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Article ; Online: Glycosaminoglycan Analysis: Purification, Structural Profiling, and GAG-Protein Interactions.

Basu, Amrita / Weiss, Ryan J

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2597, Page(s) 159–176

Abstract: Glycosaminoglycans (GAGs) are long, linear polysaccharides that are ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These complex carbohydrates are composed of alternating glucosamine and uronic acids that ... ...

Abstract	Glycosaminoglycans (GAGs) are long, linear polysaccharides that are ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These complex carbohydrates are composed of alternating glucosamine and uronic acids that can be heterogeneously N- and O-sulfated. The arrangement and orientation of the sulfated sugar residues specify the location of distinct ligand binding sites on the cell surface, and their capacity to bind ligands impacts cell growth and development, the ability to form tissues and organs, and normal physiology. The heterogeneous nature of GAGs and their inherent structural diversity across different tissues, cell types, and disease states creates challenges to characterizing their structure and function. Here, we describe detailed methods to investigate GAG-protein interactions in vitro and evaluate the structural composition of two classes of sulfated GAGs, heparan sulfate and chondroitin/dermatan sulfate, using liquid chromatography, mass spectrometry, and radiolabeling techniques. Overall, these methods facilitate the evaluation of GAG structure and function to uncover the unique roles these molecules play in cell biology and human disease.
MeSH term(s)	Humans ; Animals ; Glycosaminoglycans/chemistry ; Heparitin Sulfate/analysis ; Heparitin Sulfate/chemistry ; Chondroitin Sulfates/chemistry ; Chromatography, Liquid ; Uronic Acids ; Sulfates
Chemical Substances	Glycosaminoglycans ; Heparitin Sulfate (9050-30-0) ; Chondroitin Sulfates (9007-28-7) ; Uronic Acids ; Sulfates
Language	English
Publishing date	2022-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2835-5_13
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dissemination and implementation of an evidence-based voluntary medical male circumcision program: The Spear & Shield program.

Weiss, Stephen M / Bowa, Kasonde / Zulu, Robert / Rodriguez, Violeta J / Cook, Ryan R / Jones, Deborah L

PLOS global public health

2024 Volume 4, Issue 1, Page(s) e0002065

Abstract: Despite compelling evidence linking voluntary medical male circumcision (VMMC) with 60-70% HIV risk reduction in sub-Saharan Africa, Zambian men have been especially reluctant to undergo VMMC. The Government of Zambia set targets for VMMC uptake and ... ...

Abstract	Despite compelling evidence linking voluntary medical male circumcision (VMMC) with 60-70% HIV risk reduction in sub-Saharan Africa, Zambian men have been especially reluctant to undergo VMMC. The Government of Zambia set targets for VMMC uptake and promoted community-level interventions. Spear & Shield (S&S) is an innovative, evidence-based, service program promoting VMMC uptake while ensuring both VMMC supply and demand. This study assessed the large-scale provincial rollout of the program (S&S2) utilizing the RE-AIM model for translating interventions into the community. The S&S2 study was conducted between November 2015 and December 2020, and sequentially rolled out over four Zambian provinces in 96 clinics; 24 observation clinics received VMMC training only. Local clinic healthcare workers were trained to conduct the VMMC procedure and HIV counselors were trained to lead S&S group sessions. Using the RE-AIM model, primary outcomes were: Reach, the number, proportion, and representativeness of S&S attendees; Effectiveness, the impact of S&S2 on VMMC uptake; Adoption, the number, proportion, and representativeness of clinics implementing S&S2; Implementation, fidelity to the S&S intervention manual; and Maintenance, the extent to which S&S2 became an element of standard care within community clinics. Initially, n = 109 clinics were recruited; 96 were sustained and randomized for activation (Adoption). A total of 45,630 clinic patients (n = 23,236 men and n = 22,394 women) volunteered to attend the S&S sessions (Reach). The S&S2 program ran over 2,866 clinic-months (Implementation). Although the study did not target individual-level VMMCs, ~58,301 additional VMMCs were conducted at the clinic level (Effectiveness). Fidelity to the S&S intervention by group leaders ranged from 42%-95%. Sustainability of the program was operationalized as the number of CHCs initially activated that sustained the program. Intervention delivery ended, however, when study funding ceased (Maintenance). The S&S2 program successfully utilized the RE-AIM model to achieve study goals for implementation and dissemination in four Zambian provinces. Innovative VMMC programs such as S&S2 can improve the uptake of VMMC, one of the most effective strategies in the HIV prevention arsenal.
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0002065
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Article ; Online: Evaluating mesh fixation techniques for ventral hernia repair: A systematic review and network meta-analysis of randomised control trials.

