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Article ; Online: What Constitutes Material Alteration of Behavior?

Sikes, Robert S / Romero, L Michael

Lab animal

2022 Volume 51, Issue 7, Page(s) 181

Language	English
Publishing date	2022-06-29
Publishing country	United States
Document type	Letter
ISSN	1548-4475
ISSN (online)	1548-4475
DOI	10.1038/s41684-022-01004-0
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Article: Hands-on immunology: Engaging learners of all ages through tactile teaching tools.

Harris, Felix R / Sikes, Michael L / Bergman, Michael / Goller, Carlos C / Hasley, Andrew O / Sjogren, Caroline A / Ramirez, Melissa V / Gordy, Claire L

Frontiers in microbiology

2022 Volume 13, Page(s) 966282

Abstract: Ensuring the public has a fundamental understanding of human-microbe interactions, immune responses, and vaccines is a critical challenge in the midst of a pandemic. These topics are commonly taught in undergraduate- and graduate-level microbiology and ... ...

Abstract	Ensuring the public has a fundamental understanding of human-microbe interactions, immune responses, and vaccines is a critical challenge in the midst of a pandemic. These topics are commonly taught in undergraduate- and graduate-level microbiology and immunology courses; however, creating engaging methods of teaching these complex concepts to students of all ages is necessary to keep younger students interested when science seems hard. Building on the Tactile Teaching Tools with Guided Inquiry Learning (TTT-GIL) method we used to create an interactive
Language	English
Publishing date	2022-08-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.966282
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Article ; Online: Pharmacogenomic Analyses Implicate B Cell Developmental Status and

Small, George W / Akhtari, Farida S / Green, Adrian J / Havener, Tammy M / Sikes, Michael / Quintanhila, Julia / Gonzalez, Ricardo D / Reif, David M / Motsinger-Reif, Alison A / McLeod, Howard L / Wiltshire, Tim

Cells

2023 Volume 12, Issue 12

Abstract: Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may ... ...

Abstract	Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may influence sensitivity to treatment, the cytotoxic activity of three CD20 mAbs: rituximab; ofatumumab; and obinutuzumab, were screened in high-throughput assays using 680 ethnically diverse lymphoblastoid cell lines (LCLs) followed by a pharmacogenomic assessment. GWAS analysis identified several novel gene candidates. The most significant SNP, rs58600101, in the gene
MeSH term(s)	Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal/genetics ; Antigens, CD20/genetics ; Antineoplastic Agents ; Pharmacogenomic Testing ; Prednisolone ; Humans
Chemical Substances	Antibodies, Monoclonal ; Antigens, CD20 ; Antineoplastic Agents ; Prednisolone (9PHQ9Y1OLM)
Language	English
Publishing date	2023-06-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12121574
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Article ; Online: Pharmacogenomic Analyses Implicate B Cell Developmental Status and MKL1 as Determinants of Sensitivity toward Anti-CD20 Monoclonal Antibody Therapy

George W. Small / Farida S. Akhtari / Adrian J. Green / Tammy M. Havener / Michael Sikes / Julia Quintanhila / Ricardo D. Gonzalez / David M. Reif / Alison A. Motsinger-Reif / Howard L. McLeod / Tim Wiltshire

Cells, Vol 12, Iss 1574, p

2023 Volume 1574

Abstract	Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may influence sensitivity to treatment, the cytotoxic activity of three CD20 mAbs: rituximab; ofatumumab; and obinutuzumab, were screened in high-throughput assays using 680 ethnically diverse lymphoblastoid cell lines (LCLs) followed by a pharmacogenomic assessment. GWAS analysis identified several novel gene candidates. The most significant SNP, rs58600101, in the gene MKL1 displayed ethnic stratification, with the variant being significantly more prevalent in the African cohort and resulting in reduced transcript levels as measured by qPCR. Functional validation of MKL1 by shRNA-mediated knockdown of MKL1 resulted in a more resistant phenotype. Gene expression analysis identified the developmentally associated TGFB1I1 as the most significant gene associated with sensitivity. qPCR among a panel of sensitive and resistant LCLs revealed immunoglobulin class-switching as well as differences in the expression of B cell activation markers. Flow cytometry showed heterogeneity within some cell lines relative to surface Ig isotype with a shift to more IgG + cells among the resistant lines. Pretreatment with prednisolone could partly reverse the resistant phenotype. Results suggest that the efficacy of anti-CD20 mAb therapy may be influenced by B cell developmental status as well as polymorphism in the MKL1 gene. A clinical benefit may be achieved by pretreatment with corticosteroids such as prednisolone followed by mAb therapy.
Keywords	rituximab (Rituxan ® ) ; ofatumumab (Arzerra ® ; Kesimpta ® ) ; obinutuzumab (Gazyva ® ) ; CD20 ( MS4A1 ) ; MKL1 ( MRTFA ) ; TGFB1 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Genetic and epigenetic regulation of Tcrb gene assembly.

