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https://www.readbyqxmd.com/read/27912057/gut-microbiota-regulate-motor-deficits-and-neuroinflammation-in-a-model-of-parkinson-s-disease
#1
Timothy R Sampson, Justine W Debelius, Taren Thron, Stefan Janssen, Gauri G Shastri, Zehra Esra Ilhan, Collin Challis, Catherine E Schretter, Sandra Rocha, Viviana Gradinaru, Marie-Francoise Chesselet, Ali Keshavarzian, Kathleen M Shannon, Rosa Krajmalnik-Brown, Pernilla Wittung-Stafshede, Rob Knight, Sarkis K Mazmanian
The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911843/impact-of-the-gut-microbiota-on-enhancer-accessibility-in-gut-intraepithelial-lymphocytes
#2
Nicholas P Semenkovich, Joseph D Planer, Philip P Ahern, Nicholas W Griffin, Charles Y Lin, Jeffrey I Gordon
The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We used Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to define chromatin accessibility in predicted enhancer regions of intestinal αβ(+) and γδ(+) intraepithelial lymphocytes purified from germ-free mice, their conventionally raised (CONV-R) counterparts, and mice reared germ free and then colonized with CONV-R gut microbiota at the end of the suckling-weaning transition...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911225/successful-treatment-of-mixed-yolk-sac-tumor-and-mature-teratoma-in-the-spinal-cord-case-report
#3
Akitake Mukasa, Shunsuke Yanagisawa, Kuniaki Saito, Shota Tanaka, Keisuke Takai, Junji Shibahara, Masachika Ikegami, Yusuke Nakao, Katsushi Takeshita, Masao Matsutani, Nobuhito Saito
Primary spinal germ cell tumors are rare, and spinal nongerminomatous germ cell tumors represent an even rarer subset for which no standard therapy has been established. The authors report the case of a 24-year-old woman with multifocal primary spinal germ cell tumors scattered from T-12 to L-5 that consisted of yolk sac tumor and mature teratoma. After diagnostic partial resection, the patient was treated with 30 Gy of craniospinal irradiation and 30 Gy of local spinal irradiation, followed by 8 courses of chemotherapy based on ifosfamide, cisplatin, and etoposide (ICE)...
December 2, 2016: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/27893332/outcome-of-men-with-relapse-after-adjuvant-carboplatin-for-clinical-stage-i-seminoma
#4
Stefanie Fischer, Torgrim Tandstad, Matthew Wheater, Emilio Porfiri, Aude Fléchon, Jorge Aparicio, Dirk Klingbiel, Breda Skrbinc, Umberto Basso, Jonathan Shamash, Anja Lorch, Klaus-Peter Dieckmann, Gabriella Cohn-Cedermark, Olof Ståhl, Caroline Chau, Edurne Arriola, Kalena Marti, Paul Hutton, Brigitte Laguerre, Pablo Maroto, Jörg Beyer, Silke Gillessen
Purpose Adjuvant carboplatin is one of three management strategies that may follow inguinal orchiectomy in clinical stage I seminoma. However, little is known about the outcome of patients who experience a relapse after such treatment. Patients and Methods Data from 185 patients who relapsed after adjuvant carboplatin between January 1987 and August 2013 at 31 centers/groups from 20 countries were collected and retrospectively analyzed. Primary outcomes were disease-free survival and overall survival. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses...
November 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27893173/bmp15l-figla-smc1bl-and-larp6l-are-preferentially-expressed-in-germ-cells-in-atlantic-salmon-salmo-salar-l
#5
Lene Kleppe, Rolf Brudvik Edvardsen, Tomasz Furmanek, Eva Andersson, Amélie Juanchich, Anna Wargelius
Atlantic salmon is a valuable commercial aquaculture species that would benefit economically and environmentally by controlling precocious puberty and preventing escapees from reproducing with wild populations. One solution to both these challenges is the production of sterile individuals by inhibiting the formation of germ cells, but achieving this requires more information on the specific factors that control germ cell formation. Here, we identified and characterized novel factors that are preferentially expressed in Atlantic salmon germ cells by screening for gonad-specific genes using available adult multi-tissue transcriptomes...
