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McCarthy, John. "Tackling the challenges of interdisciplinary bioscience." Nature Reviews Molecular Cell Biology 5, no. 11 (November 2004): 933–37. http://dx.doi.org/10.1038/nrm1501.
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Davidson, Eric H. "Evolutionary bioscience as regulatory systems biology." Developmental Biology 357, no. 1 (September 2011): 35–40. http://dx.doi.org/10.1016/j.ydbio.2011.02.004.
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Suiter, Tobias, Michael Laffan, Pier M. Mannucci, Christine L. Kempton, Edward H. Romond, Amy D. Shapiro, Ingvild Birschmann, et al. "Recombinant Human Von Willebrand Factor (rhVWF): First-In-Human Study Evaluating Pharmacokinetics, Demonstrating Safety and Tolerability In Type 3 Von Willebrand Disease." Blood 116, no. 21 (November 19, 2010): 237. http://dx.doi.org/10.1182/blood.v116.21.237.237.
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Abstract Abstract 237 Von Willebrand Disease (VWD) is an inherited rare bleeding disorder caused by a deficiency of von Willebrand factor (VWF). VWF is the largest soluble multimeric plasma glycoprotein, which facilitates platelet aggregation and stabilizes FVIII in the circulation. Patients with type 3 disease display severe hemorrhagic symptoms, mainly in mucosal tissues, muscle and joints. Replacement of VWF stabilizes endogenous FVIII to hemostatic levels within hours. Commercially available VWF/FVIII concentrates are plasma-derived (pd) and subject to limitations such as donor dependency, risk of blood-borne pathogen transmission, lack of high molecular weight VWF multimers, and variation in multimer composition. A novel recombinant human VWF (rhVWF) has been developed using a plasma-free method, which represents the largest protein ever produced using recombinant technology. Safety, tolerability and pharmacokinetics of the rhVWF combined at a fixed ratio with rFVIII were investigated in a Phase 1 multicenter, international clinical study in 31 patients with type 3 VWD and severe type 1 VWD. Four concentrations of rhVWF (2, 7.5, 20 and 50 IU VWF:RCo/kg) were administered in a dose-escalating manner in separate cohorts. rhVWF was well tolerated, and no thrombotic events, VWF inhibitors or other serious adverse reactions were observed. Pharmacokinetics of rhVWF/rhFVIII (50 IU VWF:RCo/kg and 38.5 IU FVIII/kg) compared with pdVWF/pdFVIII (50 IU VWF:RCo/kg and 21 IU/kg FVIII/kg) were evaluated in a sub-group of 8/31 patients using a randomized, crossover design (8-day minimum washout period). Interim data in 8 subjects show a higher degree of secondary FVIII activity with rhVWF/rhFVIII compared to pdVWF/pdFVIII (see Figure 1) that is not solely due the difference in the rhVVF:FVIII infusion ratio (1.3:1 rhVWF/rhFVIII vs. approximately 2:1 pdVWF/pdFVIII). The pharmacokinetics of the rhVWF:RCo and pdVWF:RCo were comparable and were also reflected in the VWF:Ag and collagen binding activity. Evidence is also provided for the in vivo cleavage of the ultra-high molecular weight multimers of rhVWF by endogenous ADAMTS13. In summary, interim data from the ongoing Phase 1 study, demonstrate that rhVWF is safe and well tolerated, has VWF:RCo pharmacokinetics that are comparable to pdVWF and enhances stabilization of endogenous FVIII. Multiple doses of rhVWF/rhFVIII would be expected to have beneficial effects in major surgery and severe mucosal bleeding events. These data would also support the treatment concept to administer rhVWF alone once a therapeutic baseline level of endogenous FVIII is achieved (after 1–2 doses).Figure 1:Preliminary PK data from 8 subjects post-infusion of either rhVWF/rhFVIII or pdVWF/pdFVIII. Endogenous FVIII activity reached a plateau after 6 hours and remained stable for at least 30 hours. FVIII was still elevated well above baseline at 96 hoursFigure 1:. Preliminary PK data from 8 subjects post-infusion of either rhVWF/rhFVIII or pdVWF/pdFVIII. Endogenous FVIII activity reached a plateau after 6 hours and remained stable for at least 30 hours. FVIII was still elevated well above baseline at 96 hours Disclosures: Suiter: Baxter BioScience: Employment. Laffan:Baxter BioScience: Consultancy. Mannucci:Baxter BioScience: Consultancy. Kempton:Baxter BioScience: Consultancy. Romond:Baxter BioScience: Consultancy. Shapiro: Baxter BioSci- ence: Consultancy. Birschmann:Baxter BioScience: Consultancy. Gill:Baxter BioScience: Consultancy. Ragni:Baxter BioScience: Consultancy. Turecek:Baxter BioScience: Employment. Ewenstein:Baxter Bioscience: Employment. Baxter BioScience:Baxter BioScience: Employment.
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Shi, Yun-Bo. "The right journal for the right time - Cell & Bioscience." Cell & Bioscience 1, no. 1 (2011): 1. http://dx.doi.org/10.1186/2045-3701-1-1.
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Lee, Hojae, Hengshi Yu, and Joshua Welch. "A beginner's guide to single-cell transcriptomics." Biochemist 41, no. 5 (October 18, 2019): 34–38. http://dx.doi.org/10.1042/bio04105034.
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Beginner's Guides each cover a key technique and offer the scientifically literate but not necessarily expert audience a background briefing on the underlying science of a technique that is (or will be) widely used in molecular bioscience. The series covers a mixture of techniques, including some that are well established amongst a subset of our readership but not necessarily familiar to those in different specialisms, or the reverse. This is our Beginner's Guide to single-cell transcriptomics.
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Stevenson, Brian. "Collaborative practice re-energises bioscience teaching in schools." Microbiology Australia 31, no. 1 (2010): 27. http://dx.doi.org/10.1071/ma10027.
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This year marks the first decade of operations for the Gene Technology Access Centre (GTAC). The decade has seen a grassroots initiative by a small group of eminent research scientists and dedicated personnel from the University High School in Melbourne grow into a specialist education centre in cell and molecular biology that attracts over 6000 students and their teachers each year. GTAC has not only refocused student and teacher attention on the interdisciplinary nature of contemporary biology, but has also highlighted how a ?centre model for learning?, based upon collaboration and partnerships, can exist within ?the school system? and meet the needs of students and teachers from across Victoria and beyond.
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Flier, Jeffrey S. "Irreproducibility of published bioscience research: Diagnosis, pathogenesis and therapy." Molecular Metabolism 6, no. 1 (January 2017): 2–9. http://dx.doi.org/10.1016/j.molmet.2016.11.006.
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Li, Henry Qixiang, Jingping Liu, Xiaoyu An, Na Wang, Liang Huang, Ran Wu, Jie Cai, and Jean-Pierre Wery. "Creation Of Patient Derived AML Xenografts Displaying Distinct Phenotypes and Geneotypes." Blood 122, no. 21 (November 15, 2013): 5018. http://dx.doi.org/10.1182/blood.v122.21.5018.5018.
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Abstract We have recently successfully engrafted leukemic cells from bone marrow of several AML patients into immunocompromised NOD/SCID mice. One of them, AM7577, was reported in the last year ASH1. This model displayed typical aggressive AML disease of M5 subtype, which starts at bone marrow and gradually expand to peripheral (spleen, lymphonode and peripheral blood…). AM7577 also harbors interesting genotypes of mutations for IDH2-R140Q, FLT3-ITD, DNMT3A R882H and NPM1. Our second AML PDX model, AM8096, was established similarly using bone marrow from a recurrent patient with AML-M2 disease. AML8096 displayed similarly aggressive disease and the same 100% mortality, including typical symptoms (BW loss, hunched, inactivity, labored breathing, ruffled coat and eventual mortality) and with abundant leukemic cells in bone, etc. The leukemic cells can serially be passed in mice with 100% take-rate and cause consistent disease (even with < 1e4 cells). This also creates a renewable and potentially unlimited source of leukemia cells. The leukemic cells in mice are identical to those of the original patient leukemic cells (CD45+, CD33+, CD13+, CD123+, and CD19-. However, some aspects of disease presentations are vastly different from that of AM7577. First, the peripheral symptom is significant less characterized by lower leukemic counts in peripheral blood and only slightly enlarged spleen and smaller lymphonode. Second, the leukemic cell morphology is also rather different with AM8096 demonstrating less differentiated phenotype. Third, the genotype, in contrast to AM7577, is wild-types for all the above oncogenes. While we have not identified the likely leukemogenesis driver gene for this model, we are currently performing RNAseq of AM8096, along with AM7577, in order to explore the underlying molecular mechanisms that drive both diseases. In addition, we are also investigating the drug response to standard of care (SOC), as compared to those AM7577. In summary, the two AML models could serve as useful experimental models to investigate the diverse leukemogenesis, including molecular mechanisms by genetic profiling. Ultimately, they can be used to help to identify new treatment strategies for AML. 1. Liu, e.a. A unique leukemia mouse model established from AML patient with IDH2 R140Q and FLT3-ITD mutations among other common AML mutations. ASH-2012 Annual Meeting (2012). Disclosures: Li: Crown Bioscience: Employment. Liu:Crown Bioscience: Employment. An:Crown Bioscience: Employment. Wu:Crown Bioscience: Employment. Cai:Crown Bioscience: Employment. Wery:Crown Bioscience: Employment.
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Shi, Yun-Bo. "The 2012 Ming K Jeang award for excellence in cell & bioscience." Cell & Bioscience 3, no. 1 (2013): 23. http://dx.doi.org/10.1186/2045-3701-3-23.
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Lachica, Edward. "Keeping Life in Focus New Systems Prevent Z-axis Drift in Time Lapse Studies." Microscopy Today 14, no. 4 (July 2006): 42–46. http://dx.doi.org/10.1017/s1551929500050276.