Sikes, Michael L / Oltz, Eugene M

Current topics in microbiology and immunology

2012 Volume 356, Page(s) 91–116

Abstract: Vertebrate development requires the formation of multiple cell types from a single genetic blueprint, an extraordinary feat that is guided by the dynamic and finely tuned reprogramming of gene expression. The sophisticated orchestration of gene ... ...

Abstract	Vertebrate development requires the formation of multiple cell types from a single genetic blueprint, an extraordinary feat that is guided by the dynamic and finely tuned reprogramming of gene expression. The sophisticated orchestration of gene expression programs is driven primarily by changes in the patterns of covalent chromatin modifications. These epigenetic changes are directed by cis elements, positioned across the genome, which provide docking sites for transcription factors and associated chromatin modifiers. Epigenetic changes impact all aspects of gene regulation, governing association with the machinery that drives transcription, replication, repair and recombination, a regulatory relationship that is dramatically illustrated in developing lymphocytes. The program of somatic rearrangements that assemble antigen receptor genes in precursor B and T cells has proven to be a fertile system for elucidating relationships between the genetic and epigenetic components of gene regulation. This chapter describes our current understanding of the cross-talk between key genetic elements and epigenetic programs during recombination of the Tcrb locus in developing T cells, how each contributes to the regulation of chromatin accessibility at individual DNA targets for recombination, and potential mechanisms that coordinate their actions.
MeSH term(s)	Animals ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Humans ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Antigen, T-Cell, alpha-beta/metabolism ; Recombination, Genetic ; T-Lymphocytes/cytology ; T-Lymphocytes/metabolism
Chemical Substances	Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2012
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	0070-217X
ISSN	0070-217X
DOI	10.1007/82_2011_138
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Article: Spreading, itchy papules on the extremities.

Burton, Michael / Sikes, Martha L / Schmidt, Heather L

JAAPA : official journal of the American Academy of Physician Assistants

2014 Volume 27, Issue 4, Page(s) 16–17

MeSH term(s)	Adult ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diagnosis, Differential ; Female ; Humans ; Hyperlipidemias/complications ; Hyperlipidemias/drug therapy ; Medication Adherence ; Xanthomatosis/diagnosis ; Xanthomatosis/etiology
Language	English
Publishing date	2014-04
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2415226-2
ISSN	0893-7400 ; 1547-1896
ISSN (online)	0893-7400
ISSN	1547-1896
DOI	10.1097/01.JAA.0000444739.70034.ff
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Article ; Online: Functional annotation of proteins for signaling network inference in non-model species.

Van den Broeck, Lisa / Bhosale, Dinesh Kiran / Song, Kuncheng / Fonseca de Lima, Cássio Flavio / Ashley, Michael / Zhu, Tingting / Zhu, Shanshuo / Van De Cotte, Brigitte / Neyt, Pia / Ortiz, Anna C / Sikes, Tiffany R / Aper, Jonas / Lootens, Peter / Locke, Anna M / De Smet, Ive / Sozzani, Rosangela

Nature communications

2023 Volume 14, Issue 1, Page(s) 4654

Abstract: Molecular biology aims to understand cellular responses and regulatory dynamics in complex biological systems. However, these studies remain challenging in non-model species due to poor functional annotation of regulatory proteins. To overcome this ... ...

Abstract	Molecular biology aims to understand cellular responses and regulatory dynamics in complex biological systems. However, these studies remain challenging in non-model species due to poor functional annotation of regulatory proteins. To overcome this limitation, we develop a multi-layer neural network that determines protein functionality directly from the protein sequence. We annotate kinases and phosphatases in Glycine max. We use the functional annotations from our neural network, Bayesian inference principles, and high resolution phosphoproteomics to infer phosphorylation signaling cascades in soybean exposed to cold, and identify Glyma.10G173000 (TOI5) and Glyma.19G007300 (TOT3) as key temperature regulators. Importantly, the signaling cascade inference does not rely upon known kinase motifs or interaction data, enabling de novo identification of kinase-substrate interactions. Conclusively, our neural network shows generalization and scalability, as such we extend our predictions to Oryza sativa, Zea mays, Sorghum bicolor, and Triticum aestivum. Taken together, we develop a signaling inference approach for non-model species leveraging our predicted kinases and phosphatases.
MeSH term(s)	Bayes Theorem ; Signal Transduction ; Transcription Factors/metabolism ; Phosphorylation
Chemical Substances	Transcription Factors
Language	English
Publishing date	2023-08-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-40365-z
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Article ; Online: Molybdenum and tungsten in Campylobacter jejuni: their physiological role and identification of separate transporters regulated by a single ModE-like protein.

