TY - JOUR AB - Abstract Active drug use among HIV-infected persons is associated with poor adherence to highly active antiretroviral therapy (HAART) and suboptimal treatment outcomes. To understand adherence experiences among HIV-infected drug users, we conducted semistructured interviews with 15 participants in a randomized controlled trial evaluating the efficacy of directly observed HAART delivered in methadone maintenance clinics. Interviews were recorded, transcribed, and thematically analyzed. We identified negative and positive psychological themes associated with both drug use and adherence. Participants described tension between negative feelings (denial, shame, and perceived isolation) and positive feelings (acceptance, motivation, empowerment, and perceived connectedness), and they associated this tension with their own drug using and adherence behaviors. Sustained antiretroviral therapy adherence may require increased emphasis on understanding the psychological experience of HIV-infected drug users. AD - a Division of General Internal Medicine , Albert Einstein College of Medicine and Montefiore Medical Center , Bronx , NY , USA. AN - 23406479 AU - Batchelder, A. W. AU - Brisbane, M. AU - Litwin, A. H. AU - Nahvi, S. AU - Berg, K. M. AU - Arnsten, J. H. C1 - 6 C2 - PMC3740002 CN - 11865 DA - Feb 13 DO - 10.1080/09540121.2013.766303 DP - Nlm ET - 2013/02/15 L1 - internal-pdf://2901596637/Batchelder-2013-_Damaging what wasn't damaged.pdf LA - Eng LB - 23406479 N1 - Batchelder, A W Brisbane, M Litwin, A H Nahvi, S Berg, K M Arnsten, J H K23 DA022454/DA/NIDA NIH HHS/United States K23 DA025736/DA/NIDA NIH HHS/United States R01 DA015302/DA/NIDA NIH HHS/United States R25 DA014551/DA/NIDA NIH HHS/United States R25 DA023021/DA/NIDA NIH HHS/United States Journal article AIDS care AIDS Care. 2013 Feb 13. PY - 2013 RI - 2013 from pubmed SN - 1360-0451 (Electronic) 0954-0121 (Linking) ST - "Damaging what wasn't damaged already": Psychological tension and antiretroviral adherence among HIV-infected methadone-maintained drug users T2 - AIDS Care TI - "Damaging what wasn't damaged already": Psychological tension and antiretroviral adherence among HIV-infected methadone-maintained drug users UR - http://www.ncbi.nlm.nih.gov/pubmed/23406479 http://www.tandfonline.com/doi/pdf/10.1080/09540121.2013.766303 ID - 8 ER - TY - JOUR AB - Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis that leads to peripheral cytopenias. We observed that SMAD7, a negative regulator of transforming growth factor-beta (TGF-beta) receptor-I kinase, is markedly reduced in MDS and leads to ineffective hematopoiesis by overactivation of TGF-beta signaling. To determine the cause of SMAD7 reduction in MDS, we analyzed the 3'UTR of the gene and determined that it contains a highly conserved putative binding site for microRNA-21. We observed significantly elevated levels of miR-21 in MDS marrow samples when compared with age-matched controls. miR-21 was shown to directly bind to the 3'UTR of SMAD7 and reduce its expression in hematopoietic cells. Next, we tested the role of miR-21 in regulating TGF-beta signaling in a TGF-beta-overexpressing transgenic mouse model that develops progressive anemia and dysplasia and thus serves as a model of human bone marrow failure. Treatment with a chemically modified miR-21 inhibitor led to significant increases in hematocrit and led to an increase in SMAD7 expression in vivo. Inhibition of miR-21 also led to an increase in erythroid colony formation from primary MDS bone marrow progenitors, demonstrating its ability in