November 7, 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27892926/dual-specificity-phosphatase-6-deficiency-regulates-gut-microbiome-and-transcriptome-response-against-diet-induced-obesity-in-mice
#6
Jhen-Wei Ruan, Sarah Statt, Chih-Ting Huang, Yi-Ting Tsai, Cheng-Chin Kuo, Hong-Lin Chan, Yu-Chieh Liao, Tse-Hua Tan, Cheng-Yuan Kao
The gut microbiota plays profound roles in host metabolism and the inflammatory response associated with the development of obesity. Dusp6-deficient mice have been shown to be resistant to diet-induced obesity, but the mechanism behind this remains unclear. 16S ribosomal RNA gene analysis demonstrated that dusp6-deficient mice harbour unique gut microbiota with resistance to diet-induced-obesity-mediated alteration of the gut microbiome. Using a germ-free mouse model, we found that faecal/gut microbiota derived from dusp6-deficient mice significantly increased energy expenditure and reduced weight gain in recipient wild-type mice fed on a high-fat diet...
November 28, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27889451/diet-microbiota-interactions-mediate-global-epigenetic-programming-in-multiple-host-tissues
#7
Kimberly A Krautkramer, Julia H Kreznar, Kymberleigh A Romano, Eugenio I Vivas, Gregory A Barrett-Wilt, Mary E Rabaglia, Mark P Keller, Alan D Attie, Federico E Rey, John M Denu
Histone-modifying enzymes regulate transcription and are sensitive to availability of endogenous small-molecule metabolites, allowing chromatin to respond to changes in environment. The gut microbiota produces a myriad of metabolites that affect host physiology and susceptibility to disease; however, the underlying molecular events remain largely unknown. Here we demonstrate that microbial colonization regulates global histone acetylation and methylation in multiple host tissues in a diet-dependent manner: consumption of a "Western-type" diet prevents many of the microbiota-dependent chromatin changes that occur in a polysaccharide-rich diet...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27879538/efficacy-of-ifosfamide-cisplatin-etoposide-ice-chemotherapy-for-a-cns-germinoma-in-a-child-with-down-syndrome
#8
Seishiro Nodomi, Katsutsugu Umeda, Hiroo Ueno, Satoshi Saida, Hidefumi Hiramatsu, Takeshi Funaki, Yoshiki Arakawa, Takashi Mizowaki, Souichi Adachi, Toshio Heike
Intracranial germ cell tumor is sometimes associated with Down syndrome; however, no optimal treatment has been developed due to the high risk of recurrence and treatment-related mortality. Here, we report on a patient with an intracranial germinoma in the bilateral basal ganglia. The patient received 3 courses of ifosfamide-cisplatin-etoposide in combination with whole-brain irradiation (24 Gy), with no serious complications. The patient is alive and disease free 16 months after the initial diagnosis. This regimen is a feasible treatment for intracranial germ cell tumor associated with Down syndrome, although careful attention must be paid to the increased risk for severe infection...
November 22, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27879260/antibiotics-impair-murine-hematopoiesis-by-depleting-intestinal-microbiota
#9
Kamilla S Josefsdottir, Megan T Baldridge, Claudine S Kadmon, Katherine Y King
Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27879220/generation-of-induced-pluripotent-stem-cells-ipscs-from-a-hereditary-spastic-paraplegia-patient-carrying-a-homozygous-y275x-mutation-in-cyp7b1-spg5
#10
Stefan Hauser, Philip Höflinger, Yvonne Theurer, Tim W Rattay, Ludger Schöls
Skin fibroblasts were obtained from a 47-year-old hereditary spastic paraplegia patient carrying a homozygous mutation Y275X in CYP7B1 (Cytochrome P450, Family 7, Subfamily B, Polypeptide 1), responsible for causing hereditary spastic paraplegia type 5 (SPG5). Induced pluripotent stem cells (iPSCs) were generated by transfection with episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC and hLIN28. The generated line iPS-SPG5-Y275X was transgene-free, retained the specific mutation with no additional genomic aberrations, expressed pluripotency markers and was able to differentiate into cells of all germ layers in vitro...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27879217/generation-of-optic-atrophy-1-patient-derived-induced-pluripotent-stem-cells-ips-opa1-behr-for-disease-modeling-of-complex-optic-atrophy-syndromes-behr-syndrome
#11