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Just two decades ago, life scientists studied biological structure, developmental anatomy and intracellular processes by describing individual snapshots of kinetic events. Today, with so much bioscience research focusing on dynamic processes that occur on the molecular, cellular and whole organ level, it is important to record events as they happen, over seconds, minutes or hours, in living cells. Photographs and camera lucida drawings of fixed, stained cells have given way to live cell imaging using fluorescent probes, warming trays to promote cell viability and cinemicrography as a method of recording events.
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Singh, Anshul Kumar, and Brajesh Kumar Singh. "Applications of Human Biometrics in Digital Image Processing." International Journal of Innovative Science and Research Technology 5, no. 7 (August 14, 2020): 1273–76. http://dx.doi.org/10.38124/ijisrt20jul748.
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Digital image processing is the trending topic of research in recent time and big amount of research work related to Biometric features is done and currently it achieved good amount of accuracy. Biometric features is used for security, verification and recognition purpose. This paper is a showcase of how security systems can be developed by using biometric features of human like face, fingerprint and iris, etc. It can be used for the purpose of identification, recognition and Authentication and it is also applicable for making software for image preparation in bioscience laboratories that make use of scanned or digitally photographed images. The widespread use of such image processing techniques using photography and microscope imaging across the natural science with particular attention being paid to research in cell and molecular bioscience. This paper is a review of various methods trending to the field of biometric applications on biotechnologies.
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Fukusaki, Eiichiro, Kanokwan Jumtee, Takeshi Bamba, Takehiro Yamaji, and Akio Kobayashi. "Metabolic Fingerprinting and Profiling of Arabidopsis thaliana Leaf and its Cultured Cells T87 by GC/MS." Zeitschrift für Naturforschung C 61, no. 3-4 (April 1, 2006): 267–72. http://dx.doi.org/10.1515/znc-2006-3-419.
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Cell suspension cultures are now recognized as important model materials for plant bioscience and biotechnology. Very few studies of metabolic comparisons between cell cultures and original plants have been reported, even though the biological identity of cultured cells with the normally grown plant is of great importance. In this study, a comparison of the metabolome for primary metabolites extracted from the leaves of Arabidopsis thaliana and cultured cells from an Arabidopsis suspension culture (cell line T87) was performed. The results suggest that although cell suspension cultures and Arabidopsis leaves showed similarities in the common primary metabolite profile, nonetheless, moderate differences in quantitative profile were revealed.
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Yu, Alder, Jaclyn Wisinski, Todd Osmundson, Anton Sanderfoot, Scott Cooper, and Jennifer Klein. "Instructional Innovations in College-Level Molecular Bioscience Labs during the Pandemic-Induced Shift to Online Learning." Education Sciences 12, no. 4 (March 23, 2022): 230. http://dx.doi.org/10.3390/educsci12040230.
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The COVID-19 pandemic ushered in an unprecedented period of both crisis and innovation in higher education. The shift to an online learning environment was particularly problematic for courses in which students learn disciplinary practices. Scientific practice requires hands-on training and collaborative engagement with instructors and peers, dimensions of the learning environment that were challenging to recreate online. Here, we describe the resulting instructional innovations and challenges experienced in shifting multiple undergraduate- and graduate-level molecular bioscience labs, including Genetics, Cell Biology, Bioinformatics, and Advanced Microscopy, to an online learning environment. Instructors pursued novel approaches, techniques, and at-home lab tools with varying success. Many innovations were retained after the transition back to an in-person learning environment because they uniquely supported previously overlooked aspects of student learning. Consistent with other reports, we found that marginalized students pursuing science were disproportionately burdened by COVID-19 and the shift to an online learning environment. A description of what worked for online learning, what didn’t, and what is worth holding onto in the future is valuable for constructing learning environments that effectively support learners in their disciplinary practice.
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Bockholt, Susanne M., J. Paige West, and Walter E. Bollenbacher. "Cancer Cell Biology: A Student-Centered Instructional Module Exploring the Use of Multimedia to Enrich Interactive, Constructivist Learning of Science." Cell Biology Education 2, no. 1 (March 2003): 35–50. http://dx.doi.org/10.1187/cbe.02-08-0033.
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Multimedia has the potential of providing bioscience education novel learning environments and pedagogy applications to foster student interest, involve students in the research process, advance critical thinking/problem-solving skills, and develop conceptual understanding of biological topics. Cancer Cell Biology, an interactive, multimedia, problem-based module, focuses on how mutations in protooncogenes and tumor suppressor genes can lead to uncontrolled cell proliferation by engaging students as research scientists/physicians with the task of diagnosing the molecular basis of tumor growth for a group of patients. The process of constructing the module, which was guided by scientist and student feedback/responses, is described. The completed module and insights gained from its development are presented as a potential “multimedia pedagogy” for the development of other multimedia science learning environments.
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Egidio, Camila, Aik Ooi, Ilona Holcomb, Dave Ruff, Stephane Boutet, Jing Wang, and Ramesh Ramakrishnan. "A method for detecting protein expression in single cells using the C1™ Single-Cell Auto Prep System (TECH2P.874)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 135.5. http://dx.doi.org/10.4049/jimmunol.192.supp.135.5.
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Abstract Recent improvements in microfluidics and biochemistry have enabled single-cell molecular analysis, providing new insight into the heterogeneity of cell populations. The C1 Single-Cell Auto Prep System is an automated platform that streamlines the isolation and processing of 96 individual, live cells for RNA and DNA analysis. Single-cell protein profiling is a direct complement to genomic analysis as it provides additional insights into key molecular mechanisms and system biology. To enable this, we adapted a highly multiplexed protein detection system (Proseek Multiplex Oncology, Olink Bioscience) for use on the C1 System. We analyzed 192 individual cells from two human promyelocytic leukemia cell lines (HL60 and K562) and compared these result against 16 FACS-sorted cells in tube format. These results indicated that four key proteins (i.e. CASP3, CSTB, CD69 and MPO) are differentially expressed between the two cell lines and vary from cell-to-cell. For example, the human protein MPO, produced by neutrophils for their microbicidal activity, was differentially expression between individual HL60 and K562 cells, suggesting varying levels of neutrophil activation within the cell populations. This work demonstrates highly-multiplexed protein detection at the single-cell level and shows promise to have sufficient sensitivity, reproducibility and scale to effectively interrogate a statistically significant numbers of individual cells.
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Pasternak, Charles A. "Introduction: International Symposium on Modern Trends in Malaria." Bioscience Reports 23, no. 1 (February 1, 2003): 1. http://dx.doi.org/10.1023/a:1023908628921.
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Malaria continues to kill some two million people a year, half of whom are young children. We have no vaccine, the parasite has become resistant to the most effective drugs, and elimination of the mosquito vector through spraying with insecticide is being questioned. Yet research on malaria is — at last — being funded reasonably well. What has been achieved? Scientists gathered at the All India Institute of Medical Sciences (AIIMS) in New Delhi from 13-15 February 2003 to discuss these issues. Because many antima-larial strategies work at the cell surface (see the abstract on Membranes as future therapeutic targets) it seems appropriate to give readers of Bioscience Reports: Molecular and Cellular Biology of the Cell Surface an opportunity to catch a glimpse of the current situation through the (unedited) abstracts of the invited speakers.
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Siebuhr, A. S., M. Karsdal, P. Juhl, and A. C. Bay-Jensen. "AB0167 TOFACITINIB AND NINTEDANIB MODULATE COLLAGEN FORMATION IN DERMAL FIBROBLASTS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1383.1–1384. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4078.
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Background:Dermal fibroblasts are responsible for the excessive extracellular matrix (ECM) formation observed in the skin of systemic sclerosis (SSc) patients and fibroblasts are therefore an obvious target for anti-fibrotic treatments. TGFβ, PDGF and IL-6 are known to be central cytokines in systemic sclerosis. Nintedanib, a tyrosine-kinase inhibitor approved for treatment of idiopathic pulmonary fibrosis, did not show effect on dermal fibrosis only on pulmonary fibrosis in SSc patients with interstitial lung disease (ILD). Tofacitinib, as Pan JAK inhibitor, has shown to inhibit dermal fibrosis in mouse models and shown positive indications in patients.Objectives:We investigated the direct effect of Nintedanib and Tofacitinib on ECM production from human dermal fibroblast using translational biomarkers of type I, III and VI collagens and fibronectin.Methods:Primary healthy human dermal fibroblasts were grown in DMEM media containing 0.4% fetal calf serum, Ficoll (to produce a crowded environment) and ascorbic acid for up to 17 days. The cells were stimulated with PDGF [3 nM] and/or TGFβ [1 nM] in combination with Nintedanib [1 nM-10 μM] treatment initiated at day 0 or 7 or Tofacitinib [3-100 nM] treatment initiated at culture start together. Media and treatments were changed twice a week. Non-activated cells (w/o) were used as control. Type I, III and VI collagen formation (PRO-C1, PRO-C3 and PRO-C6, respectively) and fibronectin (FBN-C) were evaluated by validated ELISAs (Nordic Bioscience). Statistical analysis included 1-way and 2-way ANOVA, AUC and Mann-Whitney U-test.Results:PDGF significantly increased collagen type III and VI formation and collagen type I formation minimally. PDGF did not induce changes in fibronectin levels. TGFβ increased collagen type I and VI formation but did not induce formation of collagen type III. TGFβ increased fibronectin levels, where PDGF did not.Nintedanib (≥100 nM) added either from day 0 or 7 reduced PDGF induced collagen type III and VI formation to the levels of w/o throughout the remainder of the study. In TGFβ treated fibroblasts, Nintedanib added either from day 0 or 7 reduced collagen type I and VI formation. The fibronectin levels were dose-dependently reduced by Nintedanib. The biomarker levels were at study end at the level of w/o. Nintedanib at a concentration of 1 uM and higher significantly decreased the biomarker levels. Nintedanib (≥100 nM) in fibroblasts stimulated with both TGFβ and PDGF significantly reduced collagen type I, III and VI collagen and fibronectin.A Tofacitinib concentration of 100 nM was toxic to the dermal fibroblasts as the cell viability was minimal at culture end. However, the viability of Tofacitinib (100 nM) in combination with TGFβ was decreased at study end, but only to half the viability of untreated cells. Tofacitinib dose-dependently decreased the TGFβ induced type I and III collagen formation and fibronectin in the dermal fibroblasts. Tofacitinib (100 nM) decreased the level of collagen type I and III formation to the level of w/o, where as the level of fibronectin was lowered by 80 % of TGFβ. Tofacitinib as low as 12.5 nM significantly lowered the collagen type I formation and fibronectin (both p<0.05) and Tofacitinib of 25 nM decreased collagen type III formation significantly (p<0.0001).Conclusion:Tofacitinib decreased the formation of the collagens and fibronectin. Nintedanib inhibited ECM production differently in PDGF and TGFβ induced dermal fibroblast, but in the combination of TGFβ and PDGF Nintedanib significantly decreased the ongoing fibrosis. In PDGF induced fibrosis, Nintedanib acted as an on-off switch, whereas the inhibition was dose-dependent in TGFβ induced fibrosis. This cell study indicates that Nintedanib and Tofacitinib inhibits collagen production in dermal fibroblasts.Figure:Disclosure of Interests:Anne Sofie Siebuhr Employee of: Nordic Bioscience, Morten Karsdal Shareholder of: Nordic Bioscience A/S., Employee of: Full time employee at Nordic Bioscience A/S., Pernille Juhl Employee of: Nordic Bioscience, Anne-Christine Bay-Jensen Shareholder of: Nordic Bioscience A/S, Employee of: Full time employee at Nordic Bioscience A/S.