Taveirne, Michael E / Sikes, Michael L / Olson, Jonathan W

Molecular microbiology

2009 Volume 74, Issue 3, Page(s) 758–771

Abstract: Campylobacter jejuni is an important human pathogen that causes millions of cases of food-borne enteritis each year. The C. jejuni respiratory chain is highly branched and contains at least four enzymes predicted to contain a metal binding pterin (MPT), ... ...

Abstract	Campylobacter jejuni is an important human pathogen that causes millions of cases of food-borne enteritis each year. The C. jejuni respiratory chain is highly branched and contains at least four enzymes predicted to contain a metal binding pterin (MPT), with the metal being either molybdenum or tungsten. Also predicted are two separate transport systems, one for molybdenum encoded by modABC and a second for tungsten encoded by tupABC. Both transport systems were mutated and the activities of the four predicted MPT-containing enzymes were assayed in the presence of molybdenum and tungsten in wild-type and mod and tup backgrounds. Results indicate that mod is primarily a molybdenum transporter that can also transport tungsten, while tup is a tungsten-specific transporter. The MPT containing enzymes nitrate reductase, sulphite oxidase, and SN oxide reductase are strict molybdoenzymes while formate dehydrogenase prefers tungsten. A ModE-like protein regulates both transporters, repressing mod in the presence of both molybdenum and tungsten and tup only in the presence of tungsten. Like other ModE proteins, the C. jejuni ModE binds DNA through a helix-turn-helix DNA binding domain, but unlike other members of the ModE family it does not have a metal binding domain.
MeSH term(s)	ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; Amino Acid Sequence ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Campylobacter jejuni/genetics ; Campylobacter jejuni/metabolism ; Electron Transport/genetics ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Formate Dehydrogenases/genetics ; Formate Dehydrogenases/metabolism ; Humans ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/metabolism ; Molecular Sequence Data ; Molybdenum/chemistry ; Molybdenum/metabolism ; Nitrate Reductase/genetics ; Nitrate Reductase/metabolism ; Nitrate Reductase (NAD(P)H)/metabolism ; Nitrate Reductases/chemistry ; Nitrate Reductases/genetics ; Nitrate Reductases/metabolism ; Phylogeny ; Protein Engineering ; Pterins/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; Transcription Factors/metabolism ; Tungsten/chemistry ; Tungsten/metabolism
Chemical Substances	ATP-Binding Cassette Transporters ; Bacterial Proteins ; Membrane Transport Proteins ; ModE protein, bacteria ; Pterins ; Transcription Factors ; Molybdenum (81AH48963U) ; Formate Dehydrogenases (EC 1.2.1.2) ; Nitrate Reductases (EC 1.7.-) ; Nitrate Reductase (NAD(P)H) (EC 1.7.1.2) ; Nitrate Reductase (EC 1.7.99.4) ; Tungsten (V9306CXO6G)
Language	English
Publishing date	2009-10-01
Publishing country	England
Document type	Journal Article
ZDB-ID	619315-8
ISSN	1365-2958 ; 0950-382X
ISSN (online)	1365-2958
ISSN	0950-382X
DOI	10.1111/j.1365-2958.2009.06901.x
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Article ; Online: Promoter activity 5' of Dbeta2 is coordinated by E47, Runx1, and GATA-3.

McMillan, Ruth E / Sikes, Michael L

Molecular immunology

2009 Volume 46, Issue 15, Page(s) 3009–3017

Abstract: V(D)J recombination involves the stepwise assembly of B and T cell receptor genes as lymphocytes progress through the early stages of development. While the mechanisms that restrict each step in recombination to its appropriate developmental stage are ... ...

