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Article ; Online: MicroRNAs targeting TGF-β signaling exacerbate central nervous system autoimmunity by disrupting regulatory T cell development and function.

Rau, Christina N / Severin, Mary E / Lee, Priscilla W / Deffenbaugh, Joshua L / Liu, Yue / Murphy, Shawn P / Petersen-Cherubini, Cora L / Lovett-Racke, Amy E

European journal of immunology

2024 , Page(s) e2350548

Abstract: Transforming growth factor beta (TGF-β) signaling is essential for a balanced immune response by mediating the development and function of regulatory T cells (Tregs) and suppressing autoreactive T cells. Disruption of this balance can result in ... ...

Abstract	Transforming growth factor beta (TGF-β) signaling is essential for a balanced immune response by mediating the development and function of regulatory T cells (Tregs) and suppressing autoreactive T cells. Disruption of this balance can result in autoimmune diseases, including multiple sclerosis (MS). MicroRNAs (miRNAs) targeting TGF-β signaling have been shown to be upregulated in naïve CD4 T cells in MS patients, resulting in a limited in vitro generation of human Tregs. Utilizing the murine model experimental autoimmune encephalomyelitis, we show that perinatal administration of miRNAs, which target the TGF-β signaling pathway, enhanced susceptibility to central nervous system (CNS) autoimmunity. Neonatal mice administered with these miRNAs further exhibited reduced Treg frequencies with a loss in T cell receptor repertoire diversity following the induction of experimental autoimmune encephalomyelitis in adulthood. Exacerbated CNS autoimmunity as a result of miRNA overexpression in CD4 T cells was accompanied by enhanced Th1 and Th17 cell frequencies. These findings demonstrate that increased levels of TGF-β-associated miRNAs impede the development of a diverse Treg population, leading to enhanced effector cell activity, and contributing to an increased susceptibility to CNS autoimmunity. Thus, TGF-β-targeting miRNAs could be a risk factor for MS, and recovering optimal TGF-β signaling may restore immune homeostasis in MS patients.
Language	English
Publishing date	2024-04-18
Publishing country	Germany
Document type	Journal Article
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202350548
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Article ; Online: TGF-β regulation of encephalitogenic and regulatory T cells in multiple sclerosis.

Lee, Priscilla W / Severin, Mary E / Lovett-Racke, Amy E

European journal of immunology

2017 Volume 47, Issue 3, Page(s) 446–453

Abstract: Transforming growth factor beta (TGF-β) is a pleiotropic cytokine that has been shown to influence the differentiation and function of T cells. The role that TGF-β plays in immune-mediated disease, such as multiple sclerosis (MS), has become a major area ...

Abstract	Transforming growth factor beta (TGF-β) is a pleiotropic cytokine that has been shown to influence the differentiation and function of T cells. The role that TGF-β plays in immune-mediated disease, such as multiple sclerosis (MS), has become a major area of investigation since CD4
MeSH term(s)	Animals ; Autoantigens/immunology ; Autoimmunity ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Humans ; Mice ; Multiple Sclerosis/immunology ; Signal Transduction ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Transforming Growth Factor beta/immunology ; Transforming Growth Factor beta/metabolism
Chemical Substances	Autoantigens ; Transforming Growth Factor beta
Language	English
Publishing date	2017-03
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.201646716
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Article ; Online: MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis.

Severin, Mary E / Lee, Priscilla W / Liu, Yue / Selhorst, Amanda J / Gormley, Matthew G / Pei, Wei / Yang, Yuhong / Guerau-de-Arellano, Mireia / Racke, Michael K / Lovett-Racke, Amy E

Brain : a journal of neurology

2016 Volume 139, Issue Pt 6, Page(s) 1747–1761

Abstract: Transforming growth factor beta (TGFβ) signalling is critical for regulatory T cell development and function, and regulatory T cell dysregulation is a common observation in autoimmune diseases, including multiple sclerosis. In a comprehensive miRNA ... ...