stimulating hematopoiesis in vitro. Taken together, these studies demonstrate the role of miR-21 in regulating overactivated TGF-beta signaling in MDS. AD - Albert Einstein College of Medicine, Bronx, NY; AN - 23390194 AU - Bhagat, T. D. AU - Zhou, L. AU - Sokol, L. AU - Kessel, R. AU - Caceres, G. AU - Gundabolu, K. AU - Tamari, R. AU - Gordon, S. AU - Mantzaris, I. AU - Jodlowski, T. AU - Yu, Y. AU - Jing, X. AU - Polineni, R. AU - Bhatia, K. AU - Pellagatti, A. AU - Boultwood, J. AU - Kambhampati, S. AU - Steidl, U. AU - Stein, C. AU - Ju, W. AU - Liu, G. AU - Kenny, P. AU - List, A. AU - Bitzer, M. AU - Verma, A. C1 - 2 C2 - PMC3624935 C7 - +- CN - 11844 DA - Apr 11 DO - 10.1182/blood-2011-12-397067 blood-2011-12-397067 [pii] DP - Nlm ET - 2013/02/08 KW - 3' Untranslated Regions/genetics Aged Aged, 80 and over Animals Binding Sites/genetics Bone Marrow Cells/metabolism Cell Line Cells, Cultured Female Gene Expression Green Fluorescent Proteins/genetics/metabolism Hematopoiesis/*genetics Humans K562 Cells Male Mice Mice, Transgenic MicroRNAs/*genetics Microscopy, Fluorescence Middle Aged Mutation Myelodysplastic Syndromes/*genetics/metabolism Signal Transduction/*genetics Smad7 Protein/genetics Transforming Growth Factor beta1/*genetics L1 - internal-pdf://1422055886/Bhagat-2013-miR-21 mediates hematopoietic supp.pdf LA - eng LB - 23390194 M1 - 15 N1 - Bhagat, Tushar D Zhou, Li Sokol, Lubomir Kessel, Rachel Caceres, Gisela Gundabolu, Krishna Tamari, Roni Gordon, Shanisha Mantzaris, Ioannis Jodlowski, Tomasz Yu, Yiting Jing, Xiaohong Polineni, Rahul Bhatia, Kavi Pellagatti, Andrea Boultwood, Jacqueline Kambhampati, Suman Steidl, Ulrich Stein, Cy Ju, Wenjun Liu, Gang Kenny, Paraic List, Alan Bitzer, Markus Verma, Amit R01HL082946/HL/NHLBI NIH HHS/United States R01HL116336/HL/NHLBI NIH HHS/United States T32 CA009173/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Blood Blood. 2013 Apr 11;121(15):2875-81. doi: 10.1182/blood-2011-12-397067. Epub 2013 Feb 6. PY - 2013 RI - 2013 from pubmed SN - 1528-0020 (Electronic) 0006-4971 (Linking) SP - 2875-81 ST - miR-21 mediates hematopoietic suppression in MDS by activating TGF-beta signaling T2 - Blood TI - miR-21 mediates hematopoietic suppression in MDS by activating TGF-beta signaling UR - http://www.ncbi.nlm.nih.gov/pubmed/23390194 http://bloodjournal.hematologylibrary.org/content/121/15/2875.full.pdf VL - 121 ID - 6 ER - TY - JOUR AB - Phosphoinositide (PI) 3-kinases are essential regulators of cellular proliferation, survival, metabolism, and motility that are frequently dysregulated in human disease. The design of inhibitors to target the PI 3-kinase/mTOR pathway is a major area of investigation by both academic laboratories and the pharmaceutical industry. This review focuses on the Class IA PI 3-kinase p110beta, which plays a unique role in thrombogenesis and in the growth of tumors with deletion or loss-of-function mutation of the Phosphatase and Tensin Homolog (PTEN) lipid phosphatase. Several p110beta-selective inhibitors that target the ATP-binding site in the kinase domain have been identified. However, recent discoveries regarding the regulatory mechanisms that control p110beta activity suggest alternative strategies by which to disrupt signaling by this PI 3-kinase isoform. This review summarizes the current status of p110beta-specific inhibitors and discusses how these new insights into p110 regulation might be used to devise novel pharmacological inhibitors. AD - Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA. AN - 23411347 AU - Dbouk, H. A. AU - Backer, J. M. C1 - 2 C2 - PMC3606591 CN - 11861 DA - Mar DO - 10.1016/j.tips.2012.12.004 S0165-6147(12)00216-7 [pii] DP - Nlm ET - 2013/02/16 KW - Animals Class I Phosphatidylinositol 3-Kinases/*antagonists & inhibitors/chemistry/metabolism Drug Design Enzyme Inhibitors/chemistry/*pharmacology Humans Models, Molecular L1 - internal-pdf://0831248846/Dbouk-2013-Novel approaches to inhibitor desig.pdf LA - eng LB - 23411347 M1 - 3 N1 - Dbouk, Hashem A Backer, Jonathan M GM55692/GM/NIGMS NIH HHS/United States P01 CA100324/CA/NCI NIH HHS/United States R01 GM055692/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Review England Trends in pharmacological sciences Trends Pharmacol Sci. 2013 Mar;34(3):149-53. doi: 10.1016/j.tips.2012.12.004. Epub 2013 Feb 12. PY - 2013 RI - 2013 from pubmed SN - 1873-3735 (Electronic) 0165-6147 (Linking) SP - 149-53 ST - Novel approaches to inhibitor design for the p110beta phosphoinositide 3-kinase T2 - Trends Pharmacol Sci TI - Novel approaches to inhibitor design for the p110beta phosphoinositide 3-kinase UR - http://www.ncbi.nlm.nih.gov/pubmed/23411347 http://ac.els-cdn.com/S0165614712002167/1-s2.0-S0165614712002167-main.pdf?_tid=1e30d74a-c03a-11e3-a606-00000aacb362&acdnat=1397084339_85db32f54d3cb49d14fa621839bb55bc VL - 34 ID - 7 ER - TY - JOUR AB - While the clinical benefit of MEK inhibitor (MEKi)-based therapy is well established in Raf mutant malignancies, its utility as a suppressor of hyperactive MAPK signaling in the absence of mutated Raf or Ras, is an area of ongoing research. MAPK activation is associated with loss of ERalpha expression and hormonal resistance in numerous malignancies. Herein, we demonstrate that MEKi induces a feedback response that results in ERalpha overexpression, phosphorylation and transcriptional activation of ER-regulated genes. Mechanistically, MEKi-mediated ERalpha overexpression is largely independent of erbB2 and AKT feedback activation, but is ERK-dependent. We subsequently exploit this phenomenon therapeutically by combining the ER-antagonist, fulvestrant with MEKi. This results in synergistic suppression of tumor growth, in vitro and potentiation of single agent activity in vivo in nude mice bearing xenografts. Thus, we demonstrate that exploiting adaptive feedback after MEKi can be used to sensitize ERalpha-positive tumors to hormonal therapy, and propose that this strategy may have broader clinical utility in ERalpha-positive ovarian carcinoma. AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Women's Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA. AN - 23390495 AU - Hou, J. Y. AU - Rodriguez-Gabin, A. AU - Samaweera, L. AU - Hazan, R. AU - Goldberg, G. L. AU - Horwitz, S. B. AU - McDaid, H. M. C1 - 2 C2 - PMC3563537 C7 - +- CN - 11842 DO - 10.1371/journal.pone.0054103 PONE-D-12-15366 [pii] DP - Nlm ET - 2013/02/08 KW - Animals Antineoplastic Agents, Hormonal/*pharmacology Benzamides/pharmacology Carcinoma/*drug therapy/genetics/metabolism/pathology Cell Line, Tumor Diphenylamine/analogs & derivatives/pharmacology Estradiol/analogs & derivatives/pharmacology Estrogen Receptor alpha/agonists/*genetics/metabolism Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/genetics/metabolism Feedback, Physiological/drug effects Female Gene Expression Regulation, Neoplastic/*drug effects Heterocyclic Compounds, 3-Ring/pharmacology Humans MAP Kinase Kinase Kinases/antagonists & inhibitors/genetics/metabolism Mice Mice, Nude Ovarian Neoplasms/*drug therapy/genetics/metabolism/pathology Phosphorylation/drug effects Protein Kinase Inhibitors/*pharmacology Proto-Oncogene