Abstract	V(D)J recombination involves the stepwise assembly of B and T cell receptor genes as lymphocytes progress through the early stages of development. While the mechanisms that restrict each step in recombination to its appropriate developmental stage are largely unknown, they share many of the components that regulate transcription. For example, enhancer-dependent modifications in histone acetylation and methylation are essential for both germline transcription and rearrangement of antigen receptor genes. Promoters positioned proximal to individual D and J gene segments in Tcra, Tcrb, Tcrd, IgH, and Igk also contribute to antigen receptor gene assembly, though their effects appear more localized than those of enhancers. Tcrb assembly initiates with D-to-J joining at each of the two D-J-C gene segment clusters in DN1/2 thymocytes. DJ joints are fused with Vbeta elements to complete Tcrb recombination in DN3 cells. We have previously shown that Dbeta2 is flanked by upstream and downstream promoters, with the 5' promoter being held inactive until D-to-J recombination deletes the NFkappaB-dependent 3' promoter. We now report that activity of the 5' promoter reflects a complex interplay among Runx1, GATA-3, and E47 transcription factors. In particular, while multiple E47 and Runx1 binding sites clustered near the Dbeta2 5'RS and overlapping inr elements define the core 5'PDbeta2, they act in concert with an array of upstream GATA-3 sites to overcome the inhibitory effects of a 110bp distal polypurine.polypyrimidine (R.Y) tract. The dependence of 5'PDbeta2 on E47 is consistent with the reported role of E proteins in post-DN1 thymocyte development and V-to-DJbeta recombination.
MeSH term(s)	Animals ; Base Sequence ; Cell Differentiation/immunology ; Cell Line ; Chromatin/immunology ; Chromatin/metabolism ; Core Binding Factor Alpha 2 Subunit/immunology ; Core Binding Factor Alpha 2 Subunit/metabolism ; GATA3 Transcription Factor/immunology ; GATA3 Transcription Factor/metabolism ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; Homeodomain Proteins/genetics ; Homeodomain Proteins/immunology ; Homeodomain Proteins/metabolism ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Promoter Regions, Genetic ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; TCF Transcription Factors/immunology ; TCF Transcription Factors/metabolism ; Thymus Gland/immunology ; Thymus Gland/metabolism ; Transcription Factor 7-Like 1 Protein ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/immunology ; Tumor Suppressor Protein p53/metabolism ; Upstream Stimulatory Factors/immunology ; Upstream Stimulatory Factors/metabolism
Chemical Substances	Chromatin ; Core Binding Factor Alpha 2 Subunit ; GATA3 Transcription Factor ; Homeodomain Proteins ; Receptors, Antigen, T-Cell, alpha-beta ; Runx1 protein, mouse ; TCF Transcription Factors ; Tcf7l1 protein, mouse ; Transcription Factor 7-Like 1 Protein ; Tumor Suppressor Protein p53 ; Upstream Stimulatory Factors ; Usf1 protein, mouse ; RAG-1 protein (128559-51-3)
Language	English
Publishing date	2009-07-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2009.06.013
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Article ; Online: Communicating During an HIV Outbreak Among People Who Inject Drugs-West Virginia 2019.

Watson, Meg / Thomasson, Erica / Adkins, Elizabeth / Batdorf, Samantha / Kilkenny, Michael / Diaz, Shelly Sikes / Pegram, Laura / Rinderle, Jeffrey Kemp / LaFlam, Michael / Wingard, Rachel / McClung, R Paul / Oster, Alexandra M / Stryker, Jo

AIDS and behavior

2022 Volume 26, Issue Suppl 1, Page(s) 165–170

Abstract: In 2019, the West Virginia Bureau for Public Health (WV BPH), Cabell-Huntington Health Department (CHHD), and CDC collaborated to respond to an HIV outbreak among people who inject drugs (PWID). CDC, WV BPH, and CHHD formed a cross-agency communications ... ...

Abstract	In 2019, the West Virginia Bureau for Public Health (WV BPH), Cabell-Huntington Health Department (CHHD), and CDC collaborated to respond to an HIV outbreak among people who inject drugs (PWID). CDC, WV BPH, and CHHD formed a cross-agency communications team to establish situational awareness, identify knowledge gaps, and establish key audiences for messages, including the general population, PWID, and clinical and social service providers. The team disseminated up-to-date information about the outbreak, and prioritized messages addressing stigma related to drug use, syringe services programs, and HIV. Messages were continually updated to address the evolving situation and to resonate with local values. Messages were disseminated via advertisements, local news media, and directly to PWID, people experiencing homelessness, and providers. The response supplemented CHHD's assets, including strong relationships and community knowledge, with staff capacity and expertise from state and federal agencies. This collaborative approach is a useful model to address communication needs.
MeSH term(s)	Disease Outbreaks ; Drug Users ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; Humans ; Substance Abuse, Intravenous/epidemiology ; West Virginia/epidemiology
Language	English
Publishing date	2022-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1339885-4
ISSN	1573-3254 ; 1090-7165
ISSN (online)	1573-3254
ISSN	1090-7165
DOI	10.1007/s10461-021-03538-9
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