz Atschekzei, Matthew Brown, David Buchbinder, Siobhan O Burns, Manish J Butte, Krisztian Csomos, Sri V V Deevi, William Egner, Stephan Ehl, Martha M Eibl, Olajumoke Fadugba, Zsofia Foldvari, Deanna M Green, Sarah E Henrickson, Steven M Holland, Tami John, Christian Klemann, Taco W Kuijpers, Fernando Moreira, Alexander Piller, Paula Rayner-Matthews, Neil D Romberg, Ravishankar Sargur, Reinhold E Schmidt, Claudia Schröder, Catharina Schuetz, Svetlana O Sharapova, Ken G C Smith, Georgios Sogkas, Carsten Speckmann, Kathleen Stirrups, Adrian J Thrasher, Hermann M Wolf, Luigi D Notarangelo, Rashida Anwar, Joan Boyes, Boglarka Ujhazi, James Thaventhiran, Jolan E Walter, Sinisa Savic
No abstract text is available yet for this article.
February 22, 2018: Journal of Allergy and Clinical Immunology
Philip Foerstner, Rida Rehman, Sofia Anastasiadou, Melanie Haffner-Luntzer, Daniela Sinske, Anita Ignatius, Francesco Roselli, Bernd Knoell
Traumatic brain injury (TBI) induces a neuroinflammatory response resulting in astrocyte and microglia activation at the lesion site. This involves up-regulation of neuroinflammatory genes including chemokines and interleukins. However, so far there is lack of knowledge on transcription factors (TFs) modulating this TBI associated gene expression response. Herein we analyzed activating transcription factor 3 (ATF3), a TF encoding a regeneration-associated gene (RAG) predominantly studied in peripheral nervous system (PNS) injury...
February 20, 2018: Journal of Neurotrauma
Josef Finsterer, Sinda Zarrouk-Mahjoub, John M Shoffner
BACKGROUND: Given the etiologic heterogeneity of disease classification using clinical phenomenology, we employed contemporary criteria to classify variants associated with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome and to assess the strength of evidence of gene-disease associations. Standardized approaches are used to clarify the definition of MERRF, which is essential for patient diagnosis, patient classification, and clinical trial design. METHODS: Systematic literature and database search with application of standardized assessment of gene-disease relationships using modified Smith criteria and of variants reported to be associated with MERRF using modified Yarham criteria...
December 13, 2017: Pediatric Neurology
Dorothy Ng, Thomas Chan, Sohil Pothiawala
BACKGROUND: Human bites involving the genitalia rarely present to the emergency department (ED). They have the potential to cause life-threatening secondary infections as well as serious physical and functional damage. CASE REPORT: We report a case of an adult male who sustained a human bite to the scrotum, resulting in a ragged laceration on the anterior scrotum, with a devascularized flap and necrotic edges overlying the wound. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Human bites to the scrotum are rare and, hence, the experience of emergency physicians treating patients presenting with these injuries may be minimal...
February 10, 2018: Journal of Emergency Medicine
Vera Goda, Aniko Malik, Tibor Kalmar, Zoltan Maroti, Bhumika Patel, Boglarka Ujhaz, Krisztian Csomos, Jaime E Hale, Karin Chen, Jacob Bleesing, Paolo Palma, Caterina Cancrini, Anne M Comeau, Gergely Krivan, Jolan E Walter
No abstract text is available yet for this article.
February 1, 2018: Journal of Allergy and Clinical Immunology in Practice
Che-Min Lo, Yi-Shing Ma, Yau-Huei Wei, Benjamin Y T Hsieh, Mingli Hsieh
Myoclonic epilepsy with ragged-red fibers (MERRF) is a maternally inherited mitochondrial neuromuscular disease. We previously reported a significant decrease of mRNA and protein levels of nuclear DNA-encoded carbonic anhydrase VIII (CA8) in MERRF cybrids harboring A8344G mutation in mitochondrial DNA (mtDNA). In this study, we established a reporter construct of luciferase gene-carrying hCA8 promoter containing several putative transcription factor-binding sites, including GC-box, AP-2 and TATA-binding element in the 5'flanking region of the hCA8 gene...
January 31, 2018: Archives of Biochemistry and Biophysics
Mafalda Bacalhau, Marta Simões, Mariana C Rocha, Steven A Hardy, Amy E Vincent, João Durães, Maria C Macário, Maria João Santos, Olinda Rebelo, Carla Lopes, João Pratas, Cândida Mendes, Mónica Zuzarte, A Cristina Rego, Henrique Girão, Lee-Jun C Wong, Robert W Taylor, Manuela Grazina
Chronic Progressive External Ophthalmoplegia (CPEO) is characterized by ptosis and ophthalmoplegia and is usually caused by mitochondrial DNA (mtDNA) deletions or mt-tRNA mutations. The aim of the present work was to clarify the genetic defect in a patient presenting with CPEO and elucidate the underlying pathogenic mechanism. This 62-year-old female first developed ptosis of the right eye at the age of 12 and subsequently the left eye at 45 years, and was found to have external ophthalmoplegia at the age of 55 years...
November 23, 2017: Neuromuscular Disorders: NMD
Julia Keating, Malcolm Barnett, Vanessa Watkins, Stella May Gwini
BACKGROUND: The association between an incomplete placenta and postpartum haemorrhage (PPH) is well documented; however, the significance of ragged or incomplete membranes has not been explored as an independent risk factor for PPH. AIMS: To explore the association between the completeness of the amniotic and chorionic membranes and the risk of PPH, independent to placental status. MATERIALS AND METHODS: 37 176 birth records were retrospectively extracted from the period 1 July, 2008 to 30 June, 2016 from the databases of two public hospitals in Melbourne, Australia...
January 30, 2018: Australian & New Zealand Journal of Obstetrics & Gynaecology
Fernanda O Novais, Andrea C Wong, Daniel O Villareal, Daniel P Beiting, Phillip Scott
Resolution of leishmaniasis depends upon parasite control and limiting inflammation. CD4+ Th1 cells are required to control parasites, whereas CD8+ T cells play a dual role: they promote Th1 cell differentiation but can also increase inflammation at the site of infection as a consequence of cytolysis. Although CD8+ T cells taken from leishmanial lesions are cytolytic, in this study, we showed that only a few CD8+ T cells produced IFN-γ. Correspondingly, only low levels of IL-12 and/or IL-12 mRNA were present in lesions from infected mice, as well as patients...
January 24, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Marina Bartsakoulia, Angela Pyle, Diego Troncosco, Josefa Vial, Marysol V Paz-Fiblas, Jennifer Duff, Helen Griffin, Veronika Boczonadi, Hanns Lochmüller, Stephanie Kleinle, Patrick F Chinnery, Sarah Grünert, Janbernd Kirschner, Veronica Eisner, Rita Horvath
Mitochondrial dynamics play an important role in cellular homeostasis and a variety of human diseases are linked to its dysregulated function. Here we describe a 15-year-old boy with a novel disease caused by altered mitochondrial dynamics. The patient was the second child of consanguineous Jewish parents. He developed progressive muscle weakness and exercise intolerance at 6 years of age. His muscle biopsy revealed mitochondrial myopathy with numerous ragged red and cytochrome c oxidase (COX) negative fibers and combined respiratory chain complex I and IV deficiency...
January 19, 2018: Human Molecular Genetics
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