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Song, Hongfang, and Aike Qiao. "A New Approach through the Eye of a Needle and Its Potential Application in Bioscience." Molecular & Cellular Biomechanics 19, no. 3 (2022): 159–64. http://dx.doi.org/10.32604/mcb.2022.019005.
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Deichmann, Ute, Michel Morange, and Eric Davidson. "Introductory comment on six papers from a Symposium on experimental and historical aspects of evolutionary bioscience." Developmental Biology 357, no. 1 (September 2011): 2. http://dx.doi.org/10.1016/j.ydbio.2011.06.001.
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Valanciute, Asta, and Covadonga Huidobro. "Meet the science." Biochemist 37, no. 1 (February 1, 2015): 50. http://dx.doi.org/10.1042/bio03701050.
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On the 22 September 2014, two researchers from the University of Edinburgh, Covadonga Huidobro and Asta Valanciute, arrived at the High School in Plateliai, Lithuania. There were plenty of educational resources, including bags of different coloured beads, cell organelles, tubes, pipettes, gloves and so forth. With the help of sponsorship from both the Biochemical Society, via an ongoing grant, and the IGMM, the mission was to organize educational activities during the week of 22–26 September in the High Schools of Plateliai and of the Old Town in Plunge. It was also hoped to discuss the novelties in molecular/cellular biology and biochemistry, and to increase interest and knowledge about bioscience and the importance of our research to children and teachers.
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Lenn, Tchern, and Mark C. Leake. "Experimental approaches for addressing fundamental biological questions in living, functioning cells with single molecule precision." Open Biology 2, no. 6 (June 2012): 120090. http://dx.doi.org/10.1098/rsob.120090.
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In recent years, single molecule experimentation has allowed researchers to observe biological processes at the sensitivity level of single molecules in actual functioning, living cells, thereby allowing us to observe the molecular basis of the key mechanistic processes in question in a very direct way, rather than inferring these from ensemble average data gained from traditional molecular and biochemical techniques. In this short review, we demonstrate the impact that the application of single molecule bioscience experimentation has had on our understanding of various cellular systems and processes, and the potential that this approach has for the future to really address very challenging and fundamental questions in the life sciences.
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Abdullah, Jafri Malin, Zulkifli Mustafa, and Aini Ideris. "Newcastle Disease Virus Interaction in Targeted Therapy against Proliferation and Invasion Pathways of Glioblastoma Multiforme." BioMed Research International 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/386470.
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Glioblastoma multiforme (GBM), or grade IV glioma, is one of the most lethal forms of human brain cancer. Current bioscience has begun to depict more clearly the signalling pathways that are responsible for high-grade glioma initiation, migration, and invasion, opening the door for molecular-based targeted therapy. As such, the application of viruses such as Newcastle disease virus (NDV) as a novel biological bullet to specifically target aberrant signalling in GBM has brought new hope. The abnormal proliferation and aggressive invasion behaviour of GBM is reported to be associated with aberrant Rac1 protein signalling. NDV interacts with Rac1 upon viral entry, syncytium induction, and actin reorganization of the infected cell as part of the replication process. Ultimately, intracellular stress leads the infected glioma cell to undergo cell death. In this review, we describe the characteristics of malignant glioma and the aberrant genetics that drive its aggressive phenotype, and we focus on the use of oncolytic NDV in GBM-targeted therapy and the interaction of NDV in GBM signalling that leads to inhibition of GBM proliferation and invasion, and subsequently, cell death.
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Renan, Michael J. "Conserved elements in the 3′ untranslated regions of c-fos and actin mRNAs." Bioscience Reports 6, no. 9 (September 1, 1986): 819–25. http://dx.doi.org/10.1007/bf01117105.
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In this study, the nucleotide sequences of the 3′ untranslated regions (UTR) of the mouse and human c-fos genes, and the rat and human β-actin genes were examined. It is shown (i) that the 3′ UTR of c-fos is highly conserved between mouse and man, (ii) that multiple copies of a 12 bp element occur, in clusters, in the 3′ UTR both of c-fos and of β-actin. This conserved 12 bp element is analogous to the putative repressor binding site previously identified (Renan, Bioscience Reports,5 (1985), 739–753). These findings provide additional support for the proposal that regulatory signals are located in the 3′ UTR's of certain genes.
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Nygren-Babol, Linnéa. "Comments on the Article by Christensen U, Holm J and Hansen SI (2006) Bioscience Reports 26:291–299." Bioscience Reports 27, no. 6 (November 20, 2007): 413–17. http://dx.doi.org/10.1007/s10540-007-9059-7.
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Hill, Brian T., Caroline J. Roth, Rachel Kositsky, Tushar Dave, Cassandra Love, Matthew McKinney, Ahmed Galal, et al. "Impact of Molecular Features of Diffuse Large B-Cell Lymphoma on Treatment Outcomes with Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy." Blood 138, Supplement 1 (November 5, 2021): 165. http://dx.doi.org/10.1182/blood-2021-145764.
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Abstract INTRODUCTION Diffuse large B-cell lymphoma (DLBCL) represents several distinct clinical pathologic entities recently identified by molecular profiling. Treatment with anti-CD19 chimeric antigen receptor (CAR) T-cell therapies is now standard for many patients with relapsed/refractory (R/R) disease. Although antigen loss of CD19 represents a known cause of late relapses, the majority of CAR-T cell treatment failure occurs very soon after treatment at which time the impact of molecular subtype and other somatic mutations of DLBCL is undefined. We sought to determine impact of molecular features of DLBCL tumors on clinical outcomes in a cohort of patients with R/R disease who were treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in order to provide insight into the mechanism of response or resistance to CAR-T cell therapy. METHODS We collected clinical data and formalin-fixed, paraffin embedded (FFPE) biopsy specimens from 121 DLBCL patients at the time of R/R disease after prior treatment with standard chemoimmunotherapy across 12 US academic medical centers who subsequently received commercial CAR-T cell treatment. Whole exome and transcriptome sequencing was performed on all cases to measure gene expression and gene copy number alterations. Genetic analysis was done on 96 patients with pre-treatment biopsies that passed sequencing quality filters, and expression analysis on 93 patients. Progression-free and overall survival (PFS, OS) measured from the day of CAR-T cell infusion were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS Baseline demographics and treatment details of the patient population are shown in the Table (Panel A). Best overall response was CR in 43% of patients and PR in 10% patients. PFS and OS were significantly different based on best response to treatment (P<0,001 Figure, Panel B). At the time of R/R disease, the most commonly mutated genes were TP53 (25%), KMT2D (23%), CREBBP (23%), BCL2 (20%), BTG2 (12%), ARID1A (11%), CARD11 (11%), MYD88 (11%) and PIM1 (11%), (Panel C). Molecular subtyping based on the method of Wright, et al. revealed cases to be BN2 (N=16), A53 (N=13), EZB (N=14), MCD (N=13), N1 (N=4), ST2 (N=8) and unclassifiable (UC) in 28 cases. Cluster analysis as described by Chapuy et al. assigned cases to be C0 (N=6), C1 (N=18), C2 (N=14), C3 (N=27), C4 (N=17) and C5 (N=14). The impact of subgroups on of PFS are shown in Panels D and E. While not statistically significant different across all groups, there was a trend towards improved outcomes in C5/MCD as well as the C2/A53 subtypes and a trend towards inferior PFS in the C3/EZB subtypes. Inferior PFS was observed in patients with mutations in BCL2 (P=0.009) and MYC (P<0.001), but not BTG2 (P=0.095), MYD88 (P=0.106), or CD79B (P=0.086). An unbiased model comprising mutations in MYC, BCL2, CDKN2A, and KLHL6 was strongly associated with a lack of response to CAR-T therapy and a poor prognosis (HR=3.55, P<0.001, Panel F). Gene Set Enrichment Analysis (GSEA) identified a gene signature reflecting T-cell activation in the pre-treatment tumor biopsy as being associated with a higher likelihood of response to treatment (Panel G). CONCLUSIONS DLBCL patients whose tumors have molecular features that are predictive of inferior response to standard frontline treatment including the high-risk subgroups (C2/A53) and (C5/MCD) have favorable treatment outcomes with CAR-T cell therapy. In contrast, individual driver mutations including MYC and BCL2, CDKN2A, and KLHL6 are associated with inferior PFS with CAR-T cell therapy, while mutations in BTG2, MYD88, and CD79B are associated with a favorable PFS. In addition, gene expression analysis implicates a potential role for the microenvironment in modulating responses to CAR-T therapy. These findings suggest that predictive biomarkers for response to traditional chemoimmunotherapy and cellular immunotherapy are distinct. Our results provide insight into potentially targetable pathways for the development of rational treatment strategies that may augment response CAR-T cell therapy. Figure 1 Figure 1. Disclosures Hill: Celgene (BMS): Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Gentenech: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. McKinney: Novartis: Research Funding; Nordic Nanovector: Research Funding; Molecular Templates: Consultancy, Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Incyte: Research Funding; Genetech: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy; Celgene: Consultancy, Research Funding; BTG: Consultancy; Beigene: Research Funding; ADC Therapeutics: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy; Verastem: Consultancy. Neff: Spring Discovery: Consultancy, Ended employment in the past 24 months; EUSA Pharma: Speakers Bureau; Enzyvant: Consultancy. Reshef: BMS, Regeneron, TScan, Synthekine, Atara, Jasper, Bayer: Consultancy; ilead, BMS, Precision, Immatics, Atara, Takeda, Shire, Pharmacyclics, Incyte: Research Funding; Bayer: Consultancy; Gilead and Novartis: Honoraria. Oluwole: Janssen: Consultancy; Pfizer: Consultancy; Curio Science: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Ghosh: Incyte: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genmab: Consultancy, Honoraria; Epizyme: Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria; Adaptive Biotech: Consultancy, Honoraria; AbbVie: Honoraria, Speakers Bureau; Karyopharma: Consultancy, Honoraria; Genentech: Research Funding. Chen: Actinium Pharmaceuticals: Other: Principal Investigator, SIERRA Trial, Actinium. Hernandez-Ilizaliturri: AbbVie: Other: Advisory Boards; Incyte: Other: Advisory Boards; Celgene: Other: Advisory Boards; BMS: Other: Advisory Boards; Pharmacyclics: Other: Advisory Boards; Amgen: Other: Advisory Boards; Kite: Other: Advisory Boards; Gilead: Other: Advisory Boards; Epyzime: Other: Advisory Boards. Shah: Lily: Consultancy, Honoraria, Research Funding; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Kite: Consultancy; Epizyme: Consultancy; Legend: Consultancy; Incyte: Consultancy; Umoja: Consultancy. Stephens: Epizyme: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; JUNO: Research Funding; Novartis: Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; CSL Behring: Consultancy; Celgene: Consultancy; Mingsight: Research Funding; Arqule: Research Funding. Patel: Janssen: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy, Speakers Bureau; MEI Pharma: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy, Speakers Bureau; BeiGene: Consultancy; Morphosys: Consultancy; Pharmacyclics: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy; Lilly: Consultancy. Pagel: Gilead: Consultancy; Actinium Pharmaceuticals: Consultancy; Kite, a Gilead Company: Consultancy; Incyte/MorphoSys: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/AbbVie: Consultancy; Epizyme: Consultancy; BeiGene: Consultancy; MEI Pharma: Consultancy. Hsi: AbbVie Inc, Eli Lilly: Research Funding. Goy: Genentech/Hoffman la Roche: Research Funding; AbbVie/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Consultancy, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Medscape: Consultancy; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Physicians' Education Resource: Consultancy, Other: Meeting/travel support; Xcenda: Consultancy, Honoraria; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; LLC(Targeted Oncology): Consultancy; Hoffman la Roche: Consultancy; Vincerx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Rosewell Park: Consultancy; Infinity/Verastem: Research Funding; MorphoSys: Honoraria, Other; Elsevier PracticeUpdate: Oncology: Consultancy, Honoraria; Xcenda: Consultancy; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Vincerx pharma: Membership on an entity's Board of Directors or advisory committees; OncLive Peer Exchange: Honoraria; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Elsevier's Practice Update Oncology, Intellisphere, LLC(Targeted Oncology): Consultancy; Incyte: Honoraria; AbbVie/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Michael J Hennessey Associates INC: Consultancy; Novartis: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Karyopharm: Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Phamacyclics: Research Funding; Constellation: Research Funding; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment. Ohgami: Stemline Therapeutics: Research Funding. Andreadis: CRISPR Therapeutics: Research Funding; GenMAB: Research Funding; Novartis: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Epizyme: Honoraria; Incyte: Honoraria; TG Therapeutics: Honoraria; Kite: Honoraria; Karyopharm: Honoraria; Atara: Consultancy, Honoraria; BMS: Research Funding; Merck: Research Funding. Thacker: Data Driven Bioscience: Current Employment. Rozzi: Data Driven Bioscience: Current Employment. Parker: Data Driven Bioscience: Current Employment. Happ: Data Driven Bioscience: Current Employment. Dave: Data Driven Bioscience: Current equity holder in publicly-traded company.
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Battiwalla, Minoo, Sheila Sait, AnneMarie W. Block, Ibrahim Kebbewar, Manmeet S. Ahluwalia, Earl A. Timm, and Paul K. Wallace. "Fluorescence Activated Cell Sorting (FACS) Followed by Fluorescence In Situ Hybridization (FISH) To Determine Clonal Origins of Cells in Myelodysplastic Syndrome (MDS) with Paroxysmal Nocturnal Hemoglobinuria (PNH)." Blood 110, no. 11 (November 16, 2007): 4623. http://dx.doi.org/10.1182/blood.v110.11.4623.4623.
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Abstract The combination of FACS and FISH has been used to identify clonal cytogenetic abnormalities in small populations of cells in diseases such as multiple myeloma. We describe our refinement and application of this technique in a patient with known MDS/PNH to dissect the clonal origins of the disorder. The subject is a 45-year old woman with MDS diagnosed five years ago when she presented with macrocytic anemia and thrombocytopenia. Bone marrow was hypocellular (20% cellularity), with 4% blasts, FAB-RA, WHO- RCMD, Intermediate-1 by IPSS, del 20q clone by FISH. Family history is significant for a familial cytopenia with two sisters developing bone marrow failure, but negative for carriage of the hTERC mutation. HLA DRB1 type was 0101;1301. There was no evidence for T-LGL by flow cytometry or by TCR gene rearrangement assay. Management has been observational only without the need for transfusions. A new PNH clone was detected for the first time by flow cytometry six months ago. Heparinized blood was processed by the laboratory on the same day as collected. WBCs were separated from RBCs by a combination of dextran centrifugation and lysis of RBCs with ammonium chloride. Normal mouse IgG (3mg/mL) was added to block Fc receptors. The cells were stained with mAb cocktails containing CD16 PE (Clone 3G8, Invitrogen), CD55 PC5 (clone IA10, BD Bioscience), and CD15 APC (clone HI98, BD Bioscience) for granulocytes; or CD14 PE (clone TUK4, Invitrogen), CD55 PC5, and CD64 (clone M22, Trillium) for monocytes. Concurrent with mAb staining proaerolysin (FLAER Ax488, Protox Biotech) was added to each tube. The cells were incubated with mAbs and FLAER reagent at saturating concentrations in the dark, on ice, for 30 minutes. They were then washed once with PBS, fixed in 0.5% methanol free formaldehyde (Polysciences, Warrington, PA) for 20 minutes and finally resuspended in PBS. Cytofluorometric analysis and sorting was performed using a FACSAria (BD BioSciences) flow cytometer. Granulocytes were defined using a Boolean combination of forward, side scatter and CD15; monocytes were defined with forward, side scatter and CD64. Granulocytes and monocytes were sorted into PNH positive and negative cells based on FLAER, CD55 and either CD16 (granulocytes) or CD14 (monocytes) expression. Data was analyzed using WinList (Verity Software House, Topsham, ME). FISH analysis for del(20q) was performed on these cells using the Vysis LSI D20S108 SpectrumOrange Probe (Abbott Molecular Inc.). Our results (table 1) show that the PNH clone (FLAER negative) is a distinct non-overlapping population from the del(20q) dysplastic population. Conclusions: Our technique of flow-sorting followed by FISH is feasible for enriching and characterizing PNH positive and negative cellular fractions in bone marrow failure states. The PNH clone in this patient, contrary to other reports in the literature, does not overlap with the MDS clone, rather arising from normal non-dysplastic cells consistent with a putative immune evasion mechanism. This technique is a powerful clinical or research tool to elucidate clonal origins in PNH-associated bone marrow failure states. Table 1 Pre-sort Post-sort 20q− by FISH Unsorted WBCs 13/200 Monocytes PNH− 67% 76% 34/200 PNH+ 245 81% 5/200 = negative control Granulocytes PNH− 72% 94% 34/200 PNH+ 26% 94% 5/200 = negative control
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Liu, Yong, Shuangmin Liang, Bo Wang, Jinbo Zhao, Xiannian Zi, Shixiong Yan, Tengfei Dou, Junjing Jia, Kun Wang, and Changrong Ge. "Advances in Single-Cell Sequencing Technology and Its Application in Poultry Science." Genes 13, no. 12 (November 25, 2022): 2211. http://dx.doi.org/10.3390/genes13122211.
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Single-cell sequencing (SCS) uses a single cell as the research material and involves three dimensions: genes, phenotypes and cell biological mechanisms. This type of research can locate target cells, analyze the dynamic changes in the target cells and the relationships between the cells, and pinpoint the molecular mechanism of cell formation. Currently, a common problem faced by animal husbandry scientists is how to apply existing science and technology to promote the production of high-quality livestock and poultry products and to breed livestock for disease resistance; this is also a bottleneck for the sustainable development of animal husbandry. In recent years, although SCS technology has been successfully applied in the fields of medicine and bioscience, its application in poultry science has been rarely reported. With the sustainable development of science and technology and the poultry industry, SCS technology has great potential in the application of poultry science (or animal husbandry). Therefore, it is necessary to review the innovation of SCS technology and its application in poultry science. This article summarizes the current main technical methods of SCS and its application in poultry, which can provide potential references for its future applications in precision breeding, disease prevention and control, immunity, and cell identification.
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Krawetz, Stephen A., Wayne Connor, and Gordon H. Dixon. "Oligonucleotides as probes for mammalian protamine mRNAs." Bioscience Reports 6, no. 6 (June 1, 1986): 585–90. http://dx.doi.org/10.1007/bf01114956.
