Open Access. Powered by Scholars. Published by Universities.®
- Discipline
- Keyword
-
- Cardio-metabolic risk factors (1)
- Chromatin fibers (1)
- Chromatin structure in situ (1)
- Connected (1)
- DNA cytochemistry (1)
-
- Diet and lifestyle (1)
- Education (1)
- Gene drug dynamics (1)
- Gene testing (1)
- Integrative medicine (1)
- Micronutrients (1)
- Multitasking (1)
- Nucleosomes (1)
- Nutrition (1)
- Osmium-ammine (1)
- Pharmacogenetics (1)
- Prevention of non-communicable disease (1)
- Students (1)
- Thiopurine S-methyltransferase (TPMT) (1)
- Transmission electron microscopy (1)
- Warfarin (1)
Articles 1 - 20 of 20
Full-Text Articles in Medicine and Health Sciences
Statin Treatment In Specific Patient Groups: Role For Improved Cardiovascular Risk Markers, Alyssa White, Hillary R. Mishcon, John L. Redwanski, Ronald D. Hills Jr
Statin Treatment In Specific Patient Groups: Role For Improved Cardiovascular Risk Markers, Alyssa White, Hillary R. Mishcon, John L. Redwanski, Ronald D. Hills Jr
Pharmaceutical Sciences Faculty Publications
Ample evidence supports the use of statin therapy for secondary prevention in patients with a history of atherosclerotic cardiovascular disease (ASCVD), but evidence is wanting in the case of primary prevention, low-risk individuals, and elderly adults 65+. Statins are effective in lowering low-density lipoprotein (LDL), which has long been a target for treatment decisions. We discuss the weakening dependence between cholesterol levels and mortality as a function of age and highlight recent findings on lipoprotein subfractions and other superior markers of ASCVD risk. The efficacy of statins is compared for distinct subsets of patients based on age, diabetes, ASCVD, and …
Gut Microbiome: Profound Implications For Diet And Disease, Ronald D. Hills Jr., Benjamin A. Pontefract, Hillary R. Mishcon, Cody A. Black, Steven C. Sutton, Cory R. Theberge
Gut Microbiome: Profound Implications For Diet And Disease, Ronald D. Hills Jr., Benjamin A. Pontefract, Hillary R. Mishcon, Cody A. Black, Steven C. Sutton, Cory R. Theberge
Pharmaceutical Sciences Faculty Publications
The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key …
Tnf-Α Differentially Regulates Cell Cycle Genes In Promyelocytic And Granulocytic Hl-60/S4 Cells, Elsie C. Jacobson, Lekha Jain, Mark H. Vickers, Ada L. Olins, Donald E. Olins, Jo K. Perry, Justin M. O'Sullivan
Tnf-Α Differentially Regulates Cell Cycle Genes In Promyelocytic And Granulocytic Hl-60/S4 Cells, Elsie C. Jacobson, Lekha Jain, Mark H. Vickers, Ada L. Olins, Donald E. Olins, Jo K. Perry, Justin M. O'Sullivan
Pharmaceutical Sciences Faculty Publications
Tumor necrosis factor alpha (TNF-α) is a potent cytokine involved in systemic inflammation and immune modulation. Signaling responses that involve TNF-α are context dependent and capable of stimulating pathways promoting both cell death and survival. TNF-α treatment has been investigated as part of a combined therapy for acute myeloid leukemia due to its modifying effects on all-trans retinoic acid (ATRA) mediated differentiation into granulocytes. To investigate the interaction between cellular differentiation and TNF-α, we performed RNA-sequencing on two forms of the human HL-60/S4 promyelocytic leukemia cell line treated with TNF-α. The ATRA-differentiated granulocytic form of HL-60/S4 cells had an enhanced …
Atomic Resolution Cryo-Em Structure Of A Nativelike Cenp-A Nucleosome Aided By An Antibody Fragment, Bing-Rui Zhou, K. N. Sathish Yadav, Mario Borgnia, Jingjun Hong, Baohua Cao, Ada L. Olins, Donald E. Olins, Yawen Bai, Ping Zhang
Atomic Resolution Cryo-Em Structure Of A Nativelike Cenp-A Nucleosome Aided By An Antibody Fragment, Bing-Rui Zhou, K. N. Sathish Yadav, Mario Borgnia, Jingjun Hong, Baohua Cao, Ada L. Olins, Donald E. Olins, Yawen Bai, Ping Zhang
Pharmaceutical Sciences Faculty Publications