Proteins c-akt/genetics/metabolism Quinazolines/pharmacology Signal Transduction/drug effects Xenograft Model Antitumor Assays L1 - internal-pdf://1492769214/Hou-2013-Exploiting MEK inhibitor-mediated act.pdf LA - eng LB - 23390495 M1 - 2 N1 - Hou, June Y Rodriguez-Gabin, Alicia Samaweera, Leleesha Hazan, Rachel Goldberg, Gary L Horwitz, Susan Band McDaid, Hayley M CA077263/CA/NCI NIH HHS/United States K12CA132783-01A1/CA/NCI NIH HHS/United States R01 CA077263/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2013;8(2):e54103. doi: 10.1371/journal.pone.0054103. Epub 2013 Feb 4. PY - 2013 RI - 2013 from pubmed SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e54103 ST - Exploiting MEK inhibitor-mediated activation of ERalpha for therapeutic intervention in ER-positive ovarian carcinoma T2 - PLoS One TI - Exploiting MEK inhibitor-mediated activation of ERalpha for therapeutic intervention in ER-positive ovarian carcinoma UR - http://www.ncbi.nlm.nih.gov/pubmed/23390495 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563537/pdf/pone.0054103.pdf VL - 8 ID - 5 ER - TY - JOUR AB - OBJECTIVE: HIV infection and illicit drug use are each associated with diminished cognitive performance. This study examined the separate and interactive effects of HIV and recent illicit drug use on verbal memory, processing speed, and executive function in the multicenter Women's Interagency HIV Study. METHODS: Participants included 952 HIV-infected and 443 HIV-uninfected women (mean age = 42.8, 64% African-American). Outcome measures included the Hopkins Verbal Learning Test-Revised and the Stroop test. Three drug use groups were compared: recent illicit drug users (cocaine or heroin use in past 6 months, n = 140), former users (lifetime cocaine or heroin use but not in past 6 months, n = 651), and nonusers (no lifetime use of cocaine or heroin, n = 604). RESULTS: The typical pattern of recent drug use was daily or weekly smoking of crack cocaine. HIV infection and recent illicit drug use were each associated with worse verbal learning and memory (P < 0.05). Importantly, there was an interaction between HIV serostatus and recent illicit drug use such that recent illicit drug use (compared with nonuse) negatively impacted verbal learning and memory only in HIV-infected women (P < 0.01). There was no interaction between HIV serostatus and illicit drug use on processing speed or executive function on the Stroop test. CONCLUSIONS: The interaction between HIV serostatus and recent illicit drug use on verbal learning and memory suggests a potential synergistic neurotoxicity that may affect the neural circuitry underlying performance on these tasks. AD - Department of Neuroscience, University of Illinois at Chicago, Chicago, IL 60612, USA. AN - 23392462 AU - Meyer, V. J. AU - Rubin, L. H. AU - Martin, E. AU - Weber, K. M. AU - Cohen, M. H. AU - Golub, E. T. AU - Valcour, V. AU - Young, M. A. AU - Crystal, H. AU - Anastos, K. AU - Aouizerat, B. E. AU - Milam, J. AU - Maki, P. M. C1 - 6 C2 - PMC3628722 C7 - *** CN - 11840 DA - May 1 DO - 10.1097/QAI.0b013e318289565c DP - Nlm ET - 2013/02/09 KW - Adult African Americans Aged Cocaine-Related Disorders/*complications/psychology Cognition Crack Cocaine/adverse effects Executive Function Female HIV Infections/*complications/psychology Heroin/adverse effects Heroin Dependence/*complications/psychology Humans Memory/*drug effects Middle Aged Sex Factors Street Drugs/*adverse effects Verbal Learning/*drug effects Young Adult L1 - internal-pdf://0715119022/Meyer-2013-HIV and recent illicit drug use int.pdf