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Protamine-like sequences have been identified in poly A(+) mRNAs from mammalian testes by the use of a common, complementary oligonucleotide (GCAGCANCK PTANCKNGCCAT; predicted from the common N-terminal amino acid sequence, MARYRCC, seen in several mammalian P1 protamines [D. J. McKay, B. S. Renaux and G. H. Dixon, Bioscience Reports5:383–391 (1985)]). This oligonucleotide was utilized to prepare species-specific, primer-extended transcripts for use as Northern blotting probes. Analysis of the mRNA primer-extended transcripts revealed a discrete and similar set of products common to both bull and rat testis mRNAs which were distinct from those obtained from human testis mRNA. Northern analysis of total poly A(+) mRNAs from the corresponding mammalian testis was consistent with these results and suggests that bull and rat protamine mRNAs are more closely related to each other than to human protamine mRNA.
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Lis, Raphael, Charles Harrasch, Michael Gustave Poulos, Jose Gabriel Duran, William Schachterle, Michael Ginsberg, Arash Rafii, et al. "Direct Conversion of Adult Endothelial Cells into Immunecompetent Long-Term Engraftable Clinically Scalable Hematopoietic Stem Cells: Pathway to Therapeutic Translation." Blood 128, no. 22 (December 2, 2016): 372. http://dx.doi.org/10.1182/blood.v128.22.372.372.
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Abstract The molecular pathways and microenvironmental cues that choreograph the conversion of endothelial cells (ECs) into true engraftable hematopoietic stem cells (HSCs) remain undefined. This is due to lack of models to recreate the short-lived transition from EC to hemogenic cells and to HSCs. Extending on our previous work (Sandler V. et al, Reprogramming of human endothelium into hematopoietic cells requires vascular niche induction. Nature, 511:312-8. 2014), we have developed a novel, sequential, clinically-translatable in vitro model of the adult EC to hematopoietic transition (EHT). This model uses precise, conditional, on-off expression of transcription factors (FosB, Gfi1, Runx1, and Spi1 - FGRS) and an inductive vascular niche to reprogram adult mouse ECs into true HSCs (rEC-HSCs) with high efficiency. During the induction phase (days 0-8), FGRS are conditionally expressed in adult non-lymphatic ECs isolated from Runx1-IRES-GFP reporter mice and co-cultured with the supportive vascular niche cells. During the specification phase (days 8-20), FGRS-transduced VEcad+Runx1-CD45- ECs activate expression of endogenous Runx1, initiating the hematopoietic program and silencing EC fate. The VEcad+Runx1+CD45+ cells, then complete specification and full commitment to VEcad-Runx1+CD45+ hematopoietic stem and progenitor cells (rEC-HSPCs). Specified rEC-HSPCs are then expanded (days 20-28) on the vascular niche generating a large number of hematopoietic cells and, at this point, expression of exogenous FGRS is turned off. Transplantation of rEC-HSPCs (CD45.2) into lethally irradiated (CD45.1) recipient mice reconstitute both short-term and long-term hematopoiesis, and are capable of engrafting secondary and tertiary recipients (rEC-HSCs). Once engrafted, rEC-HSPCs give rise to functional myeloid and lymphoid cells with full complement of polarized T cell subsets. rEC-HSC-derived immune cells undergo T-cell receptor (TCR) rearrangement and reconstitute adaptive immune function in Rag1-/- mice. To prove the stem cell potential of rEC-HSCs, we performed clonal analyses on the VEcad+Runx1+CD45+ cells (days 8-20), in which single cells were plated in coculture with vascular niche. Notably, 7 out of 386 CD45.2+ clones gave rise to expanding colonies that were capable of 4 months primary multilineage engraftment into lethally irradiated CD45.1+ recipients. In addition, limiting dilution transplantation of isochronic VEcad-Runx1+CD45+ cells indicated that 1 out of 538 rEC-HSPCs are repopulating rEC-HSCs with primary and secondary engraftment potential. Thus, based on both clonal and limiting dilution transplantation studies, we demonstrate that rEC-HSCs represent true repopulating prototypical HSCs. In addition, since during the expansion phase there are >200 fold expansion of the SLAM-coded KLS population, these data support the notion that during the 20-28 days expansion phase there is robust proliferation of rEC-HSCs. Serial analyses of the primary, secondary and tertiary engrafted rEC-HSCs, showed no evidence of leukemias. Molecular analyses indicated that both in vitro and in vivo expanded rEC-HSCs had complete erasure of vascular signature and stable expression of hematopoietic profile. Moreover, employing Runx1-IRES-GFP reporter mice enabled deconvolution of stage-specific pathways involved in generation of engraftable rEC-HSCs. Inhibition of TGFβ signaling along with activation of BMP and CXCL12 pathways reinforced the induction phase. Active Notch and CXCL12 signaling throughout the specification and expansion phases supported self-renewal of transplantable rEC-HSCs. This stepwise reprogramming approach provides an interrogatable in vitro platform to elucidate the critical pathways involved in the transition of ECs into hemogenic-like and ultimately hematopoietic cells in vitro. Specifically, these data unequivocally support that our approach lead to generation of large number HSCs, enabling therapeutic application. Thus, our reprogramming platform that does not require transition through a pluripotent state, will facilitate devising strategies to reprogram ECs into abundant autologous long-term repopulating HSCs amenable to genetic modification for treatment of inherited and acquired hematological disorders. Disclosures Ginsberg: Angiocrine Bioscience: Employment. Butler:Angiocrine Bioscience: Research Funding. Rafii:Angiocrine Bioscience: Equity Ownership, Other: Non-paid consultant.
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Ock, S. A., B. G. Jeon, D. O. Kwack, and G. J. Rho. "283 COMPARATIVE CHARACTERIZATIONS OF PORCINE MESENCHYMAL STEM CELLS AND SKIN-DERIVED CELLS." Reproduction, Fertility and Development 21, no. 1 (2009): 238. http://dx.doi.org/10.1071/rdv21n1ab283.
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Mesenchymal stem cells (MSC) have high potential in regenerative medicine such as skin substitute for a burn healing. The present study compared the characterizations of porcine MSCs (pMSC) derived from bone marrow to the same porcine adult ear and different porcine fetal skin derived cells on morphology of cell growth, alkaline phosphatase (AP) activity, cell surface (CD) markers (CD 29, 45, 90 and 105) and cell cycle by flow cytometer and protein and mRNA expression of Oct3/4, Nanog and Sox2 by immunocytochemistry and RT-PCR (Carlin et al. 2006 Reprod. Biol. Endocrinol. 4, 8) in 1–3 passage. The pMSC were isolated with Ficoll–Paque Plus (Amersham Science, USA) and skin-derived cells were separated with trypsin-EDTA solution treatment of tissue. Basal medium used for culture of pMSC and skin-derived cells was advanced-DMEM supplemented with 10% FBS and 1% penicillin–streptomycin (10 000 IU and 10 000 μg mL–1, Gibco) and culture medium was exchanged every 3 days. Skin-derived cells were observed similar patterns of colony formation and AP expression by AP chromogen kit (BCIP/NBT) (Abcam Inc., MA, USA) to pMSC on plating culture. pMSC and skin-derived cells were found to have a stronger reaction of CD 45– (St. Louis, MO, USA), CD 29+ (BD Bioscience, US), and CD 90+ (BD Bioscience, US). However, CD 105+ (abD Serotec, UK) weakly expressed in pMSC and skin-derived cells were almost negative. The population of cells at S-phase of the cycle in pMSC was significantly (P < 0.05) greater than those in adult ear and fetal-derived skin cells (30.4 ± 5.3 v. 19.1 ± 3.6 and 21.3 ± 1.7, respectively; mean ± SD). Protein of Oct3/4 (goat polyclonal IgG, Santa Cruz, CA, USA), Nanog (goat polyclonal IgG, Santa Cruz, CA, USA) and Sox2 (rabbit polyclonal IgG, Santa Cruz, CA, USA) were observed at both nucleus and cytoplasm in all cell types. However, the pattern of mRNA expression was different among cell types. Nanog and Sox2 expression was the greatest in pMSC and fetal skin cells, respectively. Oct 4 expression should read extremely low in pMSC compared with skin-derived cells, contrary to expectation. Taken together, pMSC and skin-derived cells revealed similar characterization, indicating that pMSC can expect a role of skin substitute. This work was supported by grant from Biogreen21 (20070301034040), Ministry of Agriculture and Forestry, Republic of Korea.
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Evans, James A., and Andrey Rzhetsky. "Advancing Science through Mining Libraries, Ontologies, and Communities." Journal of Biological Chemistry 286, no. 27 (May 12, 2011): 23659–66. http://dx.doi.org/10.1074/jbc.r110.176370.
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Life scientists today cannot hope to read everything relevant to their research. Emerging text-mining tools can help by identifying topics and distilling statements from books and articles with increased accuracy. Researchers often organize these statements into ontologies, consistent systems of reality claims. Like scientific thinking and interchange, however, text-mined information (even when accurately captured) is complex, redundant, sometimes incoherent, and often contradictory: it is rooted in a mixture of only partially consistent ontologies. We review work that models scientific reason and suggest how computational reasoning across ontologies and the broader distribution of textual statements can assess the certainty of statements and the process by which statements become certain. With the emergence of digitized data regarding networks of scientific authorship, institutions, and resources, we explore the possibility of accounting for social dependences and cultural biases in reasoning models. Computational reasoning is starting to fill out ontologies and flag internal inconsistencies in several areas of bioscience. In the not too distant future, scientists may be able to use statements and rich models of the processes that produced them to identify underexplored areas, resurrect forgotten findings and ideas, deconvolute the spaghetti of underlying ontologies, and synthesize novel knowledge and hypotheses.
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Li, Guilin, Yurong Xu, Xuan Sheng, Hua Liu, Jingjing Guo, Jiayue Wang, Qi Zhong, et al. "Naringin Protects Against High Glucose-Induced Human Endothelial Cell Injury Via Antioxidation and CX3CL1 Downregulation." Cellular Physiology and Biochemistry 42, no. 6 (2017): 2540–51. http://dx.doi.org/10.1159/000480215.