Genomic DNA in eukaryotes is organized into chromatin through association with core histones to form nucleosomes, each distinguished by their DNA sequences and histone variants. Here, we used a single-chain antibody fragment (scFv) derived from the anti-nucleosome antibody mAb PL2-6 to stabilize human CENP-A nucleosome containing a native α-satellite DNA and solved its structure by the cryo-electron microscopy (cryo-EM) to 2.6 Å resolution. In comparison, the corresponding cryo-EM structure of the free CENP-A nucleosome could only reach 3.4 Å resolution. We find that scFv binds to a conserved acidic patch on the histone H2A-H2B dimer without perturbing the nucleosome structure. …
Migration Through A Small Pore Disrupts Inactive Chromatin Organization In Neutrophil-Like Cells, Elsie C. Jacobson, Jo K. Perry, David S. Long, Ada L. Olins, Donald E. Olins, Bryon E. Wright, Mark H. Vickers, Justin M. O'Sullivan
Migration Through A Small Pore Disrupts Inactive Chromatin Organization In Neutrophil-Like Cells, Elsie C. Jacobson, Jo K. Perry, David S. Long, Ada L. Olins, Donald E. Olins, Bryon E. Wright, Mark H. Vickers, Justin M. O'Sullivan
Pharmaceutical Sciences Faculty Publications
Background: Mammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. The nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through confined spaces, where the nuclear shape must change in order to fit through a constriction. This occurs many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration. Here we characterized the effects of constricted migration in neutrophil-like cells. Results: Total RNA sequencing identified that migration …
Jörg Langowski: His Scientific Legacy And The Future It Promises, Giuseppe Chirico, Alexander Gansen, Sanford H. Leuba, Ada L. Olins, Donald E. Olins, Jeremy C. Smith, Katalin Tóth
Jörg Langowski: His Scientific Legacy And The Future It Promises, Giuseppe Chirico, Alexander Gansen, Sanford H. Leuba, Ada L. Olins, Donald E. Olins, Jeremy C. Smith, Katalin Tóth
Pharmaceutical Sciences Faculty Publications
Background: With the passing of Jörg Langowski 6 May 2017 in a sailplane accident, the scientific community was deprived of a strident and effective voice for DNA and chromatin molecular and computational biophysics, for open access publishing and for the creation of effective scientific research networks. Methods: Here, after reviewing some of Jörg’s key research contributions and ideas, we offer through the personal remembrance of his closest collaborators, a deep analysis of the major results of his research and the future directions they have engendered. Conclusions: The legacy of Jörg Langowski has been to propel a way of viewing biological …
Guide To Popular Diets, Food Choices, And Their Health Outcome, Ronald D. Hills Jr., Emily Erpenbeck
Guide To Popular Diets, Food Choices, And Their Health Outcome, Ronald D. Hills Jr., Emily Erpenbeck
Pharmaceutical Sciences Faculty Publications
Integrative medicine is becoming increasingly important for a patient population afflicted with preventable illnesses such as cardiometabolic disease. Diet and nutrition are an under-tapped opportunity in health care for improving wellness and patient-centered health outcomes. Key nutritional principles are reviewed for alternate dietary strategies patients choose from in pursuit of healthy living or to alleviate chronic illness. Whole food eating plans are discussed including plant-based, Mediterranean, Paleo, and ketogenic diets as well as the specific carbohydrate and low FODMAP diets for colitis and irritable bowel syndrome. Opposed to the traditional categorization of diets by macronutrient composition, it is more useful …
Epichromatin And Chromomeres: A ‘Fuzzy’ Perspective, Donald E. Olins, Ada L. Olins
Epichromatin And Chromomeres: A ‘Fuzzy’ Perspective, Donald E. Olins, Ada L. Olins
Pharmaceutical Sciences Faculty Publications
‘Epichromatin’, the surface of chromatin beneath the interphase nuclear envelope (NE) or at the surface of mitotic chromosomes, was discovered by immunostaining with a specific bivalent mouse monoclonal anti-nucleosome antibody (mAb PL2-6). ‘Chromomeres’, punctate chromatin particles approximately 200–300 nm in diameter, identified throughout the interphase chromatin and along mitotic chromosomes, were observed by immunostaining with the monovalent papain-derived Fab fragments of bivalent PL2-6. The specific target for PL2-6 appears to include the nucleosome acidic patch. Thus, within the epichromatin and chromomeric regions, this epitope is ‘exposed’. Considering that histones possess unstructured ‘tails’ (i.e. intrinsically disordered peptide regions, IDPR), our perception …