LA - eng LB - 23392462 M1 - 1 N1 - Meyer, Vanessa J Rubin, Leah H Martin, Eileen Weber, Kathleen M Cohen, Mardge H Golub, Elizabeth T Valcour, Victor Young, Mary A Crystal, Howard Anastos, Kathryn Aouizerat, Bradley E Milam, Joel Maki, Pauline M 1F31DA028573/DA/NIDA NIH HHS/United States 1K01MH098798-01/MH/NIMH NIH HHS/United States K12 HD055892/HD/NICHD NIH HHS/United States K12HD055892/HD/NICHD NIH HHS/United States P30 AI082151/AI/NIAID NIH HHS/United States U01 AI034994/AI/NIAID NIH HHS/United States U01 AI035004/AI/NIAID NIH HHS/United States UL1 RR024131/RR/NCRR NIH HHS/United States UO1-AI-31834/AI/NIAID NIH HHS/United States UO1-AI-34989/AI/NIAID NIH HHS/United States UO1-AI-34993/AI/NIAID NIH HHS/United States UO1-AI-34994/AI/NIAID NIH HHS/United States UO1-AI-35004/AI/NIAID NIH HHS/United States UO1-AL-42590/PHS HHS/United States UO1-HD-32632/HD/NICHD NIH HHS/United States Multicenter Study Research Support, N.I.H., Extramural United States Journal of acquired immune deficiency syndromes (1999) J Acquir Immune Defic Syndr. 2013 May 1;63(1):67-76. doi: 10.1097/QAI.0b013e318289565c. PY - 2013 RI - 2013 from pubmed SN - 1944-7884 (Electronic) 1525-4135 (Linking) SP - 67-76 ST - HIV and recent illicit drug use interact to affect verbal memory in women T2 - J Acquir Immune Defic Syndr TI - HIV and recent illicit drug use interact to affect verbal memory in women UR - http://www.ncbi.nlm.nih.gov/pubmed/23392462 http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCMAMNCD00/fs047/ovft/live/gv024/00126334/00126334-201305010-00010.pdf VL - 63 ID - 3 ER - TY - JOUR AD - Obstetrics, Gynecology and Womens Health, Division of Gynecologic Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY 10467, USA. nevadunskynicole@yahoo.com AN - 23358980 AU - Nevadunsky, N. S. AU - Mbagwu, C. AU - Mizrahi, N. AU - Burton, E. AU - Goldberg, G. L. C1 - 5 CN - 11124 DA - Apr 1 DO - 10.1200/JCO.2012.44.5767 JCO.2012.44.5767 [pii] DP - Nlm ET - 2013/01/30 KW - Cystadenocarcinoma, Papillary/*drug therapy Cystadenocarcinoma, Serous/*drug therapy Diagnosis, Differential Doxorubicin/adverse effects/*analogs & derivatives Fatal Outcome Female Humans Middle Aged Polyethylene Glycols/*adverse effects Pulmonary Fibrosis/*chemically induced/diagnosis Uterine Neoplasms/*drug therapy L1 - internal-pdf://1831917983/Nevadunsky-2013-Pulmonary fibrosis after pegyl.pdf LA - eng LB - 23358980 M1 - 10 N1 - Nevadunsky, Nicole S Mbagwu, Chinyere Mizrahi, Nina Burton, Elizabeth Goldberg, Gary L K12 CA132783/CA/NCI NIH HHS/United States Case Reports United States Journal of clinical oncology : official journal of the American Society of Clinical Oncology J Clin Oncol. 2013 Apr 1;31(10):e167-9. doi: 10.1200/JCO.2012.44.5767. Epub 2013 Jan 28. PY - 2013 RI - 2013 from pubmed SN - 1527-7755 (Electronic) 0732-183X (Linking) SP - e167-9 ST - Pulmonary fibrosis after pegylated liposomal Doxorubicin in a patient with uterine papillary serous carcinoma T2 - J Clin Oncol TI - Pulmonary fibrosis after pegylated liposomal Doxorubicin in a patient with uterine papillary serous carcinoma UR - http://www.ncbi.nlm.nih.gov/pubmed/23358980 http://jco.ascopubs.org/content/31/10/e167.full.pdf VL - 31 ID - 2 ER - TY - JOUR AB - OBJECTIVE: There are limited data regarding the end-of-life care for women with gynecologic malignancies. We set out to generate pilot data describing the care that women with gynecologic malignancies received in the last 6 months of life. Patient demographics, patterns of care, and utilization of palliative medicine consultation services were evaluated. METHODS: One hundred patients who died of gynecologic malignancies were identified in our institutional database. Only patients who had received treatment with a gynecologic oncologist within 1 year of death were included. Medical records were reviewed for relevant information. Data were abstracted from the electronic medical record, and analyses were made using Student t test and Mann-Whitney U test with SPSS software. RESULTS: The mean age of patients was 60 years (range, 30-94 years). Racial/ethnic distribution was as follows: 38%, white; 34%, black; and 15%, Hispanic. Seventy-five percent of patients received chemotherapy within the last 6 months of life, and 30% received chemotherapy within the last 6 weeks of life. The median number of days hospitalized during the last 6 months of life was 24 (range, 0-183 days). During the last 6 months of life, 19% were admitted to the intensive care unit, 17% were intubated, 5% had terminal extubation, and 13% had cardiopulmonary resuscitative efforts. Sixty-four percent had a family meeting, 50% utilized hospice care, and 49% had palliative medicine consultations. There was a significant difference in hospice utilization when comparison was made between patients who had 14 days or more from consultation until death versus patients who had 14 days or less or no consultation, 21 (72%) versus 29 (41%), P = 0.004. Patients who were single were less likely to have a palliative medicine consultation, P = 0.005. CONCLUSIONS: End-of-life care for patients with gynecologic malignancies often includes futile, aggressive treatments and invasive procedures. It is unknown whether these measures contribute to longevity or quality of life. These pilot data suggest that factors for implementation of timely hospice referral, family support, and legacy building should include specialists trained in palliative medicine. AD - Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA. nnevadun@montefiore.org AN - 23429487 AU - Nevadunsky, N. S. AU - Spoozak, L. AU - Gordon, S. AU - Rivera, E. AU - Harris, K. AU - Goldberg, G. L. C1 - 5 C2 - PMC3746978 CN - 11882 DA - Mar DO - 10.1097/IGC.0b013e3182842efa 00009577-201303000-00024 [pii] DP - Nlm ET - 2013/02/23 KW - Adult Aged Aged, 80 and over Ethnic Groups Female Genital Neoplasms, Female/psychology/*therapy Hospice Care/*utilization Hospitalization Humans Intensive Care Units Medical Futility/*psychology Middle Aged Palliative Care/*utilization Pilot Projects *Quality of Life Referral and Consultation Terminal Care/*utilization L1 - internal-pdf://1427102189/Nevadunsky-2013-End-of-life care of women with.pdf LA - eng LB - 23429487 M1 - 3 N1 - Nevadunsky, Nicole S Spoozak, Lori Gordon, Sharon Rivera, Enid Harris, Kimala Goldberg, Gary L K12 CA132783/CA/NCI NIH HHS/United States United States International journal of gynecological cancer : official journal of the International Gynecological Cancer Society Int J Gynecol Cancer. 2013 Mar;23(3):546-52. doi: 10.1097/IGC.0b013e3182842efa. PY - 2013 RI - 2013 from pubmed SN - 1525-1438 (Electronic) 1048-891X (Linking) SP - 546-52 ST - End-of-life care of women with gynecologic malignancies: a pilot study T2 - Int J Gynecol Cancer TI - End-of-life care of women with gynecologic malignancies: a pilot study UR - http://www.ncbi.nlm.nih.gov/pubmed/23429487 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746978/pdf/nihms437966.pdf VL - 23 ID - 10 ER - TY - JOUR AB - Near-infrared light is favourable for imaging in mammalian tissues due to low absorbance of hemoglobin, melanin, and water. Therefore, fluorescent