Calpin, Gavin G / Davey, Matthew G / Whooley, Jack / Ryan, Eanna J / Ryan, Odhran K / Ponten, Jeroen E H / Weiss, Andreas / Conneely, John B / Robb, William B / Donlon, Noel E

American journal of surgery

2023 Volume 228, Page(s) 62–69

Abstract: Introduction: There is uncertainty regarding the optimal mesh fixation techniques for laparoscopic ventral and incisional hernia repair.: Aim: To perform a systematic review and network meta-analysis of randomised control trials (RCTs) to investigate ...

Abstract	Introduction: There is uncertainty regarding the optimal mesh fixation techniques for laparoscopic ventral and incisional hernia repair. Aim: To perform a systematic review and network meta-analysis of randomised control trials (RCTs) to investigate the advantages and disadvantages associated with absorbable tacks, non-absorbable tacks, non-absorbable sutures, non-absorbable staples, absorbable synthetic glue, absorbable sutures and non-absorbable tacks, and non-absorbable sutures and non-absorbable tacks. Methods: A systematic review was performed as per PRISMA-NMA guidelines. Odds ratios (ORs) and mean differences (MDs) were extracted to compare the efficacy of the surgical approaches. Results: Nine RCTs were included with 707 patients. Short-term pain was significantly reduced in non-absorbable staples (MD; -1.56, confidence interval (CI); -2.93 to -0.19) and non-absorbable sutures (MD; -1.00, CI; -1.60 to -0.40) relative to absorbable tacks. Recurrence, length of stay, operative time, conversion to open surgery, seroma and haematoma formation were unaffected by mesh fixation technique. Conclusion: Short-term post-operative pain maybe reduced by the use of non-absorbable sutures and non-absorbable staples. There is clinical equipoise between each modality in relation to recurrence, length of stay, and operative time.
MeSH term(s)	Humans ; Surgical Mesh ; Network Meta-Analysis ; Hernia, Ventral/surgery ; Prostheses and Implants ; Pain, Postoperative/surgery ; Laparoscopy/methods ; Sutures ; Herniorrhaphy/methods ; Recurrence ; Treatment Outcome
Language	English
Publishing date	2023-09-13
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	2953-1
ISSN	1879-1883 ; 0002-9610
ISSN (online)	1879-1883
ISSN	0002-9610
DOI	10.1016/j.amjsurg.2023.09.015
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Article: Heparan sulfate modified proteins affect cellular processes central to neurodegeneration and modulate

Schultheis, Nicholas / Connell, Alyssa / Kapral, Alexander / Becker, Robert J / Mueller, Richard / Shah, Shalini / O'Donnell, Mackenzie / Roseman, Matthew / Wang, Weihua / Yin, Fei / Weiss, Ryan / Selleck, Scott B

bioRxiv : the preprint server for biology

2024

Abstract: Mutations ... ...

Abstract	Mutations in
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.23.576895
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Article ; Online: TFCP2 is a transcriptional regulator of heparan sulfate assembly and melanoma cell growth.

Basu, Amrita / Champagne, Rachel N / Patel, Neil G / Nicholson, Elijah D / Weiss, Ryan J

The Journal of biological chemistry

2023 Volume 299, Issue 6, Page(s) 104713

Abstract: Heparan sulfate (HS) is a long, linear polysaccharide that is ubiquitously expressed in all animal cells and plays a key role in many cellular processes, including cell signaling and development. Dysregulation of HS assembly has been implicated in ... ...