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Background/Aims: The induction of endothelial injury by hyperglycemia in diabetes has been widely accepted. Naringin is a bio-flavonoid. Some studies showed that naringin alleviates diabetic complications, but the exact mechanisms by which naringin improves diabetic anomalies are not yet fully understood. The aim of this research was to study the protective effect of naringin on high glucose-induced injury of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were cultured with or without high glucose in the absence or presence of naringin for 5 days. The expression of CX3CL1 was determined by quantitative real-time RT-PCR (qPCR) and western blot. The cellular bioenergetic analysis oxygen consumption rate (OCR) was measured with a Seahorse Bioscience XF analyzer. Results: The production of reactive oxygen species (ROS), the expression of CX3CL1 and the level of AKT phosphorylation were increased in HUVECs cultured with high glucose compared with controls. However, naringin rescued these increases in ROS production, CX3CL1 expression and AKT phosphorylation. Nitric oxide (NO) production and OCR were lower in the high glucose group, and naringin restored the changes induced by high glucose. Molecular docking results suggested that Naringin might interact with the CX3CL1 protein. Conclusion: Naringin protects HUVECs from high-glucose-induced damage through its antioxidant properties by downregulating CX3CL1 and by improving mitochondrial function.
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Vella, Frank. "Standards for the Ph.D. Degree in the Molecular Biosciences." IUBMB Life 48, no. 6 (December 1, 1999): 567–76. http://dx.doi.org/10.1080/713803576.
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Pham, Xuan-Hung, Seung-Min Park, Kyeong-Min Ham, San Kyeong, Byung Sung Son, Jaehi Kim, Eunil Hahm, et al. "Synthesis and Application of Silica-Coated Quantum Dots in Biomedicine." International Journal of Molecular Sciences 22, no. 18 (September 18, 2021): 10116. http://dx.doi.org/10.3390/ijms221810116.
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Quantum dots (QDs) are semiconductor nanoparticles with outstanding optoelectronic properties. More specifically, QDs are highly bright and exhibit wide absorption spectra, narrow light bands, and excellent photovoltaic stability, which make them useful in bioscience and medicine, particularly for sensing, optical imaging, cell separation, and diagnosis. In general, QDs are stabilized using a hydrophobic ligand during synthesis, and thus their hydrophobic surfaces must undergo hydrophilic modification if the QDs are to be used in bioapplications. Silica-coating is one of the most effective methods for overcoming the disadvantages of QDs, owing to silica’s physicochemical stability, nontoxicity, and excellent bioavailability. This review highlights recent progress in the design, preparation, and application of silica-coated QDs and presents an overview of the major challenges and prospects of their application.
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Ahmed, Ishtiaq, Zain Akram, Mohammed Bule, and Hafiz Iqbal. "Advancements and Potential Applications of Microfluidic Approaches—A Review." Chemosensors 6, no. 4 (October 15, 2018): 46. http://dx.doi.org/10.3390/chemosensors6040046.
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A micro-level technique so-called “microfluidic technology or simply microfluidic” has gained a special place as a powerful tool in bioengineering and biomedical engineering research due to its core advantages in modern science and engineering. Microfluidic technology has played a substantial role in numerous applications with special reference to bioscience, biomedical and biotechnological research. It has facilitated noteworthy development in various sectors of bio-research and upsurges the efficacy of research at the molecular level, in recent years. Microfluidic technology can manipulate sample volumes with precise control outside cellular microenvironment, at micro-level. Thus, enable the reduction of discrepancies between in vivo and in vitro environments and reduce the overall reaction time and cost. In this review, we discuss various integrations of microfluidic technologies into biotechnology and its paradigmatic significance in bio-research, supporting mechanical and chemical in vitro cellular microenvironment. Furthermore, specific innovations related to the application of microfluidics to advance microbial life, solitary and co-cultures along with a multiple-type cell culturing, cellular communications, cellular interactions, and population dynamics are also discussed.
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Best, Oliver Giles, Kyle Crassini, Michael O'Neill, Michael E. O'Dwyer, and Stephen P. Mulligan. "Dual Inhibition of PIM and PI3-Kinase By Ibl-202 Is Highly Synergistic Compared to Mono-Molecular Inhibition and Represents a Novel Treatment Strategy for Chronic Lymphocytic Leukemia." Blood 124, no. 21 (December 6, 2014): 4693. http://dx.doi.org/10.1182/blood.v124.21.4693.4693.
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Abstract BACKGROUND Trials of ibrutinib and idelalisib for Chronic Lymphocytic Leukemia (CLL) targeting Btk and PI3-kinase respectively, illustrate the potential of targeting components of the B-cell receptor (BCR) signalling pathway. Emerging evidence suggests that subgroups of CLL patients develop resistance to these agents. In particular late relapses on ibrutinib appear to be associated with a high frequency of acquired mutations in Btk and PLCg2. Identification of novel combination therapies or agents that target multiple molecules in key signaling pathways represents a rational approach in the development of novel treatment strategies. Pim (provirus integration site for Moloney murine leukemia virus) family proteins are proto-oncogenic and involved in B-cell development and lymphoid malignancies. They are highly conserved serine/threonine kinases and are overexpressed in CLL. Given the clinical efficacy of idelalisib and results of preclinical studies of the PIM kinase SGI-1776 [Chen et al., 2009], we sought to investigate the potential of simultaneous inhibition of PIM and PI3-kinase for CLL therapy. METHODS The effects of the novel inhibitor of PIM kinase, pPIMi, and the dual inhibitor of PIM/PI3-kinase, IBL-202 (both from Inflection Bioscience Ltd, Ireland), were investigated against panels of primary CLL patient samples and haematological lines. The in vitro efficacy of both agents was compared to that of SGI-1776 and idelalisib and studied under conditions involving CLL cell co-culture using CD40L-expressing fibroblasts that mimic the support offered by the CLL tumor microenvironment. RESULTS Inhibition of PIM kinase by pPIMi was as effective as SGI-1776, inducing a dose dependent decrease in CLL-cell viability. The rationale for dual inhibition of PIM and PI3-kinase was investigated by combining pPIMi with idelalisib and by calculation of combination indices (CI), where CI values of < 1 are indicative of synergy. In primary CLL patient samples (Figure 1) and 3 B-cell lines (Mec1, Ramos and Raji) the combination proved highly synergistic, with CI values of 0.07 + /- 0.03 and 0.11 +/- 0.07 respectively, for fractional cell killing effects of between 0.1 and 0.9. Consistent with our assessment of synergy between pPIMi and idelalisib, dual inhibition of PIM and PI3-kinase by IBL-202 was significantly more effective at inducing cell death than either pPIMi or idelalisib as single agents (Figure 2), evidenced by the significantly lower IC50 against CLL patient samples (7.47 µM, 43.12 µM, 1.23 µM for pPIMi, idelalisib and IBL-202 respectively). The rationale for targeting PIM and PI3-kinase using IBL-202 was further highlighted by culturing CLL cells in the presence of a CD40L-expressing fibroblast monolayer, which represents a model of the tumor microenvironment. CD40L fibroblast co-culture significantly increased CLL-cell survival under control conditions but also conferred resistance to the PIM inhibitor pPIMi. In contrast CLL cells cultured under these conditions were sensitive to IBL-202 in a dose dependent manner. CONCLUSION Inhibition of PIM and PI3-kinase is potently synergistic against CLL cells and is particularly effective under conditions that mimic the tumor microenvironment. Dual targeting of PIM and PI3-kinase by IBL-202 may represent a novel therapeutic strategy for CLL that minimizes the risk of acquired mutations associated with mono-molecular inhibition of BCR-signaling components. Figure 1. Synergy between pPIMi and idelalisib in primary CLL patient samples supports dual inhibition of PIM and PI3-kinase by IBL-202. Figure 1. Synergy between pPIMi and idelalisib in primary CLL patient samples supports dual inhibition of PIM and PI3-kinase by IBL-202. Figure 2. Dose response analyses of pan PIM inhibitor (pPIMi), idelalisib (CAL-101) and PIM/PI3-kinase inhibitor (IBL-202) against primary CLL patient samples (n = 9). Figure 2. Dose response analyses of pan PIM inhibitor (pPIMi), idelalisib (CAL-101) and PIM/PI3-kinase inhibitor (IBL-202) against primary CLL patient samples (n = 9). Disclosures O'Neill: Inflection Biosciences: Employment, Equity Ownership. O'Dwyer:Inflection Biosciences Ltd: Membership on an entity's Board of Directors or advisory committees. Mulligan:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi Aventis: Research Funding; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria.
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Faron, Matthew L., Nathan A. Ledeboer, Anami Patel, Safedin H. Beqa, Belinda Yen-Lieberman, Debra Kohn, Amy L. Leber, Donna Mayne, William I. Northern, and Blake W. Buchan. "Multicenter Evaluation of Meridian Bioscience HSV 1&2 Molecular Assay for Detection of Herpes Simplex Virus 1 and 2 from Clinical Cutaneous and Mucocutaneous Specimens." Journal of Clinical Microbiology 54, no. 8 (May 18, 2016): 2008–13. http://dx.doi.org/10.1128/jcm.00483-16.
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Herpes simplex virus (HSV) causes acute and relapsing symptoms characterized by ulcerative lesions. Laboratory diagnosis of HSV in cutaneous or mucocutaneous lesions has historically been performed with the use of viral cell culture systems; however, these tests are laborious and suffer decreased sensitivity for advanced-stage lesions. The recent availability of FDA-cleared moderately complex assays has resulted in the increased use of molecular diagnostics for the routine detection of HSV in superficial swab specimens. We performed a clinical evaluation of the recently FDA-clearedillumigene HSV 1&2 loop-mediated isothermal amplification (LAMP) assay (Meridian Bioscience, Cincinnati OH) for the detection and differentiation of HSV-1 and HSV-2 in cutaneous and mucocutaneous swab specimens. A total of 1,153 clinical swab specimens were collected and tested at 7 different clinical centers. Each specimen was tested for the presence of HSV-1 and HSV-2 using theillumigene assay, and results were compared to those of the enzyme-linked virus-inducible system (ELVIS) as the reference method. Overall, theillumigene assay demonstrated a sensitivity and specificity of 94.8% and 95.5%, respectively, for the detection of HSV-1. Detection of HSV-2 was similar, with a sensitivity of 98.9% and a specificity of 95.5%. Discrepant analysis was performed using an alternative molecular test (AmpliVue HSV1+2 assay; Quidel Molecular, San Diego, CA) on 91/99 specimens that were recorded as false positive (FP) or false negative (FN) compared to the reference method. In total, 57/78 (73%) FP and 9/13 (69%) FNillumigene results were supported by the AmpliVue result. Theillumigene HSV 1&2 assay demonstrated high sensitivity and specificity to detect and differentiate HSV in clinical specimens and identified 57 additional specimens that were positive for HSV compared to culture. The use of LAMP eliminates the need for the cycling of temperatures and provides results in less than 60 min, with approximately 2 min of hands-on time per specimen.