Defining The Epichromatin Epitope, Travis J. Gould, Katalin Tóth, Norbert Mücke, Jörg Langowski, Alexandra S. Hakusui, Ada L. Olins, Donald E. Olins
Defining The Epichromatin Epitope, Travis J. Gould, Katalin Tóth, Norbert Mücke, Jörg Langowski, Alexandra S. Hakusui, Ada L. Olins, Donald E. Olins
Pharmaceutical Sciences Faculty Publications
Epichromatin is identified by immunostaining fixed and permeabilized cells with particular bivalent anti-nucleosome antibodies (mAbs PL2-6 and 1H6). During interphase, epichromatin resides adjacent to the inner nuclear membrane; during mitosis, at the outer surface of mitotic chromosomes. By STED (stimulated emission depletion) microscopy, PL2-6 stained interphase epichromatin is ∼76 nm thick and quite uniform; mitotic epichromatin is more variable in thickness, exhibiting a “wrinkled” surface with an average thickness of ∼78 nm. Co-immunostaining with anti-Ki-67 demonstrates Ki-67 deposition between the PL2-6 “ridges” of mitotic epichromatin. Monovalent papain-derived Fab fragments of PL2-6 yield a strikingly different punctate “chromomeric” immunostaining pattern throughout …
Nucleosome Repositioning During Differentiation Of A Human Myeloid Leukemia Cell Line, Vladimir B. Teif, Jan-Philipp Mallm, Tanvi Sharma, David B. Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L. Olins, Donald E. Olins
Nucleosome Repositioning During Differentiation Of A Human Myeloid Leukemia Cell Line, Vladimir B. Teif, Jan-Philipp Mallm, Tanvi Sharma, David B. Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L. Olins, Donald E. Olins
Pharmaceutical Sciences Faculty Publications
Cell differentiation is associated with changes in chromatin organization and gene expression. In this study, we examine chromatin structure following differentiation of the human myeloid leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and properties of epichromatin (surface chromatin adjacent to the nuclear envelope). Nucleosome positions changed genome-wide, exhibiting a specific class of alterations involving nucleosome loss in extended (∼1kb) regions, pronounced in enhancers and promoters. Genes that lost nucleosomes at their …
Transcriptomes Reflect The Phenotypes Of Undifferentiated, Granulocyte And Macrophage Forms Of Hl-60/S4 Cells, David B. Mark Welch, Anna Jauch, Jörg Langowski, Ada L. Olins, Donald E. Olins
Transcriptomes Reflect The Phenotypes Of Undifferentiated, Granulocyte And Macrophage Forms Of Hl-60/S4 Cells, David B. Mark Welch, Anna Jauch, Jörg Langowski, Ada L. Olins, Donald E. Olins
Pharmaceutical Sciences Faculty Publications
To understand the chromatin changes underlying differential gene expression during induced differentiation of human leukemic HL-60/S4 cells, we conducted RNA-Seq analysis on quadruplicate cultures of undifferentiated, granulocytic- and macrophage-differentiated cell forms. More than half of mapped genes exhibited altered transcript levels in the differentiated cell forms. In general, more genes showed increased mRNA levels in the granulocytic form and in the macrophage form, than showed decreased levels. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in genes that exhibited differential transcript levels after either RA or TPA treatment. Changes in transcript levels for groups …
Retrotransposon Alu Is Enriched In The Epichromatin Of Hl-60 Cells, Ada L. Olins, Naveed Ishaque, Sasithorn Chotewutmontri, Jörg Langowski, Donald E. Olins
Retrotransposon Alu Is Enriched In The Epichromatin Of Hl-60 Cells, Ada L. Olins, Naveed Ishaque, Sasithorn Chotewutmontri, Jörg Langowski, Donald E. Olins
Pharmaceutical Sciences Faculty Publications
