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https://www.readbyqxmd.com/read/27926879/in%C3%A2-vitro-derivation-and-propagation-of-spermatogonial-stem-cell-activity-from-mouse-pluripotent-stem-cells
#1
Yukiko Ishikura, Yukihiro Yabuta, Hiroshi Ohta, Katsuhiko Hayashi, Tomonori Nakamura, Ikuhiro Okamoto, Takuya Yamamoto, Kazuki Kurimoto, Kenjiro Shirane, Hiroyuki Sasaki, Mitinori Saitou
The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926513/mael-is-essential-for-cancer-cell-survival-and-tumorigenesis-through-protection-of-genetic-integrity
#2
Su-Hyeon Kim, Eun-Ran Park, Eugene Cho, Won-Hee Jung, Ju-Yeon Jeon, Hyun-Yoo Joo, Kee-Ho Lee, Hyun-Jin Shin
Germ line-specific genes are activated in somatic cells during tumorigenesis, and are accordingly referred to as cancer germline genes. Such genes that act on piRNA (Piwi-interacting RNA) processing play an important role in the progression of cancer cells. Here, we show that the spermatogenic transposon silencer maelstrom (Mael), a piRNA-processing factor, is required for malignant transformation and survival of cancer cells. A specific Mael isoform was distinctively overexpressed in diverse human cancer cell lines and its depletion resulted in cancer-specific cell death, characterized by apoptosis and senescence, accompanied by an increase in reactive oxygen-species and DNA damage...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926491/early-pathogenic-event-of-alzheimer-s-disease-documented-in-ipscs-from-patients-with-psen1-mutations
#3
Juan Yang, Hanzhi Zhao, Yu Ma, Guilai Shi, Jian Song, Yu Tang, Song Li, Ting Li, Nan Liu, Fan Tang, Junjie Gu, Lingling Zhang, Zhuohua Zhang, Xiaohui Zhang, Ying Jin, Weidong Le
Alzheimer's disease (AD) is the most common age-related dementia characterized by progressive neuronal loss. However, the molecular mechanisms for the neuronal loss is still debated. Here, we used induced pluripotent stem cells (iPSCs) derived from somatic cells of familial AD patients carrying PSEN1 mutations to study the early pathogenic event of AD. We found that premature neuronal differentiation with decreased proliferation and increased apoptosis occured in AD-iPSC-derived neural progenitor cells (AD-NPCs) once neuronal differentiation was initiated, together with higher levels of Aβ42 and phosphorylated tau...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925606/increasing-awareness-and-acceptance-through-mindfulness-and-somatic-education-movements
#4
Paulo Vicente Bloise, Mário César Rezende Andrade, Hans Machado, Sérgio Baxter Andreoli
Context • The main feature of mindfulness-based interventions (MBI) is the encouragement of present moment awareness and of self-regulation, which are associated with health benefits. Meditating with the body in movement has been referred to as one of the most accessible ways of reaching such awareness. An MBI program, Mindfulness and Movements of Integration (MMI), has the same structure as mindfulness-based stress reduction (MBSR) but puts more emphasis on the body and uses somatic education (SE) movements instead of yoga postures...
October 2016: Advances in Mind-body Medicine
https://www.readbyqxmd.com/read/27925269/lifecycle-exposure-of-fathead-minnows-to-environmentally-relevant-concentrations-of-the-%C3%AE-blocker-drug-propranolol
#5
Joanne L Parrott, Vimal K Balakrishnan
Propranolol is a human pharmaceutical β-blocker that has been detected in municipal wastewater effluents at ng/L to low µg/L. To assess the potential of this compound to affect fish, fathead minnow (Pimephales promelas) were exposed for a lifecycle in a flow-through system to nominal propranolol concentrations of 0.87, 8.7, 87, 870 and 8,700 ng/L. Measured propranolol concentrations were below detection for the two lowest exposure concentrations, and were 76, 580, and 7,800 ng/L for the three highest exposure concentrations...
December 7, 2016: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#6
Caterina Marchiò, Felipe C Geyer, Charlotte Ky Ng, Salvatore Piscuoglio, Maria R De Filippo, Marco Cupo, Anne M Schultheis, Raymond S Lim, Kathleen A Burke, Elena Guerini-Rocco, Mauro Papotti, Larry Norton, Anna Sapino, Britta Weigelt, Jorge S Reis-Filho
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair...