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Blencowe, Benjamin J. "An exon-centric perspective1Canadian Society of Molecular Biosciences (CSMB) Senior Investigator Award." Biochemistry and Cell Biology 90, no. 5 (October 2012): 603–12. http://dx.doi.org/10.1139/o2012-019.
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During the past ten years, remarkable progress has been made in our understanding of the complexity and regulation of alternative splicing. The generation of large datasets of quantitative alternative splicing profiling information has revealed that transcripts from at least 95% of multi-exon human genes undergo alternative splicing, and that thousands of exons in mammalian transcriptomes are subject to striking regulatory patterns. Together with advanced computational methods, these datasets have enabled the inference of a predictive code for tissue-dependent alternative splicing. This code has further provided new insight into splicing regulatory mechanisms. Collectively, these approaches are revealing the existence of discrete networks of exons that are coordinately regulated in diverse biologically normal and disease contexts. A major challenge ahead is to systematically determine the functions of exons comprising these exon networks as well as the factors and mechanisms responsible for their regulation. This perspective provides an account of progress in these areas and also discusses future avenues of exon-centric exploration.
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Reik, Andreas, Kai-Hsin Chang, Sandra Stehling-Sun, Yuanyue Zhou, Gary K. Lee, Lynn Truong, Travis Wood, et al. "Targeted Gene Modification In Hematopoietic Stem Cells: A Potential Treatment For Thalassemia and Sickle Cell Anemia." Blood 122, no. 21 (November 15, 2013): 434. http://dx.doi.org/10.1182/blood.v122.21.434.434.
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Abstract Beta-thalassemia (β-thal) and sickle cell disease (SCD) are monogenic diseases caused by mutations in the adult β-globin gene. A bone marrow transplant (BMT) is the only curative treatment, but its application is limited since (i) HLA-matched donors can be found for <20% of cases, and (ii) the allogeneic nature of the transplant involves the significant risk of graft vs host disease (GvHD). Elevated levels of fetal γ-globin proteins observed in a subset of individuals carrying β-thal and SCD mutations ameliorate the clinical picture or prevent the development of disease complications. Thus, strategies for the selective and persistent upregulation of γ-globin represent an attractive therapeutic approach. Recent insights into the regulation of γ-globin transcription by a network of transcription factors and regulatory elements both inside and outside the β-globin locus have revealed a set of new molecular targets, the modulation of which is expected to elevate γ-globin levels for potential therapeutic intervention. To this end, we and others have established that designed zinc finger nucleases (ZFNs) transiently introduced into stem cells ex vivo provide a safe and efficient way to permanently ablate the expression of a specific target gene in hematopoietic stem cells (HSC) by introduction of mutations following target site cleavage and error-prone DNA repair. Here we report the development and comparison of different ZFNs that target various regulators of γ-globin gene transcription in human HSCs: Bcl11a, Klf1, and specific positions in the γ-globin promoters that result in hereditary persistence of fetal hemoglobin (HPFH). In all cases these target sites / transcription factors have previously been identified as crucial repressors of γ-globin expression in humans, as well as by in vitro and in vivo experiments using human erythroid cells and mouse models. ZFN pairs with very high genome editing activity in CD34+ HSCs were identified for all targeted sites (>75% of alleles modified). In vitro differentiation of these ZFN-treated CD34+ HSCs into erythroid cells resulted in potent elevation of γ-globin mRNA and protein levels without significant effects on erythroid development. Importantly, a similar and specific elevation of γ-globin levels was observed with RBC progeny of genome-edited CD34+ cells obtained from SCD and β-thal patients. Notably, in the latter case a normalization of the β-like to α-globin ratio to ∼1.0 was observed in RBCs obtained from genome-edited CD34s from two individuals with β-thalassemia major. To deploy this strategy in a clinical setting, we developed protocols that yielded comparably high levels of target gene editing in mobilized adult CD34+ cells at large scale (>108 cells) using a clinical-grade electroporation device to deliver mRNA encoding the ZFN pair. Analysis of modification at the most likely off-target sites based on ZFN binding properties, combined with the maintenance of target genome editing observed throughout erythroid differentiation (and in isolated erythroid colonies) demonstrated that the ZFNs were both highly specific and well-tolerated when deployed at clinical scale. Finally, to assess the stemness of the genome-edited CD34+ HSCs we performed transplantation experiments in immunodeficient mice which revealed long term engraftment of the modified cells (>16 weeks, ∼25% human chimerism in mouse bone marrow) with maintenance of differentiation in vivo. Moreover, ex vivo erythroid differentiation of human precursor cells isolated from the bone marrow of transplanted animals confirmed the expected elevation of γ-globin. Taken together, these data suggest that a therapeutic level of γ-globin elevation can be obtained by the selective disruption, at the genome level, of specific regulators of the fetal to adult globin developmental switch. The ability to perform this modification at scale, with full retention of HSC engraftment and differentiation in vivo, provides a foundation for advancing this approach to a clinical trial for the hemoglobinopathies. Disclosures: Reik: Sangamo BioSciences: Employment. Zhou:Sangamo BioSciences: Employment. Lee:Sangamo BioSciences: Employment. Truong:Sangamo BioSciences: Employment. Wood:Sangamo BioSciences: Employment. Zhang:Sangamo BioSciences: Employment. Luong:Sangamo BioSciences: Employment. Chan:Sangamo BioSciences: Employment. Liu:Sangamo BioSciences: Employment. Miller:Sangamo BioSciences: Employment. Paschon:Sangamo BioSciences: Employment. Guschin:Sangamo BioSciences: Employment. Zhang:Sangamo BioSciences: Employment. Giedlin:Sangamo BioSciences: Employment. Rebar:Sangamo BioSciences: Employment. Gregory:Sangamo BioSciences: Employment. Urnov:Sangamo BioSciences: Employment.
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Hakobyan, Narine, Leonard A. Valentino, Lin Cong, Candace Enockson, and Xiagqian Song. "Development of a Scoring System for Assessment of Phenotypic Variability in a Mouse Model of Hemophilia A,." Blood 118, no. 21 (November 18, 2011): 3328. http://dx.doi.org/10.1182/blood.v118.21.3328.3328.
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Abstract Abstract 3328 Joint bleeding is the most frequent serious manifestation of hemophilia and results in significant morbidity, cost and decrement in quality of life. Although prophylaxis has significantly reduced both the frequency of joint bleeding and the development of arthropathy, hemarthrosis continues to be a problem, especially in patients with inhibitors. Understanding the pathobiology of blood-induced joint disease and developing measures to counter this problem remain as central issues in the field. The use of animal models to interrogate the earliest molecular and biochemical steps in this process is useful since such information is not available from humans. As the degree of induced joint bleeding in factor VIII deficient mice is heterogeneous, it is crucial to preclinical and basic research to assess and/or control bleeding severity in each comparable experimental group. Previously, we have created a mouse model of phenotypic variability based on injecting mice with varying concentrations of rFVIII. A chromogenic assay was used to assess the plasma levels of FVIII activity following treatment. [Hemophilia (2011), 17,565] Here we report on an objective system of four independent but inter-related measurements to document this phenotypic variability in a mouse model of hemophilia A: Visual Bleeding Score (VBS), joint diameter, Gross Bleeding Score (GBS) and Histological Bleeding Score (HBS). In order to achieve similar severities of hemarthrosis, groups of F8−/− mice were injected with rFVIII at specified time points prior to induction of bleeding. Each day following injury, the knee joints were examined for the presence of blood and the VBS was assigned. Three days after injury all mice were sacrificed, knee diameters were measured, GBS was assigned and the joints collected for histological examination to determine the HBS. At all-time points the data show a statistically significant correlation between gross (GBS) and histological (HBS) changes (0.87–0.99, P<0.0001) and the residual plasma factor VIII activity measured at the time of injury. The validation study of GBS included 256 samples and five raters blinded to the experimental conditions and showed high and statistically significant correlations between the actual joint scores and the scores of each rater (Spearman correlation, 0.93–0.97). There were no statistically significant differences among intra-observer scores (Friedman test, 0.1–0.8). In conclusion, this scoring system can be used to objectively document phenotypic variability in a mouse model of Hemophilia A. The next step is to use this model to probe the efficacy of novel agents to treat Hemophilia in pre-clinical and clinical development. Disclosures: Valentino: Baxter Bioscience, Bayer Healthcare, GTC Biotherapeutics, NovoNordisk, Pfizer, CSL Behring, Inspiration Bioscience, and Biogen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Port, H., C. Thudium, T. Gantzel, A. C. Bay-Jensen, M. Karsdal, and S. Holm Nielsen. "AB0105 A HIGHLY SENSITIVE NEO-EPITOPE BIOMARKER OF TYPE II COLLAGEN C- TERMINAL IS ASSOCIATED WITH CARTILAGE FORMATION." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1183.2–1184. http://dx.doi.org/10.1136/annrheumdis-2022-eular.674.