proteins, biosensors and optogenetic constructs for optimal imaging, optical readout and light manipulation in mammals should have fluorescence and action spectra within the near-infrared window. Interestingly, natural Bacterial Phytochrome Photoreceptors (BphPs) utilize the low molecular weight biliverdin, found in most mammalian tissues, as a photoreactive chromophore. Due to their near-infrared absorbance BphPs are preferred templates for designing optical molecular tools for applications in mammals. Moreover, BphPs spectrally complement existing genetically-encoded probes. Several BphPs were already developed into the near-infrared fluorescent variants. Based on the analysis of the photochemistry and structure of BphPs we suggest a variety of possible BphP-based fluorescent proteins, biosensors, and optogenetic tools. Putative design strategies and experimental considerations for such probes are discussed. AD - Gruss-Lipper Biophotonics Center and Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. AN - 23361376 AU - Piatkevich, K. D. AU - Subach, F. V. AU - Verkhusha, V. V. C1 - 2 C2 - PMC3618476 CN - 11121 DA - Apr 21 DO - 10.1039/c3cs35458j DP - Nlm ET - 2013/01/31 KW - Animals Bacteria/metabolism Bacterial Proteins/chemistry/genetics/*metabolism Biliverdine/chemistry/genetics/metabolism Biosensing Techniques Fluorescence Resonance Energy Transfer Luminescent Proteins/chemistry/genetics/metabolism Phytochrome/chemistry/genetics/*metabolism *Protein Engineering Spectroscopy, Near-Infrared LA - eng LB - 23361376 M1 - 8 N1 - Piatkevich, Kiryl D Subach, Fedor V Verkhusha, Vladislav V CA164468/CA/NCI NIH HHS/United States EB013571/EB/NIBIB NIH HHS/United States GM073913/GM/NIGMS NIH HHS/United States R01 CA164468/CA/NCI NIH HHS/United States R01 GM073913/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Review England Chemical Society reviews Chem Soc Rev. 2013 Apr 21;42(8):3441-52. doi: 10.1039/c3cs35458j. Epub 2013 Jan 29. PY - 2013 RI - 2013 from pubmed SN - 1460-4744 (Electronic) 0306-0012 (Linking) SP - 3441-52 ST - Engineering of bacterial phytochromes for near-infrared imaging, sensing, and light-control in mammals T2 - Chem Soc Rev TI - Engineering of bacterial phytochromes for near-infrared imaging, sensing, and light-control in mammals UR - http://www.ncbi.nlm.nih.gov/pubmed/23361376 http://pubs.rsc.org/en/Content/ArticleLanding/2013/CS/c3cs35458j VL - 42 ID - 1 ER - TY - JOUR AB - Circadian rhythms, which have long been known to play crucial roles in physiology, are emerging as important regulators of specific immune functions. Circadian oscillations of immune mediators coincide with the activity of the immune system, possibly allowing the host to anticipate and handle microbial threats more efficiently. These oscillations may also help to promote tissue recovery and the clearance of potentially harmful cellular elements from the circulation. This Review summarizes the current knowledge of circadian rhythms in the immune system and provides an outlook on potential future implications. AD - Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA. christoph.scheiermann@med.uni-muenchen.de AN - 23391992 AU - Scheiermann, C. AU - Kunisaki, Y. AU - Frenette, P. S. C1 - 3 CN - 11841 DA - Mar DO - 10.1038/nri3386 nri3386 [pii] DP - Nlm ET - 2013/02/09 KW - Adaptive Immunity/physiology Animals Blood Cell Count Chronobiology Disorders/immunology Circadian Rhythm/*immunology Circadian Rhythm Signaling Peptides and Proteins/genetics/physiology Disease Susceptibility Drug Chronotherapy Feedback, Physiological/physiology Gene