Abstract	Transforming growth factor beta (TGFβ) signalling is critical for regulatory T cell development and function, and regulatory T cell dysregulation is a common observation in autoimmune diseases, including multiple sclerosis. In a comprehensive miRNA profiling study of patients with multiple sclerosis naïve CD4 T cells, 19 differentially expressed miRNAs predicted to target the TGFβ signalling pathway were identified, leading to the hypothesis that miRNAs may be responsible for the regulatory T cell defect observed in patients with multiple sclerosis. Patients with multiple sclerosis had reduced levels of TGFβ signalling components in their naïve CD4 T cells. The differentially expressed miRNAs negatively regulated the TGFβ pathway, resulting in a reduced capacity of naïve CD4 T cells to differentiate into regulatory T cells. Interestingly, the limited number of regulatory T cells, that did develop when these TGFβ-targeting miRNAs were overexpressed, were capable of suppressing effector T cells. As it has previously been demonstrated that compromising TGFβ signalling results in a reduced regulatory T cell repertoire insufficient to control autoimmunity, and patients with multiple sclerosis have a reduced regulatory T cell repertoire, these data indicate that the elevated expression of multiple TGFβ-targeting miRNAs in naïve CD4 T cells of patients with multiple sclerosis impairs TGFβ signalling, and dampens regulatory T cell development, thereby enhancing susceptibility to developing multiple sclerosis.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/metabolism ; Cell Differentiation ; Gene Expression ; Humans ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Multiple Sclerosis/genetics ; Multiple Sclerosis/metabolism ; Signal Transduction/genetics ; T-Lymphocytes, Regulatory/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	MicroRNAs ; Transforming Growth Factor beta
Language	English
Publishing date	2016-06
Publishing country	England
Document type	Journal Article
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/aww084
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Article ; Online: Spatial transcriptomics tools allow for regional exploration of heterogeneous muscle pathology in the pre-clinical rabbit model of rotator cuff tear.

Ruoss, Severin / Esparza, Mary C / Vasquez-Bolanos, Laura S / Nasamran, Chanond A / Fisch, Kathleen M / Engler, Adam J / Ward, Samuel R

Journal of orthopaedic surgery and research

2022 Volume 17, Issue 1, Page(s) 440

Abstract: ... information was overlayed with standard hematoxylin and eosin (H&E) stains of the exact same histological ... storage duration. Unbiased clustering matched the underlying tissue type-based on H&E assessment ...

Abstract	Background: Conditions affecting skeletal muscle, such as chronic rotator cuff tears, low back pain, dystrophies, and many others, often share changes in muscle phenotype: intramuscular adipose and fibrotic tissue increase while contractile tissue is lost. The underlying changes in cell populations and cell ratios observed with these phenotypic changes complicate the interpretation of tissue-level transcriptional data. Novel single-cell transcriptomics has limited capacity to address this problem because muscle fibers are too long to be engulfed in single-cell droplets and single nuclei transcriptomics are complicated by muscle fibers' multinucleation. Therefore, the goal of this project was to evaluate the potential and challenges of a spatial transcriptomics technology to add dimensionality to transcriptional data in an attempt to better understand regional cellular activity in heterogeneous skeletal muscle tissue. Methods: The 3' Visium spatial transcriptomics technology was applied to muscle tissue of a rabbit model of rotator cuff tear. Healthy control and tissue collected at 2 and 16 weeks after tenotomy was utilized and freshly snap frozen tissue was compared with tissue stored for over 6 years to evaluate whether this technology is retrospectively useful in previously acquired tissues. Transcriptional information was overlayed with standard hematoxylin and eosin (H&E) stains of the exact same histological sections. Results: Sequencing saturation and number of genes detected was not affected by sample storage duration. Unbiased clustering matched the underlying tissue type-based on H&E assessment. Connective-tissue-rich areas presented with lower unique molecular identifier counts are compared with muscle fibers even though tissue permeabilization was standardized across the section. A qualitative analysis of resulting datasets revealed heterogeneous fiber degeneration-regeneration after tenotomy based on (neonatal) myosin heavy chain 8 detection and associated differentially expressed gene analysis. Conclusions: This protocol can be used in skeletal muscle to explore spatial transcriptional patterns and confidently relate them to the underlying histology, even for tissues that have been stored for up to 6 years. Using this protocol, there is potential for novel transcriptional pathway discovery in longitudinal studies since the transcriptional information is unbiased by muscle composition and cell type changes.
MeSH term(s)	Animals ; Eosine Yellowish-(YS)/metabolism ; Hematoxylin/metabolism ; Muscle, Skeletal/pathology ; Myosin Heavy Chains/metabolism ; Rabbits ; Retrospective Studies ; Rotator Cuff/metabolism ; Rotator Cuff Injuries/pathology ; Transcriptome/genetics
Chemical Substances	Myosin Heavy Chains (EC 3.6.4.1) ; Eosine Yellowish-(YS) (TDQ283MPCW) ; Hematoxylin (YKM8PY2Z55)
Language	English
Publishing date	2022-10-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2252548-8
ISSN	1749-799X ; 1749-799X
ISSN (online)	1749-799X
ISSN	1749-799X
DOI	10.1186/s13018-022-03326-8
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Article ; Online: Treatment of experimental autoimmune encephalomyelitis by codelivery of disease associated Peptide and dexamethasone in acetalated dextran microparticles.