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BackgroundAltered extracellular matrix (ECM) remodeling is a common event in rheumatic diseases. Type II collagen is the most abundant ECM protein in the cartilage and provides tensile elasticity and strength to enable support to the joints. Chondrocalcin, also known as the C-terminal propeptide of type II collagen, is among the most highly synthesized polypeptides in cartilage. It is cleaved off by BMP-1/C-endopeptidase during maturation and plays a role in assembly of type II collagen and in calcification of cartilage matrix. When cleaved off, the chondrocalcin fragments are released into circulation, where they can be quantified in a blood sample.ObjectivesThis study aimed at developing an immunoassay targeting a neo-epitope of chondrocalcin, named CALC2. Moreover, we explored its biomarker potential to evaluate type II collagen formation in an ex vivo human osteoarthritis (OA) cartilage explant model (HEX) with anabolic treatment, and in serum from healthy controls, patients with rheumatoid arthritis (RA) and patients with ankylosing spondylitis (AS).MethodsA novel direct immunoassay targeting the neo-epitope of type II collagen C-terminal (PIICP) was developed and technically validated. The technical validation included inter- and intra-variation, linearity, spiking recovery, stability, and specificity. Specificity of the monoclonal antibody was tested using an elongated peptide, a truncated peptide, and a non-sense peptide to exclude possible cross-reactivity. CALC2 levels were measured in supernatant from HEX cultured for 35 days in serum free DMEM/F12 medium with IGF-1 (Insulin-like Growth Factor-1) (100 ng/mL), including a control group without (w/o) treatment. The supernatant was harvested 3 times weekly and replaced with new culture medium with IGF-1. Biomarker results were confirmed by western blot. Serum samples from 18 healthy donors (mean age 35.8 ± SD 3.8, 100% Caucasian), 19 patients with AS (mean age 35.8 ± SD 3.2, 100 % Caucasian) and 18 patients with RA (mean age 35.8 ± SD 3.4), 100% Caucasian) were also measured by CALC2. Linear regression models with pairwise comparisons were performed.ResultsA technically robust and specific assay was developed. The inter- and intra-assay variation of CALC2 was determined as 12% and 7% respectively. CALC2 showed a good dilution recovery, spiking recovery, and storage /freeze-thaw stability (All, 100%±20%). CALC2 showed specificity towards the targeted sequence and did not show any reactivity towards the truncated peptide, elongated peptide, or non-sense peptide. CAL2 neoepitope levels were significantly elevated after 14, 21 and 28 days of IGF-1 treatment compared to untreated (p<0.01, p<0.0001 p<0.001, respectively). The western blot confirmed the CALC2 results by the presence of a band of ~35 kDa in all explants, corresponding to the weight of chondrocalcin previously stablished (1). Furthermore, the bands were more pronounced at day 21 in the IGF-1 treated explant compared to the untreated explant. CALC2 also showed significantly lower levels in patients with RA compared to controls (p=0.003; mean 0.32 ng/mL ± SD 0.16 vs 0.64 ng/mL ± SD 0.31).ConclusionHigher levels of CALC2 were detected in supernatants from explants after 14, 21 and 28 days of IGF-1 treatment compared to untreated. Lower levels of CALC2 were present in patients with RA compared to healthy controls. Overall, this suggests that CALC2 may have potential as biomarker for type II collagen formation. However, further preclinical and clinical studies are required to validate these findings.References[1]Poole R, Choi H. Association of an extracellular protein (chondrocalcin) with the calcification of cartilage in endochondral bone formation. J Cell Biol. 1984;98(1):54–65.Figure 1.CALC2 measurements in HEX model.Disclosure of InterestsHelena Port: None declared, Christian Thudium Shareholder of: Shareholder at Nordic Bioscience A/S, Thorbjørn Gantzel: None declared, Anne-Christine Bay-Jensen Shareholder of: Shareholder of Nordic Bioscience A/S, Morten Karsdal Shareholder of: Shareholder at Nordic Bioscience A/S, Signe Holm Nielsen Shareholder of: Shareholder at Nordic Bioscience A/S
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Sabrina, Valente, Ciavarella Carmen, Astolfi Gloria, Bergantin Elisa, Curti Nico, Buzzi Marina, Fontana Luigi, and Versura Piera. "Impact of Freeze-Drying on Cord Blood (CB), Serum (S), and Platelet-Rich Plasma (CB-PRP) Preparations on Growth Factor Content and In Vitro Cell Wound Healing." International Journal of Molecular Sciences 23, no. 18 (September 14, 2022): 10701. http://dx.doi.org/10.3390/ijms231810701.
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Blood-based preparations are used in clinical practice for the treatment of several eye disorders. The aim of this study is to analyze the effect of freeze-drying blood-based preparations on the levels of growth factors and wound healing behaviors in an in vitro model. Platelet-rich plasma (PRP) and serum (S) preparations from the same Cord Blood (CB) sample, prepared in both fresh frozen (FF) and freeze-dried (FD) forms (and then reconstituted), were analyzed for EGF and BDNF content (ELISA Quantikine kit). The human MIO-M1 glial cell line (Moorfield/Institute of Ophthalmology, London, UK) was incubated with FF and FD products and evaluated for cell migration with scratch-induced wounding (IncuCyte S3 Essen BioScience), proliferation with cyclin A2 and D1 gene expression, and activation with vimentin and GFAP gene expression. The FF and FD forms showed similar concentrations of EGF and BDNF in both the S and PRP preparations. The wound healing assay showed no significant difference between the FF and FD forms for both S and PRP. Additionally, cell migration, proliferation, and activation did not appear to change in the FD forms compared to the FF ones. Our study showed that reconstituted FD products maintained the growth factor concentrations and biological properties of FF products and could be used as a functional treatment option.
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Vella, Frank. "How Standards for the Ph.D. Degree in the Molecular Biosciences Came About." IUBMB Life 48, no. 6 (December 1, 1999): 577–79. http://dx.doi.org/10.1080/713803573.
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Danilova, A. B., T. L. Nekhaeva, V. A. Misyurin, N. A. Avdonkina, N. V. Emelyanova, and I. A. Baldueva. "COMPARATIVE ANALYSIS OF MIGRATION ACTIVITY AND INVASIVE POTENTIAL OF CULTURED SOLID TUMOR CELLS." Siberian journal of oncology 19, no. 3 (July 6, 2020): 64–77. http://dx.doi.org/10.21294/1814-4861-2020-19-3-64-77.
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Understanding of the sequence of events that ensure invasiveness of malignant cells is important for prognostic purposes. The study of the cellular and molecular pathways in the metastatic process lays the foundation for further progress in the treatment of cancer patients.Purpose: a comparative analysis of in vitro migration and invasion of human solid tumor cells isolated from primary and metastatic lesions.Material and Methods. Cell cultures of skin melanoma (SM, n=29), renal cell cancer (RCC, n=2), colorectal cancer (CRC, n=1), soft tissue and bone sarcomas (STBS, n=39) isolated from solid human tumors were studied. Cell migration and invasion were assessed using xCelligence (ACEA Bioscience Inc., USA).Results. All solid tumor cell cultures demonstrated in vitro invasive potential (IP), which was 73.79 % for RCC; 53.16 % for SM; 43.96 % for STBS and 5.16 % for CRC. The rates of migration and invasion (SlopeInv) in STBS cells were higher than those in SM cells (39.33 and 25.3 μm/h (p<0.05), 95.32 and 59.82е-3, respectively (p<0.05). The differences in IP values depending on the origin of STBC cells (primary tumor, relapse, and metastasis) were revealed: 18.11 ± 3.05 %, 25.75 ± 5.57 %, 52.97 ± 5.64 %, respectively (p<0.05). We found a correlation between migration and invasion parameters of solid tumor cells and the expression of factors ensuring their mobility and affecting other cellular components of the tumor microenvironment, including cells of the immune system.Conclusion. The biologically «aggressive» phenotype of SM and STBS cells is associated with the expression of the cancer-testis genes, such as PRAME, PASD1, SSX1 and with the production of HB-EGF, IGFBP, PLGF, PECAM-1, FST, SCF, IL-8. These products can be considered as new targets for therapeutic technologies aimed at influencing metastatic disease.
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Huang, Bo, Yu-kun Wang, Lin-yuan Qin, Qin Wei, Nian Liu, Min Jiang, Hong-ping Yu, and Xiang-yuan Yu. "Reply to Comments on ‘A functional polymorphism rs10830963 in melatonin receptor 1B associated with the risk of gestational diabetes mellitus’." Bioscience Reports 40, no. 2 (February 2020). http://dx.doi.org/10.1042/bsr20200370.
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Abstract Th authors of ‘A functional polymorphism rs10830963 in melatonin receptor 1B associated with the risk of gestational diabetes mellitus’ (Bioscience Reports (2019) 39, 12) have written a reply in response to the correspondence piece by Rosta et al. (Bioscience Reports (2020) 40, 2).
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Cooper, Christopher D. O., and Weiping Han. "A new chapter for a better Bioscience Reports." Bioscience Reports 41, no. 5 (May 2021). http://dx.doi.org/10.1042/bsr20211016.
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Abstract As Bioscience Reports enters its fifth decade of continuous multidisciplinary life science publishing, here we present a timely overview of the journal. In addition to introducing ourselves and new Associate Editors for 2021, we reflect on the challenges the new Editorial Board has faced and overcome since we took over the editorial leadership in June of 2020, and detail some key strategies on how we plan to encourage more submissions and broader readership for a better and stronger journal in the coming years.
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"45th International Conference on the Bioscience of Lipids." Chemistry and Physics of Lipids 130, no. 1 (June 2004): 1–81. http://dx.doi.org/10.1016/j.chemphyslip.2004.04.001.
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"46th International Conference on the Bioscience of Lipids." Chemistry and Physics of Lipids 136, no. 2 (September 2005): 83–166. http://dx.doi.org/10.1016/j.chemphyslip.2005.07.003.
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"47th International Conference on the Bioscience of Lipids." Chemistry and Physics of Lipids 143, no. 1-2 (September 2006): 38–39. http://dx.doi.org/10.1016/j.chemphyslip.2006.06.004.
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"Announcement: 44th International conference on the bioscience of lipids." Biochemical and Biophysical Research Communications 308, no. 4 (September 2003): 1009. http://dx.doi.org/10.1016/s0006-291x(03)01519-5.
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