Epichromatin, the surface of chromatin facing the nuclear envelope in an interphase nucleus, reveals a “rim” staining pattern with specific mouse monoclonal antibodies against histone H2A/H2B/DNA and phosphatidylserine epitopes. Employing a modified ChIP-Seq procedure on undifferentiated and differentiated human leukemic (HL-60/S4) cells, >95% of assembled epichromatin regions overlapped with Alu retrotransposons. They also exhibited enrichment of the AluS subfamily and of Alu oligomers. Furthermore, mapping epichromatin regions to the human chromosomes revealed highly similar localization patterns in the various cell states and with the different antibodies. Comparisons with available epigenetic databases suggested that epichromatin is neither “classical” heterochromatin nor highly …
Chromatin Structure In Situ: The Contribution Of Dna Ultrastructural Cytochemistry, Massimo Derenzini, Ada L. Olins, Donald E. Olins
Chromatin Structure In Situ: The Contribution Of Dna Ultrastructural Cytochemistry, Massimo Derenzini, Ada L. Olins, Donald E. Olins
Pharmaceutical Sciences Faculty Publications
Ultrastructural studies conducted in situ using conventional transmission electron microscopy have had relatively little impact on defining the structural organization of chromatin. This is due to the fact that in routine transmission electron microscopy, together with the deoxyribonucleoprotein, many different intermingled substances are contrasted, masking the ultrastructure of chromatin. By selective staining of DNA in thin sections, using the Feulgen-like osmium-ammine reaction, these drawbacks have been overcome and worthwhile data have been obtained both on the gross morphology and the ultrastructural-functional organization of chromatin in situ. In the present study these results are reviewed and discussed in light of recent …
Nuclear Envelope Composition Determines The Ability Of Neutrophil-Type Cells To Passage Through Micron-Scale Constrictions, Amy C. Rowat, Diana E. Jaalouk E. Jaalouk, Monika Zwerger, W. Lloyd Ung, Irwin A. Eydelnant, Donald E. Olins, Ada L. Olins, Harald Herrmann, David A. Weitz, Jan Lammerding
Nuclear Envelope Composition Determines The Ability Of Neutrophil-Type Cells To Passage Through Micron-Scale Constrictions, Amy C. Rowat, Diana E. Jaalouk E. Jaalouk, Monika Zwerger, W. Lloyd Ung, Irwin A. Eydelnant, Donald E. Olins, Ada L. Olins, Harald Herrmann, David A. Weitz, Jan Lammerding
Pharmaceutical Sciences Faculty Publications
Neutrophils are characterized by their distinct nuclear shape, which is thought to facilitate the transit of these cells through pore spaces less than one-fifth of their diameter. We used human promyelocytic leukemia (HL-60) cells as a model system to investigate the effect of nuclear shape in whole cell deformability. We probed neutrophil-differentiated HL-60 cells lacking expression of lamin B receptor, which fail to develop lobulated nuclei during granulopoiesis and present an in vitro model for Pelger-Huët anomaly; despite the circular morphology of their nuclei, the cells passed through micron-scale constrictions on similar timescales as scrambled controls. We then investigated the …
Phosphatidylserine Colocalizes With Epichromatin In Interphase Nuclei And Mitotic Chromosomes, Igor Prudovsky, Calvin P.H. Vary, Yolanda Markaki, Ada L. Olins, Donald E. Olins
Phosphatidylserine Colocalizes With Epichromatin In Interphase Nuclei And Mitotic Chromosomes, Igor Prudovsky, Calvin P.H. Vary, Yolanda Markaki, Ada L. Olins, Donald E. Olins
Pharmaceutical Sciences Faculty Publications
Cycling eukaryotic cells rapidly re-establish the nuclear envelope and internal architecture following mitosis. Studies with a specific anti-nucleosome antibody recently demonstrated that the surface (“epichromatin”) of interphase and mitotic chromatin possesses a unique and conserved conformation, suggesting a role in postmitotic nuclear reformation. Here we present evidence showing that the anionic glycerophospholipid phosphatidylserine is specifically located in epichromatin throughout the cell cycle and is associated with nucleosome core histones. This suggests that chromatin bound phosphatidylserine may function as a nucleation site for the binding of ER and re-establishment of the nuclear envelope.