Peine, Kevin J / Guerau-de-Arellano, Mireia / Lee, Priscilla / Kanthamneni, Naveen / Severin, Mary / Probst, G Duane / Peng, Haiyan / Yang, Yuhong / Vangundy, Zachary / Papenfuss, Tracey L / Lovett-Racke, Amy E / Bachelder, Eric M / Ainslie, Kristy M

Molecular pharmaceutics

2014 Volume 11, Issue 3, Page(s) 828–835

Abstract: ... cytokine (e.g., IL-17, GM-CSF) expression in splenocytes isolated in treated mice. Here we show a promising ...

Abstract	Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system that can cause loss of motor function and is thought to result, in part, from chronic inflammation due to an antigen-specific T cell immune response. Current treatments suppress the immune system without antigen specificity, increasing the risks of cancer, chronic infection, and other long-term side effects. In this study, we show treatment of experimental autoimmune encephalomyelitis (EAE), a model of MS, by coencapsulating the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG) with dexamethasone (DXM) into acetalated dextran (Ac-DEX) microparticles (DXM/MOG/MPs) and administering the microparticles subcutaneously. The clinical score of the mice was reduced from 3.4 to 1.6 after 3 injections 3 days apart with the coencapsulated microparticulate formulation (MOG 17.6 μg and DXM 8 μg). This change in clinical score was significantly greater than observed with phosphate-buffered saline (PBS), empty MPs, free DXM and MOG, DXM/MPs, and MOG/MPs. Additionally, treatment with DXM/MOG/MPs significantly inhibited disease-associated cytokine (e.g., IL-17, GM-CSF) expression in splenocytes isolated in treated mice. Here we show a promising approach for the therapeutic treatment of MS using a polymer-based microparticle delivery platform.
MeSH term(s)	Animals ; Cell Proliferation/drug effects ; Combined Modality Therapy ; Cytokines/metabolism ; Dexamethasone/administration & dosage ; Dexamethasone/pharmacokinetics ; Dextrans/chemistry ; Drug Delivery Systems ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Encephalomyelitis, Autoimmune, Experimental/therapy ; Female ; Flow Cytometry ; Mice ; Mice, Inbred C57BL ; Myelin-Oligodendrocyte Glycoprotein/immunology ; Myelin-Oligodendrocyte Glycoprotein/metabolism ; Nitric Oxide/metabolism ; Peptide Fragments/administration & dosage ; Peptide Fragments/immunology ; Polymers/chemistry ; Tissue Distribution
Chemical Substances	Cytokines ; Dextrans ; Mog protein, mouse ; Myelin-Oligodendrocyte Glycoprotein ; Peptide Fragments ; Polymers ; Nitric Oxide (31C4KY9ESH) ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2014-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/mp4005172
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Article ; Online: Every Newborn: health-systems bottlenecks and strategies to accelerate scale-up in countries.