December 7, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27924834/activation-induced-deaminase-mutational-signature-overlaps-with-cpg-methylation-sites-in-follicular-lymphoma-and-other-cancers
#7
Igor B Rogozin, Artem G Lada, Alexander Goncearenco, Michael R Green, Subhajyoti De, German Nudelman, Anna R Panchenko, Eugene V Koonin, Youri I Pavlov
Follicular lymphoma (FL) is an uncurable cancer characterized by progressive severity of relapses. We analyzed sequence context specificity of mutations in the B cells from a large cohort of FL patients. We revealed substantial excess of mutations within a novel hybrid nucleotide motif: the signature of somatic hypermutation (SHM) enzyme, Activation Induced Deaminase (AID), which overlaps the CpG methylation site. This finding implies that in FL the SHM machinery acts at genomic sites containing methylated cytosine...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924227/otx2-impedes-self-renewal-of-porcine-ips-cells-through-downregulation-of-nanog-expression
#8
Ning Wang, Yaxian Wang, Youlong Xie, Huayan Wang
The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells. However, the molecular features and function of porcine OTX2 have not been well elucidated in porcine-induced pluripotent stem cells (piPSCs). By studying high-throughput transcriptome sequencing and interfering endogenous OTX2 expression, we demonstrate that OTX2 is able to downgrade the self-renewal of piPSCs. OTX2 is highly expressed in porcine brain, reproductive tissues, and preimplantation embryos, but is undetectable in fibroblasts and most somatic tissues...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#9
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923047/precision-cancer-diagnostics-tracking-genomic-evolution-in-clinical-trials
#10
Francisco Beca, Andrew H Beck
In a Perspective, Francisco Beca and Andrew Beck discuss Charles Swanton and colleagues' accompanying Research Article on somatic mutations in patients with inflammatory breast cancer treated in a Phase II clinical trial.
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923045/tumor-evolution-in-two-patients-with-basal-like-breast-cancer-a-retrospective-genomics-study-of-multiple-metastases
#11
Katherine A Hoadley, Marni B Siegel, Krishna L Kanchi, Christopher A Miller, Li Ding, Wei Zhao, Xiaping He, Joel S Parker, Michael C Wendl, Robert S Fulton, Ryan T Demeter, Richard K Wilson, Lisa A Carey, Charles M Perou, Elaine R Mardis
BACKGROUND: Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#12
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27922448/the-second-randomised-evaluation-of-the-effectiveness-cost-effectiveness-and-acceptability-of-computerised-therapy-reeact-2-trial-does-the-provision-of-telephone-support-enhance-the-effectiveness-of-computer-delivered-cognitive-behaviour-therapy-a-randomised
#13
Sally Brabyn, Ricardo Araya, Michael Barkham, Peter Bower, Cindy Cooper, Ana Duarte, David Kessler, Sarah Knowles, Karina Lovell, Elizabeth Littlewood, Richard Mattock, Stephen Palmer, Jodi Pervin, David Richards, Debbie Tallon, David White, Simon Walker, Gillian Worthy, Simon Gilbody
BACKGROUND: Computerised cognitive behaviour therapy (cCBT) is an efficient form of therapy potentially improving access to psychological care. Indirect evidence suggests that the uptake and effectiveness of cCBT can be increased if facilitated by telephone, but this is not routinely offered in the NHS. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of telephone-facilitated free-to-use cCBT [e.g. MoodGYM (National Institute for Mental Health Research, Australian National University, Canberra, ACT, Australia)] with minimally supported cCBT...
November 2016: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/27922333/environmentally-relevant-chronic-low-dose-tritium-and-gamma-exposures-do-not-increase-somatic-intrachromosomal-recombination-in-pkz1-mouse-spleen
#14
Laura Bannister, Mandy Serran, Lindsey Bertrand, Dmitry Klokov, Heather Wyatt, Melinda Blimkie, Yann Gueguen, Nicholas Priest, Jean-René Jourdain, Pamela Sykes
The toxicity of tritium is a public health concern given its presence and mobility in the environment. For risk predictions using radiological protection models, it is essential to allocate an appropriate radiation weighting factor (WR). This in turn should be consistent with the observed relative biological effectiveness (RBE) of tritium beta radiation. Although the International Commission on Radiological Protection (ICRP) currently recommends a WR of 1 for the calculation of committed effective dose for X rays, gamma rays and electrons of all energies, including tritium energies, there are concerns that tritium health risks are underestimated and that current regulatory tritium drinking water standards need revision...