Abstract	Heparan sulfate (HS) is a long, linear polysaccharide that is ubiquitously expressed in all animal cells and plays a key role in many cellular processes, including cell signaling and development. Dysregulation of HS assembly has been implicated in pathophysiological conditions, such as tumorigenesis and rare genetic disorders. HS biosynthesis occurs in a non-template-driven manner in the endoplasmic reticulum and Golgi through the activity of a large group of biosynthetic enzymes. While much is known about its biosynthesis, little is understood about the regulation of HS assembly across diverse tissue types and disease states. To address this gap in knowledge, we recently performed genome-wide CRISPR/Cas9 screens to identify novel regulatory factors of HS biosynthesis. From these screens, we identified the alpha globin transcription factor, TFCP2, as a top hit. To investigate the role of TFCP2 in HS assembly, we targeted TFCP2 expression in human melanoma cells using the CRISPR/Cas9 system. TFCP2 knockout cells exhibited decreased fibroblast growth factor binding to cell surface HS, alterations in HS composition, and slowed cell growth compared to wild-type cells. Additionally, RNA sequencing revealed that TFCP2 regulates the expression of multiple enzymes involved in HS assembly, including the secreted endosulfatase, SULF1. Pharmacological targeting of TFCP2 activity similarly reduced growth factor binding and increased SULF1 expression, and the knockdown of SULF1 expression in TFCP2 mutant cells restored melanoma cell growth. Overall, these studies identify TFCP2 as a novel transcriptional regulator of HS and highlight HS-protein interactions as a possible target to slow melanoma growth.
MeSH term(s)	Animals ; Humans ; Heparitin Sulfate/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Gene Expression Regulation ; Cell Proliferation ; Melanoma/genetics ; DNA-Binding Proteins/metabolism
Chemical Substances	Heparitin Sulfate (9050-30-0) ; Transcription Factors ; TFCP2 protein, human ; DNA-Binding Proteins
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.104713
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Article ; Online: Spatiotemporal diversity and regulation of glycosaminoglycans in cell homeostasis and human disease.

Basu, Amrita / Patel, Neil G / Nicholson, Elijah D / Weiss, Ryan J

American journal of physiology. Cell physiology

2022 Volume 322, Issue 5, Page(s) C849–C864

Abstract: Glycosaminoglycans (GAGs) are long, linear polysaccharides that are ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These complex carbohydrates play important roles in many cellular processes and have been ... ...

Abstract	Glycosaminoglycans (GAGs) are long, linear polysaccharides that are ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These complex carbohydrates play important roles in many cellular processes and have been implicated in many disease states, including cancer, inflammation, and genetic disorders. GAGs are among the most complex molecules in biology with enormous information content and extensive structural and functional heterogeneity. GAG biosynthesis is a nontemplate-driven process facilitated by a large group of biosynthetic enzymes that have been extensively characterized over the past few decades. Interestingly, the expression of the enzymes and the consequent structure and function of the polysaccharide chains can vary temporally and spatially during development and under certain pathophysiological conditions, suggesting their assembly is tightly regulated in cells. Due to their many key roles in cell homeostasis and disease, there is much interest in targeting the assembly and function of GAGs as a therapeutic approach. Recent advances in genomics and GAG analytical techniques have pushed the field and generated new perspectives on the regulation of mammalian glycosylation. This review highlights the spatiotemporal diversity of GAGs and the mechanisms guiding their assembly and function in human biology and disease.
MeSH term(s)	Animals ; Extracellular Matrix/metabolism ; Genomics ; Glycosaminoglycans/chemistry ; Glycosaminoglycans/metabolism ; Glycosylation ; Homeostasis ; Humans ; Mammals/metabolism
Chemical Substances	Glycosaminoglycans
Language	English
Publishing date	2022-03-16
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00085.2022
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Article ; Online: Technological advances in study of lung regenerative medicine:perspective from the 2019 Vermont lung stem cell conference.