Dickson, Kim E / Simen-Kapeu, Aline / Kinney, Mary V / Huicho, Luis / Vesel, Linda / Lackritz, Eve / de Graft Johnson, Joseph / von Xylander, Severin / Rafique, Nuzhat / Sylla, Mariame / Mwansambo, Charles / Daelmans, Bernadette / Lawn, Joy E

Lancet (London, England)

2014 Volume 384, Issue 9941, Page(s) 438–454

Abstract: Universal coverage of essential interventions would reduce neonatal deaths by an estimated 71%, benefit women and children after the first month, and reduce stillbirths. However, the packages with the greatest effect (care around birth, care of small and ...

Abstract	Universal coverage of essential interventions would reduce neonatal deaths by an estimated 71%, benefit women and children after the first month, and reduce stillbirths. However, the packages with the greatest effect (care around birth, care of small and ill newborn babies), have low and inequitable coverage and are the most sensitive markers of health system function. In eight of the 13 countries with the most neonatal deaths (55% worldwide), we undertook a systematic assessment of bottlenecks to essential maternal and newborn health care, involving more than 600 experts. Of 2465 bottlenecks identified, common constraints were found in all high-burden countries, notably regarding the health workforce, financing, and service delivery. However, bottlenecks for specific interventions might differ across similar health systems. For example, the implementation of kangaroo mother care was noted as challenging in the four Asian country workshops, but was regarded as a feasible aspect of preterm care by respondents in the four African countries. If all high-burden countries achieved the neonatal mortality rates of their region's fastest progressing countries, then the mortality goal of ten or fewer per 1000 livebirths by 2035 recommended in this Series and the Every Newborn Action Plan would be exceeded. We therefore examined fast progressing countries to identify strategies to reduce neonatal mortality. We identified several key factors: (1) workforce planning to increase numbers and upgrade specific skills for care at birth and of small and ill newborn babies, task sharing, incentives for rural health workers; (2) financial protection measures, such as expansion of health insurance, conditional cash transfers, and performance-based financing; and (3) dynamic leadership including innovation and community empowerment. Adapting from the 2005 Lancet Series on neonatal survival and drawing on this Every Newborn Series, we propose a country-led, data-driven process to sharpen national health plans, seize opportunities to address the quality gap for care at birth and care of small and ill newborn babies, and systematically scale up care to reach every mother and newborn baby, particularly the poorest.
MeSH term(s)	Child Health Services/standards ; Developing Countries ; Female ; Health Planning ; Humans ; Infant Mortality ; Infant, Newborn ; Maternal Health Services/standards ; Pregnancy
Language	English
Publishing date	2014-05-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(14)60582-1
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Article ; Online: Born too soon: care for the preterm baby.

Lawn, Joy E / Davidge, Ruth / Paul, Vinod K / von Xylander, Severin / de Graft Johnson, Joseph / Costello, Anthony / Kinney, Mary V / Segre, Joel / Molyneux, Liz

Reproductive health

2013 Volume 10 Suppl 1, Page(s) S5

Abstract: As part of a supplement entitled “Born Too Soon”, this paper focuses on care of the preterm newborn. An estimated 15 million babies are born preterm, and the survival gap between those born in high and low income countries is widening, with one million ... ...