Expression Regulation/physiology Hormones/physiology Humans Immune System/*physiology Immunity, Humoral/physiology Inflammation/immunology/physiopathology Mammals/immunology/physiology Mice Models, Immunological Transcription, Genetic/physiology L1 - internal-pdf://0939776430/Scheiermann-2013-Circadian control of the immu.pdf LA - eng LB - 23391992 M1 - 3 N1 - Scheiermann, Christoph Kunisaki, Yuya Frenette, Paul S DK056638/DK/NIDDK NIH HHS/United States HL069438/HL/NHLBI NIH HHS/United States HL097819/HL/NHLBI NIH HHS/United States HL116340/HL/NHLBI NIH HHS/United States R01 HL097700/HL/NHLBI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review England Nature reviews. Immunology Nat Rev Immunol. 2013 Mar;13(3):190-8. doi: 10.1038/nri3386. Epub 2013 Feb 8. PY - 2013 RI - 2013 from pubmed SN - 1474-1741 (Electronic) 1474-1733 (Linking) SP - 190-8 ST - Circadian control of the immune system T2 - Nat Rev Immunol TI - Circadian control of the immune system UR - http://www.ncbi.nlm.nih.gov/pubmed/23391992 http://www.nature.com/nri/journal/v13/n3/pdf/nri3386.pdf VL - 13 ID - 4 ER - TY - JOUR AB - Nonsense-mediated mRNA decay (NMD) is a quality control mechanism responsible for "surveying" mRNAs during translation and degrading those that harbor a premature termination codon (PTC). Currently the intracellular spatial location of NMD and the kinetics of its decay step in mammalian cells are under debate. To address these issues, we used single-RNA fluorescent in situ hybridization (FISH) and measured the NMD of PTC-containing beta-globin mRNA in intact single cells after the induction of beta-globin gene transcription. This approach preserves temporal and spatial information of the NMD process, both of which would be lost in an ensemble study. We determined that decay of the majority of PTC-containing beta-globin mRNA occurs soon after its export into the cytoplasm, with a half-life of <1 min; the remainder is degraded with a half-life of >12 h, similar to the half-life of normal PTC-free beta-globin mRNA, indicating that it had evaded NMD. Importantly, NMD does not occur within the nucleoplasm, thus countering the long-debated idea of nuclear degradation of PTC-containing transcripts. We provide a spatial and temporal model for the biphasic decay of NMD targets. AD - Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. AN - 23431032 AU - Trcek, T. AU - Sato, H. AU - Singer, R. H. AU - Maquat, L. E. C1 - 7 C2 - PMC3605467 CN - 11881 DA - Mar 1 DO - 10.1101/gad.209635.112 DP - Nlm ET - 2013/02/23 J2 - Genes & development KW - Animals Cell Line Cell Nucleus/metabolism Cytoplasm/metabolism Humans In Situ Hybridization, Fluorescence *Nonsense Mediated mRNA Decay RNA, Messenger/*metabolism Time Factors beta-Globins/metabolism L1 - internal-pdf://3855079901/Trcek-2013-Temporal and spatial characterizati.pdf LA - eng LB - 23431032 M1 - 5 N1 - Trcek, Tatjana Sato, Hanae Singer, Robert H Maquat, Lynne E eng GM86217/GM/NIGMS NIH HHS/ R01 GM059614/GM/NIGMS NIH HHS/ R01 GM84364/GM/NIGMS NIH HHS/ R01GM59614/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2013/02/23 06:00 Genes Dev. 2013 Mar 1;27(5):541-51. doi: 10.1101/gad.209635.112. Epub 2013 Feb 21. PY - 2013 RI - 2013 from pubmed SN - 1549-5477 (Electronic) 0890-9369 (Linking) SP - 541-51 ST - Temporal and spatial characterization of nonsense-mediated mRNA decay T2 - Genes Dev TI - Temporal and spatial characterization of nonsense-mediated mRNA decay UR - http://www.ncbi.nlm.nih.gov/pubmed/23431032 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605467/pdf/541.pdf VL - 27 ID - 9 ER -