Stefan Hauser, Stefanie Schuster, Yvonne Theurer, Matthis Synofzik, Ludger Schöls
Human skin fibroblasts were isolated from a 48-year-old patient carrying compound heterozygous mutations (c.610+364G>A and c.1311A>G) in OPA1, responsible for early onset optic atrophy complicated by ataxia and pyramidal signs (Behr syndrome; OMIM #210000). Fibroblasts were reprogrammed using episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC and hLIN28. The generated transgene-free line iPS-OPA1-BEHR showed no additional genomic aberrations, maintained the disease-relevant mutations, expressed important pluripotency markers and was capable to differentiate into cells of all three germ layers in vitro...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27879216/generation-of-induced-pluripotent-stem-cells-ipscs-from-a-hereditary-spastic-paraplegia-patient-carrying-a-homozygous-r486c-mutation-in-cyp7b1-spg5
#12
Philip Höflinger, Yvonne Theurer, Rebecca Schüle, Ludger Schöls, Stefan Hauser
Skin fibroblasts were obtained from a 47-year-old hereditary spastic paraplegia patient carrying a homozygous mutation R486C in CYP7B1 (Cytochrome P450, Family 7, Subfamily B, Polypeptide 1), responsible for causing hereditary spastic paraplegia type 5 (SPG5). Induced pluripotent stem cells (iPSCs) were generated by transfection with episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC and hLIN28. The generated line iPS-SPG5-R486C was transgene-free, retained the specific mutation with no additional genomic aberrations, expressed pluripotency markers and was able to differentiate into cells of all germ layers in vitro...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27870561/high-dose-chemotherapy-and-autologous-peripheral-blood-stem-cell-transplantation-for-relapsed-metastatic-germ-cell-tumors-the-indiana-university-experience
#13
Nabil Adra, Rafat Abonour, Sandra K Althouse, Costantine Albany, Nasser H Hanna, Lawrence H Einhorn
Purpose Patients with relapsed metastatic germ cell tumor (GCT) can be cured with second-line and even third-line regimens. We report survival outcomes of patients treated with high-dose chemotherapy (HDCT) and peripheral-blood stem-cell transplantation (PBSCT) at Indiana University between 2004 and 2014. Patients and Methods We conducted a retrospective analysis of 364 consecutive patients with GCT who progressed after cisplatin-based combination chemotherapy and were subsequently treated with HDCT and PBSCT...
November 21, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27869789/genome-guided-design-of-a-defined-mouse-microbiota-that-confers-colonization-resistance-against-salmonella-enterica-serovar-typhimurium
#14
Sandrine Brugiroux, Markus Beutler, Carina Pfann, Debora Garzetti, Hans-Joachim Ruscheweyh, Diana Ring, Manuel Diehl, Simone Herp, Yvonne Lötscher, Saib Hussain, Boyke Bunk, Rüdiger Pukall, Daniel H Huson, Philipp C Münch, Alice C McHardy, Kathy D McCoy, Andrew J Macpherson, Alexander Loy, Thomas Clavel, David Berry, Bärbel Stecher
Protection against enteric infections, also termed colonization resistance, results from mutualistic interactions of the host and its indigenous microbes. The gut microbiota of humans and mice is highly diverse and it is therefore challenging to assign specific properties to its individual members. Here, we have used a collection of murine bacterial strains and a modular design approach to create a minimal bacterial community that, once established in germ-free mice, provided colonization resistance against the human enteric pathogen Salmonella enterica serovar Typhimurium (S...
November 21, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27867337/oligometastatic-growing-teratoma-syndrome-a-case-for-an-aggressive-surgical-approach
#15
William S Gange, Robert H Blackwell, John Biemer, Güliz A Barkan, Maria M Picken, Marcus L Quek
Growing teratoma syndrome is an infrequent presentation of testicular cancer. We present a case of growing teratoma syndrome in a patient who initially presented with clinical stage I nonseminomatous testicular germ cell tumor, who subsequently developed large volume oligometastases to the retroperitoneum, thorax, and thigh. Despite two regimens of chemotherapy, his disease progressed. Complete surgical extirpation of all gross tumors confirmed mature teratoma. An aggressive surgical approach, including postchemotherapy resection of all known metastatic sites, can provide long-term disease-free survival...