An Epichromatin Epitope: Persistence In The Cell Cycle And Conservation In Evolution, Ada L. Olins, Markus Langhans, Marc Monestier, Andreas Schlotterer, David G. Robinson, Corrado Viotti, Hanswalter Zentgraf, Monika Zwerger, Donald E. Olins
An Epichromatin Epitope: Persistence In The Cell Cycle And Conservation In Evolution, Ada L. Olins, Markus Langhans, Marc Monestier, Andreas Schlotterer, David G. Robinson, Corrado Viotti, Hanswalter Zentgraf, Monika Zwerger, Donald E. Olins
Pharmaceutical Sciences Faculty Publications
Interphase nuclear architecture is disrupted and rapidly reformed with each cell division cycle. Successive cell generations exhibit a “memory” of this nuclear architecture, as well as for gene expression. Furthermore, many features of nuclear and mitotic chromosome structure are recognizably species and tissue specific. We wish to know what properties of the underlying chromatin structure may determine these conserved features of nuclear architecture. Employing a particular mouse autoimmune anti-nucleosome monoclonal antibody (PL2-6), combined with deconvolution immunofluorescence microscopy, we present evidence for a unique epitope (involving a ternary complex of histones H2A and H2B and DNA) which is localized only at …
An In Vitro Model For Pelger-Huët Anomaly, Ada L. Olins, Aurélie Ernst, Monika Zwerger, Harald Hermann, Donald E. Olins
An In Vitro Model For Pelger-Huët Anomaly, Ada L. Olins, Aurélie Ernst, Monika Zwerger, Harald Hermann, Donald E. Olins
Pharmaceutical Sciences Faculty Publications
The principal human blood granulocyte (neutrophil) possesses a lobulated and deformable nucleus, important to facilitate rapid egress from blood vessels as these cells migrate to sites of bacterial or fungal infection. This unusual nuclear shape is a product of elevated levels of an integral membrane protein of the nuclear envelope lamin B receptor (LBR) and of decreased amounts of lamin A/C. In humans, a genetic deficiency of LBR produces Pelger-Huët anomaly, resulting in blood neutrophils that exhibit hypolobulated nuclei with redistributed heterochromatin. Structural changes in nuclear architecture occur during granulopoiesis within bone marrow. The exact mechanisms of this nuclear shape …
Lamin B Receptor, Ada L. Olins, Gale Rhodes, David B. Mark Welch, Monika Zwerger, Donald E. Olins
Lamin B Receptor, Ada L. Olins, Gale Rhodes, David B. Mark Welch, Monika Zwerger, Donald E. Olins
Pharmaceutical Sciences Faculty Publications
Lamin B Receptor (LBR) is an integral membrane protein of the interphase nuclear envelope (NE). The N-terminal end resides in the nucleoplasm, binding to lamin B and heterochromatin, with the interactions disrupted during mitosis. The C-terminal end resides within the inner nuclear membrane, retreating with the ER away from condensing chromosomes during mitotic NE breakdown. Some of these properties are interpretable in terms of our current structural knowledge of LBR, but many of the structural features remain unknown. LBR apparently has an evolutionary history which brought together at least two ancient conserved structural domains (i.e. Tudor and sterol reductase). This …
Role Of The Genomics Revolution In Pharmaceutics, Daniel A. Brazeau, Gayle A. Brazeau
Role Of The Genomics Revolution In Pharmaceutics, Daniel A. Brazeau, Gayle A. Brazeau
Pharmaceutical Sciences Faculty Publications
Highlights the examples of Thiopurine S-methyltransferase (TPMT) and Warfarin as a means of describing some of the problems that are common to many pharmacogenetic cases. The pharmacogenetic literature contains many examples of confusing, or even contradictory, studies that arise due to unknown environmental factors that result in poor outcomes; drugs whose metabolism/transport are affected by multiple genes in multiple pathways; and clinically important genes that have many rare allelic variants with similar phenotypes variation in the frequencies of allelic variants among ethnic groups that mask the role of any one variant. These issues are common to most gene/drug dynamics and …
The Challenge Of Educating In A Highly-Connected And Multitasking World, Daniel A. Brazeau, Gayle A. Brazeau
The Challenge Of Educating In A Highly-Connected And Multitasking World, Daniel A. Brazeau, Gayle A. Brazeau
Pharmaceutical Sciences Faculty Publications
Today’s students are more connected and more integrated with their world than any past generation and information is readily available today from a multitude of sources. To what extent have these advances improved our students’ ability to become learned pharmacy professionals who are informed not only of the current world and its events but the profession itself?