Abstract	As part of a supplement entitled “Born Too Soon”, this paper focuses on care of the preterm newborn. An estimated 15 million babies are born preterm, and the survival gap between those born in high and low income countries is widening, with one million deaths a year due to direct complications of preterm birth, and around one million more where preterm birth is a risk factor, especially amongst those who are also growth restricted. Most premature babies (>80%) are between 32 and 37 weeks of gestation, and many die needlessly for lack of simple care. We outline a series of packages of care that build on essential care for every newborn comprising support for immediate and exclusive breastfeeding, thermal care, and hygienic cord and skin care. For babies who do not breathe at birth, rapid neonatal resuscitation is crucial. Extra care for small babies, including Kangaroo Mother Care, and feeding support, can halve mortality in babies weighing <2000 g. Case management of newborns with signs of infection, safe oxygen management and supportive care for those with respiratory complications, and care for those with significant jaundice are all critical, and are especially dependent on competent nursing care. Neonatal intensive care units in high income settings are de-intensifying care, for example increasing use of continuous positive airway pressure (CPAP) and this makes comprehensive preterm care more transferable. For health systems in low and middle income settings with increasing facility births, district hospitals are the key frontier for improving obstetric and neonatal care, and some large scale programmes now include specific newborn care strategies. However there are still around 50 million births outside facilities, hence home visits for mothers and newborns, as well as women’s groups are crucial for reaching these families, often the poorest. A fundamental challenge is improving programmatic tracking data for coverage and quality, and measuring disability-free survival. The power of parent’s voices has been important in high-income countries in bringing attention to preterm newborns, but is still missing from the most affected countries.
MeSH term(s)	Female ; Global Health ; Humans ; Infant Care/methods ; Infant Care/trends ; Infant Mortality/trends ; Infant, Newborn ; Infant, Premature ; Pregnancy ; Premature Birth/epidemiology ; Research
Language	English
Publishing date	2013-11-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2149029-6
ISSN	1742-4755 ; 1742-4755
ISSN (online)	1742-4755
ISSN	1742-4755
DOI	10.1186/1742-4755-10-S1-S5
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Book ; Online: Every Newborn

Rafique, Nuzhat / Mwansambo, Charles / Vesel, Linda / Huicho, Luis / Simen-Kapeu, Aline / Lawn, Joy E / Lackritz, Eve / Dickson, Kim E / von Xylander, Severin / Sylla, Mariame / de Graft Johnson, Joseph / Kinney, Mary V / Daelmans, Bernadette

health-systems bottlenecks and strategies to accelerate scale-up in countries

2014

Abstract: Research Support, Non-U.S. Gov't ... Journal Article ... Universal coverage of essential interventions would reduce neonatal deaths by an estimated 71%, benefit women and children after the first month, and reduce stillbirths. However, the packages with the ... ...

Abstract	Research Support, Non-U.S. Gov't Journal Article Universal coverage of essential interventions would reduce neonatal deaths by an estimated 71%, benefit women and children after the first month, and reduce stillbirths. However, the packages with the greatest effect (care around birth, care of small and ill newborn babies), have low and inequitable coverage and are the most sensitive markers of health system function. In eight of the 13 countries with the most neonatal deaths (55% worldwide), we undertook a systematic assessment of bottlenecks to essential maternal and newborn health care, involving more than 600 experts. Of 2465 bottlenecks identified, common constraints were found in all high-burden countries, notably regarding the health workforce, financing, and service delivery. However, bottlenecks for specific interventions might differ across similar health systems. For example, the implementation of kangaroo mother care was noted as challenging in the four Asian country workshops, but was regarded as a feasible aspect of preterm care by respondents in the four African countries. If all high-burden countries achieved the neonatal mortality rates of their region's fastest progressing countries, then the mortality goal of ten or fewer per 1000 livebirths by 2035 recommended in this Series and the Every Newborn Action Plan would be exceeded. We therefore examined fast progressing countries to identify strategies to reduce neonatal mortality. We identified several key factors: (1) workforce planning to increase numbers and upgrade specific skills for care at birth and of small and ill newborn babies, task sharing, incentives for rural health workers; (2) financial protection measures, such as expansion of health insurance, conditional cash transfers, and performance-based financing; and (3) dynamic leadership including innovation and community empowerment. Adapting from the 2005 Lancet Series on neonatal survival and drawing on this Every Newborn Series, we propose a country-led, data-driven process to sharpen national health plans, seize opportunities to address the quality gap for care at birth and care of small and ill newborn babies, and systematically scale up care to reach every mother and newborn baby, particularly the poorest.
Language	English
Publishing date	2014-05-19
Document type	Book ; Online
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Book ; Online: Born too soon

Lawn, Joy E / Segre, Joel / Costello, Anthony / von Xylander, Severin / Paul, Vinod K / Molyneux, Liz / Kinney, Mary V / de Graft Johnson, Joseph / Davidge, Ruth

care for the preterm baby

2013

Abstract: Research Support, Non-U.S. Gov't ... Review ... Journal Article ...