Ikonomou, Laertis / Wagner, Darcy E / Gilpin, Sarah E / Weiss, Daniel J / Ryan, Amy L

Cytotherapy

2020 Volume 22, Issue 10, Page(s) 519–520

Language	English
Publishing date	2020-06-02
Publishing country	England
Document type	Editorial
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2020.04.001
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Article ; Online: Correction to "Photogeneration of Spin Quintet Triplet-Triplet Excitations in DNA-Assembled Pentacene Stacks".

Orsborne, Sarah R E / Gorman, Jeffrey / Weiss, Leah R / Sridhar, Akshay / Panjwani, Naitik A / Divitini, Giorgio / Budden, Peter / Palecek, David / Ryan, Seán T J / Rao, Akshay / Collepardo-Guevara, Rosana / El-Sagheer, Afaf H / Brown, Tom / Behrends, Jan / Friend, Richard H / Auras, Florian

Journal of the American Chemical Society

2023 Volume 145, Issue 14, Page(s) 8271

Language	English
Publishing date	2023-03-31
Publishing country	United States
Document type	Published Erratum
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.3c02230
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Article: Selective Enhancer Dependencies in

Iyer, Ashwin R / Gurumurthy, Aishwarya / Kodgule, Rohan / Aguilar, Athalee R / Saari, Travis / Ramzan, Abdullah / Rausch, Dylan / Gupta, Juhi / Hall, Cody N / Runge, John S / Weiss, Matthew / Rahmat, Mahshid / Anyoha, Rockwell / Fulco, Charles P / Ghobrial, Irene M / Engreitz, Jesse / Cieslik, Marcin P / Ryan, Russell J H

bioRxiv : the preprint server for biology

2023

Abstract: High expression of : Key points: CRISPR-interference screens identify a conserved germinal center B ... ...

Abstract	High expression of Key points: CRISPR-interference screens identify a conserved germinal center B cell
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.02.538892
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Article: Colopathy Associated with Pentosan Polysulfate Use.

Jung, Emily H / Zheng, Wei / Weiss, Ryan J / Mathew, Namita E / Meyer, Benjamin I / Nizam, Azhar / Iskandar, Heba / Jain, Nieraj

medRxiv : the preprint server for health sciences

2023

Abstract: Introduction: We describe a novel colopathy associated with pentosan polysulfate (PPS) use and measure the strength of the drug-disease association.: Methods: Two-part investigation. In the cohort study of individuals with a history of prior long- ... ...

Abstract	Introduction: We describe a novel colopathy associated with pentosan polysulfate (PPS) use and measure the strength of the drug-disease association. Methods: Two-part investigation. In the cohort study of individuals with a history of prior long-term PPS use, case histories were obtained and gastrointestinal disease course was followed with review of endoscopy records and histopathology specimens. Findings were summarized with descriptive statistics. In the cross-sectional study of individuals with interstitial cystitis, drug exposure and medical histories were obtained for patients seen at a single clinical center. Strength of association between PPS use and diagnoses of inflammatory bowel disease (IBD) and/or irritable bowel syndrome (IBS) was measured with multivariate logistic regression. Results: In the cohort study of 13 participants, median PPS exposure was 2.04 kg (0.99-2.54). Eleven (84.6%) developed symptoms suggestive of IBD and/or IBS after initiation of PPS therapy. Of the 10 participants whose endoscopic and histopathologic findings we reviewed, six had abnormal-appearing colonic mucosa on endoscopy and all 10 had abnormal mucosal changes on histology. Clinical and histologic improvement was observed after PPS cessation. In the cross-sectional study of 219 subjects with interstitial cystitis, PPS use was a statistically significant predictor of both the IBD [adjusted odds ratio=3.3 (95% confidence interval, 1.2-8.8, p=0.02)] and the composite IBD+IBS [adjusted odds ratio=3.3 (95% confidence interval, 1.5-7.3, p=0.002)] outcomes. Discussion: We describe a strong association between PPS use and a clinical diagnosis of IBD and/or IBS. Histopathologic findings suggest a novel drug-associated colopathy, with some subjects requiring colectomy for dysplasia.
Language	English
Publishing date	2023-04-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.03.23288071
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