October 2016: Current Urology
https://www.readbyqxmd.com/read/27865415/biosterilant-effects-of-bacillus-thuringiensis-kurstaki-hd-73-extract-on-male-wistar-albino-rats
#16
Vikas Kumar Roy, Vanlal Peki, Maibam Sunita Devi, Sanasam Sanjeev, Maurya Khusboo, R Zothansanga, Kalibulla Syed Ibrahim, Nachimuthu Senthil Kumar, Guruswami Gurusubramanian
Chemosterilants have long been used in sterilization programs for managing pet, stray, and wild animals but adverse effects such as trauma, incomplete responses to treatment, and complete abolition of gonadal sources of testosterone often occurs. This study describes the biosterilant effects of administering three doses of Bacillus thuringiensis kurstaki HD-73 (Bt 5, 50, and 250 mg/kg; 20 rats/dose) extract in adult male Wistar albino rats on testicular parameters, function, histology, and a number of biochemical markers of overall health, free radical production, and cell proliferation...
January 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/27858930/environmental-spread-of-microbes-impacts-the-development-of-metabolic-phenotypes-in-mice-transplanted-with-microbial-communities-from-humans
#17
Li Zhang, Martin Iain Bahl, Henrik Munch Roager, Cilius Esmann Fonvig, Lars I Hellgren, Henrik Lauritz Frandsen, Oluf Pedersen, Jens-Christian Holm, Torben Hansen, Tine Rask Licht
Microbiota transplantation to germ-free animals is a powerful method to study involvement of gut microbes in the aetiology of metabolic syndrome. Owing to large interpersonal variability in gut microbiota, studies with broad coverage of donors are needed to elucidate the establishment of human-derived microbiotas in mice, factors affecting this process and resulting impact on metabolic health. We thus transplanted faecal microbiotas from humans (16 obese and 16 controls) separately into 64 germ-free Swiss Webster mice caged in pairs within four isolators, with two isolators assigned to each phenotype, thereby allowing us to explore the extent of microbial spread between cages in a well-controlled environment...
November 18, 2016: ISME Journal
https://www.readbyqxmd.com/read/27856772/pkama-itachi-vectors-for-highly-efficient-crispr-cas9-mediated-gene-knockout-in-arabidopsis-thaliana
#18
Hiroki Tsutsui, Tetsuya Higashiyama
The CRISPR/Cas9 system is widely used as a tool for genome engineering in various organisms. A complex consisting of Cas9 and single guide RNA (sgRNA) induces a DNA double-strand break in a sequence-specific manner, resulting in knockout. Some binary vectors for CRISPR/Cas9 in plants have been reported, but there is a problem with low efficiency. Here, we present a newly developed, highly efficient CRISPR/Cas9 vector for Arabidopsis thaliana, pKAMA-ITACHI Red (pKIR), harboring the RIBOSOMAL PROTEIN S5 A (RPS5A) promoter to drive Cas9 The RPS5A promoter maintains high constitutive expression at all developmental stages starting from the egg cell and including meristematic cells...
November 17, 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/27851911/autoimmune-renal-disease-is-exacerbated-by-s1p-receptor-1-dependent-intestinal-th17-cell-migration-to-the-kidney
#19
Christian F Krebs, Hans-Joachim Paust, Sonja Krohn, Tobias Koyro, Silke R Brix, Jan-Hendrik Riedel, Patricia Bartsch, Thorsten Wiech, Catherine Meyer-Schwesinger, Jiabin Huang, Nicole Fischer, Philipp Busch, Hans-Willi Mittrücker, Ulrich Steinhoff, Brigitta Stockinger, Laura Garcia Perez, Ulrich O Wenzel, Matthias Janneck, Oliver M Steinmetz, Nicola Gagliani, Rolf A K Stahl, Samuel Huber, Jan-Eric Turner, Ulf Panzer
Th17 cells are most abundant in the gut, where their presence depends on the intestinal microbiota. Here, we examined whether intestinal Th17 cells contribute to extra-intestinal Th17 responses in autoimmune kidney disease. We found high frequencies of Th17 cells in the kidneys of patients with antineutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis. We utilized photoconversion of intestinal cells in Kaede mice to track intestinal T cell mobilization upon glomerulonephritis induction, and we found that Th17 cells egress from the gut in a S1P-receptor-1-dependent fashion and subsequently migrate to the kidney via the CCL20/CCR6 axis...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27843150/the-bacterial-peptidoglycan-sensing-molecule-pglyrp2-modulates-brain-development-and-behavior
#20
T Arentsen, Y Qian, S Gkotzis, T Femenia, T Wang, K Udekwu, H Forssberg, R Diaz Heijtz
Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females...
November 15, 2016: Molecular Psychiatry
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