Abstract	Research Support, Non-U.S. Gov't Review Journal Article As part of a supplement entitled “Born Too Soon”, this paper focuses on care of the preterm newborn. An estimated 15 million babies are born preterm, and the survival gap between those born in high and low income countries is widening, with one million deaths a year due to direct complications of preterm birth, and around one million more where preterm birth is a risk factor, especially amongst those who are also growth restricted. Most premature babies (>80%) are between 32 and 37 weeks of gestation, and many die needlessly for lack of simple care. We outline a series of packages of care that build on essential care for every newborn comprising support for immediate and exclusive breastfeeding, thermal care, and hygienic cord and skin care. For babies who do not breathe at birth, rapid neonatal resuscitation is crucial. Extra care for small babies, including Kangaroo Mother Care, and feeding support, can halve mortality in babies weighing <2000 g. Case management of newborns with signs of infection, safe oxygen management and supportive care for those with respiratory complications, and care for those with significant jaundice are all critical, and are especially dependent on competent nursing care. Neonatal intensive care units in high income settings are de-intensifying care, for example increasing use of continuous positive airway pressure (CPAP) and this makes comprehensive preterm care more transferable. For health systems in low and middle income settings with increasing facility births, district hospitals are the key frontier for improving obstetric and neonatal care, and some large scale programmes now include specific newborn care strategies. However there are still around 50 million births outside facilities, hence home visits for mothers and newborns, as well as women’s groups are crucial for reaching these families, often the poorest. A fundamental challenge is improving programmatic tracking data for coverage and quality, and measuring disability-free survival. The power of parent’s voices has been important in high-income countries in bringing attention to preterm newborns, but is still missing from the most affected countries.
Language	English
Publishing date	2013-11-15
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: FANTOM5 CAGE profiles of human and mouse samples.

Noguchi, Shuhei / Arakawa, Takahiro / Fukuda, Shiro / Furuno, Masaaki / Hasegawa, Akira / Hori, Fumi / Ishikawa-Kato, Sachi / Kaida, Kaoru / Kaiho, Ai / Kanamori-Katayama, Mutsumi / Kawashima, Tsugumi / Kojima, Miki / Kubosaki, Atsutaka / Manabe, Ri-Ichiroh / Murata, Mitsuyoshi / Nagao-Sato, Sayaka / Nakazato, Kenichi / Ninomiya, Noriko / Nishiyori-Sueki, Hiromi /

Noma, Shohei / Saijyo, Eri / Saka, Akiko / Sakai, Mizuho / Simon, Christophe / Suzuki, Naoko / Tagami, Michihira / Watanabe, Shoko / Yoshida, Shigehiro / Arner, Peter / Axton, Richard A / Babina, Magda / Baillie, J Kenneth / Barnett, Timothy C / Beckhouse, Anthony G / Blumenthal, Antje / Bodega, Beatrice / Bonetti, Alessandro / Briggs, James / Brombacher, Frank / Carlisle, Ailsa J / Clevers, Hans C / Davis, Carrie A / Detmar, Michael / Dohi, Taeko / Edge, Albert S B / Edinger, Matthias / Ehrlund, Anna / Ekwall, Karl / Endoh, Mitsuhiro / Enomoto, Hideki / Eslami, Afsaneh / Fagiolini, Michela / Fairbairn, Lynsey / Farach-Carson, Mary C / Faulkner, Geoffrey J / Ferrai, Carmelo / Fisher, Malcolm E / Forrester, Lesley M / Fujita, Rie / Furusawa, Jun-Ichi / Geijtenbeek, Teunis B / Gingeras, Thomas / Goldowitz, Daniel / Guhl, Sven / Guler, Reto / Gustincich, Stefano / Ha, Thomas J / Hamaguchi, Masahide / Hara, Mitsuko / Hasegawa, Yuki / Herlyn, Meenhard / Heutink, Peter / Hitchens, Kelly J / Hume, David A / Ikawa, Tomokatsu / Ishizu, Yuri / Kai, Chieko / Kawamoto, Hiroshi / Kawamura, Yuki I / Kempfle, Judith S / Kenna, Tony J / Kere, Juha / Khachigian, Levon M / Kitamura, Toshio / Klein, Sarah / Klinken, S Peter / Knox, Alan J / Kojima, Soichi / Koseki, Haruhiko / Koyasu, Shigeo / Lee, Weonju / Lennartsson, Andreas / Mackay-Sim, Alan / Mejhert, Niklas / Mizuno, Yosuke / Morikawa, Hiromasa / Morimoto, Mitsuru / Moro, Kazuyo / Morris, Kelly J / Motohashi, Hozumi / Mummery, Christine L / Nakachi, Yutaka / Nakahara, Fumio / Nakamura, Toshiyuki / Nakamura, Yukio / Nozaki, Tadasuke / Ogishima, Soichi / Ohkura, Naganari / Ohno, Hiroshi / Ohshima, Mitsuhiro / Okada-Hatakeyama, Mariko / Okazaki, Yasushi / Orlando, Valerio / Ovchinnikov, Dmitry A / Passier, Robert / Patrikakis, Margaret / Pombo, Ana / Pradhan-Bhatt, Swati / Qin, Xian-Yang / Rehli, Michael / Rizzu, Patrizia / Roy, Sugata / Sajantila, Antti / Sakaguchi, Shimon / Sato, Hiroki / Satoh, Hironori / Savvi, Suzana / Saxena, Alka / Schmidl, Christian / Schneider, Claudio / Schulze-Tanzil, Gundula G / Schwegmann, Anita / Sheng, Guojun / Shin, Jay W / Sugiyama, Daisuke / Sugiyama, Takaaki / Summers, Kim M / Takahashi, Naoko / Takai, Jun / Tanaka, Hiroshi / Tatsukawa, Hideki / Tomoiu, Andru / Toyoda, Hiroo / van de Wetering, Marc / van den Berg, Linda M / Verardo, Roberto / Vijayan, Dipti / Wells, Christine A / Winteringham, Louise N / Wolvetang, Ernst / Yamaguchi, Yoko / Yamamoto, Masayuki / Yanagi-Mizuochi, Chiyo / Yoneda, Misako / Yonekura, Yohei / Zhang, Peter G / Zucchelli, Silvia / Abugessaisa, Imad / Arner, Erik / Harshbarger, Jayson / Kondo, Atsushi / Lassmann, Timo / Lizio, Marina / Sahin, Serkan / Sengstag, Thierry / Severin, Jessica / Shimoji, Hisashi / Suzuki, Masanori / Suzuki, Harukazu / Kawai, Jun / Kondo, Naoto / Itoh, Masayoshi / Daub, Carsten O / Kasukawa, Takeya / Kawaji, Hideya / Carninci, Piero / Forrest, Alistair R R / Hayashizaki, Yoshihide

Scientific data

2017 Volume 4, Page(s) 170112

Abstract: In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. ...

Abstract	In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
MeSH term(s)	Animals ; Gene Expression Profiling ; Gene Expression Regulation ; Genome ; Humans ; Mice ; Promoter Regions, Genetic ; Species Specificity
Language	English
Publishing date	2017-08-29
Publishing country	England
Document type	Dataset ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2775191-0
ISSN	2052-4463 ; 2052-4463
ISSN (online)	2052-4463
ISSN	2052-4463
DOI	10.1038/sdata.2017.112
Database	MEDical Literature Analysis and Retrieval System OnLINE

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