December 6, 2016: Radiation Research
https://www.readbyqxmd.com/read/27922168/update-of-the-swiss-guidelines-on-post-treatment-lyme-disease-syndrome
#15
Johannes Nemeth, Enos Bernasconi, Ulrich Heininger, Mohamed Abbas, David Nadal, Carol Strahm, Stefan Erb, Stefan Zimmerli, Hansjakob Furrer, Julie Delaloye, Thierry Kuntzer, Ekkehard Altpeter, Mathias Sturzenegger, Rainer Weber, For The Swiss Society For Infectious Diseases And The Swiss Society For Neurology
Lyme borreliosis is caused by Borrelia burgdorferi sensu lato infection, which responds well to antibiotic therapy in the overwhelming majority of cases. However, despite adequate antibiotic treatment some patients report persisting symptoms which are commonly summarised as post-treatment Lyme disease syndrome (PTLDS). In 2005, the Swiss Society of Infectious Diseases published a case definition for PTLDS. We aimed to review the scientific literature with a special emphasis on the last 10 years, questioning whether the definitions from 2005 are still valid in the light of current knowledge...
2016: Swiss Medical Weekly
https://www.readbyqxmd.com/read/27922053/electrophysiological-properties-of-ca1-pyramidal-neurons-along-the-longitudinal-axis-of-the-mouse-hippocampus
#16
Giampaolo Milior, Maria Amalia Di Castro, Livio Pepe' Sciarria, Stefano Garofalo, Igor Branchi, Davide Ragozzino, Cristina Limatola, Laura Maggi
Evidence for different physiological properties along the hippocampal longitudinal axis is emerging. Here, we examined the electrophysiological features of neurons at different dorso-ventral sites of the mouse CA1 hippocampal region. Cell position was defined with respect to longitudinal coordinates of each slice. We measured variations in neuronal excitability, subthreshold membrane properties and neurotransmitter responses along the longitudinal axis. We found that (i) pyramidal cells of the dorsal hippocampus (DH) were less excitable than those of the ventral hippocampus (VH)...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921262/a-new-era-of-disease-modeling-and-drug-discovery-using-induced-pluripotent-stem-cells
#17
REVIEW
Wonhee Suh
In 2006, Shinya Yamanaka first reported that in vitro reprogramming of somatic cells toward pluripotency was achieved by simple induction of specific transcription factors. Induced pluripotent stem cell (iPSC) technology has since revolutionized the ways in which we explore the mechanisms of human diseases and develop therapeutics. Here, I describe the recent advances in human iPSC-based disease modeling and drug discovery and discuss the current challenges. Additionally, I outline potential future applications of human iPSCs in classifying patients based on their response to drugs in clinical trials and elucidating optimal patient-specific therapeutic strategies, which will contribute to reduced attrition rates and the development of precision medicine...
December 5, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27920979/transcript-profiling-in-the-milk-of-dairy-ewes-fed-extruded-linseed
#18
Tommaso Giordani, Alberto Vangelisti, Giuseppe Conte, Andrea Serra, Lucia Natali, Annamaria Ranieri, Marcello Mele, Andrea Cavallini
The identification of genes regulating milk secretion by mammary glands is a key-step for exploiting changes in milk composition induced by different diet regimens. Linseed supplementation is a reliable feeding strategy to enhance polyunsaturated fatty acid content in milk fat from sheep, increasing milk quality and nutraceutical value. To investigate the molecular bases of diet induced differences in milk composition, we collected milk from dairy ewes at 90 day of lactation and after 3 weeks of diet supplementation with extruded linseed...
March 2017: Genomics Data
https://www.readbyqxmd.com/read/27920874/leiomyoma-of-deep-soft-tissue-mimicking-calcific-myonecrosis
#19
Valerie A Fitzhugh, Cornelia Wenokor, Kathleen S Beebe, Seena C Aisner
Leiomyoma of deep soft tissue is an unusual entity reported in less than 60 cases in the English literature. The lesion is now accepted as a rare neoplasm. Leiomyomata of deep soft tissue have been divided into 2 groups, those occurring primarily in women in the retroperitoneum, histologically similar to leiomyomata of the uterus, and those occurring equally in both sexes in the somatic deep soft tissues. Irrespective of location, these lesions can demonstrate calcification, and even less commonly ossification...
December 2016: Radiology case reports
https://www.readbyqxmd.com/read/27920779/functional-versatility-of-agy-serine-codons-in-immunoglobulin-variable-region-genes
#20
Thiago Detanico, Matthew Phillips, Lawrence J Wysocki
In systemic autoimmunity, autoantibodies directed against nuclear antigens (Ags) often arise by somatic hypermutation (SHM) that converts AGT and AGC (AGY) Ser codons into Arg codons. This can occur by three different single-base changes. Curiously, AGY Ser codons are far more abundant in complementarity-determining regions (CDRs) of IgV-region genes than expected for random codon use or from species-specific codon frequency data. CDR AGY codons are also more abundant than TCN Ser codons. We show that these trends hold even in cartilaginous fishes...
2016: